Water-Capture Filter Paper Separator Realizing Ambient Li-Air Battery.

Lithium-air battery (LAB) is regarded as one of the most promising energy storage systems. However, the challenges arising from the lithium metal anode have significantly impeded the progress of LAB development. In this study, cellulose-based filter paper (FP) is utilized as a separator for ambient Li-air batteries to suppress dendrite growth and prevent H2O crossover. Thermogravimetric analysis and molecular spectrum reveal that FP enables ambient Li-air battery operation due to its surface functional groups derived from cellulose. The oxygen-enriched surface of cellulose not only enhances ion conductivity but also captures water and confines solvent molecules, thereby mitigating anode corrosion and side reactions. Compared with commercial glassfiber (GF) separator, this cellulose-based FP separator is cheaper, renewable, and environmentally friendly. Moreover, it requires less electrolyte while achieving prolonged and stable cycle life under real air environment conditions. This work presents a novel approach to realizing practical Li-air batteries by capturing water on the separator's surface. It also provides insights into the exploration and design of separators for enabling practical Li-air batteries toward their commercialization.

Comprehensive analyses of the cancer-associated fibroblast subtypes and their score system for prediction of outcomes and immunosuppressive microenvironment in prostate cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) drive cancer progression and treatment failure on one hand, while their tumor-restraining functions are also observed on the other. Recent single cell RNA sequencing (scRNA-seq) analyses demonstrates heterogeneity of CAFs and defines molecular subtypes of CAFs, which help explain their different functions. However, it remains unclear whether these CAF subtypes have the same or different biological/clinical implications in prostate cancer (PCa) or other malignancies. METHODS: PCa cells were incubated with supernatant from normal fibroblasts and CAFs to assess their effects on cell behaviors. Sequencing, genomic, and clinical data were collected from TCGA, MSKCC, CPGEA and GEO databases. CAF molecular subtypes and total CAF scores were constructed and grouped into low and high groups based on CAF-specific gene expression. Progression free interval (PFI), clinicopathological features, telomere length, immune cell infiltration, drug treatment and somatic mutations were compared among CAF molecular subtypes and low/high score groups. RESULTS: The PCa CAF-derived supernatant promoted PCa cell proliferation and invasion. Based on differentially expressed genes identified by scRNA-seq analyses, we classified CAFs into 6 molecular subtypes in PCa tumors, and each subtype was then categorized into score-high and low groups according to the subtype-specific gene expression level. Such score models in 6 CAF subtypes all predicted PFI. Telomeres were significantly shorter in high-score tumors. The total CAF score from 6 CAF subtypes was also associated with PFI in PCa patients inversely, which was consistent with results from cellular experiments. Immunosuppressive microenvironment occurred more frequently in tumors with a high CAF score, which was characterized by increased CTLA4 expression and indicated better responses to CTLA4 inhibitors. Moreover, this model can also serve as a useful PFI predictor in pan-cancers. CONCLUSION: By combining scRNA-seq and bulk RNA-seq data analyses, we develop a CAF subtype score system as a prognostic factor for PCa and other cancer types. This model system also helps distinguish different immune-suppressive mechanisms in PCa, suggesting its implications in predicting response to immunotherapy. Thus, the present findings should contribute to personalized PCa intervention.

SYTL2 promotes metastasis of prostate cancer cells by enhancing FSCN1-mediated pseudopodia formation and invasion.

