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Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1β by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

Continuous tobacco monocropping has caused soil degradation and yield reduction in China. Intercropping, as a specific and efficient cropping pattern, is highly associated with the enhancement of soil quality and land-use efficiency. Tobacco (Nicotiana tabacum L.)- Isatis (Isatis tinctoria L.) intercropping can significantly alleviate pests and diseases, and improve soil potential and fertility in tobacco fields. In this study, comparative analysis of three different tobacco-Isatis intercropping (B2, B3, B4) and tobacco monocropping (B1) on the soil nutrients, enzyme activities, and microbial community were conducted. B2, B3, and B4 importantly increased the contents of organic matter, available potassium, and available phosphorus content of the soil by 17.38%, 7.76%, and 2.78%, respectively. Moreover, B2 enhanced the activities of sucrase, urease, and catalase of soil by 2.35 times, 3.16 times, and 4.47 times, respectively, and B3 enhanced the activities of sucrase, urease, and catalase of soil by 2.74 times, 3.22 times, and 3.11 times, respectively. The intercropping pattern also optimized the structure of the soil microbial community. The relative abundances of Acidobacteriota, Chloroflexi, Gemmatimonadota, Planctomycetota, Nitrospirota, and Verrucomicrobiota in B3 and B4 were higher than those in B1. Positive links in soil bacterial correlation networks accounted for 47%, and soil bacteria formed a highly interactive and complex network. And compared with the B1, Ascomycota and Basidiomycota were lower abundance in B2 and B4, Ascomycota were lower abundance in B3 and Mortierellomycota were lower abundance in B2 and B3. Compared with monocropping, the chemical composition of tobacco leaves was harmoniously improved and the total production value of tobacco fields was significantly higher. The content of reducing sugar, total sugar, nicotine, potassium, and two-sugar ratio of leaves were increased after intercropping. The proportion of top-grade tobacco leaves after roasting in B2, B3, and B4 treatments were increased by 8.19%, 16.74%, and 27.32%, respectively. The study constructs insights into microbial community interactions at in tobacco/Isatis intercropping systems, and may facilitate the further development of tobacco/Isatis intercropping systems.

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Abstract Extreme glacier melt has important implications for climate change studies and glacier‐related hazards. Few attempts have been made to study the characteristics and mechanisms of extreme melt on the Tibetan Plateau (TP) and surroundings, one of the largest concentrations of glaciers beyond the polar regions. To address this gap, we investigated the magnitude and possible drivers of anomalous early spring glacier melt in 2022 on the central TP using multi‐source observations (October 2020–July 2022) of Kuoqionggangri and Sangqu glaciers and an energy and mass balance model. Our results show that anomalous melt of both glaciers occurred in early spring (18 March–10 April 2022), when glaciers are traditionally expected to be frozen. There were 89 cumulative hours with air temperatures above 0°C, with a positive cumulative air temperature of 121.80°C hour at 5,700 m on Kuoqionggangri Glacier. The glacier‐wide cumulative melts on Kuoqionggangri and Sangqu glaciers from 18 March to 10 April 2022 were 22 ± 14.2 and 48 ± 37.5 mm w.e., respectively. Such anomalous glacier melt was driven by high incoming shortwave radiation and sensible heat flux, which were influenced by low cloud fraction and precipitation, and high air temperature during early spring. The weakening and northward‐shift of the westerlies, coupled with descending air motions over the central TP, reduced cloud fraction and hindered the transport of cold, moist air to the central TP. These changes occurred both in the central TP and the Himalaya, indicating the influence of macroscale atmospheric circulation patterns on this extreme glacier melt.

