Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway.

Exposure to general anesthetics can adversely affect brain development, but there is little study of sedative agents used in intensive care that act via similar pharmacologic mechanisms. Using quantitative immunohistochemistry and neurobehavioral testing and an established protocol for murine sedation, we tested the hypothesis that lengthy, repetitive exposure to midazolam, a commonly used sedative in pediatric intensive care, interferes with neuronal development and subsequent cognitive function via actions on the mechanistic target of rapamycin (mTOR) pathway. We found that mice in the midazolam sedation group exhibited a chronic, significant increase in the expression of mTOR activity pathway markers in comparison to controls. Furthermore, both neurobehavioral outcomes, deficits in Y-maze and fear-conditioning performance, and neuropathologic effects of midazolam sedation exposure, including disrupted dendritic arborization and synaptogenesis, were ameliorated via treatment with rapamycin, a pharmacologic mTOR pathway inhibitor. We conclude that prolonged, repetitive exposure to midazolam sedation interferes with the development of neural circuitry via a pathologic increase in mTOR pathway signaling during brain development that has lasting consequences for both brain structure and function.

Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

Large-scale study in Chengdu, China: The prevalence of myopia full-correction decreased with increasing myopia in adolescents.

Myopia is an increasingly serious health issue among children and adolescents worldwide. This study investigated the situation related to myopia among students in Chengdu, a city in western China, and analyzed the prevalence of myopia spectacle wear and myopia full-correction and their influencing factors to understand the current status of myopia prevention. This school-based cross-sectional study investigated 1582 schools in seven districts of Chengdu City, China, enrolling a total of 417,337 students aged 6-18 years (elementary, middle, and high school) from 2020 to 2022. Examination items included uncorrected visual acuity (UCVA), slit lamp examination and non-cycloplegic autorefraction. Myopia was defined as non-cycloplegic SE ≤ -0.50 D + UCVA> 0 log MAR (age ≥6). The prevalence of myopia spectacle wear is defined as the number of people wearing glasses for myopia/the number of people with myopia (%) within the study population, and myopia full-correction is defined as normal vision after wearing glasses for myopia (≤0 log MAR for 6 years and above). With the support of the government, this programme is conducted 1-2 times a year. Statistical analyses are conducted to determine the association between myopia and various parameters. The average age of the entire survey population was 10.96 ± 3.5 years, and the overall prevalence of myopia was 48.7%, myopia spectacle wear was 65.7%, and myopia full-correction was 50.5%. With increasing age and educational levels, the prevalence of moderate to high myopia, the prevalence of myopia spectacle wear, and the prevalence of myopia full-correction all rise. The prevalence of mild myopia full-correction (46.5%) was higher than that for moderate myopia (47.1%) and even higher than that for high myopia (39.6%). The correct utilization rate of myopic spectacles was 33.17%, increasing with age and education levels, with the highest correct utilization rate of 40.7% among those with moderate myopia. The prevalence of myopia among children and adolescents in Chengdu is relatively low, and the prevalence of myopia spectacle wear and myopia full-correction need to be improved, and it was found that with the increase of myopia, the prevalence of myopia full-correction among adolescents decreased instead.

hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

Ultrafast Multifunctional Photodetector Based on the NiAl2O4/4H-SiC Heterojunction.

Solar-blind photodetectors based on wide bandgap semiconductors have recently attracted a lot of interest. Nickel-containing spinel phase oxides, such as NiAl2O4, are stable p-type semiconductors. This paper describes a multifunctional solar-blind photodetector based on a NiAl2O4/4H-SiC heterojunction that utilizes photovoltaic effects. The position sensitivity reaches a value of 1589.7 mV/mm under 405 nm laser illumination, while the relaxation times of vertical photovoltaic (VPV) effect and lateral photovoltaic (LPV) effect under 266 nm laser illumination are only 0.32 and 0.42 µs, respectively. This junction was used to create a space optical communication system with sunlight having little effect on its optoelectronic properties. The ultrafast photovoltaic relaxation time makes NiAl2O4/4H-SiC a promising candidate for self-powered high-performance solar-blind detectors.

Construction of Phosphorothiolated 2-Pyrrolidinones via Photoredox/Copper-Catalyzed Cascade Radical Cyclization/Phosphorothiolation.

A photoredox/copper-catalyzed cascade radical cyclization/phosphorothiolation reaction of N-allylbromoacetamides and P(O)SH compounds has been established. A broad range of novel nonfluorine- or difluoro-substituted 2-pyrrolidinones bearing the C(sp3)-SP(O)(OR)2 moiety can be conveniently constructed in moderate to good yields under mild conditions. Importantly, most of the tested phosphorothiolated 2-pyrrolidinones showed potent inhibitory effects toward both AChE and BChE.

