Fluorination modification enhanced the water resistance of Universitetet i Oslo-67 for multiple volatile organic compounds adsorption under high humidity conditions: Mechanism study.

The construction of metal-organic frameworks (MOFs) with highly efficient capture for volatile organic compounds (VOCs) adsorption under humid conditions is a significant yet formidable task. Herein, series of fluorinated UiO-67 modified with trifluoroacetic acid (TFA) and 4-fluorobenzoic acid were successfully synthesized for VOCs adsorption under high humidity conditions. Experiments results showed that UiO-67 modified with 4-fluorobenzoic acid (67-F) presented excellent adsorption capacity of 345 mg/g for toluene adsorption and exhibited great water resistance (10.0 vol% H2O, 374 mg/g toluene adsorption capacity). Characterization results indicated that the introduction of 4-fluorobenzoic acid induced the competitive coordination between 4-fluorobenzoic acid and 4,4-biphenyl dicarboxylic acid (BPDC) with Zr4+, causing the formation of abundant defects to provide extra adsorption sites. Meanwhile, the benzene ring in 4-fluorobenzoic acid enhanced the π-π conjugation, causing the further promotion of VOCs adsorption capacity. More importantly, the water resistance mechanism was investigated and elucidated that the introduction of F decreased the surface energy of 67-F and its affinity with water. Meanwhile, the metal complex induced by the fluorinated modification produced an electron-dense pore environment, which greatly improved its chemical and water stability. This work provided a strategy for preparing an adsorbent with high water resistance for real-world VOCs adsorption at high humidity conditions.

Chitosan nanoparticles loaded with Eucommia ulmoides seed essential oil: Preparation, characterization, antioxidant and antibacterial properties.

Eucommia ulmoides seed essential oil (EUSO) is a natural plant oil rich in various nutrients, which has been widely used due to its unique medicinal effects. However, it is prone to oxidation and rancidity under many adverse environmental influences. Nanoencapsulation technology can protect and slow down the loss of its biological activity. In this study, chitosan nanoparticles (CSNPs) loaded with EUSO were prepared by emulsification and ionic gel technology. EUSO-CSNPs were characterized by Fourier transform infrared (FTIR) spectroscopy, Thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The results confirmed the success of EUSO encapsulation and the encapsulation rate ranged from 36.95 % to 67.80 %. Nanoparticle size analyzer, Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) showed that CSNPs were spherical particles with a range of 200.6-276.0 nm. The results of in vitro release study indicated that the release of EUSO was phased, and EUSO-CSNPS had certain sustained-release properties. Furthermore, EUSO-CSNPs had higher antioxidant and antibacterial abilities than pure EUSO and chitosan, which was verified through free radical scavenging experiments and bacteria biofilm experiments, respectively. This technology can enhance the medicinal value of EUSO in biomedical and other fields, and will provide support for in vivo research of EUSO-CSNPs in the future.

Effect of benzoic acid and dopamine hydrochloride as a modulator in the water resistance of Universitetet i Oslo-67: Adsorption performance and mechanism.

The severe hazards on ecological environment and human body caused by volatile organic compounds (VOCs) have attracted worldwide substantial attention. In this research, a series of novel modified Universitetet i Oslo-67 (UiO-67) with water resistance were prepared and characterized, which had modified by benzoic acid and dopamine hydrochloride (67-ben-DH). On this basis, the adsorption performance, adsorption kinetics, defect engineering and water resistance of adsorbent were investigated. The results indicated that the excellent pore structure and specific surface area of 67-ben-DH-6 (molar ratio of Zr4+ to DH was 1:6) were retained while the adsorption performance and water resistance of the adsorbent were improved. Due to more defects, excellent adsorption diffusion and strong π-π interactions of 67-ben-DH-6, it performed the maximum adsorption capacity of toluene (793 mg g-1). Furthermore, the outstanding water resistance was attributed to the fact that N element of DH reduced the affinity of the adsorbent with water. Finally, the density functional theory (DFT) calculations showed that the adsorbent 67-ben-DH-6 had the maximum adsorption energy for toluene (-99.4 kJ mol-1) and the minimum adsorption energy for water (-17.8 kJ mol-1). Thus, the potential mechanism of 67-ben-DH for efficient toluene adsorption and water resistance was verified from a microscopic perspective.