Abstract Background Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of older persons to the influenza vaccine are usually poorer than those of young individuals, which is hypothesized due to immunosenescence. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) in a total of 167 young (

Hepatic encephalopathy (HE) is often associated with endogenous serotonin (5-HT) disorders. However, the reason for elevated brain 5-HT levels due to liver failure remains unclear. This study aimed to investigate the mechanism by which liver failure increases brain 5-HT levels and the role in behavioral abnormalities in HE. Using bile duct ligation (BDL) rats as a HE model, we verified the elevated 5-HT levels in the cortex but not in the hippocampus and striatum, and found that this cortical 5-HT overload may be caused by BDL-mediated inhibition of UDP-glucuronosyltransferase 1A6 (UGT1A6) expression and activity in the cortex. The intraventricular injection of the UGT1A6 inhibitor diclofenac into rats demonstrated that the inhibition of brain UGT1A6 activity significantly increased cerebral 5-HT levels and induced HE-like behaviors. Co-immunofluorescence experiments demonstrated that UGT1A6 is primarily expressed in astrocytes. In vitro studies confirmed that NH4Cl activates the ROS-ERK pathway to downregulate UGT1A6 activity and expression in U251 cells, which can be reversed by the oxidative stress antagonist N-acetyl-l-cysteine and the ERK inhibitor U0126. Silencing Hepatocyte Nuclear Factor 4α (HNF4α) suppressed UGT1A6 expression whilst overexpressing HNF4α increased Ugt1a6 promotor activity. Meanwhile, both NH4Cl and the ERK activator TBHQ downregulated HNF4α and UGT1A6 expression. In the cortex of hyperammonemic rats, we also found activation of the ROS-ERK pathway, decreases in HNF4α and UGT1A6 expression, and increases in brain 5-HT content. These results prove that the ammonia-mediated ROS-ERK pathway activation inhibits HNF4α expression to downregulate UGT1A6 expression and activity, thereby increasing cerebral 5-HT content and inducing manic-like HE symptoms. This is the first study to reveal the mechanism of elevated cortical 5-HT concentration in a state of liver failure and elucidate its association with manic-like behaviors in HE.

LHPP (Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase) is a protein histidine phosphatase that modulates a hidden posttranslational modification called histidine phosphorylation. LHPP also acts as a tumor suppressor, which plays a pivotal role in various cellular processes. However, whether LHPP participates in the regulation of invertebrate's immunity is still unknown. Here we characterized a LHPP homolog in P. vannamei (designated PvLHPP), with a 807 bp length of open reading frame (ORF) encoding a putative protein of 268 amino acids. Sequence analysis revealed that PvLHPP contains a typical hydrolase 6 and hydrolase-like domain, which was conserved from invertebrate to vertebrate. PvLHPP was ubiquitously expressed in tissues and induced in hemocyte and hepatopancreas by Vibrio parahaemolyticus, Streptococcus iniae and white spot syndrome virus (WSSV) challenge, indicating that PvLHPP participated in the immune responses. Moreover, silencing of PvLHPP followed by V. parahaemolyticus inhibited hemocyte apoptosis. This study enriches our current insight on shrimp immunity, and provides novel perspective to understand immune-regulatory role of PvLHPP.

Abstract Background Numerous microorganisms are found in aquaculture ponds, including several pathogenic bacteria. Infection of cultured animals by these pathogens results in diseases and metabolic dysregulation. However, changes in the metabolic profiles that occur at different infection stages in the same ponds and how these metabolic changes can be modulated by exogenous metabolites in Penaeus vannamei remain unknown. Results Here, we collected gastrointestinal tract (GIT) samples from healthy, diseased, and moribund P. vannamei in the same aquaculture pond for histological, metabolic, and transcriptome profiling. We found that diseased and moribund shrimp with empty GITs and atrophied hepatopancreas were mainly infected with Vibrio parahaemolyticus and Vibrio harveyi. Although significant dysregulation of crucial metabolites and their enzymes were observed in diseased and moribund shrimps, diseased shrimp expressed high levels of taurine and taurine metabolism-related enzymes, while moribund shrimp expressed high levels of hypoxanthine and related metabolism enzymes. Moreover, a strong negative correlation was observed between taurine levels and the relative abundance of V. parahaemolyticus and V. harveyi. Besides, exogenous taurine enhanced shrimp survival against V. parahaemolyticus challenge by increasing the expression of key taurine metabolism enzymes, mainly, cysteine dioxygenase (CDO) and cysteine sulfinic acid decarboxylase (CSD). Conclusions Our study revealed that taurine metabolism could be modulated by exogenous supplementation to improve crustacean immune response against pathogenic microbes. Video Abstract

