Overcoming the adhesion paradox and switchability conflict on rough surfaces with shape-memory polymers.

Smart adhesives that can be applied and removed on demand play an important role in modern life and manufacturing. However, current smart adhesives made of elastomers suffer from the long-standing challenges of the adhesion paradox (rapid decrease in adhesion strength on rough surfaces despite adhesive molecular interactions) and the switchability conflict (trade-off between adhesion strength and easy detachment). Here, we report the use of shape-memory polymers (SMPs) to overcome the adhesion paradox and switchability conflict on rough surfaces. Utilizing the rubbery-glassy phase transition in SMPs, we demonstrate, through mechanical testing and mechanics modeling, that the conformal contact in the rubbery state followed by the shape-locking effect in the glassy state results in the so-called rubber-to-glass (R2G) adhesion (defined as making contact in the rubbery state to a certain indentation depth followed by detachment in the glassy state), with extraordinary adhesion strength (>1 MPa) proportional to the true surface area of a rough surface, overcoming the classic adhesion paradox. Furthermore, upon transitioning back to the rubbery state, the SMP adhesives can detach easily due to the shape-memory effect, leading to a simultaneous improvement in adhesion switchability (up to 103, defined as the ratio of the SMP R2G adhesion to its rubbery-state adhesion) as the surface roughness increases. The working principle and the mechanics model of R2G adhesion provide guidelines for developing stronger and more switchable adhesives adaptable to rough surfaces, thereby enhancing the capabilities of smart adhesives, and impacting various fields such as adhesive grippers and climbing robots.

Quercetin regulates dendritic cell activation by targeting STAT4 in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.

Improving protein-protein interaction site prediction using deep residual neural network.

Accurate identification of protein-protein interaction (PPI) sites is significantly important for understanding the mechanism of life and developing new drugs. However, it is expensive and time-consuming to identify PPI sites using wet-lab experiments. Developing computational methods is a new road to identify PPI sites, which can accelerate the procedure of PPI-related research. In this study, we propose a novel deep learning-based method (called D-PPIsite) to improve the accuracy of sequence-based PPI site prediction. In D-PPIsite, four discriminative sequence-driven features, i.e., position specific scoring matrix, relative solvent accessibility, position information and physical properties, are employed to feed into a well-designed deep learning module, consisting of convolutional, squeeze and excitation, and fully connected layers, to learn a prediction model. To reduce the risk of a single prediction model getting stuck in local optima, multiple prediction models with different initialization parameters are selected and integrated into one final model using the mean ensemble strategy. Experimental results on five independent testing data sets demonstrate that the proposed D-PPIsite can achieve an average accuracy of 80.2% and precision of 36.9%, covering 53.5% of all PPI sites while achieving the average Matthews correlation coefficient value (0.330) that is significantly higher than most of existing state-of-the-art prediction methods. We implement a new standalone-version predictor for predicting PPI sites, which is freely available at https://github.com/MingDongup/D-PPIsite for academic use.

Improving DNA 6mA Site Prediction via Integrating Bidirectional Long Short-Term Memory, Convolutional Neural Network, and Self-Attention Mechanism.

Identifying DNA N6-methyladenine (6mA) sites is significantly important to understanding the function of DNA. Many deep learning-based methods have been developed to improve the performance of 6mA site prediction. In this study, to further improve the performance of 6mA site prediction, we propose a new meta method, called Co6mA, to integrate bidirectional long short-term memory (BiLSTM), convolutional neural networks (CNNs), and self-attention mechanisms (SAM) via assembling two different deep learning-based models. The first model developed in this study is called CBi6mA, which is composed of CNN, BiLSTM, and fully connected modules. The second model is borrowed from LA6mA, which is an existing 6mA prediction method based on BiLSTM and SAM modules. Experimental results on two independent testing sets of different model organisms, i.e., Arabidopsis thaliana and Drosophila melanogaster, demonstrate that Co6mA can achieve an average accuracy of 91.8%, covering 89% of all 6mA samples while achieving an average Matthews correlation coefficient value (0.839), which is higher than the second-best method DeepM6A.

CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

An unusual cause of recurrent abdominal pain in a middle-aged man.

A 54-year-old man was hospitalized with intermittent periumbilical pain for 1-month duration. Abdominal contrast-enhanced computed tomography (CT) revealed target-sign and a fat density mass measuring 2.0 × 2.5-cm in the distal ileum. Part mesenteric tissues and blood vessels were embedded and the wall of the affected intestinal tube was thickened and edematous. His symptom was alleviated after conservative treatment and he refused further management. The patient was hospitalized again with the same symptoms and abdominal CT findings 4 years later. Exploratory laparotomy was performed. A palpable mass in the ileum was found measuring 3.0 × 3.0-cm and partial enterectomy was performed. Postoperative histopathology revealed the resected mass was composed of proliferating mature adipocytes surrounded by few fibrous connective tissue. Hyperplastic fibroblast and inflammatory exudative necrotic tissue were found on the surface of the mass. The patient was diagnosed as ileum fibrolipoma with intussusception. He was discharged home uneventfully and no symptoms was observed in 12 months follow-up.

Endoscopic submucosal dissection of a rare antral mass: gastric fibrolipoma.

A 60-year-old man was hospitalized with upper abdominal pain for 2-month duration. He had no previous history of symptoms related to his upper gastrointestinal tract. Physical examination was unremarkable. A semicircular round mass with smooth surface was found at the gastric antrum measuring 2.0 × 2.0-cm by gastroscopy. Endoscopic ultrasound (EUS) demonstrated a heterogeneous hyperechoic mass originated from the submucosal layer. Abdominal computed tomography (CT) revealed a fat-density mass with internal mixed density at the gastric antrum. His complete blood test, liver, renal, coagulation function and tumor markers were within reference values. Endoscopic submucosal dissection (ESD) was performed. Postoperative histopathology examination revealed the tumor was composed of closely arranged proliferating mature adipocytes with consistent size and shape. Collagen fiber hyperplasia between adipocytes was found in focal area. The patient was diagnosed as gastric fibrolipoma. He was discharged home uneventful and no symptoms was found in 12 months follow-up.

Predicting RNA solvent accessibility from multi-scale context feature via multi-shot neural network.

Knowledge of RNA solvent accessibility has recently become attractive due to the increasing awareness of its importance for key biological process. Accurately predicting the solvent accessibility of RNA is crucial for understanding its 3D structure and biological function. In this study, we develop a novel computational method, termed M2pred, for accurately predicting the solvent accessibility of RNA from sequence-based multi-scale context feature. In M2pred, three single-view features, i.e., base-pairing probabilities, position-specific frequency matrix, and a binary one-hot encoding, are first generated as three feature sources, and immediately concatenated to engender a super feature. Secondly, for the super feature, the matrix-format features of each nucleotide are extracted using an initialized sliding window technique, and regularly stacked into a cube-format feature. Then, using multi-scale context feature extraction strategy, a pyramid feature constructed of contextual feature of four scales related to target nucleotides is extracted from the cube-format feature. Finally, a customized multi-shot neural network framework, which is equipped with four different scales of receptive fields mainly integrating several residual attention blocks, is designed to dig discrimination information from the contextual pyramid feature. Experimental results demonstrate that the proposed M2pred achieve a high prediction performance and outperforms existing state-of-the-art prediction methods of RNA solvent accessibility.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma.

BACKGROUND: The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. METHODS: This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. RESULTS: When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21-0.51), PUFA (OR: 0.32, 95% CI: 0.20-0.51), and TFA (OR: 0.44, 95% CI: 0.28-0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19-0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. CONCLUSIONS: This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

A Wideband Noise and Harmonic Distortion Canceling Low-Noise Amplifier for High-Frequency Ultrasound Transducers.