BACKGROUND: Metastatic prostate cancer (mPCa) has a poor prognosis with limited treatment options. The high mobility of tumor cells is the key driving characteristic of metastasis. However, the mechanism is complex and far from clarified in PCa. Therefore, it is essential to explore the mechanism of metastasis and discover an intrinsic biomarker for mPCa. METHODS: Transcriptome sequencing data and clinicopathologic features of PCa from multifarious public databases were used to identify novel metastatic genes in PCa. The PCa tissue cohort containing 102 formalin-fixed paraffin-embedded (FFPE) samples was used to evaluate the clinicopathologic features of synaptotagmin-like 2 (SYTL2) in PCa. The function of SYTL2 was investigated by migration and invasion assays and a 3D migration model in vitro and a popliteal lymph node metastasis model in vivo. We performed coimmunoprecipitation and protein stability assays to clarify the mechanism of SYTL2. RESULTS: We discovered a pseudopodia regulator, SYTL2, which correlated with a higher Gleason score, worse prognosis and higher risk of metastasis. Functional experiments revealed that SYTL2 promoted migration, invasion and lymph node metastasis by increasing pseudopodia formation in vitro and in vivo. Furthermore, SYTL2 induced pseudopodia formation by enhancing the stability of fascin actin-bundling protein 1 (FSCN1) by binding and inhibiting the proteasome degradation pathway. Targeting FSCN1 enabled rescue and reversal of the oncogenic effect of SYTL2. CONCLUSIONS: Overall, our study established an FSCN1-dependent mechanism by which SYTL2 regulates the mobility of PCa cells. We also found that the SYTL2-FSCN1-pseudopodia axis may serve as a pharmacological and novel target for treating mPCa.

Selective Semihydrogenation of Polarized Alkynes by a Gold Hydride Nanocluster.

The hydridic hydrogen in nanogold catalysts has long been postulated as an important intermediate in hydrogenation reactions, but it has not been directly observed. Here, we report the synthesis of a new undecagold cluster with a bidentate phosphine ligand. The chelating effects of the bidentate ligand result in a more symmetric Au11 core with two labile Cl- ligands that can exchange with BH4-, leading to a novel undecagold hydride cluster. The new hydride cluster is discovered to readily undergo hydroauration reaction with alkynes containing electron-withdrawing groups, forming key gold-alkenyl semihydrogenation intermediates, which can be efficiently and selectively converted to Z-alkenes under acidic conditions. All key reaction intermediates are isolated and characterized, providing atomic-level insights into the active sites and mechanisms of semihydrogenation reactions catalyzed by gold-based nanomaterials. The hydridic hydrogen in the undecagold cluster is found to be the key to prevent over hydrogenation of alkenes to alkanes. The current study provides fundamental insights into hydrogenation chemistry enabled by gold-based nanomaterials and may lead to the development of efficient catalysts for selective semihydrogenation or functionalization of alkynes.

A Heteroleptic Gold Hydride Nanocluster for Efficient and Selective Electrocatalytic Reduction of CO2 to CO.

It has been a long-standing challenge to create and identify the active sites of heterogeneous catalysts, because it is difficult to precisely control the interfacial chemistry at the molecular level. Here we report the synthesis and catalysis of a heteroleptic gold trihydride nanocluster, [Au22H3(dppe)3(PPh3)8]3+ [dppe = 1,2-bis(diphenylphosphino)ethane, PPh3 = triphenylphosphine]. The Au22H3 core consists of two Au11 units bonded via six uncoordinated Au sites. The three H atoms bridge the six uncoordinated Au atoms and are found to play a key role in catalyzing electrochemical reduction of CO2 to CO with a 92.7% Faradaic efficiency (FE) at -0.6 V (vs RHE) and high reaction activity (134 A/gAu mass activity). The CO current density and FECO remained nearly constant for the CO2 reduction reaction for more than 10 h, indicating remarkable stability of the Au22H3 catalyst. The Au22H3 catalytic performance is among the best Au-based catalysts reported thus far for electrochemical reduction of CO2. Density functional theory (DFT) calculations suggest that the hydride coordinated Au sites are the active centers, which facilitate the formation of the key *COOH intermediate.

Effects of hydrolysable tannins from Terminalia citrina on type III secretion system (T3SS) and their intestinal metabolite urolithin B represses Salmonella T3SS through Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway.