Ternary Eutectic Electrolyte-Assisted Formation and Dynamic Breathing Effect of the Solid-Electrolyte Interphase for High-Stability Aqueous Magnesium-Ion Full Batteries.

Aqueous rechargeable magnesium batteries hold immense potential for intrinsically safe, cost-effective, and sustainable energy storage. However, their viability is constrained by a narrow voltage range and suboptimal compatibility between the electrolyte and electrodes. Herein, we introduce an innovative ternary deep eutectic Mg-ion electrolyte composed of MgCl2·6H2O, acetamide, and urea in a precisely balanced 1:1:7 molar ratio. This formulation was optimized by leveraging competitive solvation effects between Mg2+ ions and two organic components. The full batteries based on this ternary eutectic electrolyte, Mn-doped sodium vanadate (Mn-NVO) anode, and copper hexacyanoferrate cathode exhibited an elevated voltage plateau and high rate capability and showcased stable cycling performance. Ex-situ characterizations unveiled the Mg2+ storage mechanism of Mn-NVO involving initial extraction of Na+ followed by subsequent Mg2+ intercalation/deintercalation. Detailed spectroscopic analyses illuminated the formation of a pivotal solid-electrolyte interphase on the anode surface. Moreover, the solid-electrolyte interphase demonstrated a dynamic adsorption/desorption behavior, referred to as the "breathing effect", which substantially mitigated undesired dissolution and side reactions of electrode materials. These findings underscore the crucial role of rational electrolyte design in fostering the development of a favorable solid-electrolyte interphase that can significantly enhance compatibility between electrode materials and electrolytes, thus propelling advancements in aqueous multivalent-ion batteries.

Screening Ultra-Stable (Phenazine)dioxyalkanocic Acids with Varied Water-Solubilizing Chain Lengths for High-Capacity Aqueous Redox Flow Batteries.

Aqueous redox flow batteries (ARFBs) hold great potential for large-scale energy storage. Recently, research on aqueous flow batteries has shifted toward water-soluble organic molecules with redox capabilities to reduce the use of mineral resources. The chemical and electrochemical stabilities of organic compounds are heavily influenced by their functional groups and reaction sites. In this study, we present a low-cost synthesis of the O-alkyl-carboxylate-functionalized derivatives of 2,3-dihydroxyphenazine, namely, phenazine-(2,3-diyl) dioxy dibutyric acid (DBEP) and phenazine-(2,3-diyl)dioxy diacetic acid (DAEP), which serve as negolytes and exhibit good reversibility and high redox kinetics. The evidence is provided to clarify the capacity degradation mechanisms of DAEP and DBEP by a series of comprehensive characterizations. Similar to anthraquinones functionalized with alkyl chains, the main degradation mechanism of DAEP modified with acetic acid is due to side chain loss. Longer side chains are more stable and can withstand long-term electrochemical reactions. DBEP modified with butyric acid exhibits superior chemical and electrochemical stability. Our results demonstrate that rational molecular design and suitable membranes, such as the alkaline ARFBs based on DBEP negolyte, potassium ferrocyanide (K4Fe(CN)6) posolyte, and custom sulfonated poly(ether ether ketone) membrane, can deliver a high open-circuit voltage of 1.17 V and high capacity retention of 99.997% per cycle for over 1000 cycles at 50 mA cm-2. This study highlights the importance of not only considering the modification position of the molecules but also focusing on the influence of various side chains on the redox core's stability toward sustainable grid-scale energy storage applications.

CA19­9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy.

BACKGROUND: Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 - 9 (CA19-9) and carbohydrate antigen 72 - 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. METHODS: A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan-Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. RESULTS: Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. CONCLUSION: Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma.

BACKGROUND: Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. METHODS: RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. RESULTS: We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. CONCLUSIONS: Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.

Glyceryl triacetate promotes blood-brain barrier recovery after ischemic stroke through lipogenesis-mediated IL-33 in mice.

BACKGROUND: Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood-brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33. METHODS: Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated. RESULTS: We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke. CONCLUSION: Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.

Ultrafast Thermal Shock Synthesis and Porosity Engineering of 3D Hierarchical Cu-Bi Nanofoam Electrodes for Highly Selective Electrochemical CO2 Reduction.

