MiR-34a-5p suppresses cutaneous squamous cell carcinoma progression by targeting SIRT6.

Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor originating from epidermal or appendageal keratinocytes, with a rising incidence in recent years. Understanding the molecular mechanism driving its development is crucial. This study aims to investigate whether miR-34a-5p is involved in the pathogenesis of cSCC by targeting Sirtuin 6 (SIRT6).The expression levels of miR-34a-5p and SIRT6 were determined in 15 cSCC tissue specimens, 15 normal tissue specimens and cultured cells via real-time polymerase chain reaction (RT-qPCR). Pearson's correlation analysis was conducted to evaluate the relationship between miR-34a-5p and SIRT6 expression levels in cSCC tissues. A431 and SCL-1 cells were transfected with miR-34a-5p mimic, negative control or miR-34a-5p mimic together with recombinant plasmids containing SIRT6 gene. Cell counting kit-8, clone formation assay, wound healing assay, and flow cytometry were employed to assess the effects of these transfections on proliferation, migration, and apoptosis, respectively. The interaction between miR-34a-5p and SIRT6 was characterized using a dual-luciferase reporter assay.MiR-34a-5p expression was down-regulated in cSCC tissues significantly, while the SIRT6 expression was the opposite. A negative correlation was observed between the expression of miR-34a-5p and SIRT6 in cSCC tissues. Furthermore, overexpression of miR-34a-5p led to a significant reduction in the proliferation and migration abilities of A431 and SCL-1 cells, accompanied by an increase in apoptosis levels and a decrease in SIRT6 expression levels. MiR-34a-5p was identified as a direct target of SIRT6. Importantly, overexpression of SIRT6 effectively counteracted the inhibitory effect mediated by miR-34a-5p in cSCC cells.Our findings suggest that miR-34a-5p functions as a tumor suppressor in cSCC cells by targeting SIRT6.

IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m6A-dependent manner.

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often leads to a poor prognosis due to metastasis. The investigation of N6-methyladenosine (m6A) methylation, a crucial RNA modification, and its role in ccRCC, particularly through the m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), revealed significant insights. We found that IGF2BP2 was notably downregulated in ccRCC, which correlated with tumor aggressiveness and poor prognosis. Thus, IGFBP2 has emerged as an independent prognostic factor of ccRCC. Moreover, a strong positive correlation was observed between the expression of IGF2BP2 and Netrin-4. Netrin-4 was also downregulated in ccRCC, and its lower levels were associated with increased malignancy and poor prognosis. Overexpression of IGF2BP2 and Netrin-4 suppressed the invasion and migration of ccRCC cells, while Netrin-4 knockdown reversed these effects in ccRCC cell lines. RNA immunoprecipitation (RIP)-quantitative polymerase chain reaction validated the robust enrichment of Netrin-4 mRNA in anti-IGF2BP2 antibody immunoprecipitates. MeRlP showed significantly increased Netrin4 m6A levels after lGF2BP2 overexpression. Moreover, we found that IGF2BP2 recognized and bound to the m6A site within the coding sequence of Netrin-4, enhancing its mRNA stability. Collectively, these results showed that IGF2BP2 plays a suppressive role in the invasion and migration of ccRCC cells by targeting Netrin-4 in an m6A-dependent manner. These findings underscore the potential of IGF2BP2/Netrin-4 as a promising prognostic biomarker and therapeutic target in patients with ccRCC metastasis.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. OBJECTIVE: This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. METHODS: The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. RESULTS: The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. STUDY LIMITATIONS: No animal experiments were conducted to further verify the results. CONCLUSION: Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway.

Pre-eclampsia (PE) is a severe pregnancy complication characterized by impaired trophoblast invasion and spiral artery remodeling and can have serious consequences for both mother and child. Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is involved in numerous tumor-related biological processes. However, the biological action and underlying mechanisms of PPP1R3G in PE progression remain unclear. We used western blotting and immunohistochemistry to investigate PPP1R3G expression in gestational age-matched pre-eclamptic and normal placental tissues. After lentivirus transfection, wound-healing, Transwell, cell-counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and TdT mediateddUTP Nick End Labeling (TUNEL) assays were used to assess trophoblast migration, invasion, proliferation, and apoptosis, respectively. The relative expression levels of PPP1R3G and the proteins involved in the Akt signaling pathway were determined using western blotting. The results showed that PPP1R3G levels were significantly lower in the placental tissues and GSE74341 microarray of the PE group than those of the healthy control group. We also found that neonatal weight and Apgar score were lower at birth, and peak systolic blood pressure and diastolic blood pressure were higher in the PE group than in the non-PE group. In addition, PPP1R3G knockdown decreased p-Akt/Akt expression and inhibited migration, invasion, and proliferation in HTR-8/SVneo trophoblasts but had no discernible effect on cell apoptosis. Furthermore, PPP1R3G positively regulated matrix metallopeptidase 9 (MMP-9), which was downregulated in placental tissues of pregnant women with PE. These results provided the first evidence that the reduced levels of PPP1R3G might contribute to PE by suppressing the invasion and migration of trophoblasts and targeting the Akt/MMP-9 signaling pathway.

