Microenvironment-Responsive Antibacterial, Anti-Inflammatory, and Antioxidant Pickering Emulsion Stabilized by Curcumin-Loaded Tea Polyphenol Particles for Accelerating Infected Wound Healing.

Multiphase Pickering emulsions, including two or more active agents, are of great importance to effectively manage complicated wounds. However, current strategies based on Pickering emulsions are still unsatisfying since they involve only stabilization by inactive particles and encapsulation of the hydrophobic drugs in the oil phase. Herein, thyme essential oil (TEO) was encapsulated in the shell of functional tea polyphenol (TP)-curcumin (Cur) nanoparticles (TC NPs) to exemplarily develop a novel Pickering emulsion (TEO/TC PE). Hydrophobic Cur was loaded with hydrophilic TP to obtain TC NPs, and under homogenization, these TC NPs adsorbed on the surface of TEO droplets to form a stable core-shell structure. Owing to such an oil-in-water (O/W) structure, the sequential release of the first Cur from pH-responsive disintegrated TC NPs and then the leaked TEO from the emulsion yielded synergetic functions of TEO/TC PE, leading to enhanced antibacterial, biofilm elimination, antioxidant, and anti-inflammatory activities. This injectable TEO/TC PE was applied to treat the infected full-thickness skin defects, and satisfactory wound healing effects were achieved with rapid angiogenesis, collagen deposition, and skin regeneration. The present TEO/TC PE constituted entirely of plant-sourced active products is biosafe and expected to spearhead the future development of novel wound dressings.

Relationship between hearing loss and depression: A cross-sectional analysis from the National Health and Nutrition Examination Survey 2015-2018.

BACKGROUND: Hearing loss is a prevalent issue resulting from loud noise exposure, aging, diseases, and genetic differences. As individuals age, the likelihood of experiencing hearing loss and depression escalates; yet, the link between hearing loss and the risk of depression remains ambiguous. This study explores the relationship between hearing and depression risk, taking into account sociodemographic and health-related factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a cross-sectional analysis was conducted, focusing on adult participants. It evaluated their hearing status and depression levels using the Patient Health Questionnaire-9 (PHQ-9). The study examined a range of variables, such as age, gender, socioeconomic status, lifestyle choices, and comorbidities, to understand their influence on the link between hearing loss and depression. RESULTS: Analysis indicated a significant association between moderate to severe hearing loss and an increased risk of depression, notably in older adults. This relationship remained significant even after adjusting for a variety of sociodemographic and health factors. LIMITATIONS: This is a study using the NHANES database using self-reported surveys. CONCLUSION: The findings of this study emphasize the need to integrate hearing health in the holistic assessment and treatment of depression, particularly advocating for combined care strategies for the elderly.

Soft yet mechanically robust injectable alginate hydrogels with processing versatility based on alginate/hydroxyapatite hybridization.

The salient gelling feature of alginate via forming the egg-box structure with calcium ions has received extensive interests for different applications. Owing to the interfacial incompatibility of rigid inorganic solids with soft polymers, the requirement of overall stereocomplexation with calcium released from uniformly distributed solids in alginate remains a challenge. In this study, a novel alginate-incorporated calcium source was proposed to tackle the intractable dispersion for the preparation of injectable alginate hydrogels. Calcium phosphate synthesis in alginate solution yielded CaP-alginate hybrids as a calcium source. The physicochemical characterization confirmed the CaP-alginate hybrid was a nano-scale alginate-hydroxyapatite complex. The colloidally stable CaP-alginate hybrids were uniformly dispersed in alginate solutions even under centrifugation. The calcium-induced gelling of the CaP-alginate hybrids-loaded alginate solutions formed soft yet tough hydrogels including transparent sheets and knittable threads, confirming the homogeneous gelation of the hydrogel. The gelation time, injectability and mechanical properties of the hydrogels could be adjusted by changing preparation parameters. The prepared hydrogels showed uniform porous structure, excellent swelling, wetting properties and cytocompatibility, showing a great potential for applications in different fields. The present strategy with organic/inorganic hybridization could be exemplarily followed in the future development of functional hydrogels especially associated with the interface integration.

