Realization of Time-Reversal Invariant Photonic Topological Anderson Insulators.

Disorder, which is ubiquitous in nature, has been extensively explored in photonics for understanding the fundamental principles of light diffusion and localization, as well as for applications in functional resonators and random lasers. Recently, the investigation of disorder in topological photonics has led to the realization of topological Anderson insulators characterized by an unexpected disorder-induced phase transition. However, the observed photonic topological Anderson insulators so far are limited to the time-reversal symmetry breaking systems. Here, we propose and realize a photonic quantum spin Hall topological Anderson insulator without breaking time-reversal symmetry. The disorder-induced topological phase transition is comprehensively confirmed through the theoretical effective Dirac Hamiltonian, numerical analysis of bulk transmission, and experimental examination of bulk and edge transmissions. We present convincing evidence for the unidirectional propagation and robust transport of helical edge modes, which are the key features of nontrivial time-reversal invariant topological Anderson insulators. Furthermore, we demonstrate disorder-induced beam steering, highlighting the potential of disorder as a new degree of freedom to manipulate light propagation in magnetic-free systems. Our work not only paves the way for observing unique topological photonic phases but also suggests potential device applications through the utilization of disorder.

Fabrication of Uniform Melatonin Microparticles Potentially for Nasal Delivery: A Comparison of Spray Drying and Spray Freeze Drying.

PURPOSE: Insomnia is a major health concern, and melatonin (MLT) is key for initiating sleep. Delivering MLT nasally can enhance brain bioavailability by targeting the olfactory region. This study aimed to fabricate MLT embedded microparticles for nasal delivery. METHODS: MLT-cyclodextrin (CD) derivatives complex microparticles (MCCMPs) were fabricated by spray drying and spray freeze drying MLT and CD derivative solutions. Phase solubility and 1H-1H ROSEY NMR analysis assessed MLT-CD assembly. The effects of formulation compositions and process parameters on microparticle structural attributes were investigated. The in vitro nasal release and deposition performances were evaluated by a modified paddle-over-disk apparatus and 3D-printed nasal cavity cast, respectively. RESULTS: Sodium sulphobutylether-ß-cyclodextrin (SBE-ß-CD) exhibited the best complexation ability with MLT, with the indole structure of MLT included in its cavity. Spray dried MCCMPs showed dense structure with high density, while the spray freeze dried counterpart showed the brittle and porous structure with low density. Despite the porous structure may promote the release rate of spray freeze dried samples, the high hydrophilicity of the CD derivative overshadows this advantage. Samples prepared by spray drying not only exhibited rapid release rates but also could deposit more effectively in the olfactory region, as they avoid breakage due to their higher mechanical strength. The optimal sample showed ~ 86.70% of the MLT released at 20 min and ~ 10.57% of the deposition fraction in the olfactory region. CONCLUSIONS: This work compares MCCMPs fabricated by spray drying and spray freeze drying, providing the optimal formulation and process combinations.

Adverse events of topical ocular prostaglandin medications for glaucoma treatment: a pharmacovigilance study based on the FAERS database.

Background: As prostaglandin medications, crucial in glaucoma treatment, become more widely used, their local adverse events are increasingly observed. Objectives: To evaluate the common adverse events of four clinically commonly used prostaglandin F (FP) receptor agonists in the treatment of glaucoma in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Design: We screened and analyzed the generic and brand names of latanoprost, bimatoprost, travoprost, and tafluprost in the FAERS database and summarized and cleaned the baseline information of subjects receiving the above-mentioned drugs. Methods: Perform descriptive statistical analysis on the baseline information of subjects using the drugs. Conduct disproportionality analysis of drug-related adverse events. The criteria for positive signals of adverse events are established by simultaneously meeting the thresholds set by four methods: the ratio of reported odds, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Additionally, assess the cumulative risk curves for drug-induced time of the aforementioned drugs and use one-way ANOVA to compare differences in drug-induced time across different groups. Results: The study included 1567 latanoprost, 1517 bimatoprost, 696 travoprost, and 82 tafluprost subjects. Adverse events mainly affected eye disorders, with significant issues in iris hyperpigmentation, ocular pemphigoid, corneal endothelial cell loss, periorbital fat atrophy, corneal irritation, eyelash growth, and ocular hyperemia. The time to onset varied among drugs, with latanoprost showing the longest (mean days = 344.37) and bimatoprost the shortest duration (mean days = 155.65; p < 0.001). Conclusion: Although signal detection analysis based on the FAERS database cannot establish a definitive causal relationship, our study found that FP receptor agonists used in glaucoma can cause various adverse events. Assessing their clinical suitability and potential side effects is crucial for providing personalized treatment and ensuring medication safety.

