Acremosides A-G, Sugar Alcohol-Conjugated Acyclic Sesquiterpenes from a Sponge-Derived Acremonium Species.

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 µM) with no cytotoxicity (CC50 of >200 µM).

Modifying electronic and optical properties of violet phosphorus through variable fluorine coverage.

We present a comprehensive investigation of the electronic properties of fluorinated monolayer violet phosphorus using first-principles calculations. Our results reveal a strong dependence of the electronic properties on the different fluorine coverages of fluorination. As the fluorine coverage increases, monolayer violet phosphorus undergoes a significant transition from a wide direct bandgap semiconductor to a narrow indirect bandgap semiconductor. Moreover, both semi-fluorinated and fully fluorinated monolayer violet phosphorus exhibit advantageous semiconducting characteristics, with a tunable bandgap of 0.50 ~ 1.04 eV under biaxial strain ranging from -6% to 6%. Notably, the fully fluorinated monolayer violet phosphorus demonstrates a higher coefficient of light absorption within the visible range. Therefore, our findings highlight the tunability of monolayer violet phosphorus properties through the absorption of various fluorine coverages, providing valuable insights for the design and development of novel semiconductor devices based on this material.

Predicting associations between drugs and G protein-coupled receptors using a multi-graph convolutional network.

Developing new drugs is an expensive, time-consuming process that frequently involves safety concerns. By discovering novel uses for previously verified drugs, drug repurposing helps to bypass the time-consuming and costly process of drug development. As the largest family of proteins targeted by verified drugs, G protein-coupled receptors (GPCR) are vital to efficiently repurpose drugs by inferring their associations with drugs. Drug repurposing may be sped up by computational models that predict the strength of novel drug-GPCR pairs interaction. To this end, a number of models have been put forth. In existing methods, however, drug structure, drug-drug interactions, GPCR sequence, and subfamily information couldn't simultaneously be taken into account to detect novel drugs-GPCR relationships. In this study, based on a multi-graph convolutional network, an end-to-end deep model was developed to efficiently and precisely discover latent drug-GPCR relationships by combining data from multi-sources. We demonstrated that our model, based on multi-graph convolutional networks, outperformed rival deep learning techniques as well as non-deep learning models in terms of inferring drug-GPCR relationships. Our results indicated that integrating data from multi-sources can lead to further advancement.

Effect of resuscitation of cryopreserved porcine adrenal glands at 26 °C on their recovery and functioning under xenotransplantation.

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.

Magnetic self-assembled label-free electrochemical biosensor based on Fe3O4/α-Fe2O3 heterogeneous nanosheets for the detection of Tau proteins.

A type of electrochemical biosensors based on magnetic Fe3O4/α-Fe2O3 heterogeneous nanosheets was constructed to detect Tau proteins for early diagnosis and intervention therapy of Alzheimer's disease (AD). Firstly, Fe3O4/α-Fe2O3 heterogeneous nanosheets were fabricated as the substrate to realize magnetic self-assembly and magnetic separation to improve current response, and Fe3O4/α-Fe2O3@Au-Apt/ssDNA/MCH biosensors were successfully constructed through the reduction process of chloroauric acid, the immobilizations of aptamer (Apt) and ssDNA, and the intercept process of 6-Mercapto-1-hexanol (MCH); the construction process of the electrochemical biosensor was monitored using Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the factors affecting the current response of this sensor (concentration of Fe3O4/α-Fe2O3@Au and Apt/ssDNA, incubation temperature and time of Tau) were explored and optimized using differential pulse voltammetry (DPV). Analyzing the performance of this sensor under optimal conditions, the linear range was finally obtained to be 0.1 pg/mL-10 ng/mL, the limit of detection (LOD) was 0.08 pg/mL, and the limit of quantification (LOQ) was 0.28 pg/mL. The selectivity, reproducibility and stability of the biosensors were further investigated, and in a really sample analysis using human serum, the recoveries were obtained in the range of 93.93 %-107.39 %, with RSD ranging from 1.05 % to 1.94 %.

New perspective of small-molecule antiviral drugs development for RNA viruses.

High variability and adaptability of RNA viruses allows them to spread between humans and animals, causing large-scale infectious diseases which seriously threat human and animal health and social development. At present, AIDS, viral hepatitis and other viral diseases with high incidence and low cure rate are still spreading around the world. The outbreaks of Ebola, Zika, dengue and in particular of the global pandemic of COVID-19 have presented serious challenges to the global public health system. The development of highly effective and broad-spectrum antiviral drugs is a substantial and urgent research subject to deal with the current RNA virus infection and the possible new viral infections in the future. In recent years, with the rapid development of modern disciplines such as artificial intelligence technology, bioinformatics, molecular biology, and structural biology, some new strategies and targets for antivirals development have emerged. Here we review the main strategies and new targets for developing small-molecule antiviral drugs against RNA viruses through the analysis of the new drug development progress against several highly pathogenic RNA viruses, to provide clues for development of future antivirals.