Properties of Ni-Al2O3 composite coating by laser-assisted pulse electrodeposition.

To study the influence of laser process parameters on the surface properties of the coating, N i-A l 2 O 3 composite coatings on 304 stainless-steel sheets with laser-assisted pulsed electrodeposition was proposed in this paper. Laser single pulse energy and scanning speed were selected as research factors. Single-factor experiments were performed to investigate the effect of various factors on the surface morphology, particle mass fraction, microhardness, surface roughness, and corrosion resistance of the composite coating. The experimental results show that the surface properties of the composite coating first increase and then decrease with increasing laser single pulse energy. When the laser single pulse energy is 11 µJ, the minimum surface roughness value is 0.380 µm with a smooth and uniform coating surface and the best surface morphology. Moreover, as the scanning speed increases, the corrosion resistance of the composite coating initially increases and then decreases. The corrosion resistance of the composite coatings is best with a scanning speed of 1000 mm/s. When the scanning speed was 1500 mm/s, the particle mass fraction in the coating reached a maximum of 1.984%; meanwhile, the highest hardness of the composite coating was obtained with the value of 476.38 HV.

Detection of excited triplet species from photolysis of carbonyls: Direct evidence for single oxygen formation in atmospheric environment.

Excited triplet species play an important role in the photolytic formation of 1O2 from carbonyls, but the related mechanism is still uncertain, due to lack of direct evidence. In this study, steady-state and transient photolysis of eleven carbonyls to produce 1O2 was investigated. Dicarbonyl displayed greater 1O2 production ability than monocarbonyl, while dicarbonyl containing both ketone and carboxyl groups connected by CC bond (i.e., pyruvic acid (PA)) showed the highest 1O2 steady-state concentration ([1O2]SS). For the first time, the production of 3PA* from PA with narrow energy gap was confirmed by laser flash photolysis technique and the second-order decay rate constant of 3PA* was 2.78 × 107 M-1 s-1. Quenching results verified the dominant contribution of 3PA* to 1O2 production from PA. Addition of inorganic salt or increase in solution pH showed negligible effect on 3PA*, but significantly decreased the [1O2]SS of PA by up to two orders of magnitude, due to reduction of hydrate content. Photolysis of methylglyoxal and dimethylamine mixture led to higher content of excited triplet species at pH ≈ 11 and remarkably enhanced [1O2]SS, which was 2.3 times of that from PA and dimethylamine mixture. These findings provide direct evidence for the contribution of transient species from carbonyls or their product to 1O2 formation in atmospheric environment.

Comparison of the skin microbiota of patients with acne vulgaris and healthy controls.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous units which can affect the individual's physiological and psychological health. Abnormal growth of lipophilic anaerobic bacteria such as Propionibacterium acnes is reported to be a major factor in the development of acne. However, the relationship between skin microorganisms and acne has not been fully elucidated. Our study aimed to explore the microbial differences between patients with acne and healthy controls (HCs). METHODS: The study involved 16 participants diagnosed with acne vulgaris and 5 HCs. We collected skin microbe samples from the cheeks, brow, forehead, neck, chin, or chest of the participants with sterile cotton swabs depending on the location of the acne lesions. Cutaneous microbe samples from the participants were tested by 16s sequencing. RESULTS: Patients with acne showed increased diversity of skin microbiota in their samples. OTU535601 (Lachnospiraceae), OTU4460604 (Clostridiales), OTU3217705 (Moraxellaceae), OTU1066814 (Prevotella), and OTU455671 (Lactococcus garvieae) were the top 5 most abundant species found in patients with acne but were not present in HCs. OTU423327 (Achromobacter), OTU4423360 (Stenotrophomonas), OTU993127 (Porphyromonas), OTU677680 (Prevotella), and OTU269901 (Pseudomonas) were the top 5 most abundant species in HCs but were not found in patients with acne. CONCLUSIONS: The present study has analyzed and compared the diversity and abundance of microorganisms and the characteristics of the main pathogenic bacteria in patients with acne and HCs. Our findings indicate the importance of maintaining the skin's commensal microflora balance with the development of acne vulgaris.

