Construction of novel Ag(0)-containing silver nanoclusters by regulating auxiliary phosphine ligands.

Controlled synthesis of metal clusters through minor changes in surface ligands holds significant interest because the corresponding entities serve as ideal models for investigating the ligand environment's stereochemical and electronic contributions that impact the corresponding structures and properties of metal clusters. In this work, we obtained two Ag(0)-containing nanoclusters (Ag17 and Ag32) with near-infrared emissions by regulating phosphine auxiliary ligands. Ag17 and Ag32 bear similar shells wherein Ag17 features a trigonal bipyramid Ag5 kernel while Ag32 has a bi-icosahedral interpenetrating an Ag20 kernel. Ag17 and Ag32 showed a near-infrared emission (NIR) of around 830 nm. Benefiting from the rigid structure, Ag17 displayed a more intense near-infrared emission than Ag32. This work provides new insight into the construction of novel superatomic silver nanoclusters by regulating phosphine ligands.

Spindle apparatus coiled-coil protein 1 (SPDL1) serves as a novel prognostic biomarker in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified. METHODS: Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC. RESULTS: In TNBC tissues, we found that SPDL1 (CCDC99) was considerably overexpressed at both the mRNA and protein levels compared to that in normal and non-TNBC tissues. Additionally, we found that SPDL1-high expression was strongly linked to poor prognosis in TNBC patients. Excessive SPDL1 expression was positively correlated with tumor growth and strongly linked to the cell cycle, DNA replication, and the p53 signaling pathway. In addition, CIBERSORT analysis revealed that SPDL1 can affect the tumor immune microenvironment (TME) in TNBC, encourage the development of TNBC and act as a potential prognostic biomarker for TNBC. Patients with SPDL1-high expression were more sensitive to AZD8055. Notably, we discovered that SPDL1 is highly expressed in the majority of malignancies and may have an impact on the pancancer prognosis. CONCLUSIONS: SPDL1 can serve as a novel prognostic marker for TNBC and pancancer patients.

Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus.

PURPOSE: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features. PATIENTS AND METHODS: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors. RESULTS: A total of 202 patients (median age, 58 years [IQR, 52-65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival. CONCLUSION: The optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis.

Construction of n-type homogeneous to improve interfacial carrier transfer for enhanced photoelectrocatalytic hydrolysis.

Photoelectrocatalyzed hydrogen production plays an important role in the path to carbon neutrality. The construction of heterojunctions provides an ideal example of an oxygen precipitation reaction. In this work, the performance of the n-n type heterojunction CeBTC@FeBTC/NIF in the photoelectronically coupled catalytic oxygen evolution reaction (OER) reaction is presented. The efficient transfer of carriers between components enhances the catalytic activity. Besides, the construction of heterojunctions optimizes the energy level structure and increases the absorption of light, and the microstructure forms holes with a blackbody effect that also enhances light absorption. Consequently, CeBTC@FeBTC/NIF has excellent photoelectric coupling catalytic properties and requires an overpotential of only 300 mV to drive a current density of 100 mA cm-2 under illumination. More importantly, the n-n heterojunction was found to be effective in enhancing charge and photogenerated electron migration by examining the carrier density of each component and carrier diffusion at the interface.

Fe-doping and oxygen vacancy achieved by electrochemical activation and precipitation/dissolution equilibrium in NiOOH for oxygen evolution reaction.

The poor conductivities and instabilities of accessible nickel oxyhydroxides hinder their use as oxygen evolution reaction (OER) electrocatalysts. Herein, we constructed Fe-NiOOH-OV-600, an Fe-doped nickel oxide hydroxide with abundant oxygen vacancies supported on nickel foam (NF), using a hydrothermal method and an electrochemical activation strategy involving 600 cycles of cyclic voltammetry, assisted by the precipitation/dissolution equilibrium of ferrous sulfide (FeS) in the electrolyte. This two-step method endows the catalyst with abundant Fe-containing active sites while maintaining the ordered structure of nickel oxide hydroxide (NiOOH). Characterization and density functional theory (DFT) calculations revealed that synergy between trace amounts of the Fe dopant and the oxygen vacancies not only promotes the generation of reconstructed active layers but also optimizes the electronic structure and adsorption capacity of the active sites. Consequently, the as-prepared Fe-NiOOH-OV-600 delivered large current densities of 100 and 1000 mA cm-2 for the OER at overpotentials of only 253 and 333 mV in 1 mol/L KOH. Moreover, the catalyst is stable for at least 100 h at 500 mA cm-2. This work provides insight into the design of efficient transition-metal-based electrocatalysts for the OER.