Variant-Localized High-Concentration Electrolyte without Phase Separation for Low-Temperature Batteries.

Dual-ion batteries (DIBs) present great application potential in low-temperature energy storage scenarios due to their unique dual-ion working mechanism. However, at low temperatures, the insufficient electrochemical oxidation stability of electrolytes and depressed interfacial compatibility impair the DIB performance. Here, we design a variant-localized high-concentration solvation structure for universal low-temperature electrolytes (ν-LHCE) without the phase separation via introducing an extremely weak-solvating solvent with low energy levels. The unique solvation structure gives the ν-LHCE enhanced electrochemical oxidation stability. Meanwhile, the extremely weak-solvating solvent can competitively participate in the Li+-solvated coordination, which improves the Li+ transfer kinetics and boosts the formation of robust interphases. Thus, the ν-LHCE electrolyte not only has a good high-voltage stability of >5.5 V and proper Li+ transference number of 0.51 but also shows high ionic conductivities of 1 mS/cm at low temperatures. Consequently, the ν-LHCE electrolyte enables different types of batteries to achieve excellent long-term cycling stability and good rate capability at both room and low temperatures. Especially, the capacity retentions of the DIB are 77.7 % and 51.6 %, at -40 °C and -60 °C, respectively, indicating great potential for low-temperature energy storage applications, such as polar exploration, emergency communication equipment, and energy storage station in cold regions.

A comprehensive analysis of the prognostic and immunological role of ANK3 in pan-cancer.

Background: Cancer is a common cause of death around the world. Immunotherapy plays a significant role in cancer treatment but still has limitations. The ankyrin-3 (ANK3) gene has been shown to have a variety of biological roles and has also been shown to be closely linked to individual cancers. Methods: We systematically investigated the role of ANK3 in pan-cancer, particularly in relation to immunity. We collected data from a number of databases, including the The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), tumor-immune system interactions (TISIDB), cBioPortal, Tumor Immune Estimation Resource (TIMER), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), BioGRID, and SangerBox databases. R (version 3.6.3) was used for the statistical analysis and data visualization. The expression of ANK3 in tumors and its effects on patient prognosis, immune infiltration, neoantigens, the microenvironment, immune checkpoints (ICs), the tumor mutation burden, microsatellite instability (MSI), methylation, mismatch repair (MMR) genes, and cancer-associated fibroblasts were investigated. A gene set enrichment analysis (GSEA) was also conducted. Results: The ANK3 gene was differentially expressed at the messenger RNA (mRNA) and protein levels in various human tumors. The prognosis of patients with different types of malignancies was correlated with the level of ANK3 expression. The immunological microenvironment was also linked to ANK3 expression, especially in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and liver hepatocellular carcinoma (LIHC). ANK3 was also associated with ICs, immune neoantigens, MSI, the tumor mutation load, MMR genes, and DNA methylation. Finally, we found the key pathway related to the ANK3 gene through the enrichment analysis. Conclusions: ANK3 could serve as a new biomarker specific to prognosis and immunotherapy in various cancers. Our findings could contribute to the development of novel strategies for treating malignancies.

Influences of carboxymethyl chitosan upon stabilization and gelation of O/W Pickering emulsions in the presence of inorganic salts.