Graphitic carbon nitride alleviates cadmium toxicity to microbial communities in soybean rhizosphere.

Cadmium (Cd) contamination has led to various harmful impacts on soil microbial ecosystem, agricultural crops, and thus human health. Nanomaterials are promising candidates for reducing the accumulation of heavy metals in plants. In this study, graphitic carbon nitride (g-C3N4), a two-dimensional polymeric nanomaterial, was applied for ameliorating Cd phytotoxicity to soybean (Glycine max (L.) Merr.). Its impacts on rhizosphere variables, microorganisms, and metabolism were examined. It was found that g-C3N4 increased carbon/nitrogen/phosphorus (C/N/P) content, especially when N contents were averagely 4.2 times higher in the g-C3N4-treated groups. g-C3N4 significantly induced alterations in microbial community structures (P < 0.05). The abundance of the probiotics class Nitrososphaeria was enriched (on average 70% higher in the g-C3N4-treated groups) as was Actinobacteria (226% higher in the g-C3N4 group than in the CK group). At the genus level, g-C3N4 recruited more Bradyrhizobium (122% higher) in the Cd + g-C3N4 group than in the Cd group and more Sphingomonas (on average 24% higher) in the g-C3N4-treated groups. The changes of microbial clusters demonstrated the potential of g-C3N4 to shape microbial functions, promote plant growth, and enhance Cd resistance, despite observing less pronounced modifications in microbial communities in Cd-contaminated soil compared to Cd-free soil. Moreover, abundance of functional genes related to C/N/P transformation was more significantly promoted by g-C3N4 in Cd-contaminated soil (increased by 146%) than in Cd-free one (increased by 32.8%). Therefore, g-C3N4 facilitated enhanced microbial survival and adaptation through the amplification of functional genes. These results validated the alleviation of g-C3N4 on the microbial communities in the soybean rhizosphere and shed a new light on the application of environmental-friendly nanomaterials for secure production of the crop under soil Cd exposure.

Inflammation-responsive molecular-gated contact lens for the treatment of corneal neovascularization.

Corneal neovascularization (CNV) badly damages the corneal transparency, resulting in visual disturbance and blindness. The frequent administration of glucocorticoid eye drops in clinical increases the possibility of side effects and reduces patient compliance. Considering CNV is often accompanied by an increase in ROS production, a ROS-responsive monomer 2-(methylthio)ethyl methacrylate was introduced into the matrix as a "gating switch". The prepared dexamethasone contact lenses (MCLs@Dex) showed a significant H2O2-responsive release for 168 h. To avoid corneal hypoxia and neovascularization caused by long-term wearing, high­oxygen-permeability fluorosiloxane materials were incorporated. The oxygen permeability of MCLs@Dex was 4 times that of commercially available hydrogel contact lenses and had ultra-low protein adsorption, which meets the requirements of long-term wearing. In vivo pharmacokinetic studies showed that MCLs@Dex increased the mean residence time by 19.7 times and bioavailability by 2.29 times compared with eye drops, validating the ROS response and sustained release properties. More importantly, MCLs@Dex had satisfactory effects on reducing inflammation and decreasing the related cytokines and oxidative stress levels, and demonstrated significant inhibition of neovascularization, with a suppression rate of 76.53% on the 14th day. This responsive drug delivery system provides a promising new method for the safe and effective treatment of ocular surface diseases.

Synthesis of nano-Fe3O4/ZnO composites with enhanced antibacterial properties and plant growth promotion via one-pot reaction.

