7,8-Dihydroxyflavone alleviates apoptosis and inflammation induced by retinal ischemia-reperfusion injury via activating TrkB/Akt/NF-kB signaling pathway.

Retinal ischemia-reperfusion injury (RIRI) is of common occurrence in retinal and optic nerve diseases. The BDNF/TrkB signaling pathway has been examined to be neuroprotective in RIRI. In this study, we investigated the role of a potent selective TrkB agonist 7,8-dihydroxyfavone (DHF) in rat retinas with RIRI. Our results showed that RIRI inhibited the conversion of BDNF precursor (proBDNF) to mature BDNF (mBDNF) and increased the level of neuronal cell apoptosis. Compared with RIRI, DHF+RIRI reduced proBDNF level and at the same time increased mBDNF level. Moreover, DHF administration effectively activated TrkB signaling and and downstream Akt and Erk signaling pathways which increased nerve cell survival. The combined effects of mBDNF/proBDNF increase and TrkB signaling activation lead to reduction of apoptosis level and protection of retinas with RIRI. Moreover, it was also found that astrocytes labeled by GFAP were activated in RIRI and NF-kB mediated the increased expressions of inflammatory factors and these effects were partially reversed by DHF administration. Besides, we also used RNA sequencing to analyze the differently expressed genes (DEGs) and their enriched (Kyoto Encyclopedia of Genes and Genomes) KEGG pathways between Sham, RIRI, and DHF+RIRI. It was found that 1543 DEGs were differently expressed in RIRI and 619 DEGs were reversed in DHF+RIRI. The reversed DEGs were typically enriched in PI3K-Akt signaling pathway, Jak-STAT signaling pathway, NF-kB signaling pathway, and Apoptosis. To sum up, the DHF administration alleviated apoptosis and inflammation induced by RIRI via activating TrkB signaling pathway and may serve as a promising drug candidate for RIRI related ophthalmopathy.

Vitrectomy with internal limiting membrane peeling versus inverted internal limiting membrane flap technique for macular hole-induced retinal detachment: a systematic review of literature and meta-analysis.

BACKGROUND: To evaluate the effects on vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap technique for macular hole-induced retinal detachment (MHRD). METHODS: Pubmed, Cochrane Library, and Embase were systematically searched for studies that compared ILM peeling with inverted ILM flap technique for macular hole-induced retinal detachment. The primary outcomes are the rate of retinal reattachment and the rate of macular hole closure 6 months later after initial surgery, the secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6 months later after initial surgery. RESULTS: Four studies that included 98 eyes were selected. All the included studies were retrospective comparative studies. The preoperative best-corrected visual acuity was equal between ILM peeling and inverted ILM flap technique groups. It was indicated that the rate of retinal reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69; P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P < 0.00001) after initial surgery was higher in the group of vitrectomy with inverted ILM flap technique than that in the group of vitrectomy with ILM peeling. However, there was no statistically significant difference in postoperative best-corrected visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of resolution; 95% CI -0.06 to 0.43 ; P = 0.14) between the two surgery groups. CONCLUSION: Compared with ILM peeling, vitrectomy with inverted ILM flap technique resulted significantly higher of the rate of retinal reattachment and macular hole closure, but seemed does not improve postoperative best-corrected visual acuity.

Two new cucurbitane triterpenoids from the seeds of Momordica charantia.

Two new cucurbitane triterpenoids 1 and 2 were isolated, together with six known compounds, from the seeds of Momordica charantia L. The structures of new compounds were determined to be 3-O-{[ß-d-galactopyranosyl(1 â†’ 6)]-O-ß-d-galactopyranosyl}-23(R), 24(R), 25-trihydroxycucur-bit-5-ene (1), 3-O-[ß-d-galactopyranosyl]-25-O-ß-d-galactopyranosyl-7(R), 22(S), 23(R), 24(R), 25-pentahydroxycucurbit-5-ene (2), respectively. Their structures were elucidated by the combination of mass spectrometry, one- and two-dimensional NMR experiments and chemical reactions.

Two new bidesmoside triterpenoid saponins from the seeds of Momordica charantia L.