The objective of this study was to investigate the effects of carboxymethyl chitosan (CMCS) on the stabilization and gelation of oil-in-water (O/W) Pickering emulsions (PEs) with polyphenol-amino acid particles in the presence of inorganic salts. The results revealed that the CMCS-induced depletion interactions contributed to improving the emulsification ability and interfacial adsorption efficiency of polyphenol-amino acid particles as well as constructing the network structures in the continuous phase. These relevant changes collectively resulted in elevating stability, viscosity and moduli of PEs. The additional effects of different inorganic salts with varying additions were further investigated, and the addition-dependent phenomena were observed. At low additions of inorganic salts, the occurrence of the chelation of inorganic salts with CMCS consolidated the constructed network structure, favorable to the gelation of PEs. With increasing additions, this chelation effect became stronger which compromised the CMCS-induced depletion, gradually leading to destabilization of PEs. In terms of ion species, the more pronounced effect on emulsion stability was achieved with calcium ions than with potassium and iron ions. This study expects to provide a new perspective on the extending application of cationic CMCS for improving the stability of O/W PEs in the food industry.

Collagen Scaffolds Functionalized by Cu2+-Chelated EGCG Nanoparticles with Anti-Inflammatory, Anti-Oxidation, Vascularization, and Anti-Bacterial Activities for Accelerating Wound Healing.

Skin injury is a common health problem worldwide, and the highly complex healing process poses critical challenges for its management. Therefore, wound dressings with salutary effects are urgently needed for wound care. However, traditional wound dressing with a single function often fails to meet the needs of wound repair, and the integration of multiple functions has been required for wound repair. Herein, Cu2+-chelated epigallocatechin gallate nanoparticles (EAC NPs), with radical scavenging, inflammation relieving, bacteria restraining, and vascularization accelerating capacities, are adopted to functionalize collagen scaffold, aiming to promote wound healing. Radical scavenging experiments verify that EAC NPs could efficiently scavenge radicals. Additionally, EAC NPs could effectively remove Escherichia coli and Staphylococcus aureus. H2O2 stimuli-responsive EAC NPs show slow and sustained release properties of Cu2+. Furthermore, EAC NPs exhibit protective effects against H2O2-induced oxidative-stress damage and anti-inflammatory activity in vivo. Physicochemical characterizations show that the introduction of EAC NPs does not disrupt the gelation behavior of collagen, and the composite scaffolds (CS) remain porous structure similar to collagen scaffold. Animal experiments demonstrate that CS could promote wound healing through improving the thickness of renascent epidermis and number of new vessels. CS with multiple salutary functions is a promising dressing for wound care.

Autophagy-related gene model as a novel risk factor for schizophrenia.

Autophagy, a cellular process where cells degrade and recycle their own components, has garnered attention for its potential role in psychiatric disorders, including schizophrenia (SCZ). This study aimed to construct and validate a new autophagy-related gene (ARG) risk model for SCZ. First, we analyzed differential expressions in the GSE38484 training set, identifying 4,754 differentially expressed genes (DEGs) between SCZ and control groups. Using the Human Autophagy Database (HADb) database, we cataloged 232 ARGs and pinpointed 80 autophagy-related DEGs (AR-DEGs) after intersecting them with DEGs. Subsequent analyses, including metascape gene annotation, pathway and process enrichment, and protein-protein interaction enrichment, were performed on the 80 AR-DEGs to delve deeper into their biological roles and associated molecular pathways. From this, we identified 34 candidate risk AR-DEGs (RAR-DEGs) and honed this list to final RAR-DEGs via a constructed and optimized logistic regression model. These genes include VAMP7, PTEN, WIPI2, PARP1, DNAJB9, SH3GLB1, ATF4, EIF4G1, EGFR, CDKN1A, CFLAR, FAS, BCL2L1 and BNIP3. Using these findings, we crafted a nomogram to predict SCZ risk for individual samples. In summary, our study offers deeper insights into SCZ's molecular pathogenesis and paves the way for innovative approaches in risk prediction, gene-targeted diagnosis, and community-based SCZ treatments.

pH-Responsive Carrier-Free Polyphenol Nanoparticles Assembled by Oxidative Polymerization with Enhanced Stability and Antioxidant Activity for Improved Bioaccessibility.