Bordeaux mixture is commonly used in agricultural production due to its certain antibacterial activity. However, it has been observed to promote plant growth at a slow pace. Therefore, it is crucial to explore an effective antibacterial agent that can enhance the antibacterial activity and promote plant growth in commercially available Bordeaux mixture, which can significantly contribute to the development of the agricultural economy. The investigation into inorganic agents with both bacteriostatic and plant-promoting properties has a broad application potential in agriculture. Fe3O4/ZnO (FZ) composites were synthesized from FeCl3, ZnCl2, and NaAc in a "one-pot approach" and analyzed using transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and a vibrating sample magnetometer (VSM). To investigate the antibacterial activity and mechanism of FZ nanocomposites, Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were used as model bacteria, and human mammary epithelial cells and model plant mung bean were used as targets to study the effects of FZ on human and plant growth. The results revealed that at 300 µg/mL for 80 min, the antibacterial efficacy of FZ composites was 99.8% against E. coli, which was 20% greater than that of Bordeaux liquid (FC), and 99.9% against S. aureus, which was 28.6% higher than that of FC. The inhibitory mechanism demonstrated that the substance could efficiently damage the bacterial cell wall of a concentration of 300 µg/mL. The IC50 of the material to human mammary epithelial cells was 49.518 µg/mL, and it also increased mung bean germination, root growth, and chlorophyll content, indicating that the application performance was 1.5 times better than that of FC. Its exceptional performance can be used to treat agricultural diseases.

Recent advances of metal-organic framework-based and derivative materials in the heterogeneous catalytic removal of volatile organic compounds.

Since the environmental hazards of volatile organic compounds (VOCs) are well known, heterogeneous catalysis has become one of the most popular methods to treat VOCs due to its environmental friendliness and simplicity of operation. Although a large number of reports have reviewed the application of catalytic oxidation for the degradation of VOCs, relatively few reports are based on this direction of metal organic frameworks (MOFs) and MOF derivatives. Herein, this paper reviews the recent applications of heterogeneous catalytic technologies in the degradation of VOCs, including photocatalysis, thermal catalysis and other catalytic approaches. The applications of MOFs and their derivatives in VOCs degradation, such as the progress of MOF-derived metal oxides in the treatment of toluene, were highlighted. The mechanisms of VOCs degradation by different catalytic approaches were systematically presented. Finally, we presented the views and directions of VOCs treatment technology development. We hope that this reaction type-oriented review will provide important insights into MOFs and MOF-derived materials for VOCs pollution control.

Clinical observation of posterior scleral reinforcement in the treatment of progressive high myopia in Chinese children: a retrospective study.

OBJECTIVE: To observe the efficacy and safety of posterior sclera reinforcement over time. METHODS: This retrospective single-arm cohort study included children with high myopia who underwent the modified Snyder-Thompson type posterior sclera reinforcement surgery from 03/2015 to 08/2018 at Fuzhou Children's Hospital of Fujian Medical University. Axial length (AL), corneal radius of curvature (CRC), AL/CRC, refractive error, and best-corrected visual acuity (BCVA) were observed from 1 year before the operation to 2 years after. RESULTS: Nineteen children (33 eyes) with high myopia were included. The patients were 4.9 ± 2.7 (range, 2-10) years of age (three patients were 10 years old, all others were ≤ 7 years old). AL increased from 1 year before surgery to 2 years after surgery (from 25.31 ± 1.59 to 26.76 ± 1.52, P < 0.001). The refractive error was smaller 1 year before surgery than at the other timepoints (all P < 0.05). BCVA improved over time (P < 0.001). Changes over time were also observed in horizontal CRC (hCRC), AL/hCRC, AL/vertical CRC (vCRC), and AL/CRC (all P < 0.001), but not in vCRC (P = 0.304). The increase of AL at 2 years after surgery was smaller than at 1 year before surgery and 1 year after surgery (both P < 0.001). The increase of AL/CRC at 2 years after surgery was smaller than at 1 year before surgery (0.04 ± 0.04 vs. 0.07 ± 0.04; P = 0.008). CONCLUSION: In the short term, posterior scleral reinforcement surgery can delay the increase of AL of progressive high myopia.

Simultaneous qualitative and quantitative analysis of 10 bioactive flavonoids in Aurantii Fructus Immaturus (Zhishi) by ultrahigh-performance liquid chromatography and high-resolution tandem mass spectrometry combined with chemometric methods.