Revisiting financial development and renewable energy electricity role in attaining China's carbon neutrality target.

During the last few decades, China's transformation from a low-income country to an emerging economy causes carbon emission to rise extensively. Being the largest carbon emitter, China's continuous economic growth may inevitably cause more carbon emissions in the future. To achieve carbon neutrality targets, the country is striving to promote cleaner technologies. However, to finance these environmentally friendly projects, a well-developed financial system is a pre-requisite. This study examines the role of financial development along with output, financial risk index, renewable energy electricity and human capital on carbon emissions. This study uses updated time series data from 1988 to 2018 for China employing novel econometric approaches, i.e., Narayan and Pop unit root test with structural breaks, Maki cointegration and frequency domain causality test for long, short and medium run causality. The empirical outcome shows that improvement in financial development, renewable energy electricity, and human capital index cause to limit carbon emissions. In contrast, gross domestic product, financial risk index and structural break of 2001 increase carbon emissions. Moreover, structural break year of 2008 and financial development index reduces carbon emissions. The negative association between financial development and carbon emissions supports the positive school of thoughts of financial development that promotes a sustainable environment. This study recommends the promotion of quality human capital and green financial development along with increasing the shares of renewable energy in electricity for achieving China 2030 climate targets of reducing pollution.

Carbon neutrality target for G7 economies: Examining the role of environmental policy, green innovation and composite risk index.

To achieve zero carbon or achieving carbon neutrality target is of great importance to many countries around the globe especially post Paris climate agreement. This study, unlike previous studies, evaluates the role of environmental policy, green innovation, composite risk index, and renewable energy R&D in achieving carbon neutrality targets for G7 economies from 1990 to 2019. The results confirmed the validity of the EKC hypothesis for G7 economies. Further, the result shows that environmental policy, green innovation, composite risk index, and renewable energy R&D help control carbon emissions. In contrast, income reveals a positive influence on environmental degradation. Furthermore, bidirectional causality has been reported in environmental policy, composite risk index, green innovation, and the CO2 emissions, while unidirectional causality running from GDP and renewable energy R&D to CO2 emissions. Based on the empirical findings, it is suggested that environmental policies should be strengthened, promote green innovation and renewable energy research and development expenditures, and political stability and institutional quality must be stabilized to lowers sectoral risks that would help a sustainable environment.

Lateral Fracture-Dislocation of the Calcaneus: Case Reports and a Systematic Review.

OBJECTIVE: To report a case series of calcaneal fracture-dislocations, which have not been described previously in China, and to provide a systematic review to explore the clinic manifestations, methods for diagnoses, and treatments. METHODS: Between January 2018 and December 2019, 4 patients (4 men; average age, 33.0 ± 16.67 years; range, 15-50 years) were diagnosed with fracture-dislocation of the calcaneus and treated by surgery. We also reviewed published cases and studies of calcaneal fracture-dislocations through the databases of PubMed and Web of Science between January 1977 and December 2019. RESULTS: Between January 2018 and December 2019, 4 cases were identified as calcaneal fracture-dislocations in our hospital. The main clinical manifestations include hindfoot pain, swelling, and deformity. The diagnoses were confirmed via radiographic examination. Two patients underwent open reduction and internal fixation (ORIF) and two were treated with a minimally invasive approach. Diagnosis had been missed in one patient and, consequently, presented with early signs of post-traumatic arthritis, which may require extra subtalar arthrodesis in the future. Two patients were diagnosed inaccurately but achieved satisfactory outcomes through open reduction and internal fixation. The average follow-up period was 9.75 ± 5.19 months. Except for the 1 misdiagnosed patient, the other 3 patients showed functional improvement. Only 23 fracture-dislocations of calcaneus cases were reported in the literature between January 1977 and December 2019. There were 15 Sanders type II fractures (65.22%) and 7 (30.43%) Sanders type III fractures, and there was 1 grade II open calcaneal fracture. Among them, 1 was a medial dislocation and 2 were "joint-elevation" dislocations; the rest of them (20/23, 86.96%) were lateral dislocations. A total of 11 patients (47.83%) exhibited the double-density sign, and varus tilt of the talus was revealed on plain radiographs for 9 patients (39.13%). Increased Bohler's angle was evident in lateral X-ray films for 2 patients (2/23, 8.70%). A total of 21 cases (86.96%) were treated with surgical intervention and achieved satisfactory outcomes. Only 1 patient was treated with external fixation. Another 2 patients were treated conservatively and had poor clinic outcomes. CONCLUSION: Calcaneal fracture-dislocation is a rare injury that is challenging to treat. Clinical manifestations such as fibular tendon dislocation, the double-density sign on profile radiography, and abnormal talar tilt in the distal talofibular joint are important signs that may indicate this rare injury pattern. Timely surgical intervention is essential for satisfactory clinic outcomes. Orthopaedic surgeons should be aware of this uncommon injury to avoid misdiagnosis or inappropriate treatment.

