Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.

Tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with variable demand for insulin. Here, we asked how insulin-degrading enzyme (IDE) affects beta cell adaptation to metabolic and immune stress. C57BL/6 and autoimmune non-obese diabetic (NOD) mice lacking IDE were exposed to proteotoxic, metabolic, and immune stress. IDE deficiency induced a low-level UPR with islet hypertrophy at the steady state, rapamycin-sensitive beta cell proliferation enhanced by proteotoxic stress, and beta cell decompensation upon high-fat feeding. IDE deficiency also enhanced the UPR triggered by proteotoxic stress in human EndoC-ßH1 cells. In Ide-/- NOD mice, islet inflammation specifically induced regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. These findings establish a role of IDE in islet cell protein homeostasis, demonstrate how its absence induces metabolic decompensation despite beta cell proliferation, and UPR-independent islet regeneration in the presence of inflammation.

Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis.

Background: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition. Methods: Instrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results. Results: Bacteroidia (b = -0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = -0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses. Conclusion: Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy.

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.

BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/ß-catenin pathway.

The function of Biliverdin Reductase A (BLVRA) in hepatocellular carcinoma (HCC) cells proliferation, invasion and migration remains unclear. Therefore, this research intends to explore the effect of BLVRA on HCC cells growth and metastasis. BLVRA expression was analyzed in public dataset and examined by using western blot. The malignant function of BLVRA in HCC cell lines and its effect on Wnt/ß-catenin pathway were measured. Analysis from GEPIA website showed that BLVRA expression was significantly increased in HCC tissues, and high expression of BLVRA resulted in worse prognosis of HCC patients. Results from western blot showed that BLVRA expression was obviously increased in HCC cell lines. Moreover, HepG2 and Hep3B cells in si-BLVRA-1 or si-BLVRA-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Additionally, si-BLVRA-1 or si-BLVRA-2 transfection significantly reduced the protein levels of Vimentin, Snail1 and Snail2, as well as decreased Bcl-2 expression and increased Bax and cleaved-caspase 3 expression. Furthermore, si-BLVRA treatment inhibited the protein levels of c-MYC, ß-catenin, and Cyclin D1. After IWP-4 (Wnt/ß-catenin inhibitor) treatment, the proliferation ability of HCC cells was significantly reduced. BLVRA expression was significantly increased in HCC tissues and cell lines, and knocked down of BLVRA could suppress the proliferation, invasion and migration in HCC cell lines, as well as induce cell apoptosis. Moreover, si-BLVRA transfection blocked the activation of Wnt/ß-catenin pathway.

Glucagon Enhances Chemotherapy Efficacy By Inhibition of Tumor Vessels in Colorectal Cancer.

Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti-cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo-vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR-dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon-encapsulated PEGylated liposomes to tumor-bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy.

Pancreatic islet cell stress induced by insulin-degrading enzyme deficiency promotes islet regeneration and protection from autoimmune diabetes.

Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. The factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficiently understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin and genetic association with type 2 diabetes. IDE deficiency induced a low-level UPR in both C57BL/6 and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation strongly enhanced by proteotoxic stress. Moreover, in NOD mice, IDE deficiency protected from spontaneous diabetes and triggered an additional independent pathway, conditional on the presence of islet inflammation but inhibited by proteotoxic stress, highlighted by strong upregulation of regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. Our findings establish a key role of IDE in islet cell protein homeostasis, identify a link between low-level UPR and proliferation, and reveal an UPR-independent anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.

A Two-Stage Voting-Boosting Technique for Ensemble Learning in Social Network Sentiment Classification.

In recent years, social network sentiment classification has been extensively researched and applied in various fields, such as opinion monitoring, market analysis, and commodity feedback. The ensemble approach has achieved remarkable results in sentiment classification tasks due to its superior performance. The primary reason behind the success of ensemble methods is the enhanced diversity of the base classifiers. The boosting method employs a sequential ensemble structure to construct diverse data while also utilizing erroneous data by assigning higher weights to misclassified samples in the next training round. However, this method tends to use a sequential ensemble structure, resulting in a long computation time. Conversely, the voting method employs a concurrent ensemble structure to reduce computation time but neglects the utilization of erroneous data. To address this issue, this study combines the advantages of voting and boosting methods and proposes a new two-stage voting boosting (2SVB) concurrent ensemble learning method for social network sentiment classification. This novel method not only establishes a concurrent ensemble framework to decrease computation time but also optimizes the utilization of erroneous data and enhances ensemble performance. To optimize the utilization of erroneous data, a two-stage training approach is implemented. Stage-1 training is performed on the datasets by employing a 3-fold cross-segmentation approach. Stage-2 training is carried out on datasets that have been augmented with the erroneous data predicted by stage 1. To augment the diversity of base classifiers, the training stage employs five pre-trained deep learning (PDL) models with heterogeneous pre-training frameworks as base classifiers. To reduce the computation time, a two-stage concurrent ensemble framework was established. The experimental results demonstrate that the proposed method achieves an F1 score of 0.8942 on the coronavirus tweet sentiment dataset, surpassing other comparable ensemble methods.