This paper presents a wideband low-noise amplifier (LNA) front-end with noise and distortion cancellation for high-frequency ultrasound transducers. The LNA employs a resistive shunt-feedback structure with a feedforward noise-canceling technique to accomplish both wideband impedance matching and low noise performance. A complementary CMOS topology was also developed to cancel out the second-order harmonic distortion and enhance the amplifier linearity. A high-frequency ultrasound (HFUS) and photoacoustic (PA) imaging front-end, including the proposed LNA and a variable gain amplifier (VGA), was designed and fabricated in a 180 nm CMOS process. At 80 MHz, the front-end achieves an input-referred noise density of 1.36 nV/sqrt (Hz), an input return loss (S11) of better than -16 dB, a voltage gain of 37 dB, and a total harmonic distortion (THD) of -55 dBc while dissipating a power of 37 mW, leading to a noise efficiency factor (NEF) of 2.66.

Colloidal Synthesis and Charge-Carrier Dynamics of Cs2 AgSb1-y Biy X6 (X: Br, Cl; 0 ≤y ≤1) Double Perovskite Nanocrystals.

A series of lead-free double perovskite nanocrystals (NCs) Cs2 AgSb1-y Biy X6 (X: Br, Cl; 0≤y≤1) is synthesized. In particular, the Cs2 AgSbBr6 NCs is a new double perovskite material that has not been reported for the bulk form. Mixed Ag-Sb/Bi NCs exhibit enhanced stability in colloidal solution compared to Ag-Bi or Ag-Sb NCs. Femtosecond transient absorption studies indicate the presence of two prominent fast trapping processes in the charge-carrier relaxation. The two fast trapping processes are dominated by intrinsic self-trapping (ca. 1-2 ps) arising from giant exciton-phonon coupling and surface-defect trapping (ca. 50-100 ps). Slow hot-carrier relaxation is observed at high pump fluence, and the possible mechanisms for the slow hot-carrier relaxation are also discussed.

Lead-Free Direct Band Gap Double-Perovskite Nanocrystals with Bright Dual-Color Emission.

Lead-free double-perovskite nanocrystals (NCs), that is, Cs2AgIn xBi1- xCl6 ( x = 0, 0.25, 0.5, 0.75, and 0.9), that can be tuned from indirect band gap ( x = 0, 0.25, and 0.5) to direct band gap ( x = 0.75 and 0.9) are designed. Direct band gap NCs exhibit 3 times greater absorption cross section, lower sub-band gap trap states, and >5 times photoluminescence quantum efficiency (PLQE) compared to those observed for indirect band gap NCs (Cs2AgBiCl6). A PLQE of 36.6% for direct band gap NCs is comparable to those observed for lead perovskite NCs in the violet region. Besides the band edge violet emission, the direct band gap NCs exhibit bright orange (570 nm) emission. Density functional theory calculations suggesting forbidden transition is responsible for the orange emission, which is supported by time-resolved PL and PL excitation spectra. The successful design of lead-free direct band gap perovskite NCs with superior optical properties opens the door for high-performance lead-free perovskite optoelectronic devices.

Cigarette smoke exposure inhibits contact hypersensitivity via the generation of platelet-activating factor agonists.

Previous studies have established that pro-oxidative stressors suppress host immunity because of their ability to generate oxidized lipids with platelet-activating factor receptor (PAF-R) agonist activity. Although exposure to the pro-oxidative stressor cigarette smoke (CS) is known to exert immunomodulatory effects, little is known regarding the role of PAF in these events. The current studies sought to determine the role of PAF-R signaling in CS-mediated immunomodulatory effects. We demonstrate that CS exposure induces the generation of a transient PAF-R agonistic activity in the blood of mice. CS exposure inhibits contact hypersensitivity in a PAF-R-dependent manner as PAF-R-deficient mice were resistant to these effects. Blocking PAF-R agonist production either by systemic antioxidants or treatment with serum PAF-acetyl hydrolase enzyme blocked both the CS-mediated generation of PAF-R agonists and PAF-R-dependent inhibition of contact hypersensitivity (CHS) reactions, indicating a role for oxidized glycerophosphocholines with PAF-R agonistic activity in this process. In addition, cyclooxygenase-2 inhibition did not block PAF-R agonist production but prevented CS-induced inhibition of CHS. This suggests that cyclooxygenase-2 acts downstream of the PAF-R in mediating CS-induced systemic immunosuppression. Moreover, CS exposure induced a significant increase in the expression of the regulatory T cell reporter gene in Foxp3(EGFP) mice but not in Foxp3(EGFP) mice on a PAF-R-deficient background. Finally, regulatory T cell depletion via anti-CD25 Abs blocked CS-mediated inhibition of CHS, indicating the potential involvement of regulatory T cells in CS-mediated systemic immunosuppression. These studies provide the first evidence, to our knowledge, that the pro-oxidative stressor CS can modulate cutaneous immunity via the generation of PAF-R agonists produced through lipid oxidation.