Gamma-proteobacteria is a class of gram-negative opportunistic pathogens existing in the intestinal flora, often leading to diarrhea and intestinal infectious diseases, and plays an important role in maintaining intestinal homeostasis. Type III secretion system (T3SS), an important virulence system, is closely related to the adhesion and invasion and pathogenicity to host cells. Therefore, anti-virulence agents targeting T3SS are important strategies for controlling pathogenic infections. In this study, the anti-Salmonella T3SS active compounds neochebulagic acid (1), ellagic acid (2) and urolithin M5 (3) were isolated from seed extract of Terminalia citrina by activity-guided isolation method. Based on the fact that urolithins are the main and stable intestinal microbiota metabolites of hydrolysable tannins, we found that the metabolite urolithin B repressed translation and secretion of SipC through the Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway. The results provide evidence for Terminalia seeds and ellagitannin-rich berries and nuts in regulating intestinal homeostasis and treating bacterial infection.

Girdin influences pancreatic cancer progression by regulating c-MYC expression.

Pancreatic ductal adenocarcinoma is a complex gastrointestinal tumor with high metastatic potential and poor prognosis. Actin-binding protein Girdin is highly expressed in a variety of tumors and promotes tumorigenesis and progression. However, the mechanisms underlying the involvement of Girdin in pancreatic cancer have not been clarified. In this study, we observed that the expression of Girdin was upregulated in pancreatic cancer cells. The siRNA-mediated gene knockdown experiments showed that reduced expression of Girdin in pancreatic cancer cells inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. Functional assays revealed that c-MYC overexpression in pancreatic cancer cells could significantly increase the cell proliferation ability and rates of cell migration and invasion while decreasing the apoptosis rate. It has been shown that phosphorylation plays a role in the functional regulation of the c-MYC gene. Subsequently, we examined the expression level of c-MYC in cells with manipulated expression of Girdin and identified a positive correlation between Girdin expression and c-MYC expression. Moreover, we found that Girdin knockdown in c-MYC-overexpressing pancreatic cancer cells slowed cell growth, blocked the cell cycle progression, significantly promoted apoptosis, and markedly decreased the cell migration and invasion. This finding indicated that silencing Girdin could mitigate the effect of c-MYC on promoting proliferation and metastasis of pancreatic cancer. Overall, this study provided evidence that Girdin promoted pancreatic cancer development presumably by regulating the c-MYC overexpression.

A simple method for restoring the femoral head center in hip arthroplasty: a 3-dimensional analysis in the Chinese population.

BACKGROUND: Various authors have successfully demonstrated that the distance from the greater trochanter to the femoral head center (GTFHC) and the distance from the lesser trochanter to the femoral head center (LTFHC) can be used as parameters to determine the recovery of the femoral head center (FHC) during hip arthroplasty. It is necessary to undertake an anatomical study concerning the correlations between the greater trochanter (GT), the lesser trochanter (LT), and the FHC using data obtained from the 3D-CT reconstruction method. METHODS: The study comprised 293 patients (151 males and 142 females), with an average age of 65.06 years. The femoral head diameter(FHD), the linear distance from FHC to GT (GTFHC), and the linear distance from FHC to LT(LTFHC) were all measured and recorded data. The correlation between FHD with LTFHC and GTFHC was assessed using Pearson correlation coefficients, and the ratio of LTFHC and GTFHC to FHD was calculated from this ratio. All measured parameters were compared between the left and right sides and the sexes of the participants. RESULTS: The average ratios of GTFHC/FHD and LTFHC/FHD were 0.99 and 0.95, respectively .96% of the LTFHC had absolute lateral differences of < 4 mm . 92% of the GTFHC had absolute lateral differences of < 4 mm. CONCLUSION: LTFHC and GTFHC are reliable reference parameters for preoperative planning and reconstruction of FHC of hip arthroplasty. The ratio displayed in this research may yield insight into a practical and straightforward method for orthopedic surgeons to perform hip arthroplasty in patients with femoral neck fractures. Ratios from studies based on the same race may be desirable for future work.