INTRODUCTION: Aurantii Fructus Immaturus (Zhishi in Chinese) is the dried young fruit of Citrus aurantium L. (CA) and its cultivated varieties or Citrus sinensis Osbeck (CS). The content of flavonoids in different varieties of Zhishi may be significantly different. However, there is confusion about the botanical origin of Zhishi, and there is no reliable and systematic method to control Zhishi quality. OBJECTIVES: We aimed to establish an ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution tandem mass spectrometry (UPLC-DAD-HRMS/MS) for the quantitative analysis of 10 flavonoids in Zhishi that could be used for quality control and botanical origin identification. METHODOLOGY: A UPLC-DAD-HRMS/MS method was established for simultaneous identification and quantification of 10 flavonoids. Separation was performed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) with 0.1% formic acid and acetonitrile as mobile phase under gradient elution. MS was performed in positive and negative ionisation modes. The flavonoids in 41 batches were isolated and quantified. Zhishi of different botanical origins were identified by chemometrics. RESULTS: The results showed that the established method for the determination of 10 components was reliable and accurate. Chemometrics could be used to distinguish Zhishi of different botanical origins. There were significant differences in the contents of 10 flavonoids in samples of different botanical origins. CONCLUSIONS: The quantitative analysis method in this study can be used to accurately determine the content of 10 flavonoids and provide a chemical basis for quality control and botanical origin identification of Zhishi.

Suppression of uterine and placental ferroptosis by N-acetylcysteine in a rat model of polycystic ovary syndrome.

The mechanisms that link hyperandrogenism and insulin (INS) resistance (HAIR) to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investigated the efficacy and molecular mechanism of action of the antioxidant N-acetylcysteine (NAC) in reversing gravid uterine and placental ferroptosis in pregnant rats exposed to 5α-dihydrotestosterone (DHT) and INS. Molecular and histological analyses showed that NAC attenuated DHT and INS-induced uterine ferroptosis, including dose-dependent increases in anti-ferroptosis gene content. Changes in other molecular factors after NAC treatment were also observed in the placenta exposed to DHT and INS, such as increased glutathione peroxidase 4 protein level. Furthermore, increased apoptosis-inducing factor mitochondria-associated 2 mRNA expression was seen in the placenta but not in the uterus. Additionally, NAC was not sufficient to rescue DHT + INS-induced mitochondria-morphological abnormalities in the uterus, whereas the same treatment partially reversed such abnormalities in the placenta. Finally, we demonstrated that NAC selectively normalized uterine leukemia inhibitory factor, osteopontin/secreted phosphoprotein 1, progesterone receptor, homeobox A11 mRNA expression and placental estrogen-related receptor beta and trophoblast-specific protein alpha mRNA expression. Collectively, our data provide insight into how NAC exerts beneficial effects on differentially attenuating gravid uterine and placental ferroptosis in a PCOS-like rat model with fetal loss. These results indicate that exogenous administration of NAC represents a potential therapeutic strategy in the treatment of HAIR-induced uterine and placental dysfunction.

Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia.

PURPOSE: The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. METHODS: ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. RESULT: After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. CONCLUSION: The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.

Increased uterine androgen receptor protein abundance results in implantation and mitochondrial defects in pregnant rats with hyperandrogenism and insulin resistance.

