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QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Guanosine monophosphate (GMP) is a nucleotide that can self-assemble in aqueous solution under certain conditions. An understanding of the process at the molecular level is an essential step to comprehend the involvement of DNA substructures in transcription and replication, as well as their relationship to genetic diseases such as cancer. We present the temperature-dependent terahertz (1.5-12 THz, 50-400 cm -1 ) absorptivity spectra of aqueous Na 2 GMP solution in comparison with the aqueous solutions of other RNA nucleotides. Distinct absorption features were observed in the spectrum of GMP, which we attribute to the intramolecular modes of the self-assemblies (i.e., G-complexes) that, at 1 M, start to form at 313 K and below. Changes in broad-band features of the terahertz spectrum were also observed, which we associate with the release of hydration water in the temperature-dependent formation of guanine quadruplexes. Using a state-of-the-art THz calorimetry approach correlating spectroscopic to thermodynamic changes, we propose a molecular mechanism of hydrophilic hydration driving GMP self-assembly as a function of temperature. The free energy contribution of hydrophilic hydration is shown as a decisive factor in guanine-quadruplex formation. Our findings spotlight the role of hydration in the formation of macromolecular structures and suggest the potential of hydration tuning for regulating DNA transcription and replication., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Medical image classification is a novel technology that presents a new challenge. It is essential that pathological images are automatically and correctly classified to enable doctors to provide precise treatment. Convolutional neural networks have demonstrated their effectiveness in classifying images in deep learning, which may have dozens or hundreds of layers, to illustrate the relationship between them in terms of their different neural network features. Convolutional layers consisting of small kernels take weights as input and guide them through an activation function as output. The main advantage of using convolutional neural networks (CNNs) instead of traditional neural networks is that they reduce the model parameters for greater accuracy. However, many studies have simply been focused on finding the best CNN model and classification results from a single medical image classification. Therefore, we applied a common deep learning network model in an attempt to identify the best model framework by training and validating different model parameters to classify medical images. After conducting experiments on six publicly available databases of pathological images, including colorectal cancer tissue, chest X-rays, common skin lesions, diabetic retinopathy, pediatric chest X-ray, and breast ultrasound image datasets, we were able to confirm that the recognition accuracy of the Inception V3 method was significantly better than that of other existing deep learning models.

Background: There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication (APP)., Aim: To optimize a predictive scoring system for mortality in children with APP., Methods: A total of 113 children with APP from January 1, 2010 to January 1, 2020 were enrolled in this study. These patients were divided into survivors and non-survivors. We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors. The survival rates of patients with different values of the pediatric critical illness score (PCIS) were assessed using kaplan-meier survival analysis. The best scoring system was established by using the area under the receiver operating characteristic curve analysis., Results: The overall mortality rate was 23.4%. All non-survivors died within 20 days; 48.1% (13/27) died within 3 days, and 70.3% (19/27) died within 7 days. Compared to survivors, the non-survivors were older, had higher white blood cell count, alanine aminotransferase (ALT), aspartate aminotransferase, serum creatinine, blood urea nitrogen, glucose, and pediatric early warning score, and had lower platelet count, albumin, Serum sodium (Na + ) and PCIS. ALT and PCIS were the independent prognostic risk factors for children with APP. The survival rate of children classified as extremely critical patients (100%) was lower than that of children classified as critical (60%) or noncritical (6.7%) patients. The specificity of ALT was high (96.51%), but the sensitivity was low (59.26%). The sensitivity and specificity of ALT combined with PCIS were high, 92.59% and 87.21%, respectively. The difference in mortality was significantly higher for ALT combined with PCIS (area under the receiver operating characteristic: 0.937; 95%CI: 0.875-0.974; P < 0.05)., Conclusion: In our study, ALT and PCIS were independent prognostic risk factors for children with APP. ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy., Methods: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors., Results: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA., Conclusion: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

In this article, we survey various non-contact, non-destructive testing methods by way of terahertz (THz) spectroscopy and imaging designed for use in various industrial sectors. A brief overview of the working principles of THz spectroscopy and imaging is provided, followed by a survey of selected applications from three industries-the building and construction industry, the energy and power industry, and the manufacturing industry. Material characterization, thickness measurement, and defect/corrosion assessment are demonstrated through the examples presented. The article concludes with a discussion of novel spectroscopy and imaging devices and techniques that are expected to accelerate industry adoption of THz systems.