Amplifiers of environmental risk of microplastics in sewage sludge: Thermal drying treatment.

Sewage sludge was already identified as an important source of microplastics (MPs) in the environment. Therefore, investigating the effects of sludge treatment processes on sludge-based MPs is essential for understanding the environmental risks and controlling their release. This study investigated the occurrence characteristics and elucidated the fragmentation mechanism of sludge-based MPs before and after the thermal drying treatment of sludge. The results showed that this treatment increased the abundance of sludge-based MPs by about 10-fold, with enhanced fragmentation and fracture parameters, and increased the abundance of <100 µm MPs to >60 %. Remarkably, both polypropylene-microplastics (PP-MPs) and polyethylene terephthalate-microplastics (PET-MPs) did not show significant chemical aging. The structural analysis showed that the molecular chain disorientation and secondary crystallization of PP-MPs and PET-MPs occurred. These transformations caused the contraction of the polymer molecular chains and the generation of micro-mechanical stresses, leading to the formation of warpage structures and stress cracking on the MPs' surface. These phenomena also contributed to the further fragmentation of the MPs and the development of finer MPs particles. The findings of the present investigations emphasize that the thermal drying of sewage sludge amplifies the environmental risk of sludge-based MPs.

Cross-domain policy adaptation with dynamics alignment.

The implementation of robotic reinforcement learning is hampered by problems such as an unspecified reward function and high training costs. Many previous works have used cross-domain policy transfer to obtain the policy of the problem domain. However, these researches require paired and aligned dynamics trajectories or other interactions with the environment. We propose a cross-domain dynamics alignment framework for the problem domain policy acquisition that can transfer the policy trained in the source domain to the problem domain. Our framework aims to learn dynamics alignment across two domains that differ in agents' physical parameters (armature, rotation range, or torso mass) or agents' morphologies (limbs). Most importantly, we learn dynamics alignment between two domains using unpaired and unaligned dynamics trajectories. For these two scenarios, we propose a cross-physics-domain policy adaptation algorithm (CPD) and a cross-morphology-domain policy adaptation algorithm (CMD) based on our cross-domain dynamics alignment framework. In order to improve the performance of policy in the source domain so that a better policy can be transferred to the problem domain, we propose the Boltzmann TD3 (BTD3) algorithm. We conduct diverse experiments on agent continuous control domains to demonstrate the performance of our approaches. Experimental results show that our approaches can obtain better policies and higher rewards for the agents in the problem domains even when the dataset of the problem domain is small.

Optimized Electronic Modification of S-Doped CuO Induced by Oxidative Reconstruction for Coupling Glycerol Electrooxidation with Hydrogen Evolution.

Glycerol (electrochemical) oxidation reaction (GOR) producing organic small molecule acid and coupling with hydrogen evolution reaction is a critical aspect of ensuring balanced glycerol capacity and promoting hydrogen generation on a large scale. However, the development of highly efficient and selective non-noble metal-based GOR electrocatalysts is still a key problem. Here, an S-doped CuO nanorod array catalyst (S-CuO/CF) constructed by sulfur leaching and oxidative remodeling is used to drive GOR at low potentials: It requires potentials of only 1.23 and 1.33 V versus RHE to provide currents of 100 and 500 mA cm-2, respectively. Moreover, it shows satisfactory comprehensive performance (at 100 mA cm-2, Vcell = 1.37 V) when assembled as the anode in asymmetric coupled electrolytic cell. Furthermore, we propose a detailed cycle reaction pathway (in alkaline environment) of S-doped CuO surface promoting GOR to produce formic acid and glycolic acid. Among them, the C-C bond breaking and lattice oxygen deintercalation steps frequently involved in the reaction pathway are the key factors to determine the catalytic performance and product selectivity. This research provides valuable guidance for the development of transition metal-based electrocatalysts for GOR and valuable insights into the glycerol oxidation cycle reaction pathway.

