Evolution of Cortical Neurogenesis in Amniotes Controlled by Robo Signaling Levels.

Cerebral cortex size differs dramatically between reptiles, birds, and mammals, owing to developmental differences in neuron production. In mammals, signaling pathways regulating neurogenesis have been identified, but genetic differences behind their evolution across amniotes remain unknown. We show that direct neurogenesis from radial glia cells, with limited neuron production, dominates the avian, reptilian, and mammalian paleocortex, whereas in the evolutionarily recent mammalian neocortex, most neurogenesis is indirect via basal progenitors. Gain- and loss-of-function experiments in mouse, chick, and snake embryos and in human cerebral organoids demonstrate that high Slit/Robo and low Dll1 signaling, via Jag1 and Jag2, are necessary and sufficient to drive direct neurogenesis. Attenuating Robo signaling and enhancing Dll1 in snakes and birds recapitulates the formation of basal progenitors and promotes indirect neurogenesis. Our study identifies modulation in activity levels of conserved signaling pathways as a primary mechanism driving the expansion and increased complexity of the mammalian neocortex during amniote evolution.

Functional composites by programming entropy-driven nanosheet growth.

Nanomaterials must be systematically designed to be technologically viable1-5. Driven by optimizing intermolecular interactions, current designs are too rigid to plug in new chemical functionalities and cannot mitigate condition differences during integration6,7. Despite extensive optimization of building blocks and treatments, accessing nanostructures with the required feature sizes and chemistries is difficult. Programming their growth across the nano-to-macro hierarchy also remains challenging, if not impossible8-13. To address these limitations, we should shift to entropy-driven assemblies to gain design flexibility, as seen in high-entropy alloys, and program nanomaterial growth to kinetically match target feature sizes to the mobility of the system during processing14-17. Here, following a micro-then-nano growth sequence in ternary composite blends composed of block-copolymer-based supramolecules, small molecules and nanoparticles, we successfully fabricate high-performance barrier materials composed of more than 200 stacked nanosheets (125 nm sheet thickness) with a defect density less than 0.056 µm-2 and about 98% efficiency in controlling the defect type. Contrary to common perception, polymer-chain entanglements are advantageous to realize long-range order, accelerate the fabrication process (<30 min) and satisfy specific requirements to advance multilayered film technology3,4,18. This study showcases the feasibility, necessity and unlimited opportunities to transform laboratory nanoscience into nanotechnology through systems engineering of self-assembly.

Near-complete depolymerization of polyesters with nano-dispersed enzymes.

Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates1-7. Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally accelerates the formation of microplastics with partial polymer degradation6,8,9. Here we show that by nanoscopically dispersing enzymes with deep active sites, semi-crystalline polyesters can be degraded primarily via chain-end-mediated processive depolymerization with programmable latency and material integrity, akin to polyadenylation-induced messenger RNA decay10. It is also feasible to achieve processivity with enzymes that have surface-exposed active sites by engineering enzyme-protectant-polymer complexes. Poly(caprolactone) and poly(lactic acid) containing less than 2 weight per cent enzymes are depolymerized in days, with up to 98 per cent polymer-to-small-molecule conversion in standard soil composts and household tap water, completely eliminating current needs to separate and landfill their products in compost facilities. Furthermore, oxidases embedded in polyolefins retain their activities. However, hydrocarbon polymers do not closely associate with enzymes, as their polyester counterparts do, and the reactive radicals that are generated cannot chemically modify the macromolecular host. This study provides molecular guidance towards enzyme-polymer pairing and the selection of enzyme protectants to modulate substrate selectivity and optimize biocatalytic pathways. The results also highlight the need for in-depth research in solid-state enzymology, especially in multi-step enzymatic cascades, to tackle chemically dormant substrates without creating secondary environmental contamination and/or biosafety concerns.

Hydroclimatic changes on multiple timescales since 7800 y BP in the winter precipitation-dominated Central Asia.