Application of the LMS method of constructing fetal reference charts: comparison with the original method.

Objectives: In view of the concern expressed about the current references, new references for fetal biparietal diameter and head circumference should be constructed for contemporary local populations.Methods: We conducted a retrospective cross-sectional study in two hospitals in Guangdong, Southern China. Fetal biparietal diameter and head circumference percentiles regression were fitted using Cole's LMS method. The BPD and HC data were then transformed into Z-scores that were calculated using two series of reference equations obtained from two methods: Cole's LMS method and the original "mean and SD method." Each Z-score distribution was presented as the mean and standard deviation. Finally, the sensitivity and specificity of each reference for identifying fetuses <2.5th or >97.5th percentile (based on the observed distribution of Z-scores) were calculated. The misclassified number and Youden's index were listed.Results: A total of 17,974 biparietal diameter and 18,269 head circumference measurements were chosen to establish a reference chart. The LMS method could fit the local population better than the "mean and SD method" as it had a lower number of misclassified fetuses and a higher Youden's index.Conclusion: The Cole's LMS method was able to construct a satisfied reference range of fetal head sizes in Southern China.

Rapid discrimination of adulteration in Radix Astragali combining diffuse reflectance mid-infrared Fourier transform spectroscopy with chemometrics.

Fraud in the global food and related products supply chain is becoming increasingly common due to the huge profits associated with this type of criminal activity and yet strategies to detect fraudulent adulteration are still far from robust. Herbal medicines such as Radix Astragali suffer adulteration by the addition of less expensive materials with the objective to increase yield and consequently the profit margin. In this paper, diffuse reflectance mid-infrared Fourier transform spectroscopy (DRIFTS) was used to detect the presence of Jin Quegen in Radix Astragali. 900 fake samples of Radix Astragali produced by 6 different regions were constructed at the levels of 2%, 5%, 10%, 30% and 50% (w/w). DRIFTS data were analyzed using unsupervised classification method such as principal component analysis (PCA), and supervised classification method such as linear discrimination analysis (LDA), K-nearest neighbor (K-NN), linear discrimination analysis combining K-nearest neighbor (LDA-KNN) and partial least squares discriminant analysis (PLS-DA). The results of PCA showed that it was feasible to detect the adulteration of Radix Astragali by the combination of drift technique and chemometrics. PLS-DA obtained the best classification results in all four supervised methods with mean-centralization as the data preprocessing method, the prediction accuracy of PLS-DA model for the six groups of sample ranged from 95.00% to 98.33%. At the same time, LDA-KNN also achieved good classification results, and its correct prediction rate were also between 86.67% and 100.0%. The prediction results confirmed that the combination of DRIFTS technology and chemometrics can distinguish the amount of adulteration present in Radix Astragali. Additionally, the innovative strategy designed can be used to test the fraud of various forms of herbal medicine in other products.

Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s-1mM-1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.

D-Glucuronic Acid-Coated Ultrasmall Bi2O3 Nanoparticles for CT Imaging.

Ultrasmall Bi2O3 nanoparticles (davg = 1.5 nm) coated with biocompatible and hydrophilic D-glucuronic acid were prepared for the first time through a simple one-step polyol process and their potential as CT contrast agents were investigated by measuring their X-ray attenuation properties. Their observed X-ray attenuation power was stronger than that of a commercial iodine CT contrast agent at the same atomic concentration, as consistent with the magnitudes of atomic X-ray attenuation coefficients (i.e., Bi > I), and much stronger at the same number density. The results indicate that the nanoparticle sample is a potential CT contrast agent.

In vivo neutron capture therapy of cancer using ultrasmall gadolinium oxide nanoparticles with cancer-targeting ability.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (d avg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

Polyvinylpyrrolidone as additive for perovskite solar cells with water and isopropanol as solvents.

