Skin-inspired, sensory robots for electronic implants.

Drawing inspiration from cohesive integration of skeletal muscles and sensory skins in vertebrate animals, we present a design strategy of soft robots, primarily consisting of an electronic skin (e-skin) and an artificial muscle. These robots integrate multifunctional sensing and on-demand actuation into a biocompatible platform using an in-situ solution-based method. They feature biomimetic designs that enable adaptive motions and stress-free contact with tissues, supported by a battery-free wireless module for untethered operation. Demonstrations range from a robotic cuff for detecting blood pressure, to a robotic gripper for tracking bladder volume, an ingestible robot for pH sensing and on-site drug delivery, and a robotic patch for quantifying cardiac function and delivering electrotherapy, highlighting the application versatilities and potentials of the bio-inspired soft robots. Our designs establish a universal strategy with a broad range of sensing and responsive materials, to form integrated soft robots for medical technology and beyond.

O-glycosylation in viruses: A sweet tango.

O-glycosylation is an ancient yet underappreciated protein posttranslational modification, on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseases or even cancer. But due to the innate complexity of O-glycosylation, research techniques have been limited to study its exact role in viral attachment and entry, assembly and exit, spreading in the host cells, and the innate and adaptive immunity of the host. Recently, the advent of many newly developed methodologies (e.g., mass spectrometry, chemical biology tools, and molecular dynamics simulations) has renewed and rekindled the interest in viral-related O-glycosylation in both viral proteins and host cells, which is further fueled by the COVID-19 pandemic. In this review, we summarize recent advances in viral-related O-glycosylation, with a particular emphasis on the mucin-type O-linked α-N-acetylgalactosamine (O-GalNAc) on viral proteins and the intracellular O-linked ß-N-acetylglucosamine (O-GlcNAc) modifications on host proteins. We hope to provide valuable insights into the development of antiviral reagents or vaccines for better prevention or treatment of infectious diseases.

Impact of Baduanjin exercise combined with rational emotive behavior therapy on sleep and mood in patients with poststroke depression: A randomized controlled trial.

BACKGROUND: Poststroke depression (PSD) is one of the most common stroke complications. It not only leads to a decline in patients' quality of life but also increases the mortality of patients. In this study, the method of combining Chinese traditional exercise Baduanjin with psychotherapy was used to intervene in patients with PSD and to explore the improvement of sleep, mood, and serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) levels in patients with PSD by combined treatment. METHODS: A total of 100 patients with PSD who met the inclusion criteria were randomly assigned to Baduanjin group (n = 50) or control group (n = 50). The control group received treatment with escitalopram oxalate and rational emotive behavior therapy, while the experimental group received Baduanjin training in addition to the treatment given to the control group. Changes in sleep efficiency, sleep total time, sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale score, serum BDNF, 5-HT, IL-6 levels, and Modified Barthel Index were measured at baseline, 4 weeks and 8 weeks after intervention, and the results were compared between the 2 groups. RESULTS: Significantly improvements in the sleep efficiency, sleep total time, serum 5-HT, BDNF levels, and Modified Barthel Index score were detected at week 4 in the Baduanjin group than in the control group (P < .05). Additionally, the sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale scores and IL-6 levels in the Baduanjin group were lower than those in the control group (P < .05). After 8 weeks of treatment, the above indexes in the Baduanjin group were further improved compared with the control group (P < .05), and the above indexes of the 2 groups were significantly improved compared with the baseline (P < .001). CONCLUSION: Baduanjin exercise combined with rational emotive behavior therapy effectively improves the mood and sleep status of patients with PSD; It increases the serum levels of 5-HT and BDNF while reducing the level of serum proinflammatory factor IL-6; additionally, the intervention alleviates the degree of neurological impairment, upgrades the ability of daily living, and improves the quality of life.

2D materials-based photodetectors combined with ferroelectrics.

