Evaluating the effects of graphene nanoparticles combined radio-frequency thawing on the physicochemical quality and protein conformation in hairtail (Trichiurus lepturus) dorsal muscle.

BACKGROUND: The thawing process is an essential step for a frozen marine fish. The present study aimed to investigate the effects of graphene magnetic nanoparticles combined radio-frequency thawing methods on frozen hairtail (Trichiurus lepturus) dorsal muscle. Seven thawing methods were used: air thawing, 4 °C cold storage thawing, water thawing, radio-frequency thawing (RT), radio frequency thawing combined with graphene nanoparticles (G-RT), radio frequency thawing combined with graphene oxide nanoparticles (GO-RT) and radio-frequency thawing combined with graphene magnetic nanoparticles (GM-RT). The thawing loss and centrifugal loss, electric conductivity, total volatile basic nitrogen, thiobarbituric acid reactive substances and color of thawed hairtail dorsal muscle were determined. The carbonyl content, total sulfhydryl groups, Ca2+ -ATPase activity, raman spectroscopy measurements and Fourier-transform infrared spectrometry measurements were determined using myofibrillar extracted from the dorsal muscle of hairtail. The water distribution was determined using low-field NMR techniques. RESULTS: The results demonstrated that the RT, G-RT, GO-RT and GM-RT could significantly shorten the thawing time. Moreover, GO-RT and GM-RT efficiently preserved the color of fish dorsal muscle and reduced the impact of thawing on fish quality by reducing lipid and protein oxidation. Meanwhile, the myofibrillar protein structure thawed by GO-RT and GM-RT were more stable and had a more stable secondary structure, which maintained strong systemic stability at the same time as slowing down protein oxidation. CONCLUSION: The results showed that GO-RT and GM-RT can significantly improve the thawing efficiency at the same time as effectively maintaining and improving the color and texture of thawed fish, slowing down the oxidation of proteins and lipids, and maintaining a good quality of thawed fish meat. © 2023 Society of Chemical Industry.

Optimizing the degradation of aflatoxin B1 in corn by Trametes versicolor and improving the nutritional composition of corn.

BACKGROUND: Corn, being an important grain, is prone to contamination by aflatoxin B1 (AFB1 ), and AFB1 -contaminated corn severely endangers the health of humans and livestock. Trametes versicolor, a fungus that can grow in corn, possesses the ability to directly degrade AFB1 through its laccase. This study aimed to optimize the fermentation conditions for T. versicolor to degrade AFB1 in corn and investigate the effect of T. versicolor fermentation on the nutritional composition of corn. AFB1 -contaminated corn was used as the culture substrate for T. versicolor. A combination of single-factor experiments and response surface methodology was employed to identify the optimal conditions of AFB1 degradation. RESULTS: The optimal conditions of AFB1 degradation were as follows: 9 days of fermentation, a fermentation temperature of 26.7 °C, a moisture content of 70.5% and an inoculation amount of 4.9 mL (containing 51.99 mg of T. versicolor mycelia). With the optimal conditions, the degradation rate of AFB1 in corn could reach 93.01%, and the dry basis content of protein and dietary fiber in the fermented corn was significantly increased. More importantly, the lysine content in the fermented corn was also significantly increased. CONCLUSION: This is the first report that direct fermentation of AFB1 -contaminated corn by T. versicolor not only efficiently degrades AFB1 but also improves the nutritional composition of corn. These findings suggest that the fermentation of corn by T. versicolor is a promising, environmentally friendly and efficient approach to degrade AFB1 and improve the nutritional value of corn. © 2023 Society of Chemical Industry.

Smartphone-Assisted Flexible Electrochemical Sensor Platform by a Homology DNA Nanomanager Tailored for Multiple Cancer Markers Field Inspection.

In this work, an ingenious sensor technology was established by integrating the EBFCs on a flexible paper strip carrier (PE) that was used for simultaneous detection of tumor markers in complex samples. Adopting high performance ultrathin graphdiyne (U-GDY) as the substrate can increase the enzyme load, accelerate the electron transfer rate, and significantly enhance the detection sensitivity. A homologous DNA nanomanager strategy cleverly uses signal switches to recycle and amplify target miRNAs, while the smartphone receives real-time instantaneous current values to realize multivariate detection. Electrochemical data show that the detection limits (LODs) of miRNA-21 and miRNA-155 are 0.09 and 0.15 fM in the wide concentration range. The results confirm that the tailored sensor platform provides a strategy for the early cancer diagnosis and lays the foundation for the construction of a flexible wearable platform.