Central Asia (CA) is one of the world's most significant arid regions, which is markedly impacted by global warming. A better understanding of the dynamical processes governing its Holocene climate variability is critical for a better understanding of possible future impacts of climate change in the region. To date, most of the existing CA paleoclimate records are from the summer precipitation-dominated eastern CA (ECA), with few records from the winter precipitation-dominated western CA (WCA). Here, we present a precisely dated (~6‰) and highly resolved (<4-y) record of hydroclimatic variations from the WCA covering the period between 7,774 and 656 y BP. Utilizing multiple proxies (δ18O, δ13C, and Sr/Ca) derived from a stalagmite from the Fergana Valley, Kyrgyzstan, we reveal a long-term drying trend in WCA, which is in contrast with the wetting trend in ECA. We propose that different responses of winter and summer westerly jets to seasonal solar insolation over the past 8,000 y may have resulted in an antiphased precipitation relationship between the WCA and ECA. Our data contain dominant quasiperiodicities of 1,400, 50 to 70, and 20 to 30 y, indicating close connections between the WCA climate and the North Atlantic. We further identified a series of droughts and pluvials on centennial-to-decadal timescales, which may have influenced regional societies and trans-Eurasian culture exchanges during historical and prehistorical times.

Presenilin-dependent receptor processing is required for axon guidance.

The Alzheimer's disease-linked gene presenilin is required for intramembrane proteolysis of amyloid-ß precursor protein, contributing to the pathogenesis of neurodegeneration that is characterized by loss of neuronal connections, but the role of Presenilin in establishing neuronal connections is less clear. Through a forward genetic screen in mice for recessive genes affecting motor neurons, we identified the Columbus allele, which disrupts motor axon projections from the spinal cord. We mapped this mutation to the Presenilin-1 gene. Motor neurons and commissural interneurons in Columbus mutants lacking Presenilin-1 acquire an inappropriate attraction to Netrin produced by the floor plate because of an accumulation of DCC receptor fragments within the membrane that are insensitive to Slit/Robo silencing. Our findings reveal that Presenilin-dependent DCC receptor processing coordinates the interplay between Netrin/DCC and Slit/Robo signaling. Thus, Presenilin is a key neural circuit builder that gates the spatiotemporal pattern of guidance signaling, thereby ensuring neural projections occur with high fidelity.

Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization.

BACKGROUND: The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated. RESULTS: Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization. CONCLUSIONS: In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.

Cluster sampling and scalable Bayesian optimization with constraints for negative tone development resist model calibration.

As the semiconductor technology node continues to shrink, achieving smaller critical dimension in lithography becomes increasingly challenging. Negative tone development (NTD) process is widely employed in advanced node due to their large process window. However, the unique characteristics of NTD, such as shrinkage effect, make the NTD resist model calibration more complex. Gradient descent (GD) and heuristic methods have been applied for calibration of NTD resist model. Nevertheless, these methods depend on initial parameter selection and tend to fall into local optima, resulting in poor accuracy of the NTD model and massive computational time. In this paper, we propose cluster sampling and scalable Bayesian optimization (BO) with constraints method for NTD resist model calibration. This approach utilizes cluster sampling strategy to enhance the capability for global initial sampling and employs scalable BO with constraints for global optimization of high-dimensional parameter space. With this approach, the calibration accuracy is significantly enhanced in comparison with results from GD and heuristic methods, and the computational efficiency is substantially improved compared with GD. By gearing up cluster sampling strategy and scalable BO with constraints, this method offers a new and efficient resist model calibration.

Seeded Growth of Size-Tunable Au@Ag Core-Shell Nano-Octahedra and Their Yolk-Shell Derivatives for Near Infrared Photothermal Conversion.