Abstract Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low‐cost, batch‐scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high‐precision 3D printed master mold followed by a dual‐molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat‐curing polymers or light‐curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1‐fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual‐molding process can reinvigorate HMNs development.

Abstract Abundant glutathione (GSH) is a biological characteristic of lots of tumor cells. A growing number of studies are utilizing GSH depletion as an effective adjuvant therapy for tumor. However, due to the compensatory effect of intracellular GSH biosynthesis, GSH is hard to be completely exhausted and the strategy of GSH depletion remains challenging. Herein, we report an l-buthionine-sulfoximine (BSO)-based hypertoxic self-assembled peptide derivative (NSBSO) with dual functions of GSH depletion and biosynthesis inhibition for selective tumor ferroptosis and pyroptosis. The NSBSO consists of a hydrophobic self-assembled peptide motif and a hydrophilic peptide derivative containing BSO that inhibits the synthesis of GSH. NSBSO was cleaved by GSH and thus experienced a morphological transformation from nanoparticles to nanofibers. NSBSO showed GSH-dependent cytotoxicity and depletion of intracellular GSH. In 4T1 cells with medium GSH level, it depleted intracellular GSH and inactivated GSH peroxidase 4 (GPX4) and thus induced efficient ferroptosis. While in B16 cells with high GSH level, it exhausted GSH and triggered indirect increase of intracellular ROS and activation of Caspase 3 and gasdermin E, resulting in severe pyroptosis. These findings demonstrate that GSH depletion- and biosynthesis inhibition-induced ferroptosis and pyroptosis strategy would provide insights in designing GSH-exhausted medicines. Graphical Abstract

Highlights Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode–skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Abstract Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode–skin contact impedance reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Based on the experimental data, the life characteristics of lithium-ion battery were analyzed. According to the experimental data statistics, the battery life changes with the number of cycles, the performance of the battery after repeated use is studied, and the changes of battery capacity, discharge efficiency, energy efficiency, internal resistance and other parameters with the battery life are explored. The mathematical model of battery life and battery usage times is established by curve fitting, and the SOH of battery is predicted according to this model. Finally, the SOH of Li ion battery is estimated according to the voltage curve fitting method. Firstly, the battery charging curves under different discharge rates and different SOH are normalized, and the charging voltage error after normalization calculation is compared. According to the existing experimental data, the SOH estimation algorithm of 92Ah lithium-ion battery is verified, the estimation accuracy of voltage curve fitting method is verified, and the estimation results of SOH are analyzed.

During growth and aging, the role of the hippocampus in memory depends on its interactions with related brain regions. Particularly, two subregions, anterior hippocampus (aHipp) and posterior hippocampus (pHipp), play different and critical roles in memory processing. However, age-related changes of hippocampus subregions on structure and function are still unclear. Here, we investigated age-related structural and functional characteristics of 106 participants (7-85 years old) in resting state based on fractional anisotropy (FA) and functional connectivity (FC) in aHipp and pHipp in the lifespan. The correlation between FA and FC was also explored to identify the coupling. Furthermore, the Wechsler Abbreviated Scale of Intelligence (WASI) was used to explore the relationship between cognitive ability and hippocampal changes. Results showed that there was functional separation and integration in aHipp and pHipp, and the number of functional connections in pHipp was more than that in aHipp across the lifespan. The age-related FC changes showed four different trends (U-shaped/inverted U-shaped/linear upward/linear downward). And around the age of 40 was a critical period for transformation. Then, FA analyses indicated that all effects of age on the hippocampal structures were nonlinear, and the white matter integrity of pHipp was higher than that of aHipp. In the functional-structural coupling, we found that the age-related FA of the right aHipp (aHipp.R) was negatively related to the FC. Finally, through the WASI, we found that the age-related FA of the left aHipp (aHipp.L) was positively correlated with verbal IQ (VERB) and vocabulary comprehension (VOCAB.T), the FA of aHipp.R was only positively correlated with VERB, and the FA of the left pHipp (pHipp.L) was only positively correlated with VOCAB.T. These FC and FA results supported that age-related normal memory changes were closely related to the hippocampus subregions. We also provided empirical evidence that memory ability was altered with the hippocampus, and its efficiency tended to decline after age 40.