In this study, we show that during normal rat pregnancy, there is a gestational stage-dependent decrease in androgen receptor (AR) abundance in the gravid uterus and that this is correlated with the differential expression of endometrial receptivity and decidualization genes during early and mid-gestation. In contrast, exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) or DHT alone significantly increased AR protein levels in the uterus in association with the aberrant expression of endometrial receptivity and decidualization genes, as well as disrupted implantation. Next, we assessed the functional relevance of the androgen-AR axis in the uterus for reproductive outcomes by treating normal pregnant rats and pregnant rats exposed to DHT and INS with the anti-androgen flutamide. We found that AR blockage using flutamide largely attenuated the DHT and INS-induced maternal endocrine, metabolic, and fertility impairments in pregnant rats in association with suppressed induction of uterine AR protein abundance and androgen-regulated response protein and normalized expression of several endometrial receptivity and decidualization genes. Further, blockade of AR normalized the expression of the mitochondrial biogenesis marker Nrf1 and the mitochondrial functional proteins Complexes I and II, VDAC, and PHB1. However, flutamide treatment did not rescue the compromised mitochondrial structure resulting from co-exposure to DHT and INS. These results demonstrate that functional AR protein is an important factor for gravid uterine function. Impairments in the uterine androgen-AR axis are accompanied by decreased endometrial receptivity, decidualization, and mitochondrial dysfunction, which might contribute to abnormal implantation in pregnant PCOS patients with compromised pregnancy outcomes and subfertility. KEY MESSAGES: The proper regulation of uterine androgen receptor (AR) contributes to a normal pregnancy process, whereas the aberrant regulation of uterine AR might be linked to polycystic ovary syndrome (PCOS)-induced pregnancy-related complications. In the current study, we found that during normal rat pregnancy there is a stage-dependent decrease in AR abundance in the gravid uterus and that this is correlated with the differential expression of the endometrial receptivity and decidualization genes Spp1, Prl, Igfbp1, and Hbegf. Pregnant rats exposed to 5α-dihydrotestosterone (DHT) and insulin (INS) or to DHT alone show elevated uterine AR protein abundance and implantation failure related to the aberrant expression of genes involved in endometrial receptivity and decidualization in early to mid-gestation. Treatment with the anti-androgen flutamide, starting from pre-implantation, effectively prevents DHT + INS-induced defects in endometrial receptivity and decidualization gene expression, restores uterine mitochondrial homeostasis, and increases the pregnancy rate and the numbers of viable fetuses. This study adds to our understanding of the mechanisms underlying poor pregnancy outcomes in PCOS patients and the possible therapeutic use of anti-androgens, including flutamide, after spontaneous conception.

The Treatment with Complementary and Alternative Traditional Chinese Medicine for Menstrual Disorders with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a frequent gynecological female endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and insulin resistance (IR). Menstrual disorders are one of the main clinical manifestations of PCOS. Other symptoms include hirsutism and/acne. At present, the treatment of PCOS with irregular menstruation is mainly based on oral contraceptives, but there are some side effects and adverse reactions. In recent years, more and more attention has been paid to the complementary and alternative medicine (CAM), which has been widely used in clinical practice. Modern Western medicine is called "conventional medicine" or "orthodox medicine," and the complementary and alternative medicine is called "unconventional medicine" or "unorthodox medicine." CAM includes traditional medicine and folk therapy around the world. Around 65-80% of world health management business is classified into traditional medicine by the World Health Organization, which is used as alternative medicine in Western countries. In our country, Chinese medicine, acupuncture, and other therapies are commonly used due to their significant efficacy and higher safety. Therefore, this review aims to summarize and evaluate the mechanisms and the effect of current complementary replacement therapy in the treatment of menstrual disorders caused by PCOS, so as to provide guidance for the following basic and clinical research.

Local drug delivery systems as therapeutic strategies against periodontitis: A systematic review.

Periodontitis is a chronic inflammation of the soft tissue surrounding and supporting the teeth, which causes periodontal structural damage, alveolar bone resorption, and even tooth loss. Its prevalence is very high, with nearly 60% of the global population affected. Hence, periodontitis is an important public health concern, and the development of effective healing treatments for oral diseases is a major target of the health sciences. Currently, the application of local drug delivery systems (LDDS) as an adjunctive therapy to scaling and root planning (SRP) in periodontitis is a promising strategy, giving higher efficacy and fewer side effects by controlling drug release. The cornerstone of successful periodontitis therapy is to select an appropriate bioactive agent and route of administration. In this context, this review highlights applications of LDDS with different properties in the treatment of periodontitis with or without systemic diseases, in order to reveal existing challenges and future research directions.

Fabricating nanoparticles co-loaded with survivin siRNA and Pt(IV) prodrug for the treatment of platinum-resistant lung cancer.

