Construct of qualitative diagnostic biomarkers specific for glioma by pairing serum microRNAs.

BACKGROUND: Serum microRNAs (miRNAs) are promising non-invasive biomarkers for diagnosing glioma. However, most reported predictive models are constructed without a large enough sample size, and quantitative expression levels of their constituent serum miRNAs are susceptible to batch effects, decreasing their clinical applicability. METHODS: We propose a general method for detecting qualitative serum predictive biomarkers using a large cohort of miRNA-profiled serum samples (n = 15,460) based on the within-sample relative expression orderings of miRNAs. RESULTS: Two panels of miRNA pairs (miRPairs) were developed. The first was composed of five serum miRPairs (5-miRPairs), reaching 100% diagnostic accuracy in three validation sets for distinguishing glioma and non-cancer controls (n = 436: glioma = 236, non-cancers = 200). An additional validation set without glioma samples (non-cancers = 2611) showed a predictive accuracy of 95.9%. The second panel included 32 serum miRPairs (32-miRPairs), reaching 100% diagnostic performance in training set on specifically discriminating glioma from other cancer types (sensitivity = 100%, specificity = 100%, accuracy = 100%), which was reproducible in five validation datasets (n = 3387: glioma = 236, non-glioma cancers = 3151, sensitivity> 97.9%, specificity> 99.5%, accuracy> 95.7%). In other brain diseases, the 5-miRPairs classified all non-neoplastic samples as non-cancer, including stroke (n = 165), Alzheimer's disease (n = 973), and healthy samples (n = 1820), and all neoplastic samples as cancer, including meningioma (n = 16), and primary central nervous system lymphoma samples (n = 39). The 32-miRPairs predicted 82.2 and 92.3% of the two kinds of neoplastic samples as positive, respectively. Based on the Human miRNA tissue atlas database, the glioma-specific 32-miRPairs were significantly enriched in the spinal cord (p = 0.013) and brain (p = 0.015). CONCLUSIONS: The identified 5-miRPairs and 32-miRPairs provide potential population screening and cancer-specific biomarkers for glioma clinical practice.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

COAP-Pd Catalyzed Asymmetric Allylic Alkylation of Azlactones with MBH Carbonates: Access to Unnatural α-Quaternary Stereogenic Glutamic Acid Derivatives.

A palladium-catalyzed regioselective and asymmetric allylic alkylation of azlactones with MBH carbonates has been developed with chiral oxalamide-phosphine ligands. The corresponding reaction afforded a range of optically active γ-arylidenyl glutamic acid derivatives bearing an α-chiral quaternary stereocenter in good yields with excellent linear regio- and high enantioselectivity. This protocol furnishes an alternative approach for the construction of enantio-enriched unnatural α-amino acid derivatives.

Protective effects and mechanisms of N-acetylcysteine on indomethacin-induced intestinal injury in a porcine model.

This study aimed to investigate the effect of N-acetylcysteine (NAC) on indomethacin (IDMT)-induced intestinal injury in a piglet model and explore the underlying molecular mechanisms. Piglets were randomly divided into 3 treatment groups: (1) control group; (2) IDMT group; (3) NAC+IDMT group. The results showed that NAC administration significantly increased the average daily gain of piglets, attenuated the intestine hyperemia, and restored normal jejunal morphology. Further studies indicated that NAC administration significantly increased plasma citrulline concentration and jejunal villin expression, but decreased the content of proinflammatory cytokines in plasma and jejunum of IDMT-stimulated piglets. NAC administration selectively decreased the proportion of eosinophils but not neutrophils in plasma. Furthermore, NAC administration significantly increased the activities of superoxide dismutase and catalase in plasma but decreased the concentrations of hydrogen peroxide (plasma) and malondialdehyde (plasma and jejunum), as well as the activity of myeloperoxidase (jejunum) when comparing NAC+IDMT group with IDMT group. Gene Ontology analysis showed that the significantly enriched molecular function term was "ubiquitin-like protein ligase binding" for NAC+IDMT versus IDMT differentially regulated genes. In the biological process category, differentially regulated genes of NAC+IDMT versus IDMT were mainly enriched in immune-related terms. The major enrichments for differentially regulated proteins (DRPs) of NAC+IDMT versus IDMT were terms involved in lipid metabolism and immune response. KEGG pathway enrichment analysis showed that "arginine biosynthesis" was a significant enrichment term for the DRPs of NAC+IDMT versus IDMT. Further studies demonstrated that NAC administration up-regulated argininosuccinate synthase 1 mRNA expression and down-regulated arginase mRNA expression in the jejunum of IDMT-stimulated piglets. Moreover, the content of nitric oxide was restored to a normal level with the reduction of nitric oxide synthase activity. NAC administration ameliorated intestinal injury in IDMT-challenged piglets by enhancing antioxidant and anti-inflammatory functions and modulating arginine metabolism in the small intestine.