Gold-based nanostructures with well-defined morphologies and hollow interiors have significant potential as a versatile platform for various plasmonic applications including biomedical diagnostics and sensing. In this study, we report the synthesis of Au@Ag core-shell nanocrystals with perfect octahedral shapes and tunable edge lengths via seeded growth. These nanocrystals were then oxidatively carved into yolk-shell nanocages with a retained octahedral morphology. The increase in octahedral edge length and volume of the interior hollow cavity synergistically leads to a red-shift of the LSPR peak. As a result, the optimized Au@AuAg yolk-shell octahedral nanocages showed a remarkable temperature increase of 23 °C upon 15 min irradiation of an 808 nm laser at a power density of 1 W cm-2. This study provides a feasible strategy for creating octahedral AuAg nanostructures with tunable sizes and hollow interiors and validates their promising use in NIR photothermal conversion.

Fabrication of Hollow and Hierarchical CuO Micro-Nano Cubes Wrapped by Reduced Graphene Oxide as a Prospective Anode for SIBs.

In this study, hollow and hierarchical CuO micro-nano cubes wrapped by reduced graphene oxide (H-CuO MNCs@rGO) were designed and successfully fabricated via a novel three-step wet-chemical method. Benefiting from its unique hollow and hierarchical micro-nano structures, H-CuO MNCs@rGO exhibited significantly enhanced electrochemical Na+ storage performance when utilized as anode material for sodium-ion batteries (SIBs). Specifically, H-CuO MNCs@rGO demonstrated a specific capacity of 380.9 mAh g-1 in the initial reversible cycle and a capacity retention of 218.9 mAh g-1 after 150 cycles at a current density of 300 mA g-1. Furthermore, through the dominant pseudocapacitive behavior, an optimized rate capability of 221.2 mAh g-1 at 800 mA g-1 can be obtained for H-CuO MNCs@rGO. The comprehensive Na+ storage properties of H-CuO MNCs@rGO obviously exceeded those of hollow CuO cubes (H-CuO MNCs) and bulk CuO anodes. Such enhanced Na+ storage performances of H-CuO MNCs@rGO can be attributed to its reasonable hollow and hierarchical micro-nano structures, which provide abundant redox active sites, shorten Na+ migration pathway, buffer volume expansion, and improve electronic/ionic conductivity during sodiation/desodiation process. Our strategy provides a facile and innovative approach for the design of CuO with rational micro-nano structure as a high-performance anode for SIBs, which would also be a guiding way for tailoring transition metal oxides in other scalable and functional applications.

Adherence to a healthy lifestyle including sleep and sedentary behaviors and risk of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

The AaERF64-AaTPPA module participates in cold acclimatization of Actinidia arguta (Sieb. et Zucc.) Planch ex Miq.

Actinidia arguta (A. arguta, kiwiberry) is a perennial deciduous vine with a strong overwintering ability. We hypothesized that trehalose metabolism, which plays a pivotal role in the stress tolerance of plants, may be involved in the cold acclimatization of A. arguta. Transcriptome analysis showed that the expression of AaTPPA, which encodes a trehalose-6-phosphate phosphatase (TPP), was upregulated in response to low temperatures. AaTPPA expression levels were much higher in lateral buds, roots, and stem cambia than in leaves in autumn. In AaTPPA-overexpressing (OE) Arabidopsis thaliana (A. thaliana), trehalose levels were 8-11 times higher than that of the wild type (WT) and showed different phenotypic characteristics from WT and OtsB (Escherichia coli TPP) overexpressing lines. AaTPPA-OE A. thaliana exhibited significantly higher freezing tolerance than WT and OtsB-OE lines. Transient overexpression of AaTPPA in A. arguta leaves increased the scavenging ability of reactive oxygen species (ROS) and the soluble sugar and proline contents. AaERF64, an ethylene-responsive transcription factor, was induced by ethylene treatment and bound to the GCC-box of the AaTPPA promoter to activate its expression. AaTPPA expression was also induced by abscisic acid. In summary, the temperature decrease in autumn is likely to induce AaERF64 expression through an ethylene-dependent pathway, which consequently upregulates AaTPPA expression, leading to the accumulation of osmotic protectants such as soluble sugars and proline in the overwintering tissues of A. arguta. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01475-8.

A first-principles study on the promising thermoelectric properties of SnX (X = S, Se, Te) compounds.