Encapsulation of plant polyphenols with micro-/nano-carriers for enhanced bioavailability has been well documented, but the preparation of these carriers and subsequent loading of polyphenols is a multiple process, which is generally complicated with potentially unexpected negative effects on the bioactivity of the polyphenols. Here, we reported a convenient method to assemble carrier-free polyphenol nanoparticles (NPs) based on oxidative coupling polymerization. The effectiveness was assessed with five different polyphenols including pyrocatechol (PY), catechin (CA), epigallocatechin gallate (EGCG), tannic acid (TA), and proanthocyanidin (PC). The structural characteristics of these assembled nanoparticles (PY NPs, CA NPs, EG NPs, TA NPs, and PC NPs) were systematically analyzed with dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). All NPs were colloidally stable with varying NaCl concentrations from 0 to 300 mM, were acid-resistant and alkali-intolerant, and were suitable for oral administration. An array of antioxidant assays further confirmed the superior antioxidant capabilities of NPs over Trolox and polyphenol monomers, indicating that the oxidative polymerization of polyphenols did not compromise the polyphenol activity of NPs. The in vitro simulated digestion studies validated that these responsive NPs were actually gastrointestinal pH-responsive and applicable to the gastrointestinal physiological environment. The bioaccessibility assessments by using a static in vitro digestion model revealed that better results were achieved with NPs than polyphenol monomers, with TA NPs showing about 1.5-fold higher bioaccessibility than other polyphenol nanoparticles. The present study with five polyphenols demonstrated that the oxidative polymerization of polyphenols provides an effective platform to assemble various carrier-free NPs with enhanced antioxidant activity, favorable stability, and improved bioaccessibility, which could be used promisingly as a functional food ingredient in food matrices or as oral drug delivery candidates for helping to manage human health or treating various gastrointestinal disorders in both the pharmaceutical and nutritional fields.

Tea polyphenol carrier-enhanced dexamethasone nanomedicines for inflammation-targeted treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation, cartilage damage and bone erosion. In the progression of RA, the inflammatory mediators including ROS, NO, TNF-α, and IL-6 play important roles in the aggravation of inflammation. Hence, reducing the generation and release of inflammatory mediators is of great importance. However, the high dose and frequent administration of clinical anti-inflammatory drugs such as glucocorticoids (GCs) usually lead to severe side effects. The development of nanotechnology provides a promising strategy to overcome these issues. Here, polyphenol-based nanoparticles with inherent anti-oxidative and anti-inflammatory activities were developed and used as a kind of nanocarrier to deliver dexamethasone (Dex). The in vitro experiments confirmed that the nanoparticles and drugs could act synergistically for suppressing inflammatory mediators in the LPS/INF-γ-induced inflammatory cell model. After intravenous administration, the Dex-loaded nanoparticles with good biosafety showed effective accumulation in inflamed joints and improved therapeutic efficacy by inducing anesis of synovial inflammation and cartilage destruction over free Dex in a collagen-induced arthritis (CIA) mouse model. The results demonstrated that polyphenol-based nanoparticles with therapeutic functions may serve as an innovative platform to synergize with chemotherapeutic agents for enhanced treatment of inflammatory diseases.

Tunable Stress Relaxing Biomimetic Matrices: Hyaluronan/Hydroxyapatite Hybridization Mediates Assembly of Collagen Fibrils.

The alluring correlations of cellular behaviors with viscoelastic extracellular matrices have driven increasing endeavors directed toward the understanding of mechanical cues on cell growth and differentiation via preparing biomimetic scaffolds/gels with viscoelastic controllability. Indeed, systematic investigations, especially into calcium phosphate-containing biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic mineralization with confined ion diffusion and subsequent oxidization treatment. The collagen self-assembly was applied to fabricate tunable stress relaxing fibrillar matrices in the presence of OHAHs in which the incorporated hyaluronic acid with aldehyde groups acted to improve the component compatibility as well as to supplement the molecular interactions with the occurrence of a Schiff-base reaction. With the addition of varying OHAH contents, the self-assembly behavior of collagen was altered, and the obtained collagen-hybrid (CH) matrices presented a heterogeneous fibrillar structure interspersed with OHAHs, characterized by large fibrillar bundles coexisting with small fibrils. The OHAHs improved the hydrogel stability of pure collagen, and according to rheological and nanoindentation measurements, CH matrices also exhibited tunable stress relaxation rates, following an OHAH concentration-dependent fashion. The proliferation and spreading of MC3T3-E1 cells cultured onto such CH matrices were further found to increase with the stress relaxing rate of the matrices. The present study showed that the introduction of hydroxyapatite incorporated with active hyaluronic acid during collagen reconstitution was a simple and effective strategy to realize the preparation of tunable stress relaxing biomimetic matrices potentially used for further appraising the regulation of mechanical cues on cell behaviors.