NIR Photothermal-Responsive Shape Memory Polyurethane with Protein-Inspired Aggregated Chymotrypsin-Sensitive Degradable Domains.

Biodegradable shape memory polymers are promising biomaterials for stents used in minimally invasive surgical procedures such as intestinal stents. Herein, a series of biodegradable shape memory polyurethanes (SMPUs) containing a novel phenylalanine-derived chain extender (PHP) are synthesized. Inspired by the fact that the function of biomacromolecules such as proteins is rich and varied because of the multiple combinations of the amino acid in highly evolved biosystems, this study finds that the sequence distribution of PHP in SMPU will also have a great influence on the phase structure and degradation behavior, especially the difference of surface morphology caused by degradation. Considering that the transition temperature (Ttrans ) of SMPU obtained is higher than physiological temperature, oxidized carbon black (OCB) with the ability of photothermal conversion is introduced into SMPU, which can not only endow SMPU with near-infrared response shape recovery characteristics, but also enhance phase separation degree and mechanical properties of them. SMPU/OCB composites show excellent shape memory effect and rapid photothermal response, and they can be degraded by chymotrypsin with an adjustable degradation rate. These SMPU/OCB composites show broad potential for application as intestinal stents.

A Low-Delay Lightweight Recurrent Neural Network (LLRNN) for Rotating Machinery Fault Diagnosis.

Fault diagnosis is critical to ensuring the safety and reliable operation of rotating machinery systems. Long short-term memory networks (LSTM) have received a great deal of attention in this field. Most of the LSTM-based fault diagnosis methods have too many parameters and calculation, resulting in large memory occupancy and high calculation delay. Thus, this paper proposes a low-delay lightweight recurrent neural network (LLRNN) model for mechanical fault diagnosis, based on a special LSTM cell structure with a forget gate. The input vibration signal is segmented into several shorter sub-signals in order to shorten the length of the time sequence. Then, these sub-signals are sent into the network directly and converted into the final diagnostic results without any manual participation. Compared with some existing methods, our experiments illustrate that the proposed method has less memory space occupancy and lower computational delay while maintaining the same level of accuracy.

A Lighted Deep Convolutional Neural Network Based Fault Diagnosis of Rotating Machinery.

To improve the fault diagnosis performance for rotating machinery, an efficient, noise-resistant end-to-end deep learning (DL) algorithm is proposed based on the advantages of the wavelet packet transform in vibration signal processing (the capability to extract multiscale information and more spectral distribution features) and deep convolutional neural networks (good classification performance, data-driven design and high transfer-learning ability). First, a vibration signal is subjected to pyramid wavelet packet decomposition, and each sub-band coefficient is used as the input for each channel of a deep convolutional network (DCN). Then, based on the lightweight modeling requirements and techniques, a new DCN structure is designed for the fault diagnosis. The proposed algorithm is compared with the support vector machine algorithm and the published DL algorithms based on a bearing dataset produced by Case Western Reserve University. The experimental results show that the proposed algorithm is superior to the existing algorithms in terms of accuracy, memory space, computational complexity, noise resistance, and transfer performance, producing good results.

Newcastle disease virus V protein inhibits apoptosis in DF-1 cells by downregulating TXNL1.