Dyadic effects of cognitive function on depressive symptoms among middle-aged and older Chinese couples.

BACKGROUND: Although cognitive function and depressive symptoms have been suggested to be closely related, less attention has been paid to this association within married couples. This study explored the reciprocal dyadic relationship between cognitive function and depressive symptoms over time. METHODS: This study used four waves of data from the China Health and Retirement Longitudinal Study and analyses were restricted to middle-aged and older couples aged 45 or older. Actor-partner interdependence model adjusted for confounding factors was employed to examine the reciprocal association between cognitive function and depressive symptoms at both the individual and couple levels. Measures of cognitive function consisted of episodic memory and mental status. Depressive symptoms were measured by the Center for Epidemiological Studies Depression scale. RESULTS: For both husbands and wives, cognitive function was reciprocally associated with depressive symptoms at the individual level. Spouses' lower cognitive function was significantly linked to their partners' greater depressive symptoms. However, ones' depressive symptoms were not related to their partners' cognitive function. CONCLUSIONS: These findings expand our knowledge about the dyadic relationship between cognitive function and depressive symptoms in Chinese couples. Effects of interventions for depression in middle-aged and older adults may be enhanced by considering the marital context.

Propofol inhibits glioma progression by regulating circMAPK4/miR-622/HOXA9 axis.

Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5 µg/mL for 24 h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.

A comprehensive review of food gels: formation mechanisms, functions, applications, and challenges.

Gels refer to the soft and flexible macromolecular polymeric materials retaining a large amount of water or biofluids in their three-dimensional network structure. Gels have attracted increasing interest in the food discipline, especially proteins and polysaccharides, due to their good biocompatibility, biodegradability, nutritional properties, and edibility. With the advancement of living standards, people's demand for nutritious, safe, reliable, and functionally diverse food and even personalized food has increased. As a result, gels exhibiting unique advantages in food application will be of great significance. However, a comprehensive review of functional hydrogels as food gels is still lacking. Here, we comprehensively review the gel-forming mechanisms of food gels and systematically classify them. Moreover, the potential of hydrogels as functional foods in different types of food areas is summarized, with a special focus on their applications in food packaging, satiating gels, nutrient delivery systems, food coloring adsorption, and food safety monitoring. Additionally, the key scientific issues for future food gel research, with specific reference to future novel food designs, mechanisms between food components and matrices, food gel-human interactions, and food gel safety, are discussed. Finally, the future directions of hydrogels for food science and technology are summarized.

Prognostic value of ASXL1 mutations in patients with primary myelofibrosis and its relationship with clinical features: a meta-analysis.

Additional sex combs like 1 (ASXL1) mutations are one of the most common molecular biological abnormalities in patients with primary myelofibrosis (PMF), and the effect of these mutations on prognosis remains controversial. Hence, we conducted a meta-analysis to assess the prognostic value and clinical characteristics of ASXL1 mutations in PMF patients. Eligible studies were systematically searched from PubMed, Embase, and the Cochrane Library. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and leukemia-free survival (LFS), the number of patients transformed to acute leukemia, and clinical characteristics to carry out a meta-analysis by fixed effect model or random effect model according to the heterogeneity between studies. A total of 4501 PMF patients from 16 cohorts of 14 studies were included in this meta-analysis. The results revealed that ASXL1 mutations might predict a shorter OS (HR = 2.30, 95% CI: 1.79-2.94, P < 0.00001) and a higher probability of transformation to acute leukemia (LFS: HR = 1.77, 95% CI: 1.30-2.42, P = 0.0003; the rate of acute leukemia transformation: OR = 2.06, 95% CI: 1.50-2.83, P < 0.00001). Furthermore, ASXL1 mutations were correlated with patients older than 65 years old, male, a lower level of platelet counts, and a higher risk of the international prognostic score system. These findings indicate that ASXL1 mutations have a significant adverse impact on the prognosis of PMF patients and may contribute to risk stratification and prognostic assessment for PMF patients.

Comparison of the effects between MPL and JAK2V617F on thrombosis and peripheral blood cell counts in patients with essential thrombocythemia: a meta-analysis.

