Citrobacter rodentium infection impairs dopamine metabolism and exacerbates the pathology of Parkinson's disease in mice.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes.

In situ construction of A-site high-entropy perovskites with interfacial CeO2 for a high-performance IT-SOFC air-electrode.

Developing an intermediate-temperature solid oxide fuel cell (IT-SOFC) is one of the most promising ways of achieving carbon neutrality, but its air-electrode is restricted by the conflict between the sluggish catalytic activity and durability. Herein, an A-site high-entropy perovskite composite La0.2Ba0.2Sr0.2Ca0.2Ce0.2-xCoO3-δ-xCeO2 (LBSCCC-CeO2) air-electrode material is fabricated via a one-step self-constructing strategy, which shows excellent oxygen reduction activity and stability due to the high-entropy structure and the synergy effect between LBSCCC and interfacial CeO2. This work provides a new way of fabricating high-performance air-electrodes in IT-SOFCs.

Anisotropic Semicrystalline Homopolymer Dielectrics for High-Temperature Capacitive Energy Storage.

High-temperature dielectric polymers are in high demand for powering applications in extreme environments. Here, we have developed high-temperature homopolymer dielectrics with anisotropy by leveraging the hierarchical structure in semicrystalline polymers. The lamellae have been aligned parallel to the surface in the dielectric films. This structural arrangement resembles the horizontal alignment of nanosheet fillers in polymer nanocomposites and nanosheet-like lamellae in block copolymers, which has been proven to provide the optimal topological structure for electrical energy storage. The unique ordering of lamellae in our dielectric films endue a significantly increased breakdown strength and a reduced leakage current compared to amorphous films. This novel approach of enhancing the capacitive energy storage properties by controlled orientation of lamellae in homopolymer offers a new perspective for the design of high-temperature polymer dielectrics.

Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Effect and Mechanism of L-Arginine against Alternaria Fruit Rot in Postharvest Blueberry Fruit.

This study aimed to explore the impact of L-arginine (Arg) on the development of resistance to Alternaria tenuissima (A. tenuissima) in blueberries. The metabolism of reactive oxygen species, pathogenesis-related proteins (PRs), and jasmonic acid (JA) biosynthesis pathways were analyzed, including changes in activity and gene expression of key enzymes. The results indicated that Arg treatment could prevent the development of Alternaria fruit rot in postharvest blueberries. In addition, it was also found to induce a burst of hydrogen peroxide in the blueberries early on during storage, thereby improving their resistance to A. tenuissima. Arg treatment was observed to increase the activity of antioxidant enzymes (peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase) and related gene expression, as well as the total levels of phenolics, flavonoids, and anthocyanin in the blueberries. The activity and gene expression of the PRs (chitinase and ß-1,3-glucanase) were elevated in Arg-treated blueberries, boosting their resistance to pathogens. Additionally, a surge in endogenous JA content was detected in Arg-treated blueberries, along with upregulated expression of key genes related the JA biosynthesis pathway (VcLOX1, VcAOS1, VcAOC, VcAOC3, VcOPR1, VcOPR3, VcMYC2, and VcCOI1), thereby further bolstering disease resistance. In conclusion, Arg treatment was determined to be a promising prospective method for controlling Alternaria fruit rot in blueberries.

Pyroptosis-mediator GSDMD promotes Parkinson's disease pathology via microglial activation and dopaminergic neuronal death.

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

In situ electrochemical Mn vacancies in CoMnHCF for a high level of zinc storage.

CoMnHCF is utilized in aqueous sodium/zinc mixed ion batteries and exhibits a high reversible capacity with good rate and cycle performances. At 0.05 A g-1 current density, the CoMnHCF can deliver a specific capacity for 180.4 mA h g-1, and have 99.3% capacity retention after 300 cycles at 0.3 A g-1. Such high reversible capacity profits from Mn vacancies that generate in situ during the first cycle, which provides more active sites for Zn storage. The de-intercalation of Na+ further elevates this good electrochemical performance. Co atoms in the framework are not only involved in the redox reactions, but help to support the structure, thus achieving better cycle stabilities.

Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson's disease.

Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.

Constructing Novel High Dielectric Constant Polyimides Containing Dipolar Pendant Groups with Enhanced Orientational Polarization.