One-pot synthesis of hyperbranched polymers via visible light regulated switchable catalysis.

Switchable catalysis promises exceptional efficiency in synthesizing polymers with ever-increasing structural complexity. However, current achievements in such attempts are limited to constructing linear block copolymers. Here we report a visible light regulated switchable catalytic system capable of synthesizing hyperbranched polymers in a one-pot/two-stage procedure with commercial glycidyl acrylate (GA) as a heterofunctional monomer. Using (salen)CoIIICl (1) as the catalyst, the ring-opening reaction under a carbon monoxide atmosphere occurs with high regioselectivity (>99% at the methylene position), providing an alkoxycarbonyl cobalt acrylate intermediate (2a) during the first stage. Upon exposure to light, the reaction enters the second stage, wherein 2a serves as a polymerizable initiator for organometallic-mediated radical self-condensing vinyl polymerization (OMR-SCVP). Given the organocobalt chain-end functionality of the resulting hyperbranched poly(glycidyl acrylate) (hb-PGA), a further chain extension process gives access to a core-shell copolymer with brush-on-hyperbranched arm architecture. Notably, the post-modification with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) affords a metal-free hb-PGA that simultaneously improves the toughness and glass transition temperature of epoxy thermosets, while maintaining their storage modulus.

A Porphyrinic Donor-Acceptor Conjugated Porous Polymer as Highly Efficient Photocatalyst for PET-RAFT Polymerization.

Heterogeneous catalysts offer a highly desirable platform for exploring environmental-benign transformation systems, yet, they typically suffer from significant loss of catalytic efficiency compared with their homogeneous counterparts. Here, the facile synthesis of a porphyrinic conjugated porous polymer incorporated with imidazolium bromide moieties by taking advantage of the Debus-Radziszewski reaction is reported. Owing to the unique donor-acceptor structure, this heterogeneous and metal-free photocatalyst exhibits much improved catalytic activity compared with its small molecular analogs in photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, producing polymers with narrow distribution (D = 1.06-1.18) and high degree of chain-end fidelity. Moreover, the heterogeneous catalyst can be easily separated at the end of polymerization by centrifugation and recycled for five independent PET-RAFT polymerizations without obvious decreases in catalytic efficiency.

Formation and Properties of Superhydrophobic Al Coatings on Steel.

Thermal sprayed aluminum coatings are widely scalable to corrosion protection of the offshore steel structure. However, the corrosion rate of the Al coating increases considerably due to the severe marine environment. It has remained a challenge to improve the corrosion resistance and protective ability of Al coatings. The superhydrophobic surface provides a potential way to improve the corrosion resistance of metal materials. Hence, the development of superhydrophobic Al coatings with superior corrosion resistance is of great interest. In this work, the feasibility of the preparation of superhydrophobic Al coatings on a steel substrate was explored. First, Al coatings were prepared onto the steel substrate by the arc-spraying process, followed by ultrasonic etching with 0.1 M NaOH solution, and afterward passivated using 1% fluorosilanes. The effects of the etching time on morphology, contact angle, and corrosion resistance of the Al coatings were evaluated. The schematic model of the fluorosilane passivation process on the Al coating surface was provided. The micro/nanoscale surface structure of the low-surface-energy fluorosilanes promotes the wetting angle of 153.4° and a rolling angle to 6.6°, denoting the superhydrophobic properties. The superhydrophobic Al coating surface displays excellent self-cleaning performance due to its weak adhesion to water droplets. The corrosion current density of the superhydrophobic Al coating (1.36 × 10-8 A cm-2) is 2 orders of magnitude lower than that of the as-sprayed Al coating (1.18 × 10-6 A cm-2). Similarly, the charge-transfer resistance is found to be 12 times larger for the superhydrophobic Al coating and the corresponding corrosion inhibition efficiency reaches 98.9%. The superhydrophobic Al coating displays superior corrosion resistance and promising applications in a marine corrosion environment.