To assess the effects between MPL and JAK2V617F on the thrombosis risk and peripheral blood cell counts in patients with essential thrombocythemia (ET), we identified eligible studies from PubMed, Embase, and the Cochrane Library. Seven studies were ultimately included in this meta-analysis. All studies reported the peripheral blood cell counts of ET patients, and three of them reported the eligible thrombotic events. In comparing the effect of MPL versus JAK2V617F on thrombosis, 1257 ET patients (73 MPL + and 1184 JAK2V617F +) were included. MPL-positive (MPL +) ET patients had a higher risk of thrombosis than JAK2V617F-positive (JAK2V617F +) ET patients [RR = 1.80 (1.08-3.01), P = 0.025]. And 3453 ET patients (138 MPL + and 3315 JAK2V617F +) were included in the comparison of peripheral blood cell counts. Platelet counts of MPL + ET patients were higher than that of JAK2V617F + ET patients [WMD = 81.18 (31.77-130.60), P = 0.001]. MPL + ET patients had lower hemoglobin [WMD = - 11.66 (- 14.32 to - 9.00), P = 0.000] and white blood cell counts [WMD = - 1.01 (- 1.47 to - 0.56), P = 0.000] than JAK2V617F + ET patients. These findings indicate that the MPL mutation is a high-risk factor for thrombosis in ET patients, and it may be rational to include MPL mutation in the revised IPSET as a criterion for thrombosis prediction scores. And given the differences in peripheral blood, it is necessary to further study whether MPL + ET patients differ from JAK2V617F + ET patients in bleeding and survival.

Plasmon switching of gold nanoparticles through thermo-responsive terminal breathing of surface-grafted DNA in hydrated ionic liquids.

Self-assembly performed in ionic liquids (ILs) as a unique solvent promises distinct functions and applications in sensors, therapeutics, and optoelectronic devices due to the rich interactions between nanoparticle building blocks and ILs. However, the general consideration that common nanoparticles are readily destabilized by counterions in an IL has largely prevented researchers from investigating controlled nanoparticle assembly in IL-based systems. This study explores the assembling behaviour of double-stranded (ds) DNA-functionalized gold nanoparticles (dsDNA-AuNPs) in hydrated ionic liquids. The DNA base pair stacking assembly of dsDNA-AuNPs occurs at a low IL concentration (<5%). However, a moderate ionic liquid concentration (5-40%) can de-hybridize dsDNA and leaves single-stranded (ss) DNA stabilizing the AuNPs. In concentrated ionic liquids (>40%), interestingly, the higher ionic strength leads to the assembly of DNA-AuNPs. The triphasic assembly trend is also generally observed regardless of the type of IL. By down-regulation of DNA's melting temperature with the IL, the assembly of DNA-AuNPs affords robust response to a lower temperature range, promising applications in plasmonic devices and range-tunable temperature sensors.

Palladium-catalyzed dearomative allylation of indoles with cyclopropyl acetylenes: access to indolenine derivatives.

A palladium-catalyzed redox-neutral allylic alkylation of indoles with cyclopropyl acetylenes has been disclosed. Various 1,3-diene indolenine framework bearing a quaternary stereocenter at the C3 position were synthesized straightforwardly in good to excellent yields with high regio- and stereoselectivities. The reaction could be further expanded to the dearomatization of naphthols to synthesize functionalized cyclohexadienones with 1,3-diene motifs. The reaction exhibited high atom economy and good functional group tolerance.

Counselling Patients for Trial of Labour after Cesarean (TOLAC) and Invasive Placentation: Are We Missing the Mark? The Importance of Local Data and Informed Choice.

OBJECTIVE: Rates of cesarean delivery are increasing, and these procedures carry potential complications, like the risk of invasive placentation, which increases with each cesarean. A trial of labour after cesarean (TOLAC) is a viable option for patients; however, it has been associated with uterine rupture, a complication with maternal and fetal risks. To better counsel patients considering TOLAC, we aimed to determine local uterine rupture rates and maternal and neonatal outcomes with TOLAC and compare these with outcomes related to invasive placentation. METHODS: A 4-year retrospective chart review was conducted at our tertiary centre of all patients with a history of a previous cesarean delivery. We assessed rates of TOLAC, vaginal delivery after cesarean (VBAC), and uterine rupture, as well as maternal and neonatal outcomes associated with invasive placentation. Cases of uterine rupture from 1988 to the present were also reviewed, and their outcomes were compared with those of invasive placentation. RESULTS: Our uterine rupture rate was 0.44% and VBAC rate was 73.8%. We identified 8 cases of uterine rupture since 1988 and 67 invasive placentas during the 4-year chart review. Invasive placentation was associated with a significantly increased risk of neonatal respiratory morbidity, hysterectomy, maternal complications, and longer length of maternal hospital stay when compared with uterine rupture. CONCLUSION: While uterine rupture remains a potential complication of TOLAC, it is rare with overall excellent maternal and neonatal outcomes. Invasive placentation, the risk of which increases with cesarean delivery, carries potentially higher complication rates than uterine rupture. Local complication data is important for individual sites offering TOLAC. The implications of invasive placentation cannot be overlooked when counselling patients considering TOLAC.