Directed electron regulation promoted sandwich-like CoO@FeBTC/NF with p-n heterojunctions by gel electrodeposition for oxygen evolution reaction.

Metal organic framework (MOF) is currently-one of the key catalysts for oxygen evolution reaction (OER), but its catalytic performance is severely limited by electronic configuration. In this study, cobalt oxide (CoO) on nickel foam (NF) was first prepared, which then wrapped it with FeBTC synthesized by ligating isophthalic acid (BTC) with iron ions by electrodeposition to obtain CoO@FeBTC/NF p-n heterojunction structure. The catalyst requires only 255 mV overpotential to reach a current density of 100 mA cm-2, and can maintain 100 h long time stability at 500 mA cm-2 high current density. The catalytic properties are mainly related to the strong induced modulation of electrons in FeBTC by holes in the p-type CoO, which results in stronger bonding and faster electron transfer between FeBTC and hydroxide. At the same time, the uncoordinated BTC at the solid-liquid interface ionizes acidic radicals which form hydrogen bonds with the hydroxyl radicals in solution, capturing them onto the catalyst surface for the catalytic reaction. In addition, CoO@FeBTC/NF also has strong application prospects in alkaline electrolyzers, which only needs 1.78 V to reach a current density of 1 A cm-2, and it can maintain long-term stability for 12 h at this current. This study provides a new convenient and efficient approach for the control design of the electronic structure of MOF, leading to a more efficient electrocatalytic process.

Highly Efficient Circularly Polarized Luminescence from Chiral Au13 Clusters Stabilized by Enantiopure Monodentate NHC Ligands.

Chiral Au nanoclusters have promising application prospects in chiral sensing, asymmetric catalysis, and chiroptics. However, enantiopure superatomic homogold clusters with crystallographic structures emitting bright circularly polarized luminescence (CPL) remain challenging. In this study, we designed chiral N-heterocyclic carbenes (NHCs), and for the first time enantioselectively synthesized a pair of monovalent cationic superatomic Au13 clusters. This new enantiomeric pair of clusters has a quasi-C2 symmetric core and exhibited CPL with an unprecedent solution-state quantum yield (QY) of 61 % among those of the atomically precise Au nanoclusters. DFT calculations provided insights into the circular dichroism behavior, and revealed the origin of CPL from superatomic Au clusters. This work opens a new avenue for developing novel homochiral nanoclusters using chiral NHC ligands and provides fundamental understanding of the origin of the chiroptics of metal clusters.

An inevitable but underestimated photoaging behavior of plastic waste in the aquatic environment: Critical role of nitrate.

Photoaging is an important reaction for waste plastics in the aquatic environment and plays a key role in the lifetime of plastics. Nevertheless, when natural photosensitive substances such as nitrate participate in this process, the physiochemical changes in plastics and the corresponding reaction mechanisms are not well-understood. In this work, the photochemical behavior of polyethylene terephthalate (PET) bottles in deionized water and nitrate solution was systematically investigated under ultraviolet (UV) irradiation. The analyses of the surface physicochemical properties of the photoaged PET bottles indicated that, after 20 days of photo-irradiation, the presence of nitrate reduced the contact angle from 69.8 ± 0.9° to 60.0 ± 0.3°, and increased the O/C ratio from 0.23 to 0.32, respectively. The leaching rate of dissolved organic carbon (DOC), which was 0.0193 mg g-1·day-1 in nitrate solution, was twice that of 0.00941 mg g-1·day-1 in deionized water. Furthermore, fluorescence spectroscopy revealed that the increasing DOC had aromatic rings with hydroxyl on the side-chain formed after UV irradiation. The positive effect of nitrate on the degradation of PET bottles was mainly through the generation of hydroxyl radicals that were produced through the photolysis of nitrate. In addition, two-dimensional correlation spectroscopy analysis showed that the chain scission of PET plastics could be initiated by nitrate-induced ·OH attacking the carbon-oxygen bonds instead of forming peroxides with oxygen. This work elucidates the mechanism of photodegradation of plastics that was induced by nitrate and highlights the important role of natural photosensitive substances in the photoaging process of plastics.