Mountainous regions are prone to dammed lake disasters due to their rough topography, scant vegetation, and high summer rainfall. By measuring water level variation, monitoring systems can detect dammed lake events when mudslides block rivers or boost water level. Therefore, an automatic monitoring alarm method based on a hybrid segmentation algorithm is proposed. The algorithm uses the k-means clustering algorithm to segment the picture scene in the RGB color space and the region growing algorithm on the image green channel to select the river target from the segmented scene. The pixel water level variation is used to trigger an alarm for the dammed lake event after the water level has been retrieved. In the Yarlung Tsangpo River basin of the Tibet Autonomous Region of China, the proposed automatic lake monitoring system was installed. We pick up data from April to November 2021, during which the river experienced low, high, and low water levels. Unlike conventional region growing algorithms, the algorithm does not rely on engineering knowledge to pick seed point parameters. Using our method, the accuracy rate is 89.29% and the miss rate is 11.76%, which is 29.12% higher and 17.65% lower than the traditional region growing algorithm, respectively. The monitoring results indicate that the proposed method is a highly adaptable and accurate unmanned dammed lake monitoring system.

In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor’s response time is 0.07 s in air and sensitivity is 1.4‰°C−1. The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.

The aim of the present study was to evaluate the expression levels of the aryl hydrocarbon receptor (AHR) and its target gene CYP1B1 and to correlate their expression with Wnt5a/b-β-catenin, the CD44+/CD24(−/low) cancer stem cell (CSC) subset and factors associated with poor prognosis in inflammatory breast cancer (IBC) and non-IBC patients. The methods of analysis used were quantitative real-time PCR, western blotting, immunohistochemistry and flow cytometry. Compared to non-IBC tissues, IBC tissues exhibited the overexpression of AHR and its target gene/protein CYP1B1. AHR and CYP1B1 mRNA levels were associated with the poor clinical prognosis markers tumour grade, lymphovascular invasion, cell proliferation and lymph node metastasis. Furthermore, AHR expression correlated with the expression of Wnt5a/b and β-catenin signalling molecules, and Wnt5a mRNA expression was downregulated in the SUM149 human IBC cell line and the MDA-MB-231 non-IBC cell line upon inhibition of AHR. AHR gene knockout (CRISPR-Cas9) inhibits CYP1B1 and Wnt5a expression in the IBC cell line. The CD44+/CD24(−/low) subset was significantly correlated with the expression of AHR, CYP1B1, Wnt5a/b and β-catenin in IBC tissues. The overexpression of AHR and its target CYP1B1 correlated with the expression of Wnt5a/b and β-catenin, CSCs, and poor clinical prognostic factors of IBC. Thus, targeting AHR and/or its downstream target molecules CYP1B1 and Wnt5a/b may represent a therapeutic approach for IBC. Keywords: Inflammatory breast cancer, Aryl hydrocarbon receptor, CYP1B1, Wnt5a/b and β-catenin, CD44+/CD24(−/low) subset and lymphovascular invasion

A multisensor system is used to improve the ability of monitoring and tracking accuracy of an engineering system since only one sensor is not enough, whereupon, faulty diagnosis, as a typical information fusion problem which is under multisensor environment, has attracted much attention in recent years. The evidence theory has been widely used to solve this problem. However, when there is a high level of conflict between the information gathered from different sensors, the counter-intuitive result could be obtained when using the classical Dempster’s combination rule. To address this problem, an improved multisensor data fusion method is proposed to fuse the data collected from multisensors. Some numerical examples are illustrated to show that the proposed method is effective and feasible. Moreover, the fusion results using different methods are analyzed, which indicate the superiority and stronger application of the proposed method in the field of fault diagnosis.