SnSe has emerged as an outstanding thermoelectric material due to its exceptional performance. In this study, first-principles calculations are employed to investigate the thermoelectric properties of materials within the SnX family, where X can be either S, Se, or Te. Initially, we assessed the stability of SnX (X = S, Se, Te). We found that SnS exhibits better mechanical and thermal stability than SnSe and SnTe. We then conduct phonon and electronic transport analysis. Following the general rule that heavier atoms have lower thermal conductivity, SnTe demonstrates lower thermal conductivity due to its low group velocity compared with SnS and SnSe. Regarding electrical transport properties, the band gaps for SnS, SnSe, and SnTe are 0.56, 0.54, and 0.35 eV, respectively. Notably, the small band gap and higher degeneracy in its band valleys for SnTe make it more effective for achieving a high power factor. The maximum ZT values are determined to be 1.41, 1.41, and 1.87 for SnS, SnSe, and SnTe, respectively. Remarkably, ZTmax of SnTe exceeds that of SnSe by 32.6%. Overall, the results clearly demonstrate that SnTe exhibits superior thermoelectric properties compared to SnSe and SnS. This study provides valuable insights into the electronic structure, thermal conductivity, and mechanical and thermal stability of materials within the SnSe family, such as SnS or SnTe, without the need for extensive and costly experimental work.

Potassium levels and the risk of all-cause and cardiovascular mortality among patients with cardiovascular diseases: a meta-analysis of cohort studies.

BACKGROUND: Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. RESULTS: Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. CONCLUSIONS: Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. REGISTRATION: PROSPERO, CRD42022324337.

Mask correction method for surface plasmon lithography.

Surface plasmon lithography (SPL) has emerged as an innovative approach to nano-fabrication, offering an alternative to traditional patterning methods. To enhance its pattern fidelity in manufacturing, it is essential to incorporate mask correction to reduce critical dimension (CD) errors between the intended target features and the photoresist image. Traditionally, the aerial image of SPL has been modeled and simulated using methods such as finite difference time domain (FDTD) or rigorous coupled wave analysis (RCWA). These models have allowed us to obtain aerial images of the mask patterns. However, relying solely on the aerial image proves insufficient for meeting the rigorous manufacturing standards for mask correction. In our research, we propose a comprehensive model that combines the optical model, employing the FDTD method, and the resist model, tailored to the specific surface plasmon lithography process. Test patterns were meticulously designed with a target CD of 130 nm, and the model was applied to simulate these test patterns, producing the after-development image (ADI) under predefined process conditions. Following a thorough analysis and data processing of the test patterns and ADI data, we established rule tables for the correction of both 1D line patterns and line end patterns. The simulation results unequivocally demonstrate the improved CD error performance achieved by the post-corrected patterns.

Metformin Alleviates Pain States by Regulating the Balance of Spinal Synaptic Transmission.

BACKGROUND: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. METHODS: In this study, animal behavioral tests, whole-cell patch­clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. RESULTS: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain. Network pharmacology analysis of metformin action targets in pain database-related targets revealed 25 targets, including five hub targets (nitric oxide synthase 1 (NOS1), NOS2, NOS3, epidermal growth factor receptor (EGFR), and plasminogen (PLG)). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that metformin-induced analgesia was markedly correlated with calcium signaling and synaptic transmission. Intrathecal injection of metformin significantly reversed nerve injury-induced c-Fos (neural activity biomarker) mRNA and protein expression in neuropathic rats by regulating NOS2 expression. In addition, whole-cell recordings of isolated spinal neurons demonstrated that metformin dose-dependently inhibited the enhanced frequency and amplitude of miniature excitatory synaptic currents (mEPSCs) but did not affect those of miniature inhibitory synaptic currents (mIPSCs) in neuropathic pain. CONCLUSIONS: This study further demonstrated that metformin might inhibit spinal glutamatergic transmission and abnormal nociceptive circuit transduction by monitoring synaptic transmission in pain. Results of this work provide an in-depth understanding of metformin analgesia via synaptic plasticity.