Photodetectors are essential optoelectronic devices that play a critical role in modern technology by converting optical signals into electrical signals, which are one of the most important sensors of the informational devices in current "Internet of Things" era. Two-dimensional (2D) material-based photodetectors have excellent performance, simple design and effortless fabrication processes, as well as enormous potential for fabricating highly integrated and efficient optoelectronic devices, which has attracted extensive research attention in recent years. The introduction of spontaneous polarization ferroelectric materials further enhances the performance of 2D photodetectors, moreover, companying with the reduction of power consumption. This article reviews the recent advances of materials, devices in ferroelectric-modulated photodetectors. This review starts with the introduce of the basic terms and concepts of the photodetector and various ferroelectric materials applied in 2D photodetectors, then presents a variety of typical device structures, fundamental mechanisms and potential applications under ferroelectric polarization modulation. Finally, we summarize the leading challenges currently confronting ferroelectric-modulated photodetectors and outline their future perspectives.

Long-chain unsaturated fatty acids sensor controlling the type III/VI secretion system is essential for Edwardsiella piscicida infection.

Edwardsiella piscicida is an acute marine pathogen that causes severe damage to the aquaculture industry worldwide. The pathogenesis of E. piscicida is dependent mainly on the type III secretion system (T3SS) and type VI secretion system (T6SS), both of which are critically regulated by EsrB and EsrC. In this study, we revealed that fatty acids influence T3SS expression. Unsaturated fatty acids (UFAs), but not saturated fatty acids (SFAs), directly interact with EsrC, which abolishes the function of EsrC and results in the turn-off of T3/T6SS. Moreover, during the in vivo colonization of E. piscicida, host fatty acids were observed to be transported into E. piscicida through FadL and to modulate the expression of T3/T6SS. Furthermore, the esrCR38G mutant blocked the interaction between EsrC and UFAs, leading to dramatic growth defects in DMEM and impaired colonization in HeLa cells and zebrafish. In conclusion, this study revealed that the interaction between UFAs and EsrC to turn off T3/T6SS expression is essential for E. piscicida infection.

Mechanism on microbial transglutaminase and Tremella fuciformis polysaccharide-mediated modification of lactoferrin: Development of functional food.

Lactoferrin (LF) with various biological functions demonstrates great application potential. However, its application was restricted by its poor gelation and instability. The aim of this work was to explore the effect of microbial transglutaminase (MTGase) and Tremella fuciformis polysaccharide (TP) on the functional properties of LF. The formation of a self-supporting LF gel could be induced by MTGase through generating covalent crosslinks between the LF protein molecules. Meanwhile, TP was introduced into the gel system to improve the strength of LF-TP composite gels by enhancing non-covalent interactions such as hydrogen bond and electrostatic interactions during gel formation. Additionally, the LF-TP composite gel exhibited outstanding functional characteristics such as gastrointestinal digestive stability and antioxidant property. This work clarified the mechanism on MTGase and TP-mediated modification of lactoferrin, offered a novel strategy to increase the functional characteristics of LF, and enlarged the application range of LF and TP.

Thermoelectric active cooling for transient hot spots in microprocessors.

Modern microprocessor performance is limited by local hot spots induced at high frequency by busy integrated circuit elements such as the clock generator. Locally embedded thermoelectric devices (TEDs) are proposed to perform active cooling whereby thermoelectric effects enhance passive cooling by the Fourier law in removing heat from the hot spot to colder regions. To mitigate transient heating events and improve temperature stability, we propose a novel analytical solution that describes the temperature response of a periodically heated hot spot that is actively cooled by a TED driven electrically at the same frequency. The analytical solution that we present is validated by experimental data from frequency domain thermal reflectance (FDTR) measurements made directly on an actively cooled Si thermoelectric device where the pump laser replicates the transient hot spot. We herein demonstrate a practical method to actively cancel the transient temperature variations on circuit elements with TEDs. This result opens a new path to optimize the design of cooling systems for transient localized hot spots in integrated circuits.