Ultrasound-targeted microbubble destruction rapidly improves left ventricular function in rats with ischemic cardiac dysfunction.

BACKGROUND: Previous studies have demonstrated the efficacy of ultrasound-targeted microbubble destruction (UTMD) in the treatment of ischemic heart failure (HF). The purpose of this study was to explore the mechanism by which UTMD improves ischemic HF. METHODS: An ischemic heart failure model was established using Sprague-Dawley rats. Rats were randomly divided into 7 groups: sham group, HF group, HF + MB group, HF + ultrasound (US) group, HF + UTMD group, HF + UTMD+LY294002 group, and HF + LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. PI3K/Akt/eNOS signaling pathway protein levels were detected by immunohistochemistry (IHC) and western blotting. The concentrations of nitrous oxide (NO) and ATP were detected by ELISA, and hematoxylin and eosin (HE) staining was used to evaluate myocardial tissue. RESULTS: UTMD rapidly improved ejection fraction (EF) (HF: 37.16 ± 1.21% vs. HF + UTMD: 46.31 ± 3.00%, P < 0.01) and fractional shortening (FS) (HF: 18.53 ± 0.58% vs. HF + UTMD: 24.05 ± 1.84%, P < 0.01) in rats with ischemic HF. UTMD activated the PI3K/AKT/eNOS signaling pathway (HF vs. HF + UTMD, P < 0.01) and promoted the release of NO and ATP (HF vs. HF + UTMD, both, P < 0.05). Inhibition of the PI3K/AKT/eNOS signaling pathway by LY294002 worsened EF (HF: 37.16 ± 1.21% vs. HF + LY294002: 32.73 ± 3.05%, P < 0.05), and the release of NO and ATP by UTMD (HF + UTMD vs. HF + UTMD+LY294002, P < 0.05). CONCLUSIONS: UTMD can rapidly improve cardiac function in ischemic HF by activating the PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

ABC2A: A Straightforward and Fast Method for the Accurate Backmapping of RNA Coarse-Grained Models to All-Atom Structures.

RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30-692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.

HKFGCN: A novel multiple kernel fusion framework on graph convolutional network to predict microbe-drug associations.

Accumulating clinical studies have consistently demonstrated that the microbes in the human body closely interact with the human host, actively participating in the regulation of drug effectiveness. Identifying the associations between microbes and drugs can facilitate the development of drug discovery, and microbes have become a new target in antimicrobial drug development. However, the discovery of microbe-drug associations relies on clinical or biological experiments, which are not only time-consuming but also financially burdensome. Thus, the utilization of computational methods to predict microbe-drug associations holds promise for reducing costs and enhancing the efficiency of biological experiments. Here, we introduce a new computational method, called HKFGCN (Heterogeneous information Kernel Fusion Graph Convolution Network), to predict the microbe-drug associations. Instead of extracting feature from a single network in previous studies, HKFGCN separately extracts topological information features from different networks, and further refines them by generating Gaussian kernel features. HKFGCN consists of three main steps. Firstly, we constructed two similarity networks and a microbe-drug association network based on numerous biological data. Second, we employed two types of encoders to extract features from these networks. Next, Gaussian kernel features were obtained from the drug and microbe features at each layer. Finally, we reconstructed the bipartite microbe-drug graph based on the learned representations. Experimental results demonstrate the excellent performance of the HKFGCN model across different datasets using the cross-validation scheme. Additionally, we conduced case studies on human immunodeficiency virus, and the results were corroborated by existing literatures. The prediction model's code is available at https://github.com/roll-of-bubble/HKFGCN.

Individualized white matter connectivity of the articulatory pathway: An ultra-high field study.

In current sensorimotor theories pertaining to speech perception, there is a notable emphasis on the involvement of the articulatory-motor system in the processing of speech sounds. Using ultra-high field diffusion-weighted imaging at 7 Tesla, we visualized the white matter tracts connected to areas activated during a simple speech-sound production task in 18 healthy right-handed adults. Regions of interest for white matter tractography were individually determined through 7T functional MRI (fMRI) analyses, based on activations during silent vocalization tasks. These precentral seed regions, activated during the silent production of a lip-vowel sound, demonstrated anatomical connectivity with posterior superior temporal gyrus areas linked to the auditory perception of phonetic sounds. Our study provides a macrostructural foundation for understanding connections in speech production and underscores the central role of the articulatory motor system in speech perception. These findings highlight the value of ultra-high field 7T MR acquisition in unraveling the neural underpinnings of speech.

Exploration of subgroups and predictors of loneliness among older adults in rural China: A latent profile analysis.