Objective: To compare the immediate effect of acupuncture at the contralateral versus ipsilateral Tiaokou (ST38) in patients with Chronic shoulder pain (CSP). Method: Altogether, 38 patients with unilateral CSP were randomly assigned to a contralateral ST38 group (Contra group) or ipsilateral ST38 group (Ipsi group). Each underwent 20 min of manual acupuncture: Contra group at the contralateral ST38, Ipsi group at the ipsilateral ST38. Primary outcome measure was the visual analog scale (VAS) score. Secondary outcome measure for assessing shoulder mobility was the Constant-Murley (CM) score, which included pain level, activities of daily living (ADL), and shoulder range of motion (ROM). These factors were assessed before and immediately after acupuncture. A value of P

Abstract Background Previously, we have demonstrated that IL-33 administration protecting TNBS-induced experimental colitis is associated with facilitation of Th2/Tregs responses in mice. However, whether IL-33 regulates autophagy to ameliorate experimental colitis is unclear. Results IL-33 administration (2 μg/day, intraperitoneal injection), while facilitating Th2/Tregs responses, also enhances the autophagy in mice with TNBS-induced colitis as well as macrophages. In the meantime, we observed that inhibition of the autophagy with 3-methyladenine (3-MA) (24 mg/kg, intraperitoneal injection) in mice exacerbates TNBS-induced experimental colitis. On the contrary, administration of rapamycin (2 mg/kg,intragastric administration), an autophagy-enhancer, alleviates the colitis in mice. In vivo, Immunofluorescence analysis revealed that TNBS combined with IL-33 enhanced the autophagy of macrophages in the inflammatory gut tissue. In vitro, treatment with IL-33 promoted the autophagy of macrophages generated from bone marrow cells in dose-dependant manner. Furthermore, the effect of autophagy-enhancement by IL-33 is TLR4 signaling pathway dependant. Our notion was further confirmed by IL-33-deficient bone marrow-derived macrophages cells. Conclusions IL-33 regulates the autophagy is a new immunoregulatory property on TNBS-induced experimental colitis in mice.

Abstract Supramolecular peptide hydrogel has shown promising potential in vaccine development largely because of its ability to function both as antigen depot and immune adjuvant. Nap‐GdFdFdY, a tetrapeptide hydrogel that has been previously reported to exhibit adjuvant effect, is inadvertently found to contain conserved peptide sequence for insulin, proinsulin, and glutamic acid decarboxylase, 3 major autoantigens for the autoimmune type 1 diabetes (T1D). At present, despite being managed clinically with insulin replacement therapy, T1D remains a major health threat with rapidly increasing incidences, especially in children and young adults, and antigen‐specific immune tolerance induction has been proposed as a feasible approach to prevent or delay T1D progression at an early stage. Here, it is reported that innoculation of Nap‐GdFdFdY leads to complete protection of nonobese diabetic (NOD) mice from T1D development till the age of 36 weeks. Better maintenance of pancreatic islet morphology with minimal immune cell infiltration is also observed from mice exposed to Nap‐GdFdFdY. This beneficial impact is mainly due to its facilitative role on enhancing peripheral T regulatory cell (Treg) population, shown as increased splenic Treg percentage, and function, demonstrated by maintenance of circulating TGF‐β1 level. Serum cytokine microarray data further implicate a “buffering” role of Nap‐GdFdFdY on systemic inflammatory tone in NOD mice. Thus, with its versatility, applicability, and excellent potency, Nap‐GdFdFdY is posited as a novel therapeutic intervention for T1D.