Biomimetic mineralization by confined diffusion with viscous hyaluronan network: Assembly of hierarchical flower-like supraparticles.

Biomolecules-mediated biomimetic mineralization has been extensively investigated and applied to fabricate nano-assemblies with unique hierarchical architectures and salient properties. The confined-source ion diffusion plays a key role in the biomineralization process, but little investigative efforts have focused on it. Here, we developed a simple method to mimic the in vivo condition by a confined diffusion method, and hydroxyapatite nanoflower assemblies (HNAs) with exquisite hierarchical architectures were obtained. The HNAs were assembled from needle-like hybrid nanocrystals of hydroxyapatite and hyaluronan. The results revealed that the strong interactions between ions and hyaluronan led to the nucleation of hydroxyapatite and the following aggregation. The combination of the external diffusion field and the internal multiple interactions induced the self-assembling processes. Additionally, HNAs with colloid stability and excellent biocompatibility were proved to be a promising cargo carrier for intranuclear delivery. This work presents a novel biomimetic mineralization strategy based on confined diffusion system for fabricating delicate hydroxyapatite, which offers a new perspective for the development of biomimetic strategies.

Hip arthrogram parameters predict radiographic outcomes of patients with developmental dysplasia of the hip treated by closed reduction.

Objective: This study aimed to investigate the relationship between intraoperative hip arthrogram parameters and residual acetabular dysplasia (RAD) and avascular necrosis of the femoral head (AVN) in children with developmental dysplasia of the hip (DDH) treated by closed reduction. Methods: We retrospectively analyzed the data of 102 patients (110 hips; mean age, 14.6 months ± 4.7 months) with DDH treated by closed reduction. A hip arthrogram was routinely performed during the operation. The femoral head coverage rate (FHC), medial pool distance of the hip (MPD), labral inversion, and reduction quality classification were evaluated under the hip arthrogram. The presence of RAD and AVN was assessed on radiographs at the last follow-up. The relationship between each arthrogram parameter and RAD as well as AVN was investigated using a t-test, chi-square test, and logistic regression. Results: The overall FHC and medial pool distance of the hip (MDP) averaged 42.2% ± 12% and 8.1% ± 11.7%, respectively. There were 80 hips (72.7%) with labral inversion and 30 hips (27.2%) without. The reduction quality was type A in 57 hips (51.8%), type B in 28 hips (25.4%), and type C in 25 hips (22.7%). A total of 32 hips (29%) were in the RAD group, and 78 hips (71%) were in the recovered group according to whether pelvic osteotomy was performed or not and according to the last Severin grade. The FHC was significantly higher in the recovered group than that in the RAD group (P = 0.014). No significant difference was observed in sex, age at reduction, side, preoperative acetabular index, International Hip Dysplasia Institute classification, follow-up time, quality of reduction, MDP, and proportion of labral inversion between the recovered and RAD groups. Logistic regression analysis showed that only the FHC was a risk factor for RAD. The incidence of AVN above type II was 11.8% in this group of patients, and the incidence of AVN was significantly higher in patients with labral inversion (23.2%) than that in those without (7.5%; P = 0.041). Logistic regression analysis showed that labral inversion was a risk factor for AVN. Conclusion: The FHC measured under arthrogram can predict the occurrence of RAD after closed reduction of DDH, whereas MDP, reduction quality classification, and labral inversion are of little significance. Labral inversion is a risk factor for AVN.