Current status and continuing medical education need for general practitioners in Tibet, China: a cross-sectional study.

BACKGROUND: The Tibetan area is one of China's minority regions with a shortage of general practice personnel, which requires further training and staffing. This research helps to understand the current condition and demand for general practitioner (GP) training in Tibetan areas and to provide a reference for promoting GP education and training. METHODS: We conducted a cross-sectional survey using stratified sampling targeting 854 GPs in seven cities within the Tibetan Autonomous Region, utilizing an online questionnaire. Achieving a high response rate of 95.1%, 812 GPs provided invaluable insights. Our meticulously developed self-designed questionnaire, available in both Chinese and Tibetan versions, aimed to capture a wide array of data encompassing basic demographics, clinical skills, and specific training needs of GPs in the Tibetan areas. Prior to deployment, the questionnaire underwent rigorous development and refinement processes, including expert consultation and pilot testing, to ensure its content validity and reliability. In our analysis, we employed descriptive statistics to present the characteristics and current training needs of GPs in the Tibetan areas. Additionally, chi-square tests were utilized to examine discrepancies in training needs across various demographic groups, such as age, job positions, and educational backgrounds of the participating GPs. RESULTS: The study was completed by 812 (812/854, 95.1%) GPs, of whom 62.4% (507/812) were female. The top three training needs were hypertension (81.4%, 661/812), pregnancy management (80.7%, 655/812), and treatment of related patient conditions and events (80.5%, 654/812). Further research shows that the training required by GPs of different ages in "puncturing, catheterization, and indwelling gastric tube use" (64.6% vs. 54.8%, p = 9.5 × 10- 6) varies statistically. GPs in various positions have different training needs in "community-based chronic disease prevention and management" (76.6% vs. 63.9%, p = 0.009). The training needs of GPs with different educational backgrounds in "debridement, suturing, and fracture fixation" (65.6% vs. 73.2%, p = 0.027) were also statistically significant. CONCLUSIONS: This study suggests the need for targeted continuing medical education activities and for updating training topics and content. Course developers must consider the needs of GPs, as well as the age, job positions, and educational backgrounds of GPs practicing in the Tibetan Plateau region. TRIAL REGISTRATION: Not applicable.

Computational Insights into Cyclodextrin Inclusion Complexes with the Organophosphorus Flame Retardant DOPO.

Cyclodextrins (CDs) were used as green char promoters in the formulation of organophosphorus flame retardants (OPFRs) for polymeric materials, and they could reduce the amount of usage of OPFRs and their release into the environment by forming [host:guest] inclusion complexes with them. Here, we report a systematic study on the inclusion complexes of natural CDs (α-, ß-, and γ-CD) with a representative OPFR of DOPO using computational methods of molecular docking, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations. The binding modes and energetics of [host:guest] inclusion complexes were analyzed in details. α-CD was not able to form a complete inclusion complex with DOPO, and the center of mass distance [host:guest] distance amounted to 4-5 Å. ß-CD and γ-CD allowed for a deep insertion of DOPO into their hydrophobic cavities, and DOPO was able to frequently change its orientation within the γ-CD cavity. The energy decomposition analysis based on the dispersion-corrected density functional theory (sobEDAw) indicated that electrostatic, orbital, and dispersion contributions favored [host:guest] complexation, while the exchange-repulsion term showed the opposite. This work provides an in-depth understanding of using CD inclusion complexes in OPFRs formulations.

The evolution of NLRC3 subfamily genes in Sebastidae teleost fishes.