Cobalt-Mediated Switchable Catalysis for the One-Pot Synthesis of Cyclic Polymers.

A cobalt salen pentenoate complex [salen=(R,R)-N,N'-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediamine] is rationally designed as the catalyst for the ring-opening copolymerization (ROCOP) of epoxides/anhydrides/CO2 . Via migratory insertion of carbon monoxide (CO) into the Co-O bonds, the ROCOP-active species α-alkene-ω-O-CoIII (salen) can be rapidly and quantitatively transformed into α-alkene-ω-O2 C-CoIII (salen) telechelic linear precursors. Upon dilution of reaction mixtures, the homolytic cleavage of Co-C bonds induced by visible light generates α-alkene acyl radicals that spontaneously undergo intramolecular radical addition to afford organocobalt-functionalized cyclic polyesters and CO2 -based polycarbonates with excellent regioselectivity. The cyclic products can either react with radical scavengers to generate metal-free cyclic polymers or serve as photo-initiators for organometallic-mediated radical polymerization (OMRP) to produce tadpole-shaped copolymers.

Snapshot spectral polarimetric light field imaging using a single detector.

In this Letter, we investigate a snapshot spectral-polarimetric-volumetric imaging (SSPVI) system using a single detector. Through compressed acquisition and reconstruction, SSPVI can achieve spectral imaging (x,y,λ), polarization imaging (x,y,ψ,χ), and light field imaging (x,y,θ,φ) simultaneously. The newly discovered performance is showcased by attaining the spectral-polarimetric-volumetric video and different laboratory accuracy experiments. These never-seen-before capacities of the camera open new prospects for many applications, such as biological analysis, object recognition, and remote sensing.

Developing an optical design pipeline for correcting lens aberrations and vignetting in light field cameras.

Light field cameras have been employed in myriad applications thanks to their 3D imaging capability. By placing a microlens array in front of a conventional camera, one can measure both the spatial and angular information of incoming light rays and reconstruct a depth map. The unique optical architecture of light field cameras poses new challenges on controlling aberrations and vignetting in lens design process. The results of our study show that field curvature can be numerically corrected for by digital refocusing, and vignetting must be minimized because it reduces the depth reconstruction accuracy. To address this unmet need, we herein present an optical design pipeline for light field cameras and demonstrated its implementation in a light field endoscope.

Plenoptic Face Presentation Attack Detection.

The vulnerability of current face recognition systems to presentation attacks significantly limits their application in biometrics. Herein, we present a passive presentation attack detection method based on a complete plenoptic imaging system which can derive the complete plenoptic function of light rays using a single detector. Moreover, we constructed a multi-dimensional face database with 50 subjects and seven different types of presentation attacks. We experimentally demonstrated that our approach outperforms the state-of-the-art methods on all types of presentation attacks.

Crystal-Like Glassy Structure in Sc-Doped BiSbTe Ensuring Excellent Speed and Power Efficiency in Phase Change Memory.

Phase change memory (PCM) is regarded as a promising technology for storage-class memory and neuromorphic computing, owing to the excellent performances in operation speed, data retention, endurance, and controllable crystallization dynamics, whereas the high power consumption of PCM remains to be a short-board characteristic that limits its extensive applications. Here, Sc-doped Bi0.5Sb1.5Te3 has been proposed for high-speed and low-power PCM applications. An operation speed of 6 ns and a threshold current of 0.7 mA have been achieved in 190 nm Sc0.23Bi0.5Sb1.5Te3 PCM, which consumes lower power than GeSbTe and ScSbTe PCM. A good endurance of 5 × 105 has been achieved, which is attributed to the small volume change of 4% during phase change and a good homogeneity phase in the crystalline state. The structure of amorphous Sc0.23Bi0.5Sb1.5Te3 has been characterized by experimental and theoretical methods, showing the existence of a large amount of crystal-like structural factions, which can efficiently minimize the atomic movements required for crystallization and subsequently improve the operation speed and power efficiency. The low diffusivity of Sc and Bi at room temperature and the rapidly increased diffusivity of Bi at elevated temperatures are fundamental for the high data retention of 94 °C and the fast crystallization in Sc0.23Bi0.5Sb1.5Te3. The combination of high atomic mobility and minimized atomic movements during crystallization ensures the high speed and low power consumption of Sc0.23Bi0.5Sb1.5Te3 PCM, which can promote its application to energy-efficient systems, that is, AI chips and wearable electronics.

Switchable Polymerization Triggered by Fast and Quantitative Insertion of Carbon Monoxide into Cobalt-Oxygen Bonds.