Learning Stiffness Tensors in Self-Activated Solids via a Local Rule.

Mechanical metamaterials are often designed with particular properties for specific load-bearing functions. Alternatively, this study aims to create a class of active lattice metamaterials, dubbed self-activated solids, that can learn desired stiffness tensors from the elastic deformations they experienced, a crucial feature to improve the performance, efficiency, and functionality of materials. Artificial adaptive matters that combine sensory, control, and actuation elements can offer appealing solutions. However, challenges still remain: The designs will rely on accurate off-line and global computations, as well as intricate coordination among individual elements. Here, a simple online and local learning strategy is initiated based on contrastive Hebbian learning to gradually guide self-activated solids to possess sought-after stiffness tensors autonomously and reversibly. During learning, the bond stiffness of the active lattice varies depending only on its local strain. The numerical tests show that the self-activated solid can not only achieve the desired bulk, shear, and coupling moduli but also manifest uni-mode and bi-mode extremal materials by itself after experiencing the corresponding elastic deformations. Further, the self-activated solid can also achieve the desired time-varying moduli when exposed to temporally different loads. The design is applicable to any lattice geometries and is resistant to damage and instabilities. The material design approach and the physical learning strategy suggested can benefit the design of autonomous materials, physical learning machines, and adaptive robots.

Effects of synergistic Fenton-microwave treatment on the antioxidant stress of soluble polysaccharides and the physicochemical properties of insoluble polysaccharides from Gelidium amansii.

In this study, we individually obtained crude Gelidium amansii water-soluble polysaccharides and water-insoluble polysaccharides (GAIPs) using an improved Fenton-microwave synergistic treatment. The former were purified by alcohol precipitation and deproteinization to obtain Gelidium amansii water-soluble polysaccharides (GASPs), and their effects on the oxidative stress resistance of Caenorhabditis elegans were investigated. GAIPs were studied for their physicochemical properties, including hydration characteristics, adsorption, and cation-exchange capacity. The results showed that compared with the negative control, 1.0 mg/mL GASPs significantly upregulated (>1.70-fold) the expression of antioxidant-related genes, such as daf-16, sir-2.1, and skn-1 (p < 0.05), which prolonged the mean survival time and increased the mean number of head bobbing (p < 0.05). The hydration characteristics and oil-holding capacity of GAIPs were lower than those of G. amansii powder (GAP) and G. amansii filtrate residue (GADP). However, the adsorption capacity of GAIPs for cholesterol (pH 7.0) and sodium cholate and the cation-exchange capacity were significantly better than those of GAP (5.17, 13.16 & 1.63 times, p < 0.05) and GADP (8.42, 6.39, & 2.05 times, p < 0.05). To conclude, the synergistic Fenton-microwave treatment contributed to the increase in the oxidative stress resistance of GASPs and improved the adsorption capacity and cation-exchange capacity of GAIPs.

Effects of Auricularia auricula-judae (Bull.) Quél. polysaccharide acid hydrolysate on glucose metabolism in diabetic mice under oxidative stress.