Massive production of practical metal or alloy based electrocatalysts for electrocatalytic CO2 reduction reaction is usually limited by energy-extensive consumption, poor reproducibility, and weak adhesion on electrode substrates. Herein, we report the ultrafast thermal shock synthesis and porosity engineering of free-standing Cu-Bi bimetallic nanofoam electrocatalysts with 3D hierarchical porous structure and easily adjustable compositions. During the thermal shock process, the rapid heating and cooling steps in several seconds result in strong interaction between metal nanopowders to form multiphase nanocrystallines with abundant grain boundaries and metastable CuBi intermetallic phase. The subsequent porosity engineering process via acid etching and electroreduction creates highly porous Cu-Bi structures that can increase electrochemically active surface area and facilitate mass/charge transfer. Among the Cu-Bi nanofoam electrodes with different Cu/Bi ratios, the Cu4Bi nanofoam exhibited the highest formate selectivity with a Faradaic efficiency of 92.4% at -0.9 V (vs reversible hydrogen electrode) and demonstrated excellent operation stability.

Green Synthesis of Antimicrobial Peptide-Protected Silver Nanoclusters with Regulated Antibacterial Behavior.

The antibacterial system based on the silver element has been a very promising antibacterial material. However, the antibacterial activity of silver nanomaterials largely depends on their chemical composition and physical properties. Herein, we prepared ultrasmall silver nanoclusters by directly reducing silver ions with antimicrobial peptide in a green way. The positively charged peptide ligands drove the silver nanoclusters binding to bacteria by electrostatic attraction. Contrary to the large-sized silver nanomaterials, the ultrasmall silver nanoclusters were able to rapidly penetrate bacteria membranes via strong hydrophobic association, significantly promoting the generation of reactive oxygen species, and the subsequent high oxidative stress led to bacterial death. Moreover, the silver nanoclusters with antibacterial peptide ligand exhibited good stability, low cytotoxicity, and long-term antibacterial activity. Besides, synergistic enhancement of silver nanoclusters on antibacterial activity was observed. Therefore, the silver nanoclusters conjugated with the antimicrobial peptide can act as a synergistic antibacterial agent, in which their bio-interactions with bacteria have been regulated to achieve a rapid, long-lasting, and broad-spectrum antibacterial effect.

Multiple thermocycles followed by LAMP with only two primers for ultrasensitive colorimetric viral RNA testing and tracking at single-base resolution.

Rapid, accurate and high throughput measurement of infectious viruses is an urgent need to prevent viral transmission. Loop-mediated isothermal amplification (LAMP) is an attractive isothermal amplification method for nucleic acid detection, especially for point-of-care (POC) testing, but it needs at least four primers and its sensitivity is also limited when integrating with visual detection methods. Herein, by designing only two primers to precisely recognize the four regions of the target, we developed a multiple thermocycles-based LAMP method (MTC-LAMP) for sensitive and specific testing and tracking of viral RNA. We also introduced a novel SYBR Green I (SG)-assisted stable colorimetric assay induced by the amplification products through the charge neutralization effect of positively charged SG toward gold nanoparticles (AuNPs). The ultralow nonspecific background of the double exponential amplification improved the detection sensitivity to near single-molecule level (1 aM, 3 copies in 5 µL solution), which was higher than RT-PCR and RT-LAMP. After adding AuNPs, a significant color difference between target and blank was immediately observed by naked eye. By introducing a peptide nucleic acid (PNA) clamp into our colorimetric MTC-LAMP assay, the specific distinguish of virus variants at single-base resolution was observed without the requirement of any equipment. This assay shows great potential for large-scale screening and tracking of the threatening viruses with ultrahigh sensitivity and pronounced colorimetric output, which is of great importance for pandemic control.

Colorimetric detection of ozone in aqueous solution and imaging in living cells using a novel hemicyanine dye.

Ozone (O3) is ubiquitous in the environment and exposure to high levels of O3 has been associated with various respiratory diseases, such as asthma, emphysema, and bronchitis. Therefore, it is necessary to develop a simple and efficient detection method for monitoring O3 in the environment and living cells. In this study, an intramolecular charge-transfer (ICT) compound was designed and synthesized based on a phenol-type hemicyanine dye and 4-bromo-1-butene, which could specifically detect O3 in aqueous solution. Due to the ICT process, the absorption spectrum, fluorescence spectrum, and color of the probe hemicyanine-butyl-3-enyl (HCB) changed significantly and thus the rapid and sensitive detection of O3 was realized. The interaction between O3 and the probe HCB could be completed within 40 min, and the detection limit of O3 was as low as 2.15 × 10-7 mol L-1. Finally, the proposed method was successfully applied to the visual detection of O3 in a simulated O3 environment and living cells.

Enhanced bidirectional extracellular electron transfer based on biointerface interaction of conjugated polymers-bacteria biohybrid system.