Polymer dielectrics with high dielectric constant are urgently demanded for potential electrical and pulsed power applications. The design of polymers with side chains containing dipolar groups is considered an effective method for preparing materials with a high dielectric constant and low loss. This study synthesizes and comprehensively compare the dielectric properties of novel polyimides with side chains containing urea (BU-PI), carbamate (BC-PI), and sulfonyl (BS-PI) functional groups. The novel polyimides exhibit relatively high dielectric constant and low dielectric loss values due to the enhanced orientational polarization and suppressed dipole-dipole interactions of dipolar groups. In particular, BU-PI containing urea pendant groups presents the highest dielectric constant of 6.14 and reasonably low dielectric loss value of 0.0097. The strong γ transitions with low activation energies derived from dielectric spectroscopy measurements have been further evaluated to demonstrate the enhanced free rotational motion of urea pendant dipoles. In energy storage applications, BU-PI achieves a discharged energy density of 6.92 J cm-3 and a charge-discharge efficiency above 83% at 500 MV m-1. This study demonstrates that urea group, as dipolar pendant group, can provide polymers with better dielectric properties than the most commonly used sulfonyl groups.

Ultraviolet-Irradiated All-Organic Nanocomposites with Polymer Dots for High-Temperature Capacitive Energy Storage.

Polymer dielectrics capable of operating efficiently at high electric fields and elevated temperatures are urgently demanded by next-generation electronics and electrical power systems. While inorganic fillers have been extensively utilized to improved high-temperature capacitive performance of dielectric polymers, the presence of thermodynamically incompatible organic and inorganic components may lead to concern about the long-term stability and also complicate film processing. Herein, zero-dimensional polymer dots with high electron affinity are introduced into photoactive allyl-containing poly(aryl ether sulfone) to form the all-organic polymer composites for high-temperature capacitive energy storage. Upon ultraviolet irradiation, the crosslinked polymer composites with polymer dots are efficient in suppressing electrical conduction at high electric fields and elevated temperatures, which significantly reduces the high-field energy loss of the composites at 200 °C. Accordingly, the ultraviolet-irradiated composite film exhibits a discharged energy density of 4.2 J cm-3 at 200 °C. Along with outstanding cyclic stability of capacitive performance at 200 °C, this work provides a promising class of dielectric materials for robust high-performance all-organic dielectric nanocomposites.

A rapid multispectral endoscopic imaging system for in vivo assessment of the morphological and physiological characteristics of mouse intestines.

Accurate assessment of blood content in biological tissues is critical for the diagnosis and monitoring of various diseases, including cardiovascular disease, tumors, trauma, and the success rate of organ transplants. In this study, a multispectral endoscopic imaging system was built for capturing tissue reflection optical images in 18 bands across the wavelength range from 400 nm to 760 nm, non-invasively. The system was characterized by six tri-channel narrowband filters installed in front of the light source to achieve spectral separation and was equipped with a specially designed color CCD for achieving a speed of 24 multispectral imaging cubes per second. A method based on linear matrix inversion was proposed to calibrate the CCD spectral response overlaps, while a spectral analysis algorithm was developed for evaluating blood content and detecting tissue composition. The developed system was implemented in an in vivo mouse model for illustrating the blood volume, blood oxygen saturation index, and scattering particle size of the intestinal wall mucosa. The observations not only helped us to understand the blood supply situation in the intestinal mucosa, but also further testified the feasibility of our presented system. Meanwhile, the developed system could provide critical non-invasive optical information for intracavitary cancer diagnosis, surgery guidance, and treatment assessment.

The effect of intravenous lidocaine on postoperative cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been reported as a significant complication in elderly patients. Various methods have been proposed for reducing the incidence and severity of POCD. Intravenous lidocaine administration has been reported in the literature to reduce POCD, but the effect of lidocaine remains controversial. METHODS: We screened Medline, Embase, Cochrane Library, and China National Knowledge Infrastructure (up to April 2022) databases following a search strategy for intravenous lidocaine on POCD. We also screened related bibliographies on lidocaine for POCD. Ten articles comprising 1517 patients were selected and analyzed. We divided the postoperative follow-up period as follows: short term (<30 days), medium term (30-90 days), and long term (>90 days). OUTCOMES: We found that lidocaine could attenuate the overall incidence of POCD, especially in the short term. There were no differences between lidocaine and placebo on the overall severity of POCD. CONCLUSION: Lidocaine administered intravenously could attenuate the overall incidence of POCD and its severity in the short term.

l-Arginine treatment maintains postharvest quality in blueberry fruit by enhancing antioxidant capacity during storage.