Many viral proteins are related to suppressing apoptosis in target cells and are hence beneficial to viral replication. The V protein of Newcastle disease virus (NDV) is one such protein that plays an important role in inhibiting apoptosis in a species-specific manner. However, to date, there have been no reports clarifying the antiapoptotic mechanisms of the V protein. The present study was undertaken to determine the apoptotic potential of the V protein in a chicken embryo fibroblast cell line (DF-1 cell) and to elucidate its molecular mechanisms of action. Here, a yeast two-hybrid system was used to screen the host proteins that interact with the V protein and identified thioredoxin-like protein 1 (TXNL1) as a potential binding partner. Immuno-colocalization of V protein and TXNL1 protein in DF-1 cells further verified the interaction of the two proteins. Through the overexpression of TXNL1 protein and knockdown of TXNL1 protein in DF-1 cells, the effects of NDV replication and cell apoptosis were examined. Cell apoptosis was detected by flow cytometry. The mRNA and protein expression levels of Bax, Bcl-2 and Caspase-3 were detected by quantitative real-time PCR (Q-PCR) and Western blotting. NDV expression was detected by Q-PCR and plaque assay. The results revealed that the TXNL1 protein induced apoptosis and inhibited NDV replication in DF-1 cells. Furthermore, the Western blot and Q-PCR results suggested that TXNL1 induced cell apoptosis through a pathway involving Bcl-2\Bax and Caspase-3. Finally, this work provides insight into the mechanism by which the V protein inhibits apoptosis.

Post-Crosslinked Polyurethanes with Excellent Shape Memory Property.

Shape-memory polymers are highly desirable in implant biomaterials for minimally invasive surgical procedures. However, most of them lack suitable transition temperature, mechanical properties, and biodegradability. Here, a series of shape-memory polyurethanes are synthesized by postcrosslinking in hard-segment domains using a flexible crosslinker. The materials used are all nontoxic and biodegradable. Through postcrosslinking of unsaturated linear polyurethanes with flexible and biodegradable crosslinker, the crosslinked polyurethanes (CPUs) show good mechanical properties, excellent shape-memory property, and repeatability. The post-crosslinking structure and shape-memory mechanism of CPUs are investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, and dynamic mechanical analysis tests. The crosslinker endows the fixed phase enough crosslinking and inserts in the hard segments to give the fixed phase certain elasticity. The elastic hard segments make them form more hydrogen bonds with soft segments during shape deformation. The low-molecular-weight poly (ε-caprolactone) offers the samples a shape-memory transition temperature at around 37 °C, which is suitable for implant devices in vivo. This work expands CPUs with an elastic crosslinking structure as potential candidates for implant biomaterials. Since the post-crosslinking polymerization is facile, it can be convenient for industrial production.

Tunable Thermal Conductivity of Sustainable Geopolymers by the Si/Al Ratio and Moisture Content: Insights from Atomistic Simulations.

In this work, the effects of the Si/Al ratio and moisture content on thermal transport in sustainable geopolymers have been comprehensively investigated by using the molecular dynamics simulation. The thermal conductivity of geopolymer systems increases with the increase of Si/Al ratio, and the phonon vibration frequency region, which plays a major role in the main increase of its thermal conductivity, is 8-25 THz, while the rest of the frequency interval contributes less. With the increase of moisture content, the thermal conductivity of geopolymer systems decreases at first, then increases, and finally stabilizes, which is contrary to the changing trend of the porosity of the system. This is mainly because the existence of pores leads to phonon scattering during thermal transport, which, in turn, affects the thermal conductivity of the system. When the moisture content is 5%, the thermal conductivity reaches a minimum value of about 1.103 W/(m·K), which is 40.2% lower than the thermal conductivity of the system without a water molecule. This work will help to enhance the physical level understanding of the relationship between the geopolymer structures and thermal transport properties.

Apelin receptor dimer: Classification, future prospects, and pathophysiological perspectives.

Apelin receptor (APJ), a member of the class A family of G protein-coupled receptor (GPCR), plays a crucial role in regulating cardiovascular and central nervous systems function. APJ influences the onset and progression of various diseases such as hypertension, atherosclerosis, and cerebral stroke, making it an important target for drug development. Our preliminary findings indicate that APJ can form homodimers, heterodimers, or even higher-order oligomers, which participate in different signaling pathways and have distinct functions compared with monomers. APJ homodimers can serve as neuroprotectors against, and provide new pharmaceutical targets for vascular dementia (VD). This review article aims to summarize the structural characteristics of APJ dimers and their roles in physiology and pathology, as well as explore their potential pharmacological applications.

Multienzymatic Cascade for Synthesis of Hydroxytyrosol via Two-Stage Biocatalysis.