Two new bidesmoside triterpenoid saponins which were identifed as 28-O-ß-D-xylopyranosyl(1→3)-ß-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl(1→2)-[α-L-rhamno-pyranosyl(1→3)]-ß-D-fucopyranosyl gypsogenin 3-O-ß-D-glucopyranosyl (1→2)-ß-D-glucopyranosiduronic acid (C1) and 28-O-ß-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl (1→2)-[α-L-rhamnopyranosyl(1→3)]-ß-D-fucopyranosyl gypsogenin 3-O-ß-D-gluco-pyranosyl(1→2)-ß-D-glucopyranosiduronic acid (C2) were isolated together with two known compounds from the seeds of Momordica charantia L. Their structures were elucidated by the combination of mass spectrometry (MS), one and two-dimensional NMR experiments and chemical reactions.

A novel improved total variation algorithm for the elimination of scratch-type defects in high-voltage cable cross-sections.

In the quality inspection process of high-voltage cables, several commonly used indicators include cable length, insulation thickness, and the number of conductors within the core. Among these factors, the count of conductors holds particular significance as a key determinant of cable quality. Machine vision technology has found extensive application in automatically detecting the number of conductors in cross-sectional images of high-voltage cables. However, the presence of scratch-type defects in cut high-voltage cable cross-sections can significantly compromise the precision of conductor count detection. To address this problem, this paper introduces a novel improved total variation (TV) algorithm, marking the first-ever application of the TV algorithm in this domain. Considering the staircase effect, the direct use of the TV algorithm is prone to cause serious loss of image edge information. The proposed algorithm firstly introduces multimodal features to effectively mitigate the staircase effect. While eliminating scratch-type defects, the algorithm endeavors to preserve the original image's edge information, consequently yielding a noteworthy enhancement in detection accuracy. Furthermore, a dataset was curated, comprising images of cross-sections of high-voltage cables of varying sizes, each displaying an assortment of scratch-type defects. Experimental findings conclusively demonstrate the algorithm's exceptional efficiency in eradicating diverse scratch-type defects within high-voltage cable cross-sections. The average scratch elimination rate surpasses 90%, with an impressive 96.15% achieved on cable sample 4. A series of conducted ablation experiments in this paper substantiate a significant enhancement in cable image quality. Notably, the Edge Preservation Index (EPI) exhibits an improvement of approximately 20%, resulting in a substantial boost to conductor count detection accuracy, thus effectively enhancing the quality of high-voltage cable production.

[Retracted] The therapeutic effect of artesunate on rosacea through the inhibition of the JAK/STAT signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 4A were strikingly similar to data appearing in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 8385­8390, 2018; DOI: 10.3892/mmr.2018.8887].

A simple method for microwave-assisted preparation of tire samples.

Heavy metals content in tires affects the safety of soil and agricultural products. The digestion method is a pretreatment for determining heavy metals in tire samples, and will affect the efficiency and accuracy of the heavy metal determination. The microwave digestion process and reagents for tire samples are not currently standardized. Therefore, this study attempts to provide an appropriate method of resolution for scholars. All digestion processes were performed in Mars One. We tested 15 different acid mixtures to determine the best reagent type and dose and then investigated the effect of maximum temperature, holding time, and sample grams on the degree of digestion. In summary, the best condition to digest the tire sample was a mixture of 3 ml HNO3 and 7 ml H2SO4, taking 0.1 (± 0.0005) g tire sample, at the maximum digestion temperature of 220 °C for 25 min. The experimental conclusion will provide a reliable experimental method for scientists using MARS One to study heavy metals in tires. At the same time, researchers using the MARS series can also find valuable references in this paper.

Microbial Diversity and Flavor Regularity of Soy Milk Fermented Using Kombucha.

Plant-based milk is considered a healthy and environmentally sustainable option. However, due to the low protein content of most plant-based milk and the difficulty of gaining flavor acceptance by consumers, its production scale is usually limited. Soy milk is a kind of food with comprehensive nutrition and high protein content. In addition, kombucha is naturally fermented by acetic acid bacteria (AAB), yeast, lactic acid bacteria (LAB), and other microorganisms, and the microorganisms in its system can improve the flavor characteristics of food. In the present study, LAB (commercially purchased) and kombucha were used as fermenting agents for soybean, which was used as a raw material to produce soy milk. A variety of characterization methods were used to study the relationship between the microbial composition and flavor regularity of soy milk produced with different proportions of fermenting agents and different fermentation times. In soy milk produced at 32 °C with a mass ratio of LAB to kombucha of 1:1 and a fermentation time of 42 h, the concentrations of LAB, yeast, and acetic acid bacteria in the milk were optimal at 7.48, 6.68, and 6.83 log CFU/mL, respectively. In fermented soy milk produced with kombucha and LAB, the dominant bacterial genera were Lactobacillus (41.58%) and Acetobacter (42.39%), while the dominant fungal genera were Zygosaccharomyces (38.89%) and Saccharomyces (35.86%). After 42 h, the content of hexanol in the fermentation system of kombucha and LAB decreased from 30.16% to 8.74%, while flavor substances such as 2,5-dimethylbenzaldehyde and linalool were produced. Soy milk fermented with kombucha offers the opportunity to explore the mechanisms associated with flavor formation in multi-strain co-fermentation systems and to develop commercial plant-based fermentation products.