Atherosclerosis is a major pathogenic driver of cardiovascular diseases. Foam cell formation plays a key role in atherogenesis, which is affected by lipid disorder and inflammation. Therefore, inhibition of foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from A. membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. In this study, we determined whether TFA could inhibit atherosclerosis and uncovered the underlying mechanism. In vivo, ApoE deficient mice were treated with TFA and high-fat diet for 16 weeks. Subsequently, atherosclerotic lesions, hepatic steatosis and associated genes expression in vitro and in vivo were determined. We found that TFA reduced atherosclerotic lesion size and enhanced plaque stability, which might be attributed to improved lipid disorder, reduced inflammation and decreased monocyte adhesion. Mechanistically, TFA inhibited hepatic steatosis via regulating the genes responsible for lipid metabolism, by which ameliorating the lipid disorder. Moreover, in macrophage, TFA reduced the expression of scavenger receptors such as CD36 and SRA; and promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced miR-33 expression and dampened NFκB activity, by which de-repressing ABCA1/G1 activity and inhibiting the inflammation. Collectively, TFA can attenuate atherosclerosis via dual suppression of miR-33 and NFκB pathway, and partially through inhibition of scavenger receptors in macrophage. In addition, TFA ameliorates the hepatic steatosis and lipid disorder, which in turn contributes to the amelioration of atherosclerosis, suggesting that TFA might be a novel therapeutic approach for inhibition of atherosclerosis and hepatic steatosis.

The utilization of nanotechnology to deliver vaccines and modulate immunity has shown great potential in cancer therapy. Peptide-based supramolecular hydrogels as novel vaccine adjuvants have been found to effectively improve the immune response and tumor curative effect. In this study, we designed a set of reduction-responsive self-assembled peptide precursors (Fbp-GDFDFDYD(E, S, or K)-ss-ERGD), which can be reduced by glutathione (GSH) into Fbp-GDFDFDYD(E, S or K)-SH for forming of hydrogel with different surface properties (E-gel, S-gel, and K-gel, respectively). Using the same method, co-assembled hydrogel vaccines (E-vac, S-vac, and K-vac, respectively) can also be prepared by mixing different precursors with antigens before GSH reduction. Through TEM observation of the nanostructure, we found that all the co-assembled hydrogels, especially K-vac, possessed much denser and more unified nanofiber networks as compared with antigen-free hydrogels, which were very suitable for antigen storage and vaccine delivery. Although the three peptides adopted similar β-sheet secondary structures, the mechanical properties of their resulted co-assembled hydrogel vaccines were obviously different. Compared to E-vac, S-vac had a much weaker mechanical property, while K-vac had a much higher. In vivo experiments, co-assembled hydrogel vaccines, especially K-vac, also promoted antibody production and anti-tumor immune responses more significantly than the other two vaccines. Our results demonstrated that co-assembled hydrogels formed by peptides and antigens co-assembly could act as effective vaccine delivery systems for boosting antibody production, and different immune effects can be acquired by tuning the surface properties of the involved self-assembling peptides.

The amygdala, which is involved in human social information processing and socio-emotional response neuronal circuits, is segmented into three subregions that are responsible for perception, affiliation, and aversion. Though there is different functional and effective connectivity (EC) among these networks, age-related structural changes and associations between structure and function within the amygdala remain unclear. Here, we used diffusion tensor imaging (DTI) data (106 participants) to investigate age-related structural changes in fractional anisotropy (FA) of amygdalar subregions. We also examined the relationship between FA and EC within the subregions. We found that the FA of the amygdalar subregions exhibited inverted-U-shape trends with age. Moreover, over the human lifespan, there were negative correlations between the FA of the right ventrolateral amygdala (VLA.R) and the Granger-based EC (GC) of VLA.R → perception network (PerN), the FA of the VLA.R and the GC of the net flow from VLA.R → PerN, and the FA of the left dorsal amygdala (DorA.L) and the GC of the aversion network (AveN). Conversely, there was a positive correlation between the FA of the DorA.L and the GC of the net flow from DorA.L → AveN. Our results suggest that age-related changes in the function of the brain are constrained by the underlying white matter architectures, while the functional information flow changes influence white matter structure. This work increases our understanding of the neuronal mechanisms in the maturation and aging process.

