Effects of different forced-air warming systems on the core temperature of patients: a manikin and multi-center clinical study.

BACKGROUND: The use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database. METHODS: In the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics. RESULTS: In the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p < 0.001). CONCLUSIONS: Among patients undergoing laparoscopic radical resection of colorectal cancer with general anesthesia, all four FAW systems effectively prevented perioperative hypothermia. However, the system in Group A minimized heat loss more effectively than the others, providing superior thermal protection. TRIAL REGISTRATION: ChiCTR2200065394, 03/11/2022.

Leptin reduces LPS-induced A1 reactive astrocyte activation and inflammation via inhibiting p38-MAPK signaling pathway.

Neurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague-Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6 h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2-D1, H2-T23, and Serping 1 and secretion of pro-inflammatory cytokines IL-6 and TNF-α. The levels of phospho-p38 (pp38) and nuclear factor-κB (NF-κB) phosphor-p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS-induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte-specific genes and the secretion of pro-inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose-dependent manner. Similarly, LPS upregulated pp38, NF-κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS-induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS-induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38-MAPK signaling pathway.

Soluble Guanylate Cyclase α1 Gene Influences Egg-Laying Amount and Hatching Rate in Bombyx mori.

Soluble guanylate cyclase (sGC) serves as a receptor of nitric oxide (NO) and is the core metalloenzyme in the NO signal transduction pathway. sGC plays a key role in the NO-cGMP signal transduction pathway and participates in various physiological processes, including cell differentiation, neuron transmission, and internal environment homeostasis. sGC consists of two subunits, α and ß, each subunit containing multiple isoforms. In this study, we cloned and analyzed the sGC-α1 gene in the silkworm Bombyx mori (BmsGC-α1). The BmsGC-α1 gene was expressed highest at the pupal stages. The highest BmsGC-α1 mRNA expression was observed in the head of fifth instar larvae and in fat body during the wandering stage of B. mori. Furthermore, we observed that feeding fifth instar larvae with thyroid hormone and nitroglycerin induced the expression of the BmsGC-α1 gene. Injection of BmsGC-α1 siRNA into silkworms at the prepupal stage resulted in a significant decrease in BmsGC-α1 expression levels at 48 and 72 h postinjection. After silencing BmsGC-α1, both the egg-laying amount and hatching rate of silkworm eggs were significantly reduced compared to the control group. These results suggest that BmsGC-α1 plays an important role in regulating the reproductive system of silkworms. This finding enhances our understanding of the functional diversity of sGC in insects.

Systematic discovery of DNA-binding tandem repeat proteins.

Tandem repeat proteins (TRPs) are widely distributed and bind to a wide variety of ligands. DNA-binding TRPs such as zinc finger (ZNF) and transcription activator-like effector (TALE) play important roles in biology and biotechnology. In this study, we first conducted an extensive analysis of TRPs in public databases, and found that the enormous diversity of TRPs is largely unexplored. We then focused our efforts on identifying novel TRPs possessing DNA-binding capabilities. We established a protein language model for DNA-binding protein prediction (PLM-DBPPred), and predicted a large number of DNA-binding TRPs. A subset was then selected for experimental screening, leading to the identification of 11 novel DNA-binding TRPs, with six showing sequence specificity. Notably, members of the STAR (Short TALE-like Repeat proteins) family can be programmed to target specific 9 bp DNA sequences with high affinity. Leveraging this property, we generated artificial transcription factors using reprogrammed STAR proteins and achieved targeted activation of endogenous gene sets. Furthermore, the members of novel families such as MOON (Marine Organism-Originated DNA binding protein) and pTERF (prokaryotic mTERF-like protein) exhibit unique features and distinct DNA-binding characteristics, revealing interesting biological clues. Our study expands the diversity of DNA-binding TRPs, and demonstrates that a systematic approach greatly enhances the discovery of new biological insights and tools.

Sulfate sensitivity of early life stages of freshwater mussels Unio crassus and Margaritifera margaritifera.