The postharvest quality of blueberry fruit is largely limited by deterioration. l-arginine (Arg) is a functional nontoxic amino acid with high biological activities. This study investigated the positive effects and the underlying mechanism of Arg treatment on the quality of postharvest blueberries. Arg effectively mitigated fruit decay and improved the quality of blueberries, including weight loss, firmness, and soluble solid content. Mechanistically, Arg-mediated activation of the anti-oxidative defense system reduced reactive oxygen species-mediated oxidative damage. Moreover, Arg treatment decreased the activities and gene expression of phospholipase D, lipoxygenase, and lipase-inhibiting membrane lipid peroxidation during the prolonged storage of blueberries. Meanwhile, Arg treatment increased nitric oxide (NO) content and NO synthase activity. Furthermore, correlation and principal component analyses revealed the enhancement of Arg treatment on antioxidant capacity. This study suggests that Arg treatment can maintain the postharvest quality of blueberries by improving antioxidant capacity.

HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson's Disease Pathology in Mice.

Histone deacetylase 6 (HDAC6) is involved in the regulation of protein aggregation and neuroinflammation, but its role in Parkinson's disease (PD) remains controversial. In this study, Hdac6-/- mice were generated by CRISPR-Cas9 technology for exploring the effect of HDAC6 on the pathological progression of PD. We found that male Hdac6-/- mice exhibit hyperactivity and certain anxiety. In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, though motor injury was slightly alleviated by HDAC6 deficiency, dopamine (DA) depletion in the striatum, the decrease in the number of DA neurons in the substantia nigra (SN) and the reduction in DA neuronal terminals were not affected. In addition, activation of glial cells and the expression of α-synuclein, as well as the levels of apoptosis-related proteins in the nigrostriatal pathway, were not changed in MPTP-injected wild-type and Hdac6-/- mice. Therefore, HDAC6 deficiency leads to moderate alterations of behaviors and Parkinson's disease pathology in mice.

An overview of pim kinase as a target in multiple myeloma.

Multiple myeloma (MM) is the second common hematologic malignancy manifesting as a clonal proliferation of plasma cells in the bone marrow. In recent years, high expression and activity of pim kinase have been found to be associated with both the progression and prognosis of a significant proportion of malignant diseases. Therefore, pim kinase has become a potential therapeutic target in the treatment of MM and some pim kinase inhibitors have demonstrated good efficacy in clinical trials. Based on nearly the entire literature searched from PubMed in the field of pim kinase in MM, the paper concluded how pim kinase got involved in the proliferation of myeloma cells, the progression of bone disease infiltration, and even in the regulation of the immune microenvironment. Next as a very promising drug, the effectiveness of pim kinase inhibitors as single agents or in combination with other drugs in the treatment of MM was also summarized. Our analysis will guide the clinical use of pim kinase inhibitors for managing tumor load and bone disease in MM patients.

Non-destructive and in-situ detection of shrimp freshness using mid-infrared fiber-optic evanescent wave spectroscopy.

There is strong interest in non-destructive and rapid determination of food freshness in food research. In this study, mid-infrared (MIR) fiber-optic evanescent wave (FOEW) spectroscopy was applied to monitor shrimp freshness through the evaluation of protein, chitin, and calcite contents in conjunction with a Partial Least Squares Discriminant Analysis (PLS-DA) model. Shrimp shells were wiped with a micro fiber-optic probe to obtain a FOEW spectrum which quickly and nondestructively allowed evaluation of the shrimp freshness. Peaks for proteins, chitin, and calcite, which are closely related to shrimp freshness, were detected and quantified. Compared with the standard indicator for evaluating shrimp freshness (total volatile basic nitrogen), the PLS-DA model gave recognition rates for shrimp freshness using calibration and validation sets of the FOEW data of 87.27%, 90.28%, respectively. Our results show that FOEW spectroscopy is a feasible method for non-destructive and in-site detection of shrimp freshness.