Biocompatible, bacteria-targeting resveratrol nanoparticles fabricated by Mannich molecular condensation for accelerating infected wound healing.

Excessive reactive oxygen species (ROS) and long-term inflammation can delay wound healing and cause tissue damage, while bacterial infection aggravates the wound environment further. It is impossible to resolve all these thorny problems simultaneously with a wound dressing that has only one function. The antioxidative and anti-inflammatory properties of resveratrol (Res) have been proven. However, the effect of Res is non-selective, and high levels of Res can inhibit cell growth and promote oxidation. Res is also difficult to dissolve and possesses insufficient antibacterial properties, so its role is limited. In this study, Res was assembled via Mannich reaction into nanoparticles and functionalized by phenylboric acid, giving rise to targeting bacteria and solving the water-insoluble dilemma of Res. In comparison with Trolox, the assembled Res NPs performed better at scavenging ABTS and DPPH free radicals. Furthermore, Res NPs that targeted bacteria also showed high biocompatibility at concentrations five times higher than pure Res. The activities of Res NPs were comparable to free Res in downregulating the expression of inflammatory cytokines, and reducing intracellular excessive ROS. The gel embedded with Res NPs accelerated the formation of granulation tissue, collagen deposition, and re-epithelialization, facilitating wound healing. The present study suggests that functionalized polyphenol-based materials are preferably suited to the development of tissue engineering biomaterials.

Injectable oxidized alginate/carboxylmethyl chitosan hydrogels functionalized with nanoparticles for wound repair.

Owing to its simple properties, the application of injectable hydrogel in wound repair is limited. Therefore, the multi-functionalization of injectable hydrogel to improve the therapeutic effect is imperative. Here, keratin nanoparticles (Ker NPs) with facilitating epithelization capability and nanosized-EGCG covered with Ag nanoparticles (AE NPs) with radicals scavenging capability were used to functionalize injectable oxidized alginate/carboxylmethyl chitosan hydrogel (KA hydrogel). The radical scavenging experiments proved the anti-oxidative capacity of AE NPs. Rheological test exhibited that the gelation time and storage modulus of KA hydrogel were about 216 s and 403 Pa. Additionally, wound healing experiment in vivo showed that KA hydrogel could accelerated wound healing, especially in the early stage, and improved the thickness of renascent epidermis by 21 %. In this work, Ker NPs and AE NPs functionalization endowed injectable hydrogels with the capabilities of scavenging radicals and facilitating epithelization, which is promising for the applications in wound repair.

Injectable hyaluronic acid/hydroxyapatite composite hydrogels as cell carriers for bone repair.

The natural polysaccharide/hydroxyapatite hydrogels are of great interest to bone tissue engineering, but the interfacial mismatch between rigid hydroxyapatite and soft polysaccharide phase in these hydrogels remains unsolved, which is unfavorable to achieving uniform dispersion of hydroxyapatite particles in the hydrogel matrices. Herein, hyaluronic acid (Hya), an extracellular matrix constituent, was chosen as the template for biological mineralization to synthesize Hya/hydroxyapatite hybrid particles (HAHs). The oxidized Hya/hydroxyapatite hybrid particles (OHAHs) were obtained by oxidating the Hya in the HAHs. These OHAHs were the ball-flower particles hybridized with ca. 22 % oxidized Hya. Then, different concentrations of OHAHs were introduced to prepare hydroxyapatite composite hydrogels (HCH) via Schiff-base reaction of oxidized Hya and carboxymethyl chitosan. The injectability and self-healing of HCH were evaluated and the introduction of OHAHs significantly increased the storage modulus. The gelation time of HCH showed a negative relation with the concentration of OHAHs while the storage modulus presented a positive correlation. MTT assays and live/dead staining of L929 cells co-cultured with HCH confirmed that the hydrogels had excellent cytocompatibility, and supported the adhesion and proliferation of cells under the three-dimension culture conditions. These injectable self-healing hydrogels suitable for cell encapsulation were potentially useful for bone defect repair.