PDA-Based Drug Delivery Nanosystems: A Potential Approach for Glioma Treatment.

Glioma is characterized by high mortality and low postoperative survival. Despite the availability of various therapeutic approaches and molecular typing, the treatment failure rate and the recurrence rate of glioma remain high. Given the limitations of existing therapeutic tools, nanotechnology has emerged as an alternative treatment option. Nanoparticles, such as polydopamine (PDA)-based nanoparticles, are embodied with reliable biodegradability, efficient drug loading rate, relatively low toxicity, considerable biocompatibility, excellent adhesion properties, precisely targeted delivery, and strong photothermal conversion properties. Therefore, they can further enhance the therapeutic effects in patients with glioma. Moreover, polydopamine contains pyrocatechol, amino and carboxyl groups, active double bonds, catechol, and other reactive groups that can react with biofunctional molecules containing amino, aldehyde, or sulfhydryl groups (main including, self-polymerization, non-covalent self-assembly, π-π stacking, electrostatic attraction interaction, chelation, coating and covalent co-assembly), which form a reversible dynamic covalent Schiff base bond that is extremely sensitive to pH values. Meanwhile, PDA has excellent adhesion capability that can be further functionally modified. Consequently, the aim of this review is to summarize the application of PDA-based NPs in glioma and to acquire insight into the therapeutic effect of the drug-loaded PDA-based nanocarriers (PDA NPs). A wealthy understanding and argument of these sides is anticipated to afford a better approach to develop more reasonable and valid PDA-based cancer nano-drug delivery systems. Finally, we discuss the expectation for the prospective application of PDA in this sphere and some individual viewpoints.

IHNV Infection Induces Strong Mucosal Immunity and Changes of Microbiota in Trout Intestine.

The fish intestinal mucosa is among the main sites through which environmental microorganisms interact with the host. Therefore, this tissue not only constitutes the first line of defense against pathogenic microorganisms but also plays a crucial role in commensal colonization. The interaction between the mucosal immune system, commensal microbiota, and viral pathogens has been extensively described in the mammalian intestine. However, very few studies have characterized these interactions in early vertebrates such as teleosts. In this study, rainbow trout (Oncorhynchus mykiss) was infected with infectious hematopoietic necrosis virus (IHNV) via a recently developed immersion method to explore the effects of viral infection on gut immunity and microbial community structure. IHNV successfully invaded the gut mucosa of trout, resulting in severe tissue damage, inflammation, and an increase in gut mucus. Moreover, viral infection triggered a strong innate and adaptive immune response in the gut, and RNA-seq analysis indicated that both antiviral and antibacterial immune pathways were induced, suggesting that the viral infection was accompanied by secondary bacterial infection. Furthermore, 16S rRNA sequencing also revealed that IHNV infection induced severe dysbiosis, which was characterized by large increases in the abundance of Bacteroidetes and pathobiont proliferation. Moreover, the fish that survived viral infection exhibited a reversal of tissue damage and inflammation, and their microbiome was restored to its pre-infection state. Our findings thus demonstrated that the relationships between the microbiota and gut immune system are highly sensitive to the physiological changes triggered by viral infection. Therefore, opportunistic bacterial infection must also be considered when developing strategies to control viral infection.

SPOCK1 silencing decreases 5-FU resistance through PRRX1 in colorectal cancer.

SPOCK1 is an extracellular proteoglycan and involved in tumor growth and metastasis in various cancers. 5-fluorouracil (5-FU) is commonly used for the treatment of colorectal cancer (CRC) in patients who receive concurrent chemoradiotherapy. However, the relationship between development of resistance to 5-FU and SPOCK1 remain unclear. In this study, we established two 5-fluorouracil (5-FU)-resistant CRC cell lines, HCT116/FU and LOVO/FU, and found that SPOCK1 is upregulated in 5-FU-resistance CRC cells compared with its parental cell line. knockdown of SPOCK1 in 5-FU-resistant CRC cells increases their sensitivity to 5-FU. In contrast, transient transfection of SPOCK1 enhanced HCT116 and LOVO cell resistance to 5-FU and reduced cell apoptosis. Mechanistically, SPOCK1 promoted 5-FU resistance by regulating PRRX1 expression and the downstream apoptosis signaling pathway. Taken together, our results revealed for the first time that SPOCK1 plays a crucial role in the resistance of CRC cells to 5-FU and indicated that targeting SPOCK1 may be a promising therapeutic strategy to overcome 5-FU resistance in CRC.