Hydrogen Bonding of Aramid Boosts High-Temperature Capacitive Properties of Polyetherimide Blends.

Polyetherimide (PEI) is the state-of-the-art commercial high-temperature polymer dielectric with excellent thermal and chemical stability and relatively high high-temperature capacitive energy storage properties. The rotation of the dipoles in the PEI chains brings the ß-relaxation which seriously increases the leakage current and decreases the charge-discharge efficiency. In this work, hydrogen bonds have been introduced to limit the dipole rotation of PEI by blending aramids [1,4-poly(ether fluoromethyl naphthalene amide), PNFA] into the PEI matrix. By introducing 10 wt % PNFA, the ß-relaxation of the blend has been significantly reduced which could be observed from the dielectric spectrum. To explore the mechanism of limited ß-relaxation, we analyze the hydrogen bonds in the blend films by infrared spectroscopy and found that the maximum content of hydrogen-bonded carbonyl formed between PNFA and PEI chains was 14.3% when the content of PNFA was 30 wt %. The content of hydrogen bonds formed between PNFA and PEI was positively correlated with the energy storage performance of the blends. The maximum discharged energy density with an efficiency above 90% of the blend film with 30 wt % PNFA reaches 4.1 J cm-3 at 150 °C, which is about 350% higher than that of pristine PEI. This work shows that composing hydrogen bonds by the blending method could be a viable strategy for enhancing the high-temperature energy storage performance of polymer dielectrics, which could be achieved by large-scale preparation and has feasible industrial production prospects.

Learning matrix factorization with scalable distance metric and regularizer.

Matrix factorization has always been an encouraging field, which attempts to extract discriminative features from high-dimensional data. However, it suffers from negative generalization ability and high computational complexity when handling large-scale data. In this paper, we propose a learnable deep matrix factorization via the projected gradient descent method, which learns multi-layer low-rank factors from scalable metric distances and flexible regularizers. Accordingly, solving a constrained matrix factorization problem is equivalently transformed into training a neural network with an appropriate activation function induced from the projection onto a feasible set. Distinct from other neural networks, the proposed method activates the connected weights not just the hidden layers. As a result, it is proved that the proposed method can learn several existing well-known matrix factorizations, including singular value decomposition, convex, nonnegative and semi-nonnegative matrix factorizations. Finally, comprehensive experiments demonstrate the superiority of the proposed method against other state-of-the-arts.

Combining polyp diameter and polyp-to-bile ratio by dynamic contrast-enhanced CT scanning can improve the diagnostic specificity of gallbladder neoplastic polyps.

OBJECTIVE: This study aimed to distinguish between cholesterol and neoplastic gallbladder polyps using dynamic contrast-enhanced CT. METHODS: The dataset retrospectively comprised 222 cases, including 106 cases of cholesterol polyps and 116 cases of neoplastic polyps (59 adenoma and 57 adenocarcinoma). The perception and Hounsfield units of the polyps and gallbladder bile were assessed by contrast-enhanced CT, and the polyp-to-bile ratio (PBR) was calculated. Receiver operating characteristic (ROC) curves and area under the curve analyses were used to assess the diagnostic value of the diameter and PBR for neoplastic polyps. RESULTS: The diameter of cholesterol polyps was significantly smaller than that of neoplastic polyps. The proportion of perceived cholesterol polyps in the plain and arterial phases of CT were significantly lower than those of neoplastic polyps (p < .001). On the contrary, the CT values of gallbladder bile of cholesterol polyps were always significantly higher than those of neoplastic polyps (p < .001). The median PBR values of cholesterol polyps were significantly lower than those of neoplastic polyps (p ≤ .001). ROC analysis showed that diameter and a plain phase PRB had better diagnostic value for neoplastic polyps. Polyp diameter ≥ 11.95 mm and the plain phase PBR ≥1.48 were the optimal cut-off values for diagnosis of neoplastic polyps. Combining a diameter ≥ 12 mm and a PBR in the plain phase ≥1.48 further improved neoplastic polyp diagnostic specificity and positive likelihood ratio (10.453). CONCLUSIONS: Polyp-to-bile ratio in contrast-enhanced CT scanning is a new and convenient index for identifying cholesterol and neoplastic gallbladder polyps.