Screening signal peptidase based on split-GFP assembly technology to promote the secretion of alkaline protease AprE in Bacillus amyloliquefaciens.

Improving the ability of bacteria to secrete protein is essential for large-scale production of food enzymes. However, due to the lack of effective tracking technology for target proteins, the optimization of the secretory system is facing many problems. In this study, we utilized the split-GFP system to achieve self-assembly into mature GFP in Bacillus amyloliquefaciens and successfully tracked the alkaline protease AprE. The split-GFP system was employed to assess the signal peptidases, a crucial component in the secretory system, and signal peptidase sipA was identified as playing a role in the secretion of AprE. Deletion of sipA resulted in a higher accumulation of the precursor protein of AprE compared to other signal peptidase deletion strains. To explore the mechanism of signal peptidase on signal peptide, molecular docking and calculation of free energy were performed. The action strength of the signal peptidase is determined by its binding affinity with the tripeptides at the C-terminal of the signal peptide. The functions of signal peptides YdbK and NucB rely on sipA, and overexpression of sipA by integrating it into genome of B. amyloliquefaciens increased the activity of extracellular AprE by 19.9 %. These findings provide insights into enhancing the secretion efficiency of chassis strains.

Enhancing polycyclic aromatic hydrocarbon soil remediation in cold climates using immobilized low-temperature-resistant mixed microorganisms.

Polycyclic aromatic hydrocarbons (PAHs), widespread organic pollutants, significantly impact human health and environmental integrity. Recent approaches to ameliorate PAH-contaminated soils, particularly in cold environments, have been insufficient. This study investigates the use of immobilized low-temperature-resistant mixed microorganisms (LTRMM) for enhancing the degradation of PAHs in soils from coke plants and the Shenfu irrigation area. Our results demonstrate that treatment with immobilized mixed microorganisms (MC-HS) is more effective than treatments with free bacteria (H-S) and control (CK). Specifically, the degradation rates in the MC-HS1 treatment were 10.10 %-41.13 % higher than those in the coking plant soil treated with CK1 and H-S1. Similarly, in the Shenfu irrigation area soil, MC-HS2 showed improvements of 6.00 % to 52.56 % over CK2 and H-S2. A kinetic model was used to analyze the enhanced degradation capabilities, revealing that the half-life of PAHs under the immobilized mixed microorganism treatment (T3) was significantly shorter compared to the free bacteria (T2) and control treatments (T1). These findings suggest that employing immobilized LTRMM could significantly improve the remediation efficiency of PAH-contaminated soils in cold climates.

Networks of Nerve Fibers, and Blood and Lymphatic Vessels in the Mouse Auricle: The Structural Basis of Ear Acupuncture.

Objective: Ear acupuncture, as a system for treating and preventing diseases through stimulation of points on the auricle, has been systematically introduced during the last 60 years. Although the auricular cartography was described somatotopically as an inverted fetus by Paul Nogier, MD, the underlying mechanism of auricular stimulation remains unclear. The aim of this research was to gain an understanding of the structural basis of auricular stimulation, as well as showing the distribution of the nerve fibers, and the blood and lymphatic vessels. Materials and Methods: The distribution of nerve fibers, and blood and lymphatic vessels was examined in whole-mount auricular skins of mice by combining the biomarkers protein gene product 9.5, cluster of differentiation 31, and lymphatic-vessel endothelial hyaluronan receptor-1 following tissue-clearing treatment with multiple immunofluorescent staining. Results: The labeled nerve fibers, and the blood and lymphatic vessels were distributed extensively in the inner and outer parts of the auricular skin. Auricular nerves aligning with blood vessels ran from the basal region to the peripheral region and crossed over lymphatic vessels, thus forming the neural, vascular, and lymphatic networks. Conclusions: As these are important tissue components of auricular skin, this result implies that the auricular nerve fibers, and blood and lymphatic vessels may coordinate with each other to respond directly to auricular stimulation.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Effect of sanxan as novel natural gel modifier on the physicochemical and structural properties of microbial transglutaminase-induced mung bean protein isolate gels.