N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin.

The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4 nm for uncoated liposomes and 657.7 nm for TMC-coated liposomes), and zeta potential (-9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C(max) = 46.13 µg/L, t(1/2) = 12.05 hours, AUC = 416.58 µg/L·h), compared with CUR encapsulated by uncoated liposomes (C(max) = 32.12 µg/L, t(1/2) = 9.79 hours, AUC = 263.77 µg/L·h) and CUR suspension (C(max) = 35.46 µg/L, t(1/2) = 3.85 hours, AUC = 244.77 µg/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR.

Pathological Changes and Expression of JAK-STAT Signaling Pathway Hallmark Proteins in Rat Retinas at Different Time Points After Retinal Ischemia Reperfusion Injury.

Retinal ischemia reperfusion injury (RIRI) is a conventional pathological process in various retinal vascular diseases. Many studies select only one specific time point to apply drugs and then assess the therapeutic effect of drugs; however, the baselines are not the same at different time points, which may cause variation in the judgement. Therefore, further investigation is needed. Accordingly, this study aimed to investigate the pathological changes of retinal structure, expression of JAK-STAT signaling pathway hallmark proteins, and apoptosis at different time points after retinal ischemia reperfusion injury in rats. Sixty-six male SPF Sprague-Dawley rats were randomly divided into six groups: control group, RIRI 0, 6-, 24-, 72-, and 144-h groups. RIRI models were induced by perfusing equilibrium solution into the right eye anterior chamber to increase intraocular pressure to 110 mmHg for 60 min. Rats were sacrificed at different time points after reperfusion. Then hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, western blot, and TUNEL were used. Hematoxylin-eosin showed the pathological changes while transmission electron microscope revealed the ultra-structure changes of retina after RIRI. Immunohistochemistry showed that JAK2, STAT3, p-JAK2, p-STAT3, Bax, and Bcl-2 proteins mainly located in ganglion cell layer and inner nuclear layer, the relative expression of former five proteins had significant differences vs. control group (p < 0.05), while Bcl-2 had no significant difference. In western blot, the protein expressing of JAK2, STAT3, p-JAK2, p-STAT3, p-Akt, and Bax had significant differences vs. control group (p < 0.05), while Akt and Bcl-2 had no significant differences. TUNEL staining showed the number of apoptosis positive cells rose initially but declined later, with a peak value at RIRI 24 h group. The dynamic changes of hallmark proteins at different time points after RIRI indicate that JAK-STAT signaling pathway activates rapidly but weakens later and plays a vital role in RIRI, and apoptosis is involved in RIRI with a peak value at 24 h in the process, suggesting a potential therapeutic direction and time window for treating RIRI.

Research progress in tumor targeted immunotherapy.

INTRODUCTION: Compared with traditional cancer treatment methods, tumor-targeted immunotherapy can combine targeted therapy and immunotherapy with long-lasting responses to achieve synergistic therapy, which brings hope to the complete cure of cancer. AREAS COVERED: This review summarizes the newest and most up-to-date advances in tumor-targeted immunotherapy, including tumor-associated macrophages (TAMs) targeted immunotherapy, regulatory T (Treg) cells targeted immunotherapy, tumor-associated fibroblasts (TAFs) targeted immunotherapy and immune checkpoints targeted immunotherapy. EXPERT OPINION: Immunotherapy can restore anti-tumor immunity in the tumor microenvironment and produce a lasting immune surveillance effect. Smart multifunctional nano delivery system can effectively combine targeted therapy with immunotherapy, which has attracted extensive attention. With the deepening of research, more and more tumor-targeted immunotherapy enter into the clinical trial phases, especially antibodies and inhibitors. Tumor-targeted immunotherapy is a promising approach for conquering cancer and bringing hope for human health.