The recent years have witnessed a fast-paced development of perovskite solar cells (PSCs). Unfortunately, the vast majority of PSCs relies on the use of highly polar aprotic solvents during the preparation process, such as dimethylformamide (DMF), which is toxic and detrimental to both humans and the environment. Here, we describe the preparation of PSCs under ambient conditions from an aqueous solution of lead nitrate, to which polyvinylpyrrolidone (PVP) was added in order to enhance the photoelectric performance of the PSCs. By a combination of SEM, EIS, PL and UV spectroscopy and other characterization approaches, we show that the PVP additive is effective in inhibiting carrier recombination, enhancing composite resistance and reducing film defects. Ultimately, we achieved an outstanding photoelectric performance of the PVP-doped PSCs shown by a power conversion efficiency (PCE) of 15.19% and an average steady-state PCE of 14.55% under AM 1.5G simulated solar irradiation with a shadow mask of 0.1 cm2. The PCE continued to be over 80% of the initial PCE after 60 days of storage. FInally, the introduced PVP-doped PSCs present a low-cost and low-toxicity way to commercialize perovskite solar cells.

Case series of neck accessory tragus.

We report three cases of neck accessory tragus, which is the largest number of cases with dermatologists reported in China. Neck accessory tragus belongs to special accessory auricular anomaly. Case 1: A 5-year-old girl presented with a skin-colored mass above her right clavicle since birth. Physical examination revealed a pea-sized mass positioned above the right clavicle. Case 2 and case 3 were a 3-month-old female infant and a 4-month-old male infant, respectively. Both of their parents complained that the masses gradually increased in front of the neck. Histopathologically, all of the three cases showed cartilage beneath the subcutaneous tissue. All cases were diagnosed as cervical auricles.

Relaxometric, Optical and Cell Viability Properties of D-Glucuronic Acid Coated Cr2O3 Nanoparticles.

D-glucuronic acid-coated ultrasmall chromium oxide (Cr2O3) nanoparticles were synthesized by a one-pot polyol method and their relaxometric and optical properties were investigated. The as-synthesized D-glucuronic acid-coated nanoparticles were amorphous owing to ultrasmall particle diameters (davg = 2.0 nm), whereas orthorhombic Cr2O3 nanoparticles with two size groups (davg = 3.6 and 5.7 nm) were observed after thermogravimetric analysis (900 °C) as a result of particle growth. The nanoparticles exhibited size-dependent UV-visible absorption maxima at 238, 274, and 372 nm with increasing particle diameter, corresponding to band gaps of 5.13, 4.45, and 3.28 eV, respectively. D-glucuronic acid-coated ultrasmall Cr2O3 nanoparticles revealed low water proton relaxivities of r1 = 0.05 s-1mM-1 and r2 = 0.20 s-1mM-1, consistent with the antiferromagnetic property of Cr2O3. They showed good biocompatibility up to 500 µM of Cr.

Neonatal Exposure to Low-Dose (1.2%) Sevoflurane Increases Rats' Hippocampal Neurogenesis and Synaptic Plasticity in Later Life.

The increasing usage of general anesthetics on young children and infants has drawn extensive attention to the effects of these drugs on cognitive function later in life. Recent animal studies have revealed improvement in hippocampus-dependent performance after lower concentrations of sevoflurane exposure. However, the long-term effects of low-dose sevoflurane on the developing brain remain elusive. On postnatal day (P) 7, rats were treated with 1.2% sevoflurane (1.2% sevo group), 2.4% sevoflurane (2.4% sevo group), and air control (C group) for 6 h. On P35-40, rats' hippocampus-dependent learning and memory was tested using the Morris water maze. Cognition-related and synapse-related proteins in the hippocampus were measured using Western blotting on P35. On the same day, neurogenesis and synapse ultrastructure were evaluated using immunofluorescence and transmission electron microscopy (TEM). On P35, the rats neonatally exposed to 1.2% sevoflurane showed better behavioral results than control rats, but not in the 2.4% sevo group. Exposure to 1.2% sevoflurane increased the number of 5'-bromo-2-deoxyuridine (BrdU)-positive cells in the dentate gyrus and improved both synaptic number and ultrastructure in the hippocampus. The expression levels of BDNF, TrkB, postsynaptic density (PSD)-95, and synaptophysin in the hippocampus were also increased in the 1.2% sevo group. In contrast, no significant changes in neurogenesis or synaptic plasticity were observed between the C group and the 2.4% sevo group on P35. These results showed that exposure of the developing brain to a low concentration of sevoflurane for 6 h could promote spatial learning and memory function, along with increased hippocampal neurogenesis and synaptic plasticity, in later life.