BACKGROUND: With more than 36,000 valid fish species, teleost fishes constitute the most species-rich vertebrate clade and exhibit extensive genetic and phenotypic variation, including diverse immune defense strategies. NLRC3 subfamily genes, which are specific to fishes, play vital roles in the immune system of teleosts. The evolution of teleosts has been impacted by several whole-genome duplication (WGD) events, which might be a key reason for the expansions of the NLRC3 subfamily, but detailed knowledge of NLRC3 subfamily evolution in the family Sebastidae is still limited. RESULTS: Phylogenetic inference of NLRC3 subfamily protein sequences were conducted to evaluate the orthology of NLRC3 subfamily genes in black rockfish (Sebastes schlegilii), 13 other fish species from the families Sebastidae, Serranidae, Gasterosteidae and Cyclopteridae, and three species of high vertebrates (bird, reptile and amphibian). WGD analyses were used to estimate expansions and contractions of the NLRC3 subfamily, and patterns of expression of NLRC3 subfamily genes in black rockfish following bacterial infections were used to investigate the functional roles of these genes in the traditional and mucosal immune system of the Sebastidae. Different patterns of gene expansions and contractions were observed in 17 fish and other species examined, and one and two whole-genome duplication events were observed in two members of family Sebastidae (black rockfish and honeycomb rockfish, Sebastes umbrosus), respectively. Subsequently, 179 copy numbers of NLRC3 genes were found in black rockfish and 166 in honeycomb rockfish. Phylogenetic analyses corroborated the conservation and evolution of NLRC3 orthologues between Sebastidae and other fish species. Finally, differential expression analyses provided evidence of the immune roles of NLRC3 genes in black rockfish during bacterial infections and gene ontology analysis also indicated other functional roles. CONCLUSIONS: We hypothesize that NLRC3 genes have evolved a variety of different functions, in addition to their role in the immune response, as a result of whole genome duplication events during teleost diversification. Importantly, this study had underscored the importance of sampling across taxonomic groups, to better understand the evolutionary patterns of the innate immunity system on which complex immunological novelties arose. Moreover, the results in this study could extend current knowledge of the plasticity of the immune system.

PTPN3 acts as a tumor suppressor and boosts TGF-ß signaling independent of its phosphatase activity.

TGF-ß controls a variety of cellular functions during development. Abnormal TGF-ß responses are commonly found in human diseases such as cancer, suggesting that TGF-ß signaling must be tightly regulated. Here, we report that protein tyrosine phosphatase non-receptor 3 (PTPN3) profoundly potentiates TGF-ß signaling independent of its phosphatase activity. PTPN3 stabilizes TGF-ß type I receptor (TßRI) through attenuating the interaction between Smurf2 and TßRI. Consequently, PTPN3 facilitates TGF-ß-induced R-Smad phosphorylation, transcriptional responses, and subsequent physiological responses. Importantly, the leucine-to-arginine substitution at amino acid residue 232 (L232R) of PTPN3, a frequent mutation found in intrahepatic cholangiocarcinoma (ICC), disables its role in enhancing TGF-ß signaling and abolishes its tumor-suppressive function. Our findings have revealed a vital role of PTPN3 in regulating TGF-ß signaling during normal physiology and pathogenesis.

Effects of bleeding of Actinidia arguta (Sieb. & Zucc) Planch. ex miq. on its plant growth, physiological characteristics and fruit quality.

Bleeding is as particularly a serious phenomenon in Actinidia arguta and has important effects on this plant's growth and development. Here we used A. arguta to study the effects of bleeding on the growth and development of leaves and fruits after a bleeding episode. We detect and analyze physiological indices of leaves and fruit after bleeding. The result revealed that the relative electrical conductivity and malondialdehyde (MDA) of leaves increased in treatment. Nitro blue tetrazolium chloride (NBT) and 3,3-diaminobenzidine (DAB) staining revealed the accumulation of reactive oxygen species (ROS) in leaves after bleeding. The chlorophyll content and photosynthetic parameter of plants were also decreased. In fruits, pulp and seed water content decreased after the damage, as did fruit vitamin C (Vc), soluble sugar content, and soluble solids content (SSC); the titratable acid content did not change significantly. We therefore conclude that bleeding affects the physiological indices of A. arguta. Our study provides a theoretical basis for understanding the physiological changes of A. arguta after bleeding episodes and laying a timely foundation for advancing research on A. arguta bleeding and long-term field studies should be executed in order to gain insights into underlying mechanisms.