Molecular structure, expression, and function analysis of BAFF gene in Chinese sucker, Myxocyprinus asiaticus.

B cell activating factor (BAFF), belonging to the tumor necrosis factor superfamily (TNFSF), is a critical cytokine for B cell survival and immunoglobulin secretion. Here, the BAFF gene of Chinese sucker (Myxocyprinus asiaticus) (MaBAFF) was cloned using RT-PCR and RACE (rapid amplification of cDNA end) techniques. The open reading frame (ORF) of MaBAFF encodes a 272-amino acid protein containing a transmembrane domain, a TNF family signature, and a putative furin protease cleavage site as seen in BAFFs from other species. Tissue expression profiles of MaBAFF determined by absolute and relative quantification of real-time quantitative PCR (qPCR) showed that MaBAFF is widely distributed in various tissues, with the highest expression in spleen. MaBAFF can be detected during fertilized egg period by RT-PCR. Upon induction by A. hydrophila, the expression of MaBAFF was up-regulated in spleen from 48 to 72 h, and the expression of BAFF and IgM all reached a peak at 48 h in head kidney. The soluble BAFF gene (MasBAFF) had been cloned into pET30a. SDS-PAGE and Western blotting analysis confirmed that the His-MasBAFF was efficiently expressed in Escherichia coli Rosset (DE3). CCK-8 assay indicated that the MasBAFF recombinant protein (200 ng/ml) could prolong the survival of peripheral blood leukocytes. Based on ELISA screening and Western blotting, monoclonal antibody 1-F2A3 against recombinant MasBAFF was selected and used for immunohistochemistry, which showed that BAFF-positive cells were detected in spleen and head kidney. Our results raise the possibility that MaBAFF may be useful to enhance immune efficacy in Chinese sucker disease defense.

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. We analyzed and summarized the data of ruxolitinib-based combinations. Ruxolitinib combined with prednisone + thalidomide + danazol (TPD), panobinostat, pracinostat, azacytidine, or hydroxyurea has well reduced spleen. Ruxolitinib combined with danazol or TPD had well therapies in improvement of hemoglobin (Hgb) and platelets (PLT). Most ruxolitinib-based combinations therapies showed a superior benefit on reduced treatment-related AEs than ruxolitinib monotherapy. Treatment-related AEs and dose modification affect the safety and tolerability of ruxolitinib-based combinations. Genetic testing before treatment is recommended. To provide better clinical guidance, comparisons of these randomized controlled trials with the trials of ruxolitinib alone are necessary. This review suggests that the clinical application of ruxolitinib-based combinations is worth waiting for.

Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3.

BACKGROUND: Propofol, an extensively used intravenous anesthetic agents during cancer resection surgery, has been confirmed to execute anti-tumor effect on multiple cancers, including colorectal cancer (CRC). Although the role of propofol in CRC has been previously reported, its action mechanism remains poorly understood. This study further explored the biological function and underlying mechanism of propofol in CRC cells. METHODS: The cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, wound healing assay and transwell assay, respectively. The expression levels microRNA-124-3p.1 (miR-124-3p.1) and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time polymerase chain reaction. Western blot assay was employed to measure the protein expression of MMP-9, Vimentin and Cyclin D1. The interaction between miR-124-3p.1 and AKT3 was predicted by TargetScan and confirmed by dual-luciferase reporter assay. RESULTS: Propofol inhibited CRC cell proliferation, migration and invasion. Knockdown of miR-124-3p.1 or AKT3 upregulation reversed the inhibitory effects of propofol on CRC cell proliferation and metastasis. Besides, AKT3 was a direct target of miR-124-3p.1 and its overexpression abated the anti-tumor effect of miR-124-3p.1 on CRC cell proliferation and metastasis. CONCLUSION: Propofol inhibited CRC cell proliferation, migration and invasion by upregulating miR-124-3p.1 and downregulating AKT3, providing a new sight for propofol treatment of CRC.