High-temperature stress will put the thermo-sensitive teleost yellow catfish (Tachysurus fulvidraco) in danger through reducing reproductivity.

Recently, concerns for species that sex differentiation is influenced by temperature in the context of global warming have increased because disrupted operational sex ratios could threaten population maintenance. In contrast, little attention has been given to the reproductive ability of populations that experienced elevated temperatures. In this study, we demonstrated that high temperature (HT) would decrease population size via three different aspects of reproductive ability for the first time. We show that, in a thermo-sensitive teleost yellow catfish, a short period of HT (+3 °C) exposure during the critical period of sex differentiation leads to a different percentage of masculinization of XX genotypic females (1-23%) in wet-lab and natural water bodies. Combining the results of gonadal appearance, histology, sperm parameters, and fertilization rate, we found that XX pseudo-males induced by HT display significantly discounted fertility and reproductive performance compared to XY normal males. We demonstrate that the survival of the XY genotype is lower than XX genotype under environmental stress, including HT, hypoxia, and parasite infection, and the differential survival seems unrelated to male-biased sexual size dimorphism. The mathematical model predicts that the phenotypic female percent will be stabilized at 50% and the population will be sustainably maintained when masculinizing force is less than 0.5, while HT will put the population in danger when the masculinizing force exceeds 0.5. However, when we combine the real-world data of reproductive ability and mathematic model, our results suggest the population size decreases and the long-term survival of the studied species are threatened under the projected pace of increasing temperature. These findings will be useful for understanding the long-term effects of increasing temperature on sex ratio, reproduction and population maintenance in teleost.

CT-Based Classification Systems for Intra-Articular Calcaneal Fractures: The Inter- and Intraobserver Variations as well as Integrality.

The aim of this study was to measure the inter- and intraobserver variations as well as integrality of the Zwipp, Crosby-Fitzgibbons, Sanders, and Eastwood-Atkins classification systems based on more accurate CT scans. Five hundred and forty-nine patients with intra-articular calcaneal fractures from January 2018 to December 2019 taken from a database in our level-I trauma center (3 affiliated hospitals) were included. For each case, normative CT (1 mm slices) scans were available. Four different observers reviewed all CT scans 2 times according to these 4 most prevalent fracture classification systems (FCSs) within a 2-month interval. For these 4 FCSs, the kappa [κ] coefficient was used to evaluate interobserver reliability and intraobserver reproducibility, and the percentage that can be classified was used to indicate integrality. The κ values were measured for Zwipp (κ = 0.38 interobserver, κ = 0.61 intraobserver), Crosby-Fitzgibbons (κ = 0.48 interobserver, κ = 0.79 intraobserver), Sanders (κ = 0.40 interobserver, κ = 0.57 intraobserver), and Eastwood-Atkins (κ = 0.44 interobserver, κ = 0.72 intraobserver). Furthermore, the integralities were calculated for Zwipp (100%), Crosby-Fitzgibbons (100%), Sanders (92%) as well as Eastwood-Atkins (89.6%). Compared with previous literatures, CT scanning with higher accuracy can significantly improve intraobserver reproducibility of Zwipp and Eastwood-Atkins FCSs, but it has no positive effect on variability of Sanders FCS and interobserver reliability of Crosby-Fitzgibbons FCS. In terms of integrality, Zwipp and Crosby-Fitzgibbons FCSs appear to be superior to the other 2 FCSs.

The synthesis and characterization of a new diphosphine-protected gold hydride nanocluster.