BACKGROUND: Loneliness is a negative emotional state that can lead to physical and mental health problems. This study's objective was to acquire an in-depth understanding of the heterogeneity and the predictors of loneliness among older adults in rural China and provide valuable references for practical interventions. METHODS: Older rural adults in China (N = 680) were recruited between January and April 2023. Latent profile analysis (LPA) was employed to identify subgroups of loneliness among participants. Single-factor and multinomial logistic regression analyses were conducted to investigate predictors of loneliness. RESULTS: The loneliness of rural older adults could be divided into three subgroups: low interaction loneliness group (55.0%), moderate emotional loneliness group (31.8%), and high loneliness group (13.2%). The subgroup predictors included age, gender, religious beliefs, marital status, living alone, number of chronic diseases, and smartphone use (P < 0.05). CONCLUSION: This study identified a classification pattern for loneliness among older adults in rural areas of China, revealed the characteristics of different demographic variables in loneliness categories, and highlighted the heterogeneity of loneliness in this population. It serves as a theoretical reference for formulating intervention plans aimed at addressing various loneliness categories for local rural older adults. CLINICAL TRIAL REGISTRATION: ChiCTR2300071591.

Breeding exceptionally fragrant soybeans for soy milk with strong aroma.

Knockout of the soybean (Glycine max) betaine aldehyde dehydrogenase genes GmBADH1 and GmBADH2 using CRISPR/Cas12i3 enhances the aroma of soybeans. Soy milk made from the gmbadh1/2 double mutant seeds exhibits a much stronger aroma, which consumers prefer; this mutant has potential for enhancing quality in soy-based products.

Histone H1.2 Inhibited EMCV Replication through Enhancing MDA5-Mediated IFN-ß Signaling Pathway.

Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-ß and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation-inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.

Study on Linewidth and Phase Noise Characteristics of a Narrow Linewidth External Cavity Diode Laser.

In the field of inter-satellite laser communication, achieving high-quality communication and compensating for the Doppler frequency shift caused by relative motion necessitate lasers with narrow linewidths, low phase noise, and the ability to achieve mode-hop-free tuning within a specific range. To this end, this paper investigates a novel external cavity diode laser (ECDL) with a frequency-selective F-P etalon structure, leveraging the external cavity F-P etalon structure in conjunction with an auxiliary filter to achieve single longitudinal mode selection. The laser undergoes linewidth testing using a delayed self-heterodyne beating method, followed by the testing of its phase noise and frequency noise characteristics using a noise analyzer, yielding beat spectra and noise power spectral density profiles. Furthermore, the paper introduces an innovative bidirectional temperature-scanning laser method to achieve optimal laser-operating point selection and mode-hop-free tuning. The experimental results showcase that the single longitudinal mode spectral side-mode suppression ratio (SMSR) is around 70 dB, and the output power exceeds 10 mW. Enhancing the precision of the F-P etalon leads to a more pronounced suppression of low-frequency phase noise, reducing the Lorentzian linewidth from the initial 10 kHz level to a remarkable 5 kHz level. The bidirectional temperature-scanning laser method not only allows for the selection of the optimal operating point but also enables mode-hop-free tuning within 160 pm.

Innovative Techniques in Video-Assisted Thoracoscopic Surgery: Lu's Approach.

Purpose: Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach. Patients and Methods: The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant. Results: A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P <0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups. Conclusion: Lu's approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.

Proton-Gradient-Driven Porphyrin-Based Liposome Remote-Loaded with Imiquimod as In Situ Nanoadjuvants for Synergistically Augmented Tumor Photoimmunotherapy.

Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation. R837@PBL upon laser irradiation triggered immunogenic cell death of tumor cells and tumor-associated antigen release after subcutaneous injection, activated TLR7, formed in situ tumor nanoadjuvants, and enhanced the antigen presentation efficiency. Photoimmunotherapy promoted the infiltration of cytotoxic T lymphocytes into tumor tissues, inhibited the growth of the treated and abscopal tumors, and exerted highly effective photoimmunotherapeutic effects. Hence, our designed in situ tumor nanoadjuvants are expected to be an effective treatment for treated and abscopal tumors, providing a novel approach for synergistic photoimmunotherapy of tumors.

ESRG regulates alternative splicing of TCF3 to maintain hESCs self-renewal and pluripotency.

Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.

In Vitro and In Vivo Anti-Candida albicans Activity of a Scorpion-Derived Peptide.

The increasing infection and drug resistance frequency has encouraged the exploration of new and effective anti-Candida albicans agents. In this study, CT-K3K7, a scorpion antimicrobial peptide derivative, effectively inhibit the growth of C. albicans. CT-K3K7 killed C. albicans cells in a dose-dependent manner, mainly by damaging the plasma membrane. CT-K3K7 could also disrupt the nucleus and interact with nucleic acid. Moreover, CT-K3K7 induced C. albicans cells necrosis via a reactive oxygen species (ROS)-related pathway. Furthermore, CT-K3K7 inhibited the hyphal and biofilm formation of C. albicans. In the mouse skin subcutaneous infection model, CT-K3K7 significantly prevented skin abscess formation and reduced the number of C. albicans cells recovered from the infection area. Taken together, CT-K3K7 has the potential to be a therapeutic for C. albicans skin infections.