The Internet Hospital Plus Drug Delivery Platform for Health Management During the COVID-19 Pandemic: Observational Study.

BACKGROUND: Widespread access to the internet has boosted the emergence of online hospitals. A new outpatient service called "internet hospital plus drug delivery" (IHDD) has been developed in China, but little is known about this platform. OBJECTIVE: The aim of this study is to investigate the characteristics, acceptance, and initial impact of IHDD during the outbreak of COVID-19 in a tertiary hospital in South China. METHODS: The total number of and detailed information on online prescriptions during the first 2 months after work resumption were obtained. Patients' gender, age, residence, associated prescription department, time of prescription, payment, and drug delivery region were included in the analysis. RESULTS: A total of 1380 prescriptions were picked up or delivered between March 2 and April 20, 2020. The largest group of patients were 36-59 years old (n=680, 49.3%), followed by the 18-35 years age category (n=573, 41.5%). In total, 39.4% (n=544) of the patients chose to get their medicine by self-pickup, while 60.6% (n=836) preferred to receive their medicine via drug delivery service. The top five online prescription departments were infectious diseases (n=572, 41.4%), nephrology (n=264, 19.1%), endocrinology (n=145, 10.5%), angiocardiopathy (n=107, 7.8%), and neurology (n=42, 3%). Of the 836 delivered prescriptions, 440 (52.6%) were sent to Guangdong Province (including 363 [43.4%] to Shenzhen), and 396 (47.4%) were sent to other provinces in China. CONCLUSIONS: The IHDD platform is efficient and convenient for various types of patients during the COVID-19 crisis. Although offline visits are essential for patients with severe conditions, IHDD can help to relieve pressure on hospitals by reducing an influx of patients with mild symptoms. Further efforts need to be made to improve the quality and acceptance of IHDD, as well as to regulate and standardize the management of this novel service.

Effects of High Pressure Modification on Conformation and Digestibility Properties of Oyster Protein.

To expand the utilization of oyster protein (OP), the effects of high pressure (100 to 500 MPa) on chemical forces, structure, microstructure, and digestibility properties were investigated. High pressure (HP) treatment enhanced the electrostatic repulsion (from -13.3Control to -27.8HP200 mV) between protein molecules and avoided or retarded the formation of protein aggregates. In addition, the HP treated samples showed uniform distribution and small particle size. The changes in electrostatic interaction and particle size contributed to the improvement of solubility (from 10.53%Control to 19.92%HP500 at pH 7). The stretching and unfolding of protein were modified by HP treatment, and some internal hydrophobic groups and -SH groups were exposed. HP treatment modified the secondary structure of OP. The treated samples contained less α-helix and ß-sheet structures, whereas the proportions of ß-sheet and random coil structures were increased. The treated samples have high digestibility in the stomach (from 26.3%Control to 39.5%HP500) and in the total digestive process (from 62.1%Control to 83.7%HP500). In addition, the total digestive production showed higher percentages of small peptides (<1 kDa) after HP treatment. The protein solubility and digestibility were increased after HP treatment, and high solubility and high digestibility might increase the chance that OP become a kind of protein supplement.

MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1.

BACKGROUND/AIMS: Parkinson's disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models of PD to investigate the expression of microRNA-128 (miR-128) and mechanism through which it affects apoptosis of dopamine (DA) neurons and the expression of excitatory amino acid transporter 4 (EAAT4) via binding to axis inhibition protein 1 (AXIN1). METHODS: Gene expression microarray analysis was performed to screen differentially expressed miRNAs that are associated with PD. The targeting relationship between miR-128 and AXIN1 was verified via a bioinformatics prediction and dual-luciferase reporter gene assay. After separation, DA neurons were subjected to a series of inhibitors, activators and shRNAs to validate the mechanisms of miR-128 in controlling of AXIN1 in PD. Positive protein expression of AXIN1 and EAAT4 in DA neurons was determined using immunocytochemistry. miR-128 expression and the mRNA and protein levels of AXIN1 and EAAT4 were evaluated via RT-qPCR and Western blot analysis, respectively. DA neuron apoptosis was evaluated using TUNEL staining. RESULTS: We identified AXIN1 as an upregulated gene in PD based on the microarray data of GSE7621. AXIN1 was targeted and negatively mediated by miR-128. In the DA neurons, upregulated miR-128 expression or sh-AXIN1 increased the positive expression rate of EAAT4 together with mRNA and protein levels, but decreased the mRNA and protein levels of AXIN1, apoptosis rate along with the positive expression rate of AXIN1; however, the opposite trend was found in response to transfection with miR-128 inhibitors. CONCLUSION: Evidence from experimental models revealed that miR-128 might reduce apoptosis of DA neurons while increasing the expression of EAAT4 which might be related to the downregulation of AXIN1. Thus, miR-128 may serve as a potential target for the treatment of PD.