Teleost swim bladder, an ancient air-filled organ that elicits mucosal immune responses.

The air-filled organs (AOs) of vertebrates (lungs and swim bladders) have evolved unique functions (air-breathing or buoyancy control in water) to adapt to different environments. Thus far, immune responses to microbes in AOs have been described exclusively in the lungs of tetrapods. Similar to lungs, swim bladders (SBs) represent a mucosal surface, a feature that leads us to hypothesize a role for SB in immunity. In this study, we demonstrate that secretory IgT (sIgT) is the key SB immunoglobulin (Ig) responding to the viral challenge, and the only Ig involved in viral neutralization in that organ. In support of these findings, we found that the viral load of the SB from fish devoid of sIgT was much higher than that of control fish. Interestingly, similar to the lungs in mammals, the SB represents the mucosal surface in fish with the lowest content of microbiota. Moreover, sIgT is the main Ig class found coating their surface, suggesting a key role of this Ig in the homeostasis of the SB microbiota. In addition to the well-established role of SB in buoyancy control, our findings reveal a previously unrecognized function of teleost SB in adaptive mucosal immune responses upon pathogenic challenge, as well as a previously unidentified role of sIgT in antiviral defense. Overall, our findings indicate that despite the phylogenetic distance and physiological roles of teleost SB and mammalian lungs, they both have evolved analogous mucosal immune responses against microbes which likely originated independently through a process of convergent evolution.

Dynamic Interaction Between Mucosal Immunity and Microbiota Drives Nose and Pharynx Homeostasis of Common Carp (Cyprinus carpio) After SVCV Infection.

The crosstalk between the immune system and microbiota drives an amazingly complex mutualistic symbiosis. In mammals, the upper respiratory tract acts as a gateway for pathogen invasion, and the dynamic interaction between microbiota and mucosal immunity on its surface can effectively prevent disease development. However, the relationship between virus-mediated mucosal immune responses and microbes in lower vertebrates remains uncharacterized. In this study, we successfully constructed an infection model by intraperitoneally injecting common carp (Cyprinus carpio) with spring viremia of carp virus (SVCV). In addition to the detection of the SVCV in the nose and pharynx of common carp, we also identified obvious histopathological changes following viral infection. Moreover, numerous immune-related genes were significantly upregulated in the nose and pharynx at the peak of SVCV infection, after which the expression levels decreased to levels similar to those of the control group. Transcriptome sequencing results revealed that pathways associated with bacterial infection in the Toll-like receptor pathway and the Nod-like receptor pathway were activated in addition to the virus-related Rig-I-like receptor pathway after SVCV infection, suggesting that viral infection may be followed by opportunistic bacterial infection in these mucosal tissues. Using 16S rRNA gene sequencing, we further identified an upward trend in pathogenic bacteria on the mucosal surface of the nose and pharynx 4 days after SVCV infection, after which these tissues eventually reached new homeostasis. Taken together, our results suggest that the dynamic interaction between mucosal immunity and microbiota promotes the host to a new ecological state.

Sex-Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK-3ß-TFEB.