Resistance to platinum agents is a crucial challenge in the treatment of cancer using platinum drugs. To overcome the resistance of cells, the survivin protein is supposed to be decreased, since it has previously been found to be overexpressed in drug-resistant cancer cells in anti-apoptosis pathways, while the intracellular effective platinum accumulation should be increased. In the present work, a protamine/hyaluronic acid nanocarrier was used to load survivin siRNA with Pt(IV) loaded outside the coated polyglutamic acid (PGA) by chemical conjugation. The siRNA was released from the co-loaded nanoparticle prior to Pt(IV), in this way, the expression of survivin protein was effectively reduced, which, in turn, could avoid the anti-apoptosis of drug resistant cells. Here, Pt(IV) displayed a sustained release effect and gradually reduced to the toxic Pt(II) species, which reduced drug efflux and enhance apoptosis of the cancer cells. In vitro studies demonstrated that co-loaded nanoparticles resulted in similar cell killing performance in A549/DDP cells (cisplatin resistant) compared with non-siRNA loaded nanoparticles in A549 cells (cisplatin sensitive). NP-siRNA/Pt(IV) exhibited a greatly improved therapeutic effect (TIR, 82.46%) in a nude mice A549/DDP tumor model, with no serious adverse effects observed. Thus, co-loading of Pt(IV) and survivin siRNA nanoparticles could reverse cisplatin resistance and therefore has promising prospects for efficient cancer chemotherapy.

G604S-HERG mutation in LQT2 leads to autophagy via the UPR-related pathway.

Congenital long QT syndrome (LQTS) is a heart channel disease associated with fatal ventricular arrhythmias or cardiac arrest. Human ether-a-go-go-related gene (HERG) mutation is one of the main causes in type 2 LQTS since it may lead to abundant immature HERG channel protein accumulate in the endoplasmic reticulum (ER). In our study, we have successfully constructed the G604S-HERG mutation in HEK293 cells and demonstrated that the immature HERG protein on ER via Western blot and immunofluorescence. Herein we found that unfolded protein reaction (UPR) process has been activated in order to counter this endoplasmic reticulum stress (ERS) since the main sensors got upregulated. Meanwhile, autophagy was also observed in this process and verified by Western blot and transmission electron microscopy. To explore the relationship underlying autophagy and UPR in the condition of ERS, we found that PERK-EIF2a-CHOP axis was activated. Our findings provides insight for G604S-HERG mutation in type 2 LQTS.

Human ether­à­go­go­related gene mutation L539fs/47­hERG leads to cell apoptosis through the endoplasmic reticulum stress pathway.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy that often results in fatal arrhythmias. LQTS mutations not only lead to abnormal myocardial electrical activities but are associated with heart contraction abnormalities, cardiomyopathy and congenital heart defects. In vivo and in vitro studies have found that LQTS mutations are associated with cardiomyocyte apoptosis, cardiac developmental disorders and even embryonic mortality. Cardiac delayed rectifier potassium channel dysfunction due to the human ether­à­go­go­related gene (hERG) mutation causes congenital LQTS type 2. The majority of LQTS 2 mutations are characterized by mutant protein accumulation in the endoplasmic reticulum (ER). Unfolded or misfolded protein retention in the ER causes an unfolded protein reaction, which is characteristic of ER stress (ERS). Therefore, the present study hypothesized that LQTS mutations can cause cardiac structural abnormalities via ERS­mediated cardiomyocyte apoptosis. To test this hypothesis, 293 cells were transiently transfected with an L539fs/47­hERG plasmid to generate an LQTS 2 model. L539fs/47­hERG is an LQTS 2 mutation, which consists of a 19­bp deletion at 1619­1637 and a point mutation at 1692. Using confocal laser scanning microscopy analysis, it was verified that the L539fs/47­hERG protein was retained in the ER. Hoechst 33342 apoptosis staining indicated that apoptosis was increased in the L539fs/47­hERG­transfected cells, and this be reversed by treatment with 4­phenyl butyric acid. Western blot analysis revealed increased expression levels of the ERS chaperone glucose regulated protein 78 and pro­apoptotic ERS­induced factors, including protein kinase R­like endoplasmic reticulum kinase, eukaryotic translation­initiation factor­2α and C/EBP homologous protein, in the L539fs/47­hERG­transfected cells. The B­cell lymphoma (Bcl­2)­associated X protein/Bcl­2 ratio and caspase­12 were also increased in the mutated cells. These results demonstrate that L539fs/47­hERG induces cell apoptosis and the potential molecular mechanism involves the activation of ERS and ERS­mediated cell apoptosis.