Background: The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP 3 R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection., Methods: The expression of IP 3 R, Grp75, VDAC1, and MCU and mitochondrial Ca 2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP 3 R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP 3 R, Grp75, and MCU agonists and antagonists on mitochondrial Ca 2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy., Results: Increased expression of IP 3 R, Grp75, VDAC1 and MCU, enhanced interaction among the IP 3 R-Grp75-VDAC1 complex, mitochondrial Ca 2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca 2+ overload and podocyte apoptosis, whereas specific antagonists against IP 3 R, Grp75, or MCU prevented mitochondrial Ca 2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats., Conclusions: This study identified a novel pathway in which the IP 3 R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca 2+ overload. Antagonists that inhibit Ca 2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs.

We study unextendible maximally entangled bases (UMEBs) in [Formula: see text] (d < d'). An operational method to construct UMEBs containing d(d' - 1) maximally entangled vectors is established, and two UMEBs in [Formula: see text] and [Formula: see text] are given as examples. Furthermore, a systematic way of constructing UMEBs containing d(d' - r) maximally entangled vectors in [Formula: see text] is presented for r = 1, 2, …, d - 1. Correspondingly, two UMEBs in [Formula: see text] are obtained.

Aims: Although cognitive dysfunction is a common neurological complication in elderly patients with diabetes, the mechanisms underlying this relationship remain unclear, and effective preventive interventions have yet to be developed. Thus, this study investigated the preventive effects and mechanisms of action associated with granulocyte colony-stimulating factor (G-CSF) on cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease., Methods: This study included 40 male db/db diabetic and wild-type (WT) mice that were categorized into the following four groups at the age of 3 weeks: db/db group (DG), db/db+G-CSF group (DGG), WT group (WG), and WT+G-CSF group (WGG). The mice were fed normal diets for 4 months and then given G-CSF (75 μg/kg) via intraperitoneal injections for 1 month. At 7.5 months of age, the cognitive abilities of the mice were assessed with the Y-maze test and the Social Choice Test; body weight, blood pressure (BP), and blood glucose measurements were obtained throughout the study. Brain imaging and blood oxygen level-dependent (BOLD) contrast imaging analyses were performed with a small animal magnetic resonance imaging (MRI) system, autophagosome levels were detected with a transmission electron microscope (TEM), hippocampal neurons were assessed with hematoxylin and eosin (HE) staining, and protein expressions and distributions were evaluated using immunohistochemistry and Western blot analyses., Results: (i) The body weight and blood glucose levels of the DG and DGG mice were significantly higher than those of the WG and WGG mice; (ii) social choice and spatial memory capabilities were significantly reduced in DG mice but were recovered by G-CSF in DGG mice; (iii) the MRI scans revealed multiple lacunar lesions and apparent hippocampal atrophy in the brains of DG mice, but G-CSF reduced the number of lacunar lesions and ameliorated hippocampal atrophy; (iv) the MRI-BOLD scans showed a downward trend in whole-brain activity and reductions in the connectivities of the hippocampus and amygdala with subcortical structures in DG mice, but G-CSF clearly improved the altered brain activity as well as the connectivity of the hippocampus in DGG mice; (v) HE staining revealed fewer neurons in the hippocampus in DG mice; (vi) TEM analyses revealed significantly fewer autophagosomes in the hippocampi of DG mice, but G-CSF did not increase these numbers; (vii) there were significant reductions in mechanistic target of rapamycin (mTOR) and LC3-phosphatidylethanolamine conjugate (LC3)-II/I levels in the hippocampi of DG mice, whereas p62 was upregulated, and G-CSF significantly enhanced the levels of Beclin1, mTOR, and LC-II/I in DGG mice; and (viii) G-CSF significantly reversed increases in nuclear factor κB (NF-κB) protein levels in DG but not in WG mice., Conclusions: In this study, aged diabetic mice were prone to cognitive dysfunction and cerebral small vessel disease. However, administration of G-CSF significantly improved cognitive function in elderly db/db diabetic mice, and this change was likely related to the regulation of autophagy and NF-κB signaling pathways., (© 2017 John Wiley & Sons Ltd.)

Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian , Bo , and Rou method in Yinmen (BL37), Yanglingquan (GB34), and Weizhong (BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood. This study established rat models of sciatic nerve injury using the crushing method. Rats received Chinese tuina in accordance with the principle of "Three Methods and Three Points," once daily for 20 days. Tuina intervention reduced paw withdrawal latency and improved wet weight of the gastrocnemius muscle, as well as promoting morphological recovery of sciatic nerve fibers, Schwann cells, and axons. The protein expression levels of phospho-p38 mitogen-activated protein kinase, tumor necrosis factor-α, and interleukin-1β also decreased. These findings indicate that "Three Methods and Three Points" promoted morphological recovery and improved behavior of rats with peripheral nerve injury., Competing Interests: Conflicts of Interest: None declared.

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP., Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin., Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3., Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.

Aims: The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway., Methods: After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects., Results: After being cultured in 200 μM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor., Conclusion: GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway., (© 2013 Blackwell Publishing Ltd.)

Background: Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma., Methods: Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group: control group, asthma group, ovalbumin (OVA) + OVA group, lipopolysaccharide (LPS) group and LPS + OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge 14 days later. The OVA + OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS + OVA group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin (IL)-4, interferon-gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Th1 and Th2 cells., Results: The pathological changes in the LPS + OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS + OVA groups were higher than in the control group and the OVA + OVA group (P < 0.05). The level of IgE was higher in the asthma, LPS and LPS + OVA groups than in the control group and the OVA + OVA group (P < 0.05). By flow cytometry analysis, the Th1/Th2 ratio was lower in the LPS + OVA and asthma groups than in other groups (P < 0.05)., Conclusions: The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

Background: Growing preclinical evidence shows that zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo., Methods: Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection (s.c.) and H22-intraperitoneal injection (i.p.) mice model., Results: ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo., Conclusion: ZOL inhibits growth of HCC cells in vitro and in vivo.

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter, is metabolized by the successive action of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Inhibition of both enzymes in brain tissues increases the GABA level and may have therapeutic applications in neurological diseases. Erigeron breviscapus ethanol extract was evaluated for their effect on both enzymes. This extract, its ethyl acetate fraction and aqueous fraction, significantly inhibited them at >100 microg/ml. Flavonoid components of E. breviscapus potently and noncompetitively inhibited both enzymes, and the different structure-activity relations were observed with respect to inhibition of both enzymes. Baicalein was the most potent inhibitor for GABA-T with an IC50 value of 12.8+/-1.2 microM, and scutellarein exhibited the best inhibitory effect on SSADH with an IC50 value of 7.20+/-0.9 microM. The present results may imply new pharmacological actions of E. breviscapus and contribute partially to the beneficial effect of the herb and flavonoids on the central nervous system.

This study was to build a web-based short messaging service (SMS) system in operating room. We approached the efficiency of SMS for patient's families during the time series (pre-, intra-, and post-operation). In this study, 322 participants received 685 text messages. The findings show the usability of SMS that applied to the clinical care, especially for reducing family anxiety, improved their satisfaction. Therefore, it is suggested to exploit the effectiveness of personal medical care.