Mung bean protein isolate (MBPI) has attracted much attention as an emerging plant protein. However, its application was limited by the poor gelling characteristics. Thus, the effect of sanxan (SAN) on the gelling behavior of MBPI under microbial transglutaminase (MTG)-induced condition were explored in this study. The results demonstrated that SAN remarkably enhanced the storage modulus, water-holding capacity and mechanical strength. Furthermore, SAN changed the microstructure of MBPI gels to become more dense and ordered. The results of zeta potential indicated the electrostatic interactions existed between SAN and MBPI. The incorporation of SAN altered the secondary structure and molecular conformation of MBPI, and hydrophobic interactions and hydrogen bonding were necessary to maintain the network structure. Additionally, in vitro digestion simulation results exhibited that SAN remarkably improved the capability of MBPI gels to deliver bioactive substances. These findings provided a practical strategy to use natural SAN to improve legume protein gels.

Discovery of LLC0424 as a Potent and Selective in Vivo NSD2 PROTAC Degrader.

Nuclear receptor-binding SET domain-containing 2 (NSD2), a methyltransferase that primarily installs the dimethyl mark on lysine 36 of histone 3 (H3K36me2), has been recognized as a promising therapeutic target against cancer. However, existing NSD2 inhibitors suffer from low activity or inferior selectivity, and none of them can simultaneously remove the methyltransferase activity and chromatin binding function of NSD2. Herein we report the discovery of a novel NSD2 degrader LLC0424 by leveraging the proteolysis-targeting chimera technology. LLC0424 potently degraded NSD2 protein with a DC50 value of 20 nM and a Dmax value of 96% in acute lymphoblastic leukemia (ALL) RPMI-8402 cells. Mechanistic studies revealed LLC0424 to selectively induce NSD2 degradation in a cereblon- and proteasome-dependent fashion. LLC0424 also caused continuous downregulation of H3K36me2 and growth inhibition of ALL cell lines with NSD2 mutation. Importantly, intravenous or intraperitoneal injection of LLC0424 showed potent NSD2 degradation in vivo.

NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis.

The androgen receptor (AR) is a ligand-responsive transcription factor that binds at enhancers to drive terminal differentiation of the prostatic luminal epithelia. By contrast, in tumors originating from these cells, AR chromatin occupancy is extensively reprogrammed to drive hyper-proliferative, metastatic, or therapy-resistant phenotypes, the molecular mechanisms of which remain poorly understood. Here, we show that the tumor-specific enhancer circuitry of AR is critically reliant on the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone 3 lysine 36 di-methyltransferase. NSD2 expression is abnormally gained in prostate cancer cells and its functional inhibition impairs AR trans-activation potential through partial off-loading from over 40,000 genomic sites, which is greater than 65% of the AR tumor cistrome. The NSD2-dependent AR sites distinctly harbor a chimeric AR-half motif juxtaposed to a FOXA1 element. Similar chimeric motifs of AR are absent at the NSD2-independent AR enhancers and instead contain the canonical palindromic motifs. Meta-analyses of AR cistromes from patient tumors uncovered chimeric AR motifs to exclusively participate in tumor-specific enhancer circuitries, with a minimal role in the physiological activity of AR. Accordingly, NSD2 inactivation attenuated hallmark cancer phenotypes that were fully reinstated upon exogenous NSD2 re-expression. Inactivation of NSD2 also engendered increased dependency on its paralog NSD1, which independently maintained AR and MYC hyper-transcriptional programs in cancer cells. Concordantly, a dual NSD1/2 PROTAC degrader, called LLC0150, was preferentially cytotoxic in AR-dependent prostate cancer as well as NSD2-altered hematologic malignancies. Altogether, we identify NSD2 as a novel subunit of the AR neo-enhanceosome that wires prostate cancer gene expression programs, positioning NSD1/2 as viable paralog co-targets in advanced prostate cancer.