BACKGROUND: Oxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PURPOSE: Using diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull.) Quél. on improving diabetes. STUDY DESIGN AND METHODS: The structural information of sample polysaccharides was measured by high performance gel permeation chromatography, nuclear magnetic resolution, and high performance liquid chromatography. The diabetic model was established by intraperitoneal injection of streptozotocin. For eight consecutive weeks, the mice were orally administered sample polysaccharides (100, 200, and 300 mg/kg b.w. per day) for intervention. The improvement effect of the samples on diabetes was explored by detecting the changes in biochemical indicators in mice, and the underlying mechanism was studied by transcriptomic and metabolomic analysis. RESULTS: The results showed that acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides consisted mainly of mannose, xylose, glucuronic acid, and glucose; its weight-averaged molecular weight was 6.3842 × 104 Dalton, its number average molecular weight was 2.9594 × 104 Dalton; and the molecule contained α-Glc(1→4)-, ß-Glc(1→3)-, and ß-Man(1→4)-linked glycosidic bonds. A total of 100 mg/kg b.w. per day sample was the best intervention concentration. After eight weeks of intervention, the sample polysaccharides significantly reduced dynamic blood glucose and serum lipids, enhanced antioxidant enzyme activities, promoted glucagon like peptide-1 and insulin secretion, improved insulin sensitivity and alleviated insulin resistance in diabetic mice. Transcriptomic and metabolomic analyses showed that sample polysaccharides was able to ameliorate disorders of glucose metabolism by modulating gene expression such as glucokinase; and modulate the state of oxidative stress in mice in vivo by regulating the glutathione metabolism pathway. CONCLUSION: Acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides improved glucose metabolism disorders by slowing down the oxidative stress injury in mice, thereby alleviating diabetes. This study provided a basis for determining the underlying mechanism of the antidiabetic effect of Auricularia auricula-judae (Bull.) Quél. polysaccharides, which would significantly improve the deep development and application of these materials in diabetes control.

Study on the mechanisms by which pumpkin polysaccharides regulate abnormal glucose and lipid metabolism in diabetic mice under oxidative stress.

Pumpkin polysaccharide (PPe-H) can perform physiological functions through its antioxidative and hypoglycemic effects; however, the mechanisms through which PPe-H regulates abnormal glucose and lipid metabolism caused by oxidative stress injury remain unclear. In the present study, streptozotocin was used to generate an acute diabetic mouse model, and the effects of PPe-H on glucose and lipid metabolism impaired by oxidative stress in diabetic mice were studied. PPe-H significantly reduced blood glucose levels and enhanced the oral glucose tolerance of diabetic mice under stress injury (p < 0.05). The analysis of liver antioxidant enzymes showed that PPe-H significantly enhanced the activities of SOD and CAT (p < 0.05), increased the GSH level, and decreased the level of MDA (p < 0.05). Transcriptomic and metabolomic analyses of the liver tissues of mice revealed characteristic differences in the genetic and metabolic levels of the samples, which showed that PPe-H treatment may play a positive role in regulating the metabolism of methionine, cysteine, glycerol phospholipid, and linoleic acid. These results indicated that PPe-H alleviated the symptoms of hyperglycemia by regulating metabolites related to oxidative stress and glycolipid metabolism in diabetic mice.

Chloroplast-boosted photodynamic therapy for effective drug-resistant bacteria killing and biofilm ablation.

Due to the misuse of various antibiotics, the problem of bacterial resistance has become more serious worldwide, and the associated diseases have significantly increased the medical burden of society. Antimicrobial photodynamic therapy (PDT) has received widespread attention because of its safety, efficiency, and facile implementation. Here, we report an oxygen-supply antibacterial agent (Ce6@CS/CP), which could enhance the efficacy of antibacterial PDT via photosynthesis of O2. Ce6@CS/CP displayed a robust interaction with bacteria, hence facilitating the delivery efficiency of Ce6. In vitro experiments demonstrated that the photodynamic bactericidal potency of Ce6@CS/CP was remarkably greater than that of free Ce6. Furthermore, Ce6@CS/CP also exhibited superior significant antibiofilm activity to free Ce6. As a live oxygen-supply antibacterial agent, Ce6@CS/CP possesses excellent bacteria delivery ability of Ce6 and could enhance the potency of antibacterial PDT by photosynthesis, offering a new strategy for fighting against drug-resistant bacteria.