Sulfate is increasingly found in elevated concentrations in freshwater ecosystems due to anthropogenic activities. Chronic exposure to sulfate has been reported to cause sublethal effects on freshwater invertebrates. Previous sulfate toxicity tests have mostly been conducted in hard or moderately hard waters, and research on species inhabiting soft water is needed, given that freshwater organisms face heightened sensitivity to toxicants in water of lower hardness. In the present study, we examined sulfate sensitivity of two endangered freshwater mussel species, Unio crassus, and Margaritifera margaritifera. Glochidia and juveniles of both species were subjected to acute and/or chronic sulfate exposures in soft water to compare sulfate sensitivity across age groups, and effective concentrations (EC)/lethal concentrations (LC) values were estimated. Mussels were individually exposed to allow relatively larger numbers of replicates per treatment. Chronic sulfate exposure significantly reduced growth, foot movement, and relative water content (RWC) in juvenile mussels of M. margaritifera. Mussels at younger stages were not necessarily more sensitive to sulfate. In the acute tests, LC50 of glochidia of M. margaritifera and U. crassus was 1301 and 857 mg/L, respectively. Chronic LC10 was 843 mg/L for 3-week-old U. crassus juveniles, 1051 mg/L for 7-week-old M. margaritifera juveniles, and 683 mg/L for 2-year-old M. margaritifera juveniles. True chronic Lowest Effective Concentration for 7-week-old M. margaritifera may be within the 95% interval of EC10 based on RWC (EC10 = 446 mg/L, 95%CI = 265-626 mg/L). Our study contributed to the understanding of sulfate toxicity to endangered freshwater mussel species in soft water.

PLM_Sol: predicting protein solubility by benchmarking multiple protein language models with the updated Escherichia coli protein solubility dataset.

Protein solubility plays a crucial role in various biotechnological, industrial, and biomedical applications. With the reduction in sequencing and gene synthesis costs, the adoption of high-throughput experimental screening coupled with tailored bioinformatic prediction has witnessed a rapidly growing trend for the development of novel functional enzymes of interest (EOI). High protein solubility rates are essential in this process and accurate prediction of solubility is a challenging task. As deep learning technology continues to evolve, attention-based protein language models (PLMs) can extract intrinsic information from protein sequences to a greater extent. Leveraging these models along with the increasing availability of protein solubility data inferred from structural database like the Protein Data Bank holds great potential to enhance the prediction of protein solubility. In this study, we curated an Updated Escherichia coli protein Solubility DataSet (UESolDS) and employed a combination of multiple PLMs and classification layers to predict protein solubility. The resulting best-performing model, named Protein Language Model-based protein Solubility prediction model (PLM_Sol), demonstrated significant improvements over previous reported models, achieving a notable 6.4% increase in accuracy, 9.0% increase in F1_score, and 11.1% increase in Matthews correlation coefficient score on the independent test set. Moreover, additional evaluation utilizing our in-house synthesized protein resource as test data, encompassing diverse types of enzymes, also showcased the good performance of PLM_Sol. Overall, PLM_Sol exhibited consistent and promising performance across both independent test set and experimental set, thereby making it well suited for facilitating large-scale EOI studies. PLM_Sol is available as a standalone program and as an easy-to-use model at https://zenodo.org/doi/10.5281/zenodo.10675340.

LncRNA Snhg12/IGFBP3 axis is involved in liver fibrosis by promoting the proliferation and activation of mouse hepatic stellate cells.

Liver fibrosis is a persistent damage repair response triggered by various injury factors, which leads to an abnormal accumulation of extracellular matrix within liver tissue samples. The current clinical treatment of liver fibrosis is currently ineffective; therefore, elucidating the mechanism of liver fibrogenesis is of significant importance. Herein, the function and related mechanisms of lncRNA Snhg12 within hepatic fibrosis were investigated. Snhg12 expression was shown to be increased in mouse hepatic fibrotic tissue samples, and Snhg12 knockdown suppressed hepatic pathological injury and down-regulated the expression levels of fibrosis-associated proteins. Mechanistically, Snhg12 played a role in the early activation of mouse hepatic stellate cells (mHSCs) based on bioinformatics analysis, and Snhg12 was positively correlated with Igfbp3 expression. Further experimental results demonstrated that Snhg12 knockdown impeded mHSCs proliferation and activation and also downregulated the protein expression of Igfbp3. Snhg12 could interact with IGFBP3 and boost its protein stability, and overexpression of Igfbp3 partially reversed the inhibition of mHSCsproliferation and activation by the knockdown of Snhg12. In conclusion, LncRNA Snhg12 mediates liver fibrosis by targeting IGFBP3 and promoting its protein stability, thereby promoting mHSC proliferation and activation. Snhg12 has been identified as an underlying target for treating liver fibrosis.

Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.

Knockout of nuclear receptor HR38 gene impairs pupal-adult development in silkworm Bombyx mori.

Nuclear receptors are ligand-regulated transcription factors that play important role in regulating insect metamorphosis through the ecdysone signalling pathway. In this study, we investigated the nuclear receptor HR38 gene in Bombyx mori (BmHR38), belonging to the NR4A subfamily. BmHR38 mRNA was highly expressed in the head and epidermis at the pupal stage. The expression of the BmHR38 gene was influenced by different doses of 20E at different times. A BmHR38 deletion mutant silkworm was generated using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system. Compared with the wild-type B. mori, the BmHR38 deletion mutant resulted in abnormal development during the pupal stage, leading to either failed eclosion or the formation of abnormal adult wings. After silencing of BmHR38 in the pupal stage, the phenotype of pupa or moth had no significant change, but it did result in reduced egg production. The mRNA levels of USP, E75 and E74 were significantly increased, while the transcript levels of FTZ-F1 were suppressed after RNA interference. Furthermore, interference with BmHR38 also inhibited the expressions of chitin metabolism genes, including Chs1, Chs2, Chi, Chi-h and CDA. Our results suggest that BmHR38 is essential for pupal development and pupa-adult metamorphosis in B. mori by regulating the expression of NRs and chitin metabolism genes.

Leptin Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells through the Cooperative Action of MAPK/ERK1/2, JAK2/STAT3 and PI3K/AKT Signaling Pathways.

The potential of neural stem cells (NSCs) for neurological disorders the treatment has relied in large part upon identifying the NSCs fate decision. The hormone leptin has been reported to be a crucial regulator of brain development, able to influence the glial and neural development, yet, the underlying mechanism of leptin acting on NSCs' biological characteristics is still poorly understood. This study aims to investigate the role of leptin in the biological properties of NSCs. In this study, we investigate the possibility that leptin may regulate the NSCs' fate decision, which may promote the proliferation and neuronal differentiation of NSCs and thus act positively in neurological disorders. NSCs from the embryonic cerebral cortex were used in this study. We used CCK-8 assay, ki67 immunostaining, and FACS analysis to confirm that 25-100 ng/mL leptin promotes the proliferation of NSCs in a concentration-dependent pattern. This change was accompanied by the upregulation of p-AKT and p-ERK1/2, which are the classical downstream signaling pathways of leptin receptors b (LepRb). Inhibition of PI3K/AKT or MAPK/ERK signaling pathways both abolished the effect of leptin-induced proliferation. Moreover, leptin also enhanced the directed neuronal differentiation of NSCs. A blockade of the PI3K/AKT pathway reversed leptin-stimulated neurogenesis, while a blockade of JAK2/STAT3 had no effect on it. Taken together, our results support a role for leptin in regulating the fate of NSCs differentiation and promoting NSCs proliferation, which could be a promising approach for brain repair via regulating the biological characteristics of NSCs.

Investigating the dynamic decoupling relationship between regional social economy and lake water environment: The application of DPSIR-Extended Tapio decoupling model.

The water environmental problems associated with rapid socioeconomic growth have drawn widespread attention from the government and the public. Revealing the decoupling mechanism between the social economy and lake water environment has become an important breakthrough point to seek the pathways of sustainable economic development. To investigate the decoupling process of the social economy‒lake water environmental system, this study proposes a comprehensive evaluation model, which integrates the Driving force-Pressure-State-Impact-Response (DPSIR) model, projection pursuit method, and Tapio decoupling model; and then applies it to the case study of Hefei City and Lake Chaohu in China in 2021-2035. Three typical scenarios of current, social economy, and water environment are designed and simulated using the DPSIR model to evaluate the dynamic decoupling relationships under various development patterns. We found that the DPSIR indexes had a fluctuating upward trend from 2009 to 2020, with a synchronous improvement trend of the social economy and lake water environment. Meanwhile, the Tapio decoupling analysis showed that the decoupling relationships between socioeconomic driver forces, response strategies and the status of lake water environment was mostly strongly decoupled and weakly decoupled during 2009-2020. However, there was still an inconsistency between the improvement rate of the lake water environment and the increase rate of the response strategies. During the 2021-2035 simulation period, the DPSIR indexes of all scenarios depicts an overall increasing trend. The decoupling states of S&I-D&P and S&I-R generally tend to be consistent under three regulation scenarios. Among them, the water environment scenario outperforms other scenarios, and the social economy scenario performs worst. Overall, the decoupling of the social economy and lake water environment can attribute to both the transformation of socioeconomic development patterns and the increase of water environmental protection efforts.