SCOPE: It remains unclear whether dietary advanced glycation end products (dAGEs)-induced cognitive impairment is sex-dependent. Trehalose may antagonize dAGEs-induced neurotoxicity via glycogen synthase kinase-3 beta (GSK3ß)-transcription factor EB (TFEB) signaling. METHODS AND RESULTS: The sex-specific neurotoxicity of dAGEs and the protective role of trehalose are investigated both in vivo and in vitro. Both sexes of APP/PS1 mice are divided into three groups: that is, control, dAGEs, and dAGEs supplemented with trehalose. SHSY-5Y cells incubated with AGE-BSA and trehalose are also utilized. Dietary AGEs impair cognitive function only in female mice, which is restored by trehalose. Trehalose upregulates phosphorylated-GSK3ß serine9 (p-GSK3ß ser9), TFEB and transient receptor potential mucolipin 1, ADAM10, oligosaccharyl transferase-48, estrogen receptor α and induces TFEB nuclear translocation in hippocampus, elevates IDE and ERß in cortex, while reduces p-tau ser396&404, CDK5, cathepsin B, and glial fibrillary acidic protein in hippocampus. Trehalose elevates p-GSK3ß ser9, induces TFEB nuclear translocation, consequently reverses AGE-BSA-induced tau phosphorylation in vitro. CONCLUSIONS: Female mice are more susceptible to the deleterious effects of dAGEs on cognitive function, which may be owing to its regulation on ERß. Trehalose can strongly reverse dAGEs-induced tau phosphorylation by potentiating TFEB nuclear translocation via inhibiting GSK-3ß.

Molecular cloning and expression analysis of CD79a and CD79b in rainbow trout (Oncorhynchus mykiss) after bacterial, parasitic, and viral infection.

CD79a and CD79b heterodimers are important components that consist of B cell receptor compound, which play a crucial role in transduction activation signal of the antigen binding BCR, and B cell development and antibody production. In order to investigate the characters and potential functions of CD79a and CD79b in rainbow trout (Oncorhynchus mykiss), we firstly cloned and analyzed the expression of CD79a and CD79b and found that the cDNA sequences of CD79a and CD79b both contained open reading frame of 711 and 645 bp in length for encoding the protein of 237 and 215 amino acid residues, respectively. The predicted amino acid sequences from trout were highly conserved with those of other teleost fishes in structure. Phylogenetic tree was constructed to analyze the evolutionary relationship between the trout and other known species, the result indicated that CD79a and CD79b of trout clustered at high bootstrap values with Salmo salar. Moreover, three trout infection models with F. columnare G4, I. multifiliis and infectious hematopoietic necrosis virus (IHNV) were constructed, which resulted in morphological changes and serious lesions in skin and gills. Importantly, the high expression of CD79a and CD79b occurred in skin, gills, and followed by head kidney in response to bacterial, parasitic, and viral infection, as its expression was closely related to that of Igs. Our findings indicated that CD79a and CD79b play vital roles in both systemic and mucosal immune responses of rainbow trout during bacterial, parasitic, and viral infection, which will contribute to explore the roles of CD79 subunits in B cell signaling during ontogeny and disease.

Molecular Characterization and Expression Analysis of Intercellular Adhesion Molecule-1 (ICAM-1) Genes in Rainbow Trout (Oncorhynchus mykiss) in Response to Viral, Bacterial and Parasitic Challenge.

The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l) important for trans-endothelial migration of leukocytes. The level of ICAM-1 expression is upregulated in response to some inflammatory stimulations, including pathogen infection and proinflammatory cytokines. Yet, to date, our knowledge regarding the functional role of ICAM-1 in teleost fish remains largely unknown. In this study, we cloned and characterized the sequence of ICAM-1 in rainbow trout (Oncorhynchus mykiss) for the first time, which exhibited that the molecular features of ICAM-1 in fishes were relatively conserved compared with human ICAM-1. The transcriptional level of ICAM-1 was detected in 12 different tissues, and we found high expression of this gene in the head kidney, spleen, gills, skin, nose, and pharynx. Moreover, upon stimulation with infectious hematopoietic necrosis virus (IHNV), Flavobacterium columnare G4 (F. columnare), and Ichthyophthirius multifiliis (Ich) in rainbow trout, the morphological changes were observed in the skin and gills, and enhanced expression of ICAM-1 mRNA was detected both in the systemic and mucosal tissues. These results indicate that ICAM-1 may be implicated in the mucosal immune responses to viral, bacterial, and parasitic infections in teleost fish, meaning that ICAM-1 emerges as a master regulator of mucosal immune responses against pathogen infections in teleost fish.