About 35 million people worldwide were suffered from Alzheimer’s disease (AD) in 2014 and the number of patients was expected to increase by 4-fold in 2050. As a neurodegenerative disease impacting our society, the pathogenesis and prognosis of AD have not yet fully understood. Senile plaque is generally regarded as one of the hallmarks of the disease, which may be due to the imbalance of Aβ peptides in the brain. Over the last decades, studies of early onset familial AD have led us to a deeper understanding of the genetics and molecular biology of AD. There is increasing evidence to suggest that the pathogenesis of AD is more likely to be caused by multiple genetic mutations. However, the precise genetic component leading to AD pathogenesis remains unclear. In this review, we will briefly introduce the classification of AD in the context of genetics. Then we will discuss the gene mutations in chromosome 21, 19 and presenilin as well as their links to Aβ peptides. Imaging data will be discussed alongside to complement the associated structural and physiological changes in the brain. It is our hope that future research in genetics will continue to enhance our understanding of the pathogenesis of AD and the mechanisms leading to the formation of senile plaques.

Resting-state functional magnetic resonance imaging was utilized to measure the amplitude low frequency fluctuations (ALFF) in human subjects with Alzheimer’s disease (AD) and normal control (NC). Two specific frequency bands (Slow5: 0.01-0.027Hz and Slow4: 0.027-0.073Hz) were analysed in the main cognitive control related four subregions of the right ventral lateral prefrontal cortex (VLPFC), i.e. IFJ, posterior-VLPFC, mid-VLPFC, and anterior-VLPFC. Differences in ALFF values between the AD and the NC group were found throughout the subregions of the right VLPFC. Compared to normal control group, decreased ALFF values were observed in AD patients in the IFJ (in two given frequency bands), and the mid-VLPFC (in Slow5). In contrast, increased ALFF valued were observed in AD patients in the posterior- and anterior-VLPFC (in both Slow5 and Slow4), and also in the mid-VLPFC in Slow4. Moreover, significant ALFF differences between the IFJ and three other subregions of the right VLPFC were found. Furthermore, ALFF values in the right VLPFC showed significant correlations with the time course of disease. Taken together, our findings suggest that AD patients have largely abnormalities in intrinsic neural oscillations which are in line with the AD pathophysiology, and further reveal that the abnormalities are dependent on specific frequency bands. Thus, frequency-domain analyses of the ALFF may provide a useful tool to investigate the AD pathophysiology.

To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual damage through comparison to healthy controls (HCs).25 PA patients with visual damage and 25 age- and sex-matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic evaluation, including automated perimetry, fundus examinations, and a magnetic resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS-fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and the functional connectivity (FC) of 6 seeds within the visual cortex (the primary visual cortex (V1), the secondary visual cortex (V2), and the middle temporal visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to identify the differences between the two groups.Compared with the HCs, the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+, BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2, MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe (especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre-SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus, whereas V2 and MT+ exhibited increased FCs with the thalamus, especially pulvinar.In our study, we identified significant neural reorganization in the vision-related cortex of PA patients with visual damage compared with HCs. Most subareas within the visual cortex exhibited remarkable neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced FC with the thalamic pulvinar, which indicates an important role in the compensatory mechanism following visual impairment. In addition, neural dysfunction within the visual cortex was associated with neural activity alternation in the higher-order cognitive cortex, especially subareas in default mode network (DMN) and salience network (SN).