Fast identification of the BmNPV infected silkworms by portable NIR spectroscopy and chemometrics.

A convenient, low-cost, and rapid detection of BmNPV-infected silkworms is of great significance for the safety of the sericulture industry. In this study, a portable NIR system was used to collect the spectra of normal silkworms and the infected silkworms induced by the administration of Bombyx mori nuclear polyhedrosis virus (BmNPV). Different spectral pretreatment methods were applied, then principal component analysis (PCA), linear discriminant analysis (LDA), and partial least squares discriminant analysis (PLSDA) were used for the classification analysis. The results showed that PCA and LDA were unable to achieve the purpose. For the PLSDA calibration, after the pretreatment of SNV combining 2nd derivative, it had a high identification performance, and obtained low classification errors of 0.023, 0.033, and 0.030 for the calibration set, cross-validation set, and test set, respectively, with higher sensitivity and specificity. Therefore, the BmNPV-infected silkworms can be identified by portable NIR spectroscopy, which will effectively reduce losses for the sericulture industry.

Cyclocodon lancifolius fruit prolongs the lifespan of Caenorhabditis elegans via antioxidation and regulation of purine metabolism.

Cyclocodon lancifolius fruit is a promising commercial fruit with antioxidant activity and is rich in polyphenolic compounds. In this study, the anti-aging activity of C. lancifolius fruit extract (CF) on Caenorhabditis elegans (C. elegans) was evaluated by observing the longevity, stress response, reproduction, oscillation, lipofuscin, and antioxidant enzymes of worms. Moreover, the effects and potential mechanisms of CF on delaying C. elegans senescence at the mRNA and metabolite levels were investigated. The results showed that CF treatment significantly increased the lifespan and stress resistance, decreased the levels of lipofuscin and reactive oxygen species (ROS), and improved the antioxidant system of C. elegans. The extension of the lifespan of C. elegans was remarkably correlated with the upregulation of mtl-1 and Hsp-16.2, along with the downregulation of age-1, daf-2, and akt-1. Metabolomics analysis revealed that purine metabolism is a key regulatory pathway for CF to exert anti-aging effects. The present study suggests that C. lancifolius fruit has potential for use as a functional food to enhance antioxidant capacity and delay aging.

Single-cell N6-methyladenosine-related genes function within the tumor microenvironment to affect the prognosis and treatment sensitivity in patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) ranks fifth for morbidity and third for mortality worldwide. The N6-methyladenosine (m6A) mRNA methylation is crucial in cancer biology and progression. However, the relationship between m6A methylation and gastric tumor microenvironment (TME) remains to be elucidated. METHODS: We combined single-cell and bulk transcriptome analyses to explore the roles of m6A-related genes (MRG) in gastric TME. RESULTS: Nine TME cell subtypes were identified from 23 samples. Fibroblasts were further grouped into four subclusters according to different cell markers. M6A-mediated fibroblasts may guide extensive intracellular communications in the gastric TME. The m6A-related genes score (MRGs) was output based on six differentially expressed single-cell m6A-related genes (SCMRDEGs), including GHRL, COL4A1, CAV1, GJA1, TIMP1, and IGFBP3. The protein expression level was assessed by immunohistochemistry. We identified the prognostic value of MRGs and constructed a nomogram model to predict GC patients' overall survival. MRGs may affect treatment sensitivity in GC patients. CONCLUSION: Our study visualized the cellular heterogeneity of TME at the single-cell level, revealed the association between m6A mRNA modification and intracellular communication, clarified MRGs as an independent risk factor of prognosis, and provided a reference for follow-up treatment.