Hydroxytyrosol, a naturally occurring compound with antioxidant and antiviral activity, is widely applied in the cosmetic, food, and nutraceutical industries. The development of a biocatalytic approach for producing hydroxytyrosol from simple and readily accessible substrates remains a challenge. Here, we designed and implemented an effective biocatalytic cascade to obtain hydroxytyrosol from 3,4-dihydroxybenzaldehyde and l-threonine via a four-step enzymatic cascade composed of seven enzymes. To prevent cross-reactions and protein expression burden caused by multiple enzymes expressed in a single cell, the designed enzymatic cascade was divided into two modules and catalyzed in a stepwise manner. The first module (FM) assisted the assembly of 3,4-dihydroxybenzaldehyde and l-threonine into (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid, and the second module (SM) entailed converting (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid into hydroxytyrosol. Each module was cloned into Escherichia coli BL21 (DE3) and engineered in parallel by fine-tuning enzyme expression, resulting in two engineered whole-cell catalyst modules, BL21(FM01) and BL21(SM13), capable of converting 30 mM 3,4-dihydroxybenzaldehyde to 28.7 mM hydroxytyrosol with a high space-time yield (0.88 g/L/h). To summarize, the current study proposes a simple and effective approach for biosynthesizing hydroxytyrosol from low-cost substrates and thus has great potential for industrial applications.

Wind Aggregation Enhanced Triboelectric-Electromagnetic Hybrid Generator with Slit Effect.

It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.

Ferroptosis-inducing photosensitizers alleviate hypoxia tumor microenvironment for enhanced fluorescence imaging-guided photodynamic therapy.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence.

Injectable thermogel constructed from self-assembled polyurethane micelle networks for 3D cell culture and wound treatment.

Injectable hydrogels have attracted significant interest in the biomedical field due to their minimal invasiveness and accommodation of intricate scenes. Herein, we developed an injectable polyurethane-based thermogel platform by modulating the hydrophilic-hydrophobic balance of the segmented components with pendant PEG. The thermogelling behavior is achieved by a combination of the bridging from the hydrophilic PEG and the percolated network from the hydrophobic micelle core. Firstly, the thermogelation mechanism of this system was demonstrated by both DPD simulation and experimental investigation. The gelling temperature could be modulated by varying the solid content, the component of soft segments, and the length of the pendant PEG. We further applied 3D printing technology to prepare personalized hydrogel structures. This integration highlights the adaptability of our thermogel for fabricating complex and patient-specific constructs, presenting a significant advance in the field of regenerative medicine and tissue engineering. Subsequently, in vitro cell experiments demonstrated that the thermogel had good cell compatibility and could promote the proliferation and migration of L929 cells. Impressively, A549 cells could be expediently in situ parceled in the thermogel for three-dimensional cultivation and gain lifeful 3D cell spheres after 7 days. Further, in vivo experiments demonstrated that the thermogel could promote wound healing with the regeneration of capillaries and hair follicles. Ultimately, our study demonstrates the potential of hydrogels to prepare personalized hydrogel structures via 3D printing technology, offering innovative solutions for complex biomedical applications. This work not only provides a fresh perspective for the design of injectable thermogels but also offers a promising avenue to develop thermoresponsive waterborne polyurethane for various medical applications.

Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in Vascular Dementia.

Vascular dementia (VD), a progressive vascular cognitive impairment, is characterised by the presence of cerebral hypoperfusion, increased blood-brain barrier permeability, and white matter lesions. Although current treatment strategies primarily focus on risk factors such as hypertension, diabetes, and heart disease, efficient and targeted therapies are lacking and the underlying mechanisms of VD remain unclear. We previously discovered that Apelin receptors (APJ), which are G protein-coupled receptors (GPCRs), can homodimerize and generate signals that are distinct from those of APJ monomers in VD rats. Apelin-13 reduces the level of APJ homodimers and leads to the proliferation of endogenous neural stem cells in the hippocampal dentate gyrus area, suggesting that it has a neuroprotective role. In this study, we established a rat and cellular oxygen-glucose deprivation/reoxygenation VD model to investigate the impact of APJ homodimerisation on autophagy. We found that APJ homodimers protect against VD by inhibiting autophagy through the Gαq and PI3K/Akt/mTOR pathways upon Gαi signalling, both in vivo and in vitro. This discovery provides a promising therapeutic target for chronic cerebral ischaemia-reperfusion diseases and an experimental foundation for the development of drugs that target APJ homodimers.

Janus Polyurethane Adhesive Patch with Antibacterial Properties for Wound Healing.