Hepatic Induction of Fatty Acid Binding Protein 4 Plays a Pathogenic Role in Sepsis in Mice.

Sepsis is defined as the host's deleterious systemic inflammatory response to microbial infections. Herein, we report an essential role of the fatty acid binding protein 4 (FABP4; alias adipocyte protein 2 or aP2), a lipid-binding chaperone, in sepsis response. Bioinformatic analysis of the Gene Expression Omnibus data sets showed the level of FABP4 was higher in the nonsurvival sepsis patients' whole blood compared to the survival cohorts. The expression of Fabp4 was induced in a liver-specific manner in cecal ligation and puncture (CLP) and lipopolysaccharide treatment models of sepsis. The induction of Fabp4 may have played a pathogenic role, because ectopic expression of Fabp4 in the liver sensitized mice to CLP-induced inflammatory response and worsened the animal's survival. In contrast, pharmacological inhibition of Fabp4 markedly alleviated the CLP responsive inflammation and tissue damage and improved survival. We conclude that FABP4 is an important mediator of the sepsis response. Early intervention by pharmacological inhibition of FABP4 may help to manage sepsis in the clinic.

The NLRP3 inflammasome contributes to sarcopenia and lower muscle glycolytic potential in old mice.

The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. "Inflammaging," increased inflammation with advancing age, may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1-containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild-type (WT) and NLRP3-/- mice were aged to 10 (adult) and 24 mo (old). NLRP3-/- mice were protected from decreased muscle mass (relative to body mass) and decreased size of type IIB and IIA myofibers, which occurred between 10 and 24 mo of age in WT mice. Old NLRP3-/- mice also had increased relative muscle strength and endurance and were protected from age-related increases in the number of myopathic fibers. We found no evidence of age-related or NLRP3-dependent changes in markers of systemic inflammation. Increased caspase-1 activity was associated with GAPDH proteolysis and reduced GAPDH enzymatic activity in skeletal muscles from old WT mice. Aging did not alter caspase-1 activity, GAPDH proteolysis, or GAPDH activity in skeletal muscles of NLRP3-/- mice. Our results show that the NLRP3 inflammasome participates in age-related loss of muscle glycolytic potential. Deletion of NLRP3 mitigates both the decline in glycolytic myofiber size and the reduced activity of glycolytic enzymes in muscle during aging. We propose that the etiology of sarcopenia involves direct communication between immune responses and metabolic flux in skeletal muscle.

Molecular characterization of the CD79a and CD79b and its role against Aeromonas hydrophila infection in Chinese sucker (Myxocyprinus asiaticus).

CD79a and CD79b heterodimers are the important signaling components of B cell receptor (BCR) complex which plays a crucial role in B cell development and antibody production. In the present study, CD79a and CD79b homologues from Chinese sucker (Myxocyprinus asiaticus), namely MaCD79a and MaCD79b, were identified and their expression at early developmental stages and under constitutive and stimulated conditions were investigated. The cDNA sequences for MaCD79a and MaCD79b contained open reading frame of 678 and 636 bp in length for 225 and 211 amino acid residues, respectively. The conserved features and important functional residues were found by sequence analysis. RT-PCR analysis revealed that transcripts of MaCD79s were detected in eggs and hatchling at 1-3 and 5-11 days post hatching (dph), but not detected at 13-17 and 19-27 dph, and constantly detected from 30 dph. Tissue distribution analysis showed that MaCD79s was most highly expressed in immune tissues, such as the spleen, head kidney, and kidney; the relatively low levels were detected in the heart, gill, and liver. Results of in situ hybridization also confirmed that MaCD79s is mainly expressed in systematic immune organs. Meanwhile, similar to IgM, MaCD79s-expressing cells in mucosal immune organ including the digestive track and gill were observed. Additionally, significant upregulation of MaCD79s was seen in the head kidney and spleen of Chinese sucker injected with Aeromonas hydrophila by quantitative real-time PCR. Taken together, our findings provided further information regarding fish CD79s gene and its role in adaptive immunity, which will contribute to the preservation and aquaculture of Chinese sucker.