Understanding side effects of eye drops for glaucoma: a study using the FAERS database Why was the study done? Prostaglandin medications are crucial in treating glaucoma but can cause local adverse events. As the use of these medications increases, it's important to understand their common side effects. The Food and Drug Administration Adverse Event Reporting System (FAERS) is a database that contains adverse event reports, medication error reports and product quality complaints resulting in adverse events that were submitted to the Food and Drug Administration. What did the researchers do? We analyzed the FAERS database to evaluate the common adverse events of four prostaglandin medications commonly used to treat glaucoma: latanoprost, bimatoprost, travoprost, and tafluprost. What did the researchers find? The study included 1567 latanoprost users, 1517 bimatoprost users, 696 travoprost users, and 82 tafluprost users. The main adverse events affected eye disorders, with significant issues including iris hyperpigmentation, ocular pemphigoid, corneal endothelial cell loss, periorbital fat atrophy, corneal irritation, eyelash growth, and ocular hyperemia. The time to onset varied among drugs, with latanoprost showing the longest and bimatoprost the shortest duration. What do the findings mean? Although signal detection analysis from the FAERS database cannot establish a definitive causal relationship, prostaglandin medications used in glaucoma treatment can cause various ocular adverse events during long-term use. Understanding these side effects is crucial for providing personalized treatment and ensuring medication safety.

Preparation of curcumin-loaded chitosan/lecithin nanoparticles with increased anti-oxidant activity and in vivo bioavailability.

As a natural polyphenol, curcumin (Cur) has exhibited a range of bioactive properties, including anti-inflammatory, anti-oxidant, and anti-infection properties. However, the chemical instability and low water solubility of Cur hinder its wide application. Herein, Cur-loaded chitosan/lecithin nanoparticles (CCL NPs) were prepared by the electrostatic self-assembly method. The prepared CCL NPs showed a small particle size (122.86 ± 1.53 nm) with homogeneous distribution (PDI = 0.17 ± 0.01). The high EE (79.34 ± 2.93 %) and LC (9.33 ± 0.34 %) indicated that most of Cur was encapsulated in CCL NPs. Meanwhile, the Cur was released from CCL NPs in a quick and sustained way after being exposed to simulated gastrointestinal fluids. The CCL NPs displayed superior anti-oxidant activity than that of free Cur. Moreover, the in vivo pharmacokinetic studies showed that the CCL NPs could lead to a ~ 2.64-fold increase in oral bioavailability compared with that of free Cur. All these findings indicated that the formation of CCL NPs would be a promising platform to deliver Cur in the food industry.

Real-world large sample assessment of drug-related dry eye risk: Based on the FDA adverse event reporting system database.