Preparation and Characterization of Calcium-Incorporated Rosa roxburghii Tratt and Its Efficacy on Bone Mineral Density in Rats.

The deficiency of traditional calcium preparation will gradually be replaced by the new type of calcium preparation. Rosa roxburghii fruit (R. roxburghii) is popular for its rich nutrients and functional ingredients. The fermentation broth of R. roxburghii, involving amino acids, flavonoids, triterpenes, polysaccharides, and other compounds, is favorable for calcium chelation. Thus, this study fabricated calcium-incorporated R. roxburghii (FECa) and further illustrated its efficacy on bone mineral density (BMD) in rats. The calcium holding capacity of FECa was identified and confirmed using AAS. Ion complexation of FECa was characterized using 1H-NMR, UV, SEM and EDS, and FTIR. The calcium contents of femurs were increased by 36%, and the bone trabeculae of femurs were significantly increased. Net calcium balance was enhanced to further improve BMD by oral administration of FECa. The above results indicate that FECa can be a potential and efficient calcium supplementation agent.

Repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages prevents schizophrenia-relevant phenotypes in adult offspring after maternal immune activation: a role of TrkB signaling.

Maternal immune activation (MIA) plays a role in the etiology of schizophrenia. MIA by prenatal exposure of polyinosinic:polycytidylic acid [poly(I:C)] in rodents caused behavioral and neurobiological changes relevant to schizophrenia in adult offspring. We investigated whether the novel antidepressant (R)-ketamine could prevent the development of psychosis-like phenotypes in adult offspring after MIA. We examined the effects of (R)-ketamine (10 mg/kg/day, twice weekly for 4 weeks) during juvenile and adolescent stages (P28-P56) on the development of cognitive deficits, loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex (mPFC), and decreased dendritic spine density in the mPFC and hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, we examined the role of TrkB in the prophylactic effects of (R)-ketamine. Repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages significantly blocked the development of cognitive deficits, reduced PV-immunoreactivity in the prelimbic (PrL) of mPFC, and decreased dendritic spine density in the PrL of mPFC, CA3 and dentate gyrus of the hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, pretreatment with ANA-12 (TrkB antagonist: twice weekly for 4 weeks) significantly blocked the beneficial effects of (R)-ketamine on cognitive deficits of adult offspring after prenatal poly(I:C) exposure. These data suggest that repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages could prevent the development of psychosis in adult offspring after MIA. Therefore, (R)-ketamine would be a potential prophylactic drug for young subjects with high-risk for psychosis.

Robust strategy for disease resistance and increasing production breeding in red swamp crayfish (Procambarus clarkii).

Red swamp crayfish (Procambarus clarkii) is an important aquaculture species in China. With increasing crayfish culture, a number of outbreaks of various diseases have been identified in crayfish. Despite this, there are no reports on the application of disease resistance genes in the molecular breeding of crayfish. In this study, transcriptome analysis was performed to explore the disease resistance genes in crayfish, with a focus on investigating the genetic variations in the open reading frames of these genes, for subsequent haplotype analysis. Furthermore, pathogen-challenge experiments were carried out in the crayfish, to identify the favoured haplotypes. A novel disease resistance gene, R (Resistance), was identified by means of transcriptome analysis. In total, two, four, and five haplotypes of the three disease resistance genes, ALF, R, and crustin2, respectively, were detected. ALF1, R1, and Cru1 were the favoured haplotypes of ALF, R, and crustin2, respectively. Subsequently, the favoured haplotype combinations of the different genes were obtained, and a series of molecular markers were developed to identify them. Finally, we propose a molecular breeding strategy to enhance the disease resistance of crayfish, and thus, improve its production.