A novel progress of drug delivery system for organelle targeting in tumour cells.

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.

Design and performance evaluation of additively manufactured composite lattice structures of commercially pure Ti (CP-Ti).

Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural, mechanical, and biological properties. In this study, six types of composite lattice structures with different strut radius that consist of simple cubic (structure A), body-centered cubic (structure B), and edge-centered cubic (structure C) unit cells are designed. The designed structures are firstly simulated and analysed by the finite element (FE) method. Commercially pure Ti (CP-Ti) lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting (SLM), and the dimensions, microtopography, and mechanical properties are characterised. The results show that among the six types of composite lattice structures, combined BA, CA, and CB structures exhibit smaller maximum von-Mises stress, indicating that these structures have higher strength. Based on the fitting curves of stress/specific surface area versus strut radius, the optimized strut radius of BA, CA, and CB structures is 0.28, 0.23, and 0.30 mm respectively. Their corresponding compressive yield strength and compressive modulus are 42.28, 30.11, and 176.96 MPa, and 4.13, 2.16, and 7.84 GPa, respectively. The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone, which makes it a potential candidate for subchondral bone restorations.

Effect of Graphene Nanosheet Addition on the Wettability and Mechanical Properties of Sn-20Bi-xGNS/Cu Solder Joints.

Graphene nanosheets (GNSs) have an extensive application in materials modification. In this study, the effects of graphene nanosheets on the wettability of Sn-20Bi lead-free solder on copper (Cu) substrate and the growth behavior of intermetallic compound (IMC) layers at Sn-20Bi-xGNS/Cu solder joints were investigated. The experimental results indicate that the wettability of Sn-20Bi solder firstly diminished and then increased by the addition of GNSs. Meanwhile, a prism-shaped and scallop-shaped Cu6Sn5 IMC layer was clearly observed at the interface of the solder/substrate system. Moreover, it was found that a small amount of GNS addition can significantly inhibit the growth of the IMC layer at the interface as well as refine the microstructure. Additionally, by nano-indentation apparatus, it can be concluded that the hardness and elastic module of IMCs show the same variation trend, which firstly decreased and then increased. Besides, to intuitively demonstrate the reliability of IMCs, the relationship between the hardness and elastic module was established, and the ratio of hardness/elastic module (H/E) was adopted to characterize the reliability of IMCs. The results show that when the addition of GNSs was 0.02 wt%, the value of H/E is the minimum and the solder joint has the highest reliability.

[Preparation and characterization of curcumin loaded gelatin microspheres for lung targeting].

OBJECTIVE: To study the preparation technology and physicochemical characterization of curcumin loaded gelatin microspheres for lung targeting. METHODS: Curcumin loaded gelatin microspheres for lung targeting were prepared by the emulsion crosslinking method, and the preparation technology was optimized by orthogonal experimental design with biodegradable gelatin as the carrier, liquid paraffin as the oil phase, span 80 as the emulsifier. RESULTS: The optimal curcumin loaded gelatin microspheres were global with smooth surface, 6.15% for the drug loading, 75.5% for the encapsulation efficiency. 86.6% of microspheres size was in the range of 5-30 microm. The release test in vitro showed that 50% of curcumin could release from gelatin microspheres in 22 h and 77% in 48 h. CONCLUSIONS: The preparation technology is good and stable, and the obtained microspheres can control the release of curcumin.

The progresses in curcuminoids-based metal complexes: especially in cancer therapy.

Curcuminoids (CURs), a series of derivatives in turmeric (Curcuma longa), are commonly discovered to control the deterioration of cancers. However, the physiochemical properties and the original side effects of many CURs complexes put barriers in their medical applications. To address them, the investigation of metal-based complexes with CURs is in progress. The complexes were summarized according to articles in recent years. The results showed that the complexes improved the physicochemical properties or therapeutic performances compared with pure CURs. Further, it is possible for the novel complexes to be applied in chemical detecting, paramagnetic-luminescent and bio-imaging fields. Therefore, the formation of the metal-based CURs complexes (MBCCs) is beneficial for the development of CURs especially in medical fields.

Effect of anterior capsule polish on visual function: A meta-analysis.