Computation-Aided Phylogeny-Oriented Engineering of ß-Xylosidase: Modification of "Blades" to Enhance Stability and Activity for the Bioconversion of Hemicellulose to Produce Xylose.

Hemicellulose is a highly abundant, ubiquitous, and renewable natural polysaccharide, widely present in agricultural and forestry residues. The enzymatic hydrolysis of hemicellulose has generally been accomplished using ß-xylosidases, but concomitantly increasing the stability and activity of these enzymes remains challenging. Here, we rationally engineered a ß-xylosidase from Bacillus clausii to enhance its stability by computation-aided design combining ancestral sequence reconstruction and structural analysis. The resulting combinatorial mutant rXYLOM25I/S51L/S79E exhibited highly improved robustness, with a 6.9-fold increase of the half-life at 60 °C, while also exhibiting improved pH stability, catalytic efficiency, and hydrolytic activity. Structural analysis demonstrated that additional interactions among the propeller blades in the catalytic module resulted in a much more compact protein structure and induced the rearrangement of the opposing catalytic pocket to mediate the observed improvement of activity. Our work provides a robust biocatalyst for the hydrolysis of agricultural waste to produce various high-value-added chemicals and biofuels.

Th9/IL-9 may participate in the pathogenesis of multiple myeloma.

INTRODUCTION: This research is aimed to evaluate the correlation between Th9-associated cytokine levels in MM patients, clinical features, and therapy. METHODS: Peripheral blood samples were taken in 52 MM patients and 20 healthy volunteers matched by sex and age. The patients with MM were separated into two groups: the untreated group (27) and the remission group (25). An enzyme-linked immunosorbent assay (ELISA) was used to measure the IL-9 plasma levels. The levels of Th9-associated cytokines' mRNA expression (IL-9, PU.1, and IRF4) were measured in RT-qPCR. We also analyzed the correlations between the IL-9 plasma levels and the clinical parameters of newly diagnosed MM patients. RESULTS: The IL-9 plasma levels and the Th9-associated cytokines (IL-9, PU.1, and IRF4) mRNA levels in newly diagnosed MM patients were significantly elevated than those in healthy volunteers and significantly decreased after achieving remission. Moreover, PU.1 and IRF4 had a positive correlation with the IL-9 mRNA expression. Then, we found that the upregulation of IL-9 plasma levels correlates with the severity of anemia and decreased albumin Levels. CONCLUSION: The results demonstrate that Th9/IL-9 may be involved in the pathogenesis of MM and is correlated with worse patient conditions such as lower hemoglobin and serum albumin. More work is necessary to confirm whether they might serve as a useful therapeutic target and prognostic marker for MM.

Quantivine: A Visualization Approach for Large-Scale Quantum Circuit Representation and Analysis.

Quantum computing is a rapidly evolving field that enables exponential speed-up over classical algorithms. At the heart of this revolutionary technology are quantum circuits, which serve as vital tools for implementing, analyzing, and optimizing quantum algorithms. Recent advancements in quantum computing and the increasing capability of quantum devices have led to the development of more complex quantum circuits. However, traditional quantum circuit diagrams suffer from scalability and readability issues, which limit the efficiency of analysis and optimization processes. In this research, we propose a novel visualization approach for large-scale quantum circuits by adopting semantic analysis to facilitate the comprehension of quantum circuits. We first exploit meta-data and semantic information extracted from the underlying code of quantum circuits to create component segmentations and pattern abstractions, allowing for easier wrangling of massive circuit diagrams. We then develop Quantivine, an interactive system for exploring and understanding quantum circuits. A series of novel circuit visualizations is designed to uncover contextual details such as qubit provenance, parallelism, and entanglement. The effectiveness of Quantivine is demonstrated through two usage scenarios of quantum circuits with up to 100 qubits and a formal user evaluation with quantum experts. A free copy of this paper and all supplemental materials are available at https://osf.io/2m9yh/?view_only=0aa1618c97244f5093cd7ce15f1431f9.