Gold is the most inert metal and does not form a bulk hydride. However, gold becomes chemically active in the nanometer scale and gold nanoparticles have been found to exhibit important catalytic properties. Here, we report the synthesis and characterization of a highly stable ligand-protected gold hydride nanocluster, [Au22H3(dppee)7]3+ [dppee = bis(2-diphenylphosphino) ethyl ether]. A synthetic method is developed to obtain high purity samples of the gold trihydride nanocluster with good yields. The properties of the new hydride cluster are characterized with different experimental techniques, as well as theoretical calculations. Solid samples of [Au22H3(dppee)7]3+ are found to be stable under ambient conditions. Both experimental evidence and theoretical evidence suggest that the Au22H3 core of the [Au22H3(dppee)7]3+ hydride nanocluster consists of two Au11 units bonded via two triangular faces, creating six uncoordinated Au sites at the interface. The three H atoms bridge the six uncoordinated Au atoms at the interface. The Au11 unit behaves as an eight-electron trivalent superatom, forming a superatom triple bond (Au11 ≡ Au11) in the [Au22H3(dppee)7]3+ trihydride nanocluster assisted by the three bridging H atoms.

Failed reduction of posterior hip dislocation accompanied by femoral head fracture: causes and resolving strategy.

BACKGROUND: We investigated the causes of failure of the Allis manoeuvre for posterior hip dislocations with an associated Pipkin type I femoral head fractures. The effectiveness of a modified Allis manoeuvre was also evaluated. METHODS: From January 2013 to December 2016, we enrolled five patients with a posterior hip dislocation associated by a Pipkin type I femoral head fracture who were treated initially with the Allis manoeuvre that subsequently failed. Radiographic evaluations were performed to determine the cause of failure, and then a modified Allis manoeuvre was performed. During this procedure, the hip and knee joints of the injured lower limb were both flexed to 90°, and the leg was pulled posteriorly following an upward force to reduce the dislocation. Reduction was assessed by radiographic evaluation. RESULTS: In all patients, the fractured femoral head was incarcerated on the superior edge of the posterior rim of the acetabulum, resulting in failure of the conventional Allis manoeuvre. Satisfactory reduction was achieved with a modified Allis manoeuvre. The mean follow-up duration was 31 months. The femoral head fracture healed after four months on average. The mean Harris score was 91 at the final follow-up. Re-dislocation or femoral head necrosis was not observed. CONCLUSIONS: For posterior hip dislocations associated with a Pipkin type I femoral head fracture, failed reduction is often caused by incarceration of the fractured femoral head on the superior edge of the posterior rim of the acetabulum. The modified Allis manoeuvre can effectively reduce the combined injury in a closed fashion.

The blister occurring in severe tibial plateau fractures (Schatzker V-VI) decreases the risk of acute compartment syndrome.

BACKGROUND: Severe tibial plateau fractures may result in acute compartment syndrome (ACS) of the leg, which is always considered to be an orthopaedic emergency. Blistering is not an uncommon sign and may be related to decreased compartment pressure. No experiments on the risk of ACS based on the presence of blisters after tibial plateau fractures have been conducted, and controversies about the high rate of ACS in patients with tibial plateau fractures still exist. QUESTIONS/PURPOSES: This research retrospectively followed the bicondylar tibial plateau fractures treated with locking plates and verified if the risk of ACS was decreased after a blister was observed. METHODS: A total of 100 patients with closed tibial fractures (63 men and 37 women) were included and divided into with blister (group A, 40) and without blister groups (group B, 60). The creatine kinase (CK), BUN, and chloride levels were recorded on the first day after hospitalization. The hospitalization costs and injury to operation time were collected in the two groups. The Lysholm knee score and a visual analogue scale (VAS) for pain were used to assess the rehabilitation after follow-up. Clinical and serological results of ACS in the two groups were compared. RESULTS: There was significant delay in the time from injury to operation (11.0 ± 3.5 VS 7.6 ± 7.2, Z = - 3.771, P < 0.001) in the with blister (group A) and without blister groups (group B). The levels of chloride and BUN were significantly lower in the with blister group than in the without blister group (102.7 ± 3.0 VS 104.7 ± 2.57 mg/dL, Z = - 3.33, P = 0.001) (10.3 ± 2.5 VS 10.3 ± 2.8 mg/dL, Z = - 2.366, P = 0.018). There were no significant differences in the CK levels in the with blister and without blister groups (285.8 ± 202.6 VS 408.4 ± 633.6 U/L, Z = - 1.379, P = 0.168), but a trend of decreasing to normal was obvious in patients with blisters. There were no significant differences in the Lysholm knee score (40 VS 60, 80 ± 4.9 VS 79.8 ± 3.0, Z = - 0.872, P = 0.383), or the VAS (40 VS 60, 1.6 ± 0.7 VS 2.2 ± 1.3, Z = - 1.568, P = 0.117) for pain compared with patients without blisters. CONCLUSION: In conclusion, the presence of blisters in patients with severe tibial plateau fractures decreases the pressure in the compartment. There was a significant improvement in serological results after blisters appeared, which may be related to the reason for the decreased pressure decreased, and conservative management is recommended for these patients.