Microglia-Astrocyte Interaction in Neural Development and Neural Pathogenesis.

The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis in the healthy central nervous system (CNS). Disease stimuli alter microglia-astrocyte interaction patterns and elicit cell-type-specific responses, resulting in their contribution to various pathological processes. Here, we review the similarities and differences in the activation modes between microglia and astrocytes in various scenarios, encompassing different stages of neural development and a wide range of neural disorders. The aim is to provide a comprehensive understanding of their roles in neural development and regeneration and guiding new strategies for restoring CNS homeostasis.

A Protein Asteroid with PIN Domain in Silkworm Bombyx mori Is Involved in Anti-BmNPV Infection.

Nuclease is a type of protein that degrades nucleic acids, which plays an important role in biological processes, including RNA interference efficiency and antiviral immunity. However, no evidence of a link between nuclease and Bombyx mori nucleopolyhedrovirus (BmNPV) infection in silkworm B. mori has been found. In this study, a protein asteroid (BmAst) containing the PIN domain and XPG domain was identified in silkworm B. mori. BmAst gene was highest expressed in hemocytes and fat body of the 5th instar larvae, and high expression in the pupa stage. The transcriptional levels of the BmAst gene in 5th instar larvae were significantly induced by BmNPV or dsRNA. After knocking down BmAst gene expression by specific dsRNA, the proliferation of BmNPV in B. mori was increased significantly, whereas the survival rate of larvae was significantly lower when compared with the control. Our findings indicate that BmAst is involved in silkworm resistance to BmNPV infection.

3D Bioprinting of Neurovascular Tissue Modeling with Collagen-Based Low-Viscosity Composites.

In vitro neurovascular unit (NVU) models are valuable for investigating brain functions and developing drugs. However, it remains challenging to recapitulate the native architectural features and ultra-soft extracellular matrix (ECM) properties of the natural NVU. Cell-laden bioprinting is promising to prepare complex living tissues, but hard to balance the fidelity and cell growth. This study proposes a novel two-stage methodology for biomanufacturing functional 3D neurovascular constructs in vitro with low modulus of ECM. At the shaping stage, a low-viscosity alginate/collagen is printed through an embedded approach; at the culturing stage, the alginate is removed through targeted lysing. The low-viscosity and rapid crosslinking properties provide a printing resolution of ≈10 µm, and the lysis processing can decrease the hydrogels' modulus to ≈1 kPa and adjust the porosity of the microstructure, providing cells with an environment closing to the brain ECM. A 3D hollow coaxial neurovascular model is fabricated, in which the endothelial cells has expressed tight junction proteins and shown selective permeability, and the astrocytes outside of the endothelial layer are found to spread out with branches and directly interact with endothelial cells. The present study offers a promising modeling method for better understanding the NVU function and screening neuro-drugs.

Sulfate sensitivity of aquatic organism in soft freshwaters explored by toxicity tests and species sensitivity distribution.