A strategy that uses carbon monoxide (CO) as a molecular trigger to switch the polymerization mechanism of a cobalt Salen complex [salen=(R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine] from ring-opening copolymerization (ROCOP) of epoxides/anhydrides to organometallic mediated controlled radical polymerization (OMRP) of acrylates is described. The key phenomenon is a rapid and quantitative insertion of CO into the Co-O bond, allowing for in situ transformation of the ROCOP active species (Salen)CoIII -OR into the OMRP photoinitiator (Salen)CoIII -CO2 R. The proposed mechanism, which involves CO coordination to (Salen)CoIII -OR and subsequent intramolecular rearrangement via migratory insertion has been rationalized by DFT calculations. Regulated by both CO and visible light, on-demand sequence control can be achieved for the one-pot synthesis of polyester-b-polyacrylate diblock copolymers (D<1.15).

One-Step and Metal-Free Synthesis of Triblock Quaterpolymers by Concurrent and Switchable Polymerization.

A one-step and metal-free route to triblock quaterpolymers from mixtures of vinyl monomers, epoxides, anhydrides, and racemic lactide (rac-LA) has been described, which bridges three polymerization cycles involving ring-opening copolymerization (ROCOP) of epoxides/anhydrides, ring-opening polymerization (ROP) of rac-LA, and RAFT polymerization of vinyl monomers. Taking advantage of the switchable polymerization between ROCOP and ROP, concurrent chain propagation of ROCOP/RAFT and ROP/RAFT sequentially occurs by using a trithiocarbonate compound with carboxylic group (TTC-COOH) as a versatile chain transfer agent. The multiple-chain transfer effect enables independent and precise control over the molecular weights of the three blocks and ensures narrow distribution of the resultant triblock quaterpolymers (D < 1.20). This work demonstrates the possibility to acquire block copolymers with high degree of structural complexities in a single efficient process by combining different block polymerization strategies.

In vivo monitoring of rashes caused by systemic lupus erythematosus disease using snapshot spectral imaging.

Monitoring the activity of systemic lupus erythematosus (SLE) is important to patient management. Blood biochemical indexes are commonly assessed but are both time demanding and traumatizing. In this study, a noninvasive and real-time spatial-spectral data tool was used to monitor SLE patients through rash spectral data. To build the relationship between the rash spectrum changes and changes in the patients' status, a snapshot hyperspectral Fourier transform imaging spectrometer was built to monitor the rash reflectance changes of hospitalized SLE patients. A simple rash activity index (RAI) which was normally distributed with the doctor's visual rating of rash severity was calculated from hyperspectral images. The sensitivity of the change in RAI is higher than complement 3/4 levels. RAI and anti-dsDNA antibodies both decreased as the patients recovered. Anti-dsDNA and complement 3/4 were important indicators of SLE activity suggesting that the RAI directly correlated with patient status. The snapshot spectrometer therefore provides an auxiliary method to monitor SLE disease.

High-quality panchromatic image acquisition method for snapshot hyperspectral imaging Fourier transform spectrometer.

The acquisition of high-quality panchromatic images is vital to the multi-spectral images pan sharpening, especially to snapshot imaging spectrometers with a low spatial resolution. As an aperture-division snapshot imaging spectrometer, a snapshot hyperspectral imaging Fourier transform spectrometer has the characteristic that images of all the sub-apertures share almost the same spatial information with a small shift. With these sub-images, super-resolution is possible. In this paper, a high-quality panchromatic image acquisition method is proposed. A pre-trained deep learning network is utilized without enlarging the instrument size. The training dataset is obtained experimentally, and the network is designed to realize the contrast enhancement and super-resolution simultaneously. The experimental results demonstrate that the proposed method performs well in high-quality panchromatic image acquisition.

Complete plenoptic imaging using a single detector.

Multi-dimensional imaging is a powerful technique for many applications, such as biological analysis, remote sensing, and object recognition. Most existing multi-dimensional imaging systems rely on scanning or camera array, which make the system bulky and unstable. To some extent, these problems can be mitigated by employing compressed sensing algorithms. However, they are computationally expensive and highly rely on the ill-posed assumption that the information is sparse in a given domain. Here, we propose a snapshot spectral-volumetric imaging (SSVI) system by introducing the paradigm of light-field imaging into Fourier transform imaging spectroscopy. We demonstrate that SSVI can reconstruct a complete plenoptic function, P(x,y,z,θ,φ,λ,t), of the incoming light rays using a single detector. Compared with other multidimensional imagers, SSVI features prominent advantages in compactness, robustness, and low cost.