Despite the rapid development of tissue adhesives, flaws including allergies, poor stability, and indiscriminate double-sided adhesive properties limit their application in the medical field. In this work, Janus polyurethane patches were spontaneously prepared by adjusting the difference in the functional group distribution between the top and bottom sides of the patch during emulsion drying. Consequently, poor adhesion was exhibited on the bottom surface, while the top surface can easily adhere to metals, polymers, glasses, and tissues. The difference in adhesive strength to pork skin between the two surfaces is more than 5 times. The quaternary ammonium salt and hydrophilic components on the surface of the polyurethane patch enable the rapid removal and absorption of water from the tissue surface to achieve wet adhesion. Animal experiments have demonstrated that this multifunctional Janus polyurethane patch can promote skin wound closure and healing of infected wounds. This facile and effective strategy to construct Janus polyurethane patch provides a promising method for the development of functional tissue-adhesives.

A non-peptide-based fluorescent probe capable of sensitively visualizing asparagine endopeptidase.

The non-peptide-based fluorescent probe QMC11 is capable of specifically targeting asparagine endopeptidase (AEP) and imaging cellular endogenous AEP. The motion of the probe can be restricted by AEP to activate fluorescence while keeping a low background signal.

Improvements in the Appearance and Nutritional Quality of Tomato Fruits Resulting from Foliar Spraying with Silicon.

Research on silicon (Si), an element considered beneficial for plant growth, has focused on abiotic and biotic stress mitigation. However, the effect of Si on tomato fruit quality under normal growth conditions remains unclear. This study investigated the effects of applying different levels of Si (0 mmol·L-1 [CK], 0.6 mmol·L-1 [T1], 1.2 mmol·L-1 [T2], and 1.8 mmol·L-1 [T3]) in foliar sprays on tomato fruit quality cultivated in substrates, and the most beneficial Si level was found. Compared to CK, exogenous Si treatments had a positive influence on the appearance and nutritional quality of tomato fruits at the mature green, breaker, and red ripening stages. Of these, T2 treatment significantly increased peel firmness and single-fruit weight in tomato fruits. The contents of soluble sugars, soluble solids, soluble proteins, and vitamin C were significantly higher, and the nitrate content was significantly lower in the T2 treatment than in the CK treatment. Cluster analysis showed that T2 produced results that were significantly different from those of the CK, T1, and T3 treatments. During the red ripening stage, the a* values of fruits in the T2 treatment tomato were significantly higher than those in the other three treatments. Moreover, the lycopene and lutein contents of the T2 treatment increased by 12.90% and 17.14%, respectively, compared to CK. T2 treatment significantly upregulated the relative gene expression levels of the phytoene desaturase gene (PDS), the lycopene ε-cyclase gene (LCY-E), and the zeaxanthin cyclooxygenase gene (ZEP) in the carotenoid key genes. The total amino acid content in tomato fruits in the T2 treatment was also significantly higher than that of CK. In summary, foliar spraying of 1.2 mmol·L-1 exogenous Si was effective in improving the appearance and nutritional quality of tomato fruits under normal growth conditions. This study provides new approaches to further elucidate the application of exogenous silicon to improve tomato fruit quality under normal conditions.

Clearly fluorescent delineating ER+ breast tumor incisal edge and identifying tiny metastatic tumor foci at high resolution.

Fluorescence-image guided surgery (FGS) can intraoperatively provide real-time visualization of a tumor incisal edge and high-resolution identification of tumor foci to improve treatment outcomes. In this contribution, we report a fluorescent probe NB-TAM based on intramolecularly folded photoinduced electron transfer (PET), which displayed a prominent turn-on response in the near-infrared (NIR) window upon specific interaction with the estrogen receptor (ER). Significantly, NB-TAM could delineate a clear tumor incisal edge (tumor-to-normal tissue ratio > 5) in a 70-min time window, and was successfully used to guide the facile and precise resection of ER+ breast tumors in mice. To our surprise, NB-TAM was found to be capable of identifying very tiny lung metastatic ER+ breast tumor foci (0.4 × 0.3 mm), and this ultrahigh resolution was essential to effectively promote tumor resection precision and early diagnosis of tiny tumors. These results clearly elucidate the promising application of NB-TAM as a diagnostic agent for intraoperative fluorescence imaging of ER+ breast cancer.