The Synthesis, Bonding, and Transformation of a Ligand-Protected Gold Nanohydride Cluster.

Gold does not react with H2 to form bulk hydrides. Here we report the synthesis and characterization of a gold nanohydride protected by diphosphine ligands, [Au22 H4 (dppo)6 ]2+ [dppo=1,8-bis(diphenylphosphino)octane]. The Au22 core consists of two Au11 units bonded by eight Au atoms not coordinated by the diphosphine ligands. The four H atoms are found to bridge the eight uncoordinated Au atoms at the interface. Each Au11 unit can be viewed as a tetravalent superatom forming four delocalized Au-H-Au bonds, similar to the quadruple bond first discovered in the [Re2 Cl8 ]2- inorganic cluster. The [Au22 H4 (dppo)6 ]2+ nanohydride is found to lose H atoms over an extended time via H evolution (H2 ), proton (H+ ) and hydride (H- ) releases. This complete repertoire of H-related transformations suggests that the [Au22 H4 (dppo)6 ]2+ nanohydride is a versatile model catalyst for understanding the mechanisms of chemical reactions involving hydrogen on the surface of gold nanoparticles.

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks.

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.

Development of Teleost Intermuscular Bones Undergoing Intramembranous Ossification Based on Histological-Transcriptomic-Proteomic Data.

Intermuscular bones (IBs) specially exist in lower teleost fish and the molecular mechanism for its development remains to be clarified. In this study, different staining methods and comparative proteomics were conducted to investigate the histological structure and proteome of IB development in Megalobrama amblycephala, including four key IB developmental stages (S1-IBs have not emerged in the tail part; S2-several small IBs started to ossify in the tail part; S3-IBs appeared rapidly; S4-all the IBs appeared with mature morphology). Alcian blue and alizarin red S stained results indicated that IBs were gradually formed from S2 to S4, undergoing intramembranous ossification without a cartilaginous phase. A total of 3368 proteins were identified by using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. Functional annotation showed that proteins which were differentially expressed among stages were involved in calcium, MAPK, Wnt, TGF-ß, and osteoclast pathways which played a critical role in bone formation and differentiation. Three proteins (collagen9α1, stat1, tnc) associated with chondrocytes did not exhibit significant changes through S2 to S4; however, proteins (entpd5, casq1a, pvalb, anxa2a, anxa5) which associated with osteoblasts and bone formation and differentiation showed significantly a higher expression level from S1 to S2, as well as to S3 and S4. These further demonstrated that development of IBs did not go through a cartilaginous phase. The inhibitors of TGF-ß and Wnt pathways were tested on zebrafish (sp7/eGFP) and the results indicated that both inhibitors significantly delayed IB development. This study provides a comprehensive understanding of the IB ossification pattern, which will help further elucidate the molecular mechanisms for IB development in teleosts.

Anti-Myocardial Infarction Effects of Radix Aconiti Lateralis Preparata Extracts and Their Influence on Small Molecules in the Heart Using Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging.