PURPOSE: To investigate the relationship between anterior capsule polish and visual function. METHODS: Data were obtained from Pubmed, Embase, Web of Science, WanFang, VIP and CNKI up to the end of May 2018, without any date or language restrictions for trials. The modified Jadad scale and the newcastle-ottawa scale were used to assess the quality of included studies. Uncorrected visual acuity (UCVA) and posterior capsule opacification (PCO) were used as outcome variables. Data on anterior capsule polish were pooled using weighted, random-effect meta-analysis. RESULTS: One randomized controlled trial and 4 observational cohort studies involving 2533 patients were included in the analyses. There was a statistically significant difference of UCVA (OR 1.92, 95% CI 1.41-2.61) between the polish group and the control group, indicating that anterior capsule polish improved UCVA. Further studies with continuous data also suggested that anterior capsule polish was associated with good UCVA (MD 0.11, 95% CI 0.06-0.16). Posterior capsule opacification rate for 1-year or longer follow-up were extracted for 2561 eyes in 3 studies. Posterior capsule opacification rate was lower in the anterior capsule polish group according to summary odds ratio on PCO rate (OR 0.42 95% CI 0.24-0.73). CONCLUSIONS: Anterior capsule polish prevents complication of modern cataract surgery and benefits on visual function in short term follow-up period.

Recent progress of functionalised graphene oxide in cancer therapy.

In recent years, graphene oxide (GO) nanomaterials have attracted wide attention due to their large surface area, strong light sensitivity and good biocompatibility in cancer treatment. The rich oxygen-containing functional groups on the surface provide it with the opportunity to be modified by many functional molecules to expand biological applications and reduce toxicity. In this review, the properties of GO and the methods of surface modification are presented, and the toxicity of GO is analysed. In addition, the current applications of GO in cancer diagnoses and treatments including biological imaging, drug and gene delivery, phototherapy and imaging-mediated combination therapy are summarised. Finally, the prospects and challenges of GO in cancer treatment are discussed.

Effect of Aluminum Addition on the Microstructure and Properties of Non-Eutectic Sn-20Bi Solder Alloys.

This study investigates the effect of aluminum (Al) on the microstructure, micro-hardness, and wettability of environmentally friendly Sn-20Bi-xAl (x = 0, 0.1, 0.3, 0.5 (wt.%)) solder alloys. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) analysis, and X-ray diffraction (XRD), were used to identify the microstructure morphology and composition. The spreading area and contact angle of the Sn-20Bi-xAl alloys on Cu substrates were used to measure the wettability of solder alloys. The results indicate that Al increased the hardness to a maximum value of ~27.1 HV for x = 0.5. When the content of Al was more than 0.3 wt.%, the hardness change value gradually flattened. From the spreading test results, Al reduced the wettability of solder alloys. When the content of Al was 0.1 wt.%, the change was slight. When more than 0.3 wt.%, the wettability of Sn-20Bi-xAl solder alloys sharply dropped. The corrosion resistance of Sn-20Bi-0.1Al alloy was the best, and the corrosion rate was at the lowest value at 0.092 mm/a due to the dense corrosion products.

Formulation design of microemulsion for dermal delivery of penciclovir.

The purpose of the present study was to evaluate the potential application of microemulsions as a dermal drug delivery loading penciclovir. The pseudo-ternary phase diagrams were developed for various microemulsion formulations composed of oleic acid (oil phase), Cremorphor EL (surfactant) and ethanol (cosurfactant). Composition of microemulsion systems was optimized using simplex lattice mixture design including the concentrations of surfactant, cosurfactant and water (independent variables) and the solubility and the cumulative amount of penciclovir permeated through excised mouse skins per unit area (response variables). The physicochemical properties of the optimized microemulsion and the permeating ability of penciclovir from microemulsions were also investigated. The results showed that the optimized microemusion formulation was composed of oleic acid (5%, w/w), Cremorphor EL (20%, w/w), ethanol (30%, w/w) and water (45%, w/w). The mean particle diameter was 36.5nm and solubility of penciclovir in the emulsion was 7.41 mg g(-1). The cumulative amount of penciclovir permeated through excised mouse skins from microemulsion was about 3.5 times that of the commercial cream. The conclusion was that the permeating ability of penciclovir was significantly increased from the microemulsion formulation compared with commercial cream.