Elevated concentrations of sulfate in waterways are observed due to various anthropogenic activities. Elevated levels of sulfate can have harmful effects on aquatic life in freshwaters: sulfate can cause osmotic stress or specific ion toxicity in aquatic organisms, especially in soft waters where Ca2+ and Mg2+ concentrations are low. Formerly, chronic toxicity test data in soft water have been scarce. The chronic and acute sulfate toxicity tests conducted with aquatic organisms from 10 families across various trophic levels in this study multiplied the number of tests conducted in soft freshwater conditions and enabled derivation of the species sensitivity distribution (SSD) and sulfate hazardous concentrations for soft freshwaters. The cladoceran Daphnia longispina and freshwater snail Lymnaea stagnalis were the most sensitive to sulfate among the studied species. Harmful effects on the reproduction of D. longispina were observed at 49 mg SO4 /L while growth of L. stagnalis was inhibited at 217 mg SO4 /L. Most studied organisms tolerated high sulfate concentrations: the median of chronic effective concentrations (EC10 or LC10) was 1008 mg/L for all the species tested in this study. Based on the species sensitivity distribution of the studied species the hazardous concentration for 5 % of aquatic organism (HC5) in soft waters was 117-194 mg SO4/L. Different data set combinations were used to demonstrate the data variability in SSD-based HC5 estimates. The lowest values were produced from combining biotest results from the present study and earlier literature, while the highest values were calculated from the present study only. The derived chronic no-effect concentrations (PNEC) varied between 39 and 65 mg SO4/L.

Characterisation of X chromosome status of human extended pluripotent stem cells.

Different pluripotent cell types have been established by capturing pluripotency in different states. Human extended pluripotent stem cells (hEPSCs), recently established by two independent studies, have the capability of differentiating into both embryonic and extraembryonic lineages, as well as forming human blastoids, showing great potential for early human development modeling and regenerative medicine. Considering that X chromosome status in female human pluripotent stem cells is dynamic and heterogeneous, and often leads to functional consequences, we characterized it in hEPSCs. We derived hEPSCs from primed human embryonic stem cells (hESCs) with defined X chromosome status (pre- or post-X chromosome inactivation) using two previously published methods. We showed that hEPSCs derived using both methods had highly similar transcription profiles and X chromosome status. However, the X chromosome status of hEPSCs is largely determined by the primed hESCs from which they were derived, suggesting a lack of complete reprogramming of X chromosome during primed to extended/expanded pluripotency conversion. Furthermore, we found that the X chromosome status of hEPSCs affected their ability to differentiate into embryonic or extraembryonic lineage cells. Taken together, our work characterized the X chromosome status of hEPSCs, providing important information for the future application of hEPSCs.

Voluntary Exercise to Reduce Anxiety Behaviour in Traumatic Brain Injury Shown to Alleviate Inflammatory Brain Response in Mice.

Traumatic brain injury is a leading cause of neuroinflammation and anxiety disorders in young adults. Immune-targeted therapies have garnered attention for the amelioration of TBI-induced anxiety. A previous study has indicated that voluntary exercise intervention following TBI could reduce neuroinflammation. It is essential to determine the effects of voluntary exercise after TBI on anxiety via inhibiting neuroinflammatory response. Mice were randomly divided into four groups (sham, TBI, sham + voluntary wheel running (VWR), and TBI + VWR). One-week VWR was carried out on the 2nd day after trauma. The neurofunction of TBI mice was assessed. Following VWR, anxiety behavior was evaluated, and neuroinflammatory responses in the perilesional cortex were investigated. Results showed that after one week of VWR, neurofunctional recovery was enhanced, while the anxiety behavior of TBI mice was significantly alleviated. The level of pro-inflammatory factors decreased, and the level of anti-inflammatory factors elevated. Activation of nucleotide oligomerization domain-like thermal receptor protein domain associated protein 3 (NLRP3) inflammasome was inhibited significantly. All these alterations were consistent with reduced microglial activation at the perilesional site and positively correlated with the amelioration of anxiety behavior. This suggested that timely rehabilitative exercise could be a useful therapeutic strategy for anxiety resulting from TBI by targeting neuroinflammation.

The kinase inhibitory region of SOCS3 attenuates reactive astrogliosis and astroglial scar in mice after traumatic brain injury.