Radix Aconiti Lateralis Preparata (fuzi) is the processed product of Aconitum carmichaelii Debeaux tuber, and has great potential anti-myocardial infarction effects, including improving myocardial damage and energy metabolism in rats. However, the effects of Radix Aconiti Lateralis Preparata extracts in a rat model of myocardial infarction have not yet been fully illustrated. Herein, Radix Aconiti Lateral Preparata was used to prepare Radix Aconiti Lateralis Preparata extract (RAE), fuzi polysaccharides (FPS), and fuzi total alkaloid (FTA). Then, we aimed to compare the effects of RAE, FPS, and FTA in MI rats and further explore their influence on small molecules in the heart. We reported that Radix Aconiti Lateralis Preparata extract (RAE) and fuzi total alkaloid (FTA) significantly improved left ventricular function and structure, and reduced myocardial damage and infarct size in rats with myocardial infarction by the left anterior descending artery ligation. In contrast, fuzi polysaccharides (FPS) was less effective than RAE and FTA, indicating that alkaloids might play a major role in the treatment of myocardial infarction. Moreover, via matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), we further showed that RAE and FTA containing alkaloids as the main common components regulated myocardial energy metabolism-related molecules and phospholipids levels and distribution patterns against myocardial infarction. In particular, it was FTA, not RAE, that could also regulate potassium ions and glutamine to play a cardioprotective role in myocardial infarction, which revealed that an appropriate dose of alkaloids generated more obvious cardiotonic effects. These findings together suggested that Radix Aconiti Lateralis Preparata extracts containing an appropriate dose of alkaloids as its main pharmacological active components exerted protective effects against myocardial infarction by improving myocardial energy metabolism abnormalities and changing phospholipids levels and distribution patterns to stabilize the cardiomyocyte membrane structure. Thus, RAE and FTA extracted from Radix Aconiti Lateralis Preparata are potential candidates for the treatment of myocardial infarction.

Comparative expression analysis of let-7 microRNAs during ovary development in Megalobrama amblycephala.

As a critical regulator of gene expression, let-7 family miRNAs have been reported to be involved in multiple physiological processes. In this study, in order to elucidate the putative regulatory effect of let-7 miRNAs during fish gonadal development and to identify which member is crucial for this regulation, the expression of ten members including let-7a/b/c/d/e/f/g/h/i/j were quantified in ovary, pituitary, and brain tissues during the different ovarian developmental stages of blunt snout bream Megalobrama amblycephala. According to the data from analysis of expression patterns, let-7a showed the highest expression value in almost all the tested ovaries, pituitaries, and brains, with let-7b and let-7d moderately expressed, following by other let-7 miRNAs. In terms of the differential expression levels of ten let-7 miRNAs at each developmental stage, the results showed that let-7a/b/d/f/h expression gradually increased during the ovary development from stage I to V and dropped significantly at the phase VI in ovary tissues. However, the expression of let-7a/b/e/f in pituitary increased during the ovary development from stage I to IV and declined at stage V. Among all the let-7 miRNAs, let-7a/b/d had the highest expression and their expression patterns were consistent with the gonad development of M. amblycephala. Furthermore, the mostly predicted target genes of let-7 miRNAs are significantly enriched in signaling pathways closely related to gonadal development through KEGG enrichment analysis. These results indicate that let-7 miRNA members, especially let-7a/b/d, may play important roles in the regulation of ovary development in M. amblycephala through negatively regulating expression of their target genes.

Is the Nutritional Value of Fish Fillet Related to Fish Maturation or Fish Age? Integrated Analysis of Transcriptomics and Metabolomics in Blunt Snout Bream (Megalobrama amblycephala).