The low bacteria loading capacity and low extracellular electron transfer (EET) efficiency are two major bottlenecks restricting the performance of the bioelectrochemical systems from practical applications. Herein, we demonstrated that conjugated polymers (CPs) could enhance the bidirectional EET efficiency through the intimate biointerface interactions of CPs-bacteria biohybrid system. Upon the formation of CPs/bacteria biohybrid, thick and intact CPs-biofilm formed which ensured close biointerface interactions between bacteria-to-bacteria and bacteria-to-electrode. CPs could promote the transmembrane electron transfer through intercalating into the cell membrane of bacteria. Utilizing the CPs-biofilm biohybrid electrode as anode in microbial fuel cell (MFC), the power generation and lifetime of MFC had greatly improved based on accelerated outward EET. Moreover, using the CPs-biofilm biohybrid electrode as cathode in electrochemical cell, the current density was increased due to the enhanced inward EET. Therefore, the intimate biointerface interaction between CPs and bacteria greatly enhanced the bidirectional EET, indicating that CPs exhibit promising applications in both MFC and microbial electrosynthesis.

Physio-psycho-social interaction mechanism in dyadic health of young and middle-aged stroke survivors and their spousal caregivers: a longitudinal observational study protocol.

INTRODUCTION: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. The findings of this study will provide implications for developing interventions to improve dyadic health of this growing population. METHODS AND ANALYSES: We will collect data from 57 dyads of young and middle-aged stroke survivors and their spousal caregivers during hospitalisation and at 1, 3, 6, 9 and 12 months after discharge. Questionnaires will be used to collect participants' demographic information, stress, depression, anxiety, benefit finding, social support, mutuality and quality of life. The following physiological reactions will be collected at baseline, including interleukin 6, tumour necrosis factor-alpha and salivary cortisol. ETHICS AND DISSEMINATION: The study was approved by the ethics review committee of life sciences of Zhengzhou University (No. ZZUIRB2020-53). Prior to being enrolled in the study, participants will be given full and detailed information about the possible risks involved, the informed consent process, confidentiality, the study procedure and secure data storage. Participants will be guaranteed that they can withdraw from the study at any time without providing a reason or leading to any consequences. Both oral and written informed consent will be obtained from all participants. The findings of this proposed study will be disseminated through peer-reviewed journals and academic conferences.

Manipulating the monomer-dimer transformation of a heptamethine cyanine ligand: near infrared chromogenic recognition of biothiols.

A novel absorbance recovery method has been developed for the determination of biothiols with a near-infrared reagent. This method employs a two-reagent system composed of cation heptamethine cyanine (CyL) and Hg2+. The absorbance of CyL, with a maximum peak at 760 nm, was decreased due to addition of Hg2+, but recovered when biothiols were added. Under optimal conditions, the reciprocal extent of recovered absorbance was proportional to the concentration of biothiols. The calibration curves are linear over the range of (0.3-7.0) × 10-6 M for cysteine, (1.0-10.0) × 10-6 M for homocysteine and (1.0-9.0) × 10-6 M for glutathione. Because of the specific affinity of Hg2+for biothiols, there is minimal interference from other amino acids. This method has been successfully applied to the determination of homocysteine in human urine samples with satisfactory results.

Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway.

Anesthetics such as sevoflurane are commonly administered to infants and children. However, the possible neurotoxicity caused by prolonged or repetitive exposure to it should be a concern. The neuroprotective effects of metformin are observed in many models of neurological disorders. In this study, we investigated whether metformin could reduce the developmental neurotoxicity induced by sevoflurane exposure in neonatal rats and the potential mechanism. Postnatal day 7 (PND 7) Sprague-Dawley rats and neural stem cells (NSCs) were treated with normal saline or metformin before sevoflurane exposure. The Morris water maze (MWM) was used to observe spatial memory and learning at PND 35-42. Immunofluorescence staining was used to detect neurogenesis in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus at PND 14. MTT assays, immunofluorescence staining, and TUNEL staining were used to assess the viability, proliferation, differentiation, and apoptosis of NSCs. Western blotting and ELISA were used to assess the protein expression of cleaved caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), and glucose-6-phosphate dehydrogenase (G6PD) pathway-related molecules. Exposure to sevoflurane resulted in late cognitive defects, impaired neurogenesis in both the SVZ and SGZ, reduced NSC viability and proliferation, increased NSC apoptosis, and decreased protein expression of G6PD in vitro. Metformin pretreatment attenuated sevoflurane-induced cognitive functional decline and neurogenesis inhibition. Metformin pretreatment also increased the protein expression of Nrf2 and G6PD. However, treatment with the Nrf2 inhibitor, ML385 or the G6PD inhibitor, dehydroepiandrosterone (DHEA) reversed the protective effect of metformin on sevoflurane-induced NSC damage in vitro. Our findings suggested that metformin could reduce sevoflurane-induced neurogenesis damage and neurocognitive defects in the developing rat brain by influencing the Nrf2/G6PD signaling pathways.