Traumatic brain injury (TBI) leads to reactive astrogliosis that impedes neural repair/regeneration. It has been proven that SOCS3 attenuates astrocyte activation by inhibiting the JAK2-STAT3 pathway. However, whether the kinase inhibitory region (KIR) of SOCS3 can be directly applied to mediate astrocyte activation after TBI is not clear. The present study aimed at investigating the inhibitory effect of KIR on reactive astrogliosis and its potential neuroprotection after TBI insult. For this purpose, A TBI model was developed by the free impact of heavy objects in adult mice. KIR was linked to the TAT peptide (TAT-KIR) to facilitate cell membrane penetration and intracranially injected into the cerebral cortex adjacent to the TBI lesion. Then reactive astrogliosis, activity of JAK2-STAT3 pathway, neuron loss, and function deficit were observed. Our results showed a decrease in neuron loss and an improvement in neural function. Meanwhile, Intracranial injection of TAT-KIR in TBI mice demonstrated a reduction of GFAP-positive astrocytes as well as C3/GFAP double-labeled A1 reactive astrocytes. Western blot analysis illustrated that the activity of the JAK2-STAT3 pathway was significantly inhibited by TAT-KIR. We conclude that exogenous treatment TAT-KIR, through suppression of JAK2-STAT3 activity, inhibits TBI -induced reactive astrogliosis induced, thereby alleviating the loss of neurons and relieving the neural function deficit. This investigation suggests that TAT-KIR could be a potential therapeutic strategy for enhancing neural regeneration following.

Kinase inhibit region of SOCS3 attenuates IL6-induced proliferation and astrocytic differentiation of neural stem cells via cross talk between signaling pathways.

AIMS: Efficiency of neural stem cells (NSCs) therapy for brain injury is restricted by astrogliosis around the damaged region, in which JAK2/STAT3 signaling plays a key role. The SOCS3 that can directly inhibit JAK/STAT3 pathway. Here, we investigated the effects of a fusion peptide that combined kinase inhibitory region (KIR) of SOCS3 and virus trans-activator of transcription (TAT) on biological behavior of cultured NSCs under inflammatory conditions. METHODS: NSCs were isolated from embryonic brain of SD rats, TAT-KIR was synthesized, and penetration rate was evaluated by flow cytometry (FACS). CCK8, immunostaining, and FACS were used to detected of TAT-KIR on the proliferation of NSCs. The expressions of GFAP and ß tubulin III positive cells induced by IL6 with/without TAT-KIR were examined by immunostaining and Western blotting to observe the NSCs differentiation, and the effect of TAT-KIR on signaling cross talk was observed by Western blotting. RESULTS: Penetration rate of TAT-KIR into primary cultured NSCs was up to 94%. TAT-KIR did not affect the growth and viability of NSCs. It significantly reduced the NSCs proliferation that enhanced by IL-6 stimulation via blocking the cell cycle progression from the G0/G1 to S phase. In addition, TAT-KIR attenuated astrocytic differentiation and kept high level of neuronal differentiation derived from IL-6-induced NSCs. The fate of NSCs differentiation under inflammatory conditions was affected by TAT-KIR, which was associated with synchronous inhibition of STAT3 and AKT, while promoting JNK expression. CONCLUSION: TAT-KIR mimetic of SOCS3 could be a promising approach for brain repair via regulating the biological behaviors of exogenous NSCs.

π-Conjugated Small Organic Molecule-Modified 2D MoS2 with a Charge-Localization Effect Enabling Direct and Sensitive SERS Detection.

Organic semiconductors have been discovered to exhibit impressive surface-enhanced Raman scattering (SERS) activity recently. However, owing to the underdeveloped candidate materials and relatively low SERS sensitivity, practical application of SERS detection based on organic materials is still a challenge. Herein, we explored ways to further enhance the SERS sensitivity of π-conjugated fluorinated 7,7,8,8-tetracyanoquinodimethane derivatives (FnTCNQ, n = 2, 4) by utilizing the charge-localization effect induced by two-dimensional (2D) MoS2 flakes. A strong Raman signal enhancement in SERS has been realized via an organic/2D heterostructure constructed by FnTCNQ nanostructures grown on a 2D MoS2 flake. Moreover, F2TCNQ and F4TCNQ show different SESR sensitivities due to different numbers of cyano groups leading to different charge transfer (CT) directions. The SERS enhancement factor (EF) of methylene blue (MB) molecules on the optimal F4TCNQ/MoS2 nanocomposite substrate can reach as high as 2.531 × 106, and the concentration of the limit of detection (LOD) is as low as 10-10 M. The SERS results for MB, rhodamine 6G (R6G), and 4-aminothiophenol (4-ATP) molecules demonstrate that high versatility, low cost, good stability, and easy preparation will make the FnTCNQ/MoS2 SERS platform promising for the detection of trace molecules. The studies on the complex microscopic interaction of organic/2D composite nanomaterials will provide some novel insights into improved SERS performance and mechanisms.