Exposure to a chronic high-fat diet promotes atrial structure and gap junction remodeling in rats.

Obesity has been demonstrated to be linked to atrial fibrillation (AF) with atrial enlargement and tissue fibrosis. Long-term high calorie intake is the main reason for the prevalence of obesity. To investigate the possible causes of AF, such as chronic high-fat diet (HFD), and to identify the underlying mechanisms, the present study analyzed a variety of structural and gap junctional electrophysiological alterations in the atria of female rats fed an HFD. After consistent HFD feeding of female rats for 12 weeks, hematoxylin and eosin (H&E) and Masson's staining, RT-qPCR, western blotting, immunofluorescence and TUNEL staining were performed. In our study, approximately 3/5 of the HFD-fed rats (HFD-OB, n=13) displayed a significant increase in body weight, while the other 2/5 did not (HFD-NOB, n=8). In addition, the atrial weight of the HFD-OB and HFD-NOB rats was markedly heavier, as compared to the rats fed a normal diet (CT, n=20). According to the plasma lipid levels, both HFD-OB and HFD-NOB rats exhibited dyslipidemia. Furthermore, H&E staining revealed broadened interstitial space and myocyte disarray in atria of the HFD-fed rats (i.e., HFD-OB and HFD-NOB rats). Expression levels of atrial fibrosis relevant factors, transforming growth factor-ß1 and matrix metalloproteinase-2, were significantly upregulated in the HFD-fed rat atria. In addition, we found a gap junction remodeling with distinct alterations in expression and distribution of connexin 40 (Cx40) and Cx43 in the HFD-fed rat atria. Moreover, a modest increase in apoptotic cell death in both the HFD-OB and HFD-NOB rat atria was detected. Taken together, our findings demonstrated that the impact of chronic HFD on atria displayed in the diet-induced obese rats was observed in HFD-fed rats in the absence of obesity as well.

Raman Spectroscopy Analysis of the Biochemical Characteristics of Experimental Keratomycosis.

PURPOSE: To investigate the biochemical characteristics in experimental keratomycosis by Raman spectroscopy analysis in vitro and in vivo. METHODS: Raman spectroscopy was used to analyze the biochemical characteristics of cultured mouse keratocytes stimulated by Fusarium solani suspension in vitro, and the infected cornea of Fusarium solani keratitis of mice. RESULTS: The peak intensities at 1005, 1186, 1311, 1449 and 1657 cm-1, which represented phenylalanine, tyrosine, nucleic acid bases, phospholipids and α-helix, were decreased in the infected keratocytes compared with the control keratocytes. The consistency of Raman spectra between the infected cornea tissue and the control cornea tissue was high. However, the intensity of some peaks declined, especially at 853, 940 and 1244 cm-1, which represent the tyrosine, proline and collagen content, respectively. CONCLUSIONS: After infection with Fusarium solani, the biochemical characteristics of keratocyte and cornea showed a decrease of amino acids, nucleic acid phospholipids and collagen, which may closely relate to the pathophysiology of keratomycosis.

RNA interference-based therapeutics for inherited long QT syndrome.

Inherited long QT syndrome (LQTS) is an electrical heart disorder that manifests with syncope, seizures, and increased risk of torsades de pointes and sudden cardiac death. Dominant-negative current suppression is a mechanism by which pathogenic proteins disrupt the function of ion channels in inherited LQTS. However, current approaches for the management of inherited LQTS are inadequate. RNA interference (RNAi) is a powerful technique that is able to suppress or silence the expression of mutant genes. RNAi may be harnessed to knock out mRNAs that code for toxic proteins, and has been increasingly recognized as a potential therapeutic intervention for a range of conditions. The present study reviews the literature for RNAi-based therapeutics in the treatment of inherited LQTS. Furthermore, this review discusses the combined use of RNAi with the emerging technology of induced pluripotent stem cells for the treatment of inherited LQTS. In addition, key challenges that must be overcome prior to RNAi-based therapies becoming clinically applicable are addressed. In summary, RNAi-based therapy is potentially a powerful therapeutic intervention, although a number of difficulties remain unresolved.