BACKGROUND/AIMS: Fish is a protein-rich food and is increasingly favored by consumers. It has been well recognized that the flesh composition of fish is closely related to its maturation and growth stage, but few studies have explored these differences. Additionally, hormone residues in fish after artificial induction of reproduction also attract consumer concern. In this study, we attempt to address these concerns by using a combination of transcriptomics and metabolomics analyses to identify key regulated pathways, genes, and metabolites that may affect the flesh nutrition of one typical aquaculture species in China, blunt snout bream (Megalobrama amblycephala). METHODS: The four groups of fish were used for transcriptomics and metabolomics analyses, including one-year-old immature (group I), two-year-old immature (group II), two-year-old mature (group III) and successfully spawned (group IV) female M. amblycephala after artificial induction of reproduction. RESULTS: We identified a total of 1460 differential compounds and 1107 differentially expressed unigenes in muscle among the different groups. Differential metabolites related to fish age (group II vs group I, group III vs group I) were largely enriched in "Glycerophospholipid metabolism", "Linoleic acid metabolism", "α-Linolenic acid metabolism", and "Biosynthesis of unsaturated fatty acids". Between these two pairwise comparisons, metabolites that are beneficial to human health, such as docosapentaenoic acid, α-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were found to be significantly decreased in two-year-old (group II, group III) compared with one-year-old (group I) M. amblycephala. Only one differential metabolite related to fish maturation, a triglyceride, was detected between groups III and II. Transcriptomics data showed that differently expressed genes (between group III vs group II, group III vs group I) related to maturation were highly enriched in "Cell adhesion molecules (CAMs)", "Sphingolipid metabolism" and "Phagosome". DEGs (between group II vs group I, group III vs group I) relating to fish age were enriched in the "cGMP-PKG signaling pathway", "FoxO signaling pathway", and "AMPK signaling pathway". The gene-metabolite interaction network showed pivotal genes, including fumarate hydratase and GNPAT, which played a major role in the regulation of glycerphospholipid metabolism. The nutritional components were also measured, which verified the metabolomics results. Moreover, the metabolomics results showed that after 24 hours of artificial hormone injection, the drug was completely metabolized. CONCLUSION: Integrated analysis demonstrated that the nutrition value of fish fillet was much more related to fish age compared with maturation status in M. amblycephala females.

Comparative proteomics analysis of teleost intermuscular bones and ribs provides insight into their development.

BACKGROUND: Intermuscular bones (IBs) and ribs both are a part of skeletal system in teleosts, but with different developing process. The chemical composition of fish IBs and ribs as well as the underlying mechanism about their development have not been investigated. In the present study, histological structures showed that one bone cavity containing osteoclasts were existed in ribs, but not in IBs of Megalobrama amblycephala. We constructed the first proteomics map for fish bones including IBs and ribs, and identified the differentially expressed proteins between IBs and ribs through iTRAQ LC-MS/MS proteomic analysis. RESULTS: The proteins extracted from IBs and ribs at 1- to 2-year old M. amblycephala were quantified 2,342 proteins, with 1,451 proteins annotated with GO annotation in biological processes, molecular function and cellular component. A number of bone related proteins as well as pathways were identified in the study. A total of 93 and 154 differently expressed proteins were identified in comparison groups of 1-IB-vs-1-Rib and 2-IB-vs-2-Rib, which indicated the obvious differences of chemical composition between these two bone tissues. The two proteins (vitronectin b precursor and matrix metalloproteinase-2) related to osteoclasts differentiation were significantly up-regulated in ribs compared with IBs (P < 0.05), which was in accordance with the results from histological structures. In comparison groups of 1-IB-vs-2-IB and 1-Rib-vs-2-Rib, 33 and 51 differently expressed proteins were identified and the function annotation results showed that these proteins were involved in regulating bone development and differentiation. Subsequently, 11 and 13 candidate proteins in comparison group of 1-IB-vs-1-Rib and 1-IB-vs-2-IB related to bone development were validated by MRM assays. CONCLUSIONS: Our present study suggested the different key proteins involved in the composition of fish ribs and IBs as well as their growth development. These findings could provide important clues towards further understanding of fish skeletal system and the roles of proteins playing in regulating diverse biological processes in fish.