PURPOSE AND DESIGN: This study aimed to evaluate the risk of drug-related dry eye using real-world data, underscoring the significance of tracing pharmacological etiology for distinct clinical types of dry eye. METHODS: Analyzing adverse event reports in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to September 2023, we employed disproportionality analysis and the Bayesian confidence propagation neural network algorithm. The analysis involved categorizing drugs causing dry eye, assessing risk levels, and conducting segmental assessments based on the time of onset of drug-related dry eye adverse reactions. RESULTS: In the FAERS database, adverse reactions related to dry eye were linked to 1160 drugs. Disproportionality analysis identified 33 drugs with significant risk, notably in ophthalmic (brimonidine, bimatoprost), oncology (tisotumab vedotin, erdafitinib), and other medications (isotretinoin, oxymetazoline). The top three drugs with the highest risk of drug-related dry eye are isotretinoin (Bayesian confidence propagation neural network (BCPNN) = 6.88), tisotumab vedotin (BCPNN = 6.88), and brimonidine (BCPNN = 6.77). Among different categories of drugs, respiratory medications have the shortest mean onset time for drug-related dry eye, averaging 50.99 days. The prevalence skewed towards females (69.9 %), particularly in menopausal and elderly individuals (45-70 years old, mean age 54.7 ± 18.2). Reports of drug-related dry eye adverse reactions showed an annual increase. CONCLUSION: Informed clinical decision-making is crucial for preventing drug-related dry eye. Assessing the risk of dry eyes associated with both local and systemic medications helps optimize treatment and provide necessary cautionary information.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis. Methods: This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to December 2023. A disproportionality analysis was conducted to assess drug-related keratitis with positive signals, and drugs were classified and assessed with regard to their drug-induced timing and risk of drug-related keratitis. Results: A total of 1606 drugs were reported to pose a risk of drug-related keratitis in the FAERS database, and, after disproportionality analysis and screening, 17 drugs were found to significantly increase the risk of drug-related keratitis. Among them, seven were ophthalmic medications, including dorzolamide (reporting odds ratio [ROR] = 3695.82), travoprost (ROR = 2287.27), and brimonidine (ROR = 2118.52), and 10 were non-ophthalmic medications, including tralokinumab (ROR = 2609.12), trazodone (ROR = 2377.07), and belantamab mafodotin (ROR = 680.28). The top three drugs having the highest risk of drug-related keratitis were dorzolamide (Bayesian confidence propagation neural network [BCPNN] = 11.71), trazodone (BCPNN = 11.11), and tralokinumab (BCPNN = 11.08). The drug-induced times for non-ophthalmic medications were significantly shorter than those for ophthalmic medications (mean days, 141.02 vs. 321.96, respectively; P < 0.001). The incidence of drug-related keratitis reached its peak in 2023. Conclusions: Prevention of drug-related keratitis is more important than treatment. Identifying the specific risks and timing of drug-induced keratitis can support the development of preventive measures. Translational Relevance: Identifying the specific drugs related to medication-related keratitis is of significant importance for drug vigilance in the occurrence of drug-related keratitis.

[Analysis of the therapeutic effect of trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture].

OBJECTIVE: Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture. METHODS: Between January 2020 and December 2022, 20 patients with high acetabular posterior wall fractures were retrospectively analyzed, including 12 males and 8 females, aged 18 to 75 years old. They were divided into two groups according to the different surgical methods. Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group, including 5 males and 5 females, aged from 18 to 75 years old. Ten patients were treated with Kocher-Langenbeck approach alone as the control group, including 7 males and 3 females, aged from 18 to 71 years old. Matta reduction criteria were used to evaluate the reduction quality of the two groups, and Harris score was used to compare the hip function of the two groups at the latest follow-up. The operation time, blood loss and postoperative complications of the two groups were analyzed. RESULTS: All patients were followed up for 10 to 24 months. According to the Matta fracture reduction quality evaluation criteria, the observation group achieved anatomical reduction in 6 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 1 case, while the control group only achieved anatomical reduction in 3 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 4 cases. At the final follow-up, the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group. According to the results of Harris score. The hip joint function of the observation group was excellent in 6 cases, good in 3 cases, and fair in 1 case. The hip joint function of the control group was excellent in 2 cases, good in 3 cases, fair in 3 cases, and poor in 2 cases. In the observation group, the intraoperative blood loss ranged from 300 to 700 ml, and the operation duration ranged from 120 to 180 min;in the control group, the intraoperative blood loss ranged from 300 to 650 ml, and the operation duration ranged from 100 to 180 min. Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification, while complications in the control group included 3 cases of traumatic arthritis, 3 cases of heterotopic ossification and 1 case of hip abduction weakness. CONCLUSION: Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates, enhanced excellent and good hip joint function outcomes, and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone. Clinical application of this combined approach is promising, although larger studies are needed for further validation.

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor: A systematic review and meta-analysis.

BACKGROUND: Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action. AIM: To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST. METHODS: The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024. RESULTS: A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg's funnel plot in all studies. CONCLUSION: RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Dandelion inspired microparticles with highly efficient drug delivery to deep lung.

Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of ∼ 68.96 % and extra fine particle fraction of ∼ 36.87 %, equivalently ∼ 4.60 mg and ∼ 2.46 mg could reach the lung and alveoli, respectively, when inhaling 10 mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.

Impact of Air Pollutants on Lung Function and Inflammatory Response in Asthma in Shanghai.

Objective: Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai. Methods: The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM 2.5. Results: Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O 3) and nitrogen dioxide (NO 2). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM 2.5 and PM 10 concentrations. In asthmatic mouse models, exposure to PM 2.5 increased cytokine levels and worsened lung function. Additionally, PM 2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways. Conclusion: Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM 2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM 2.5 impacts asthma.

Impact of wall materials and DHA sources on the release, digestion and absorption of DHA microcapsules: Advancements, challenges and future directions.

Docosahexaenoic acid (DHA), an essential omega-3 fatty acid, offers significant health benefits but faces challenges such as distinct odor, oxidation susceptibility, and limited intestinal permeability, hindering its broad application. Microencapsulation, widely employed, enhances DHA performance by facilitating controlled release, digestion, and absorption in the gastrointestinal tract. Despite extensive studies on DHA microcapsules and related delivery systems, understanding the mechanisms governing encapsulated DHA release, digestion, and absorption, particularly regarding the influence of wall materials and DHA sources, remains limited. This review starts with an overview of current techniques commonly applied for DHA microencapsulation. It then proceeds to outline up-to-date advances in the release, digestion and absorption of DHA microcapsules, highlighting the roles of wall materials and DHA sources. Importantly, it proposes strategies for overcoming challenges and exploiting opportunities to enhance the bioavailability of DHA microcapsules. Notably, spray drying dominates DHA microencapsulation (over 90 % usage), while complex coacervation shows promise for future applications. The combination of proteins and carbohydrates or phospholipids as wall material exhibits potential in controlling release and digestion of DHA microcapsules. The source of DHA, particularly algal oil, demonstrates higher lipid digestibility and absorptivity of free fatty acids (FFAs) than fish oil. Future advancements in DHA microcapsule development include formulation redesign (e.g., using plant proteins as wall material and algal oil as DHA source), technique optimization (such as co-microencapsulation and pre-digestion), and creation of advanced in vitro systems for assessing DHA digestion and absorption kinetics.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Creating similar food boluses as that in vivo using a novel in vitro bio-inspired oral mastication simulator (iBOMS-â ¢): The cases with cooked rice and roasted peanuts.

Food bolus is the major outcome of oral processing of foods. Its structure and properties are crucial for safe swallowing and subsequent gastric digestion. However, collecting the ready-to-swallow bolus for further analysis in either normal or deficient human subjects is difficult, regulatorily or practically. Here, a novel in vitro bio-inspired oral mastication simulator (iBOMS-Ⅲ) was developed to be capable of replicating food boluses comparable to those in vivo. Cooked rice and roasted peanuts were used as the model foods (soft and hard) respectively. Particle size distribution, moisture content and rheology of the food boluses produced in the iBOMS-Ⅲ were assessed. A conventional food blender was also employed as a non-consequential comparation. Eighteen healthy young volunteers of the ages from 20-30 years (10 male and 8 female) were invited to provide the in vivo data. For cooked rice boluses produced by the iBOMS-Ⅲ with 10, 12, 14, and 20 chewing number of cycles, the moisture content exhibited minimal variation (68.3-68.8 wt%), aligning closely with values obtained from the average value of the human subjects (67.5 wt%). Similarly, the boluses from roasted peanut displayed similar moisture contents across masticatory number of cycles (36, 40, and 44 number of cycles), averaging at 35.3 %, mirroring the average in vivo results (33.8 wt%). Furthermore, the shear viscosity of both cooked rice and roasted peanut boluses exhibited minimal variations with iBOMS-Ⅲ chewing number of cycles. The particle size distributions of the boluses produced with 14 and 44 chewing number of cycles matched well with the in vivo data for cooked rice and roasted peanuts, with median particle size (d50) being 1.07 and 0.78 mm, respectively. The physical properties of the food boluses collected from the food blender, with varying grinding times, differed significantly. This study demonstrates the value of the iBOMS-Ⅲ in achieving realistic boluses with two very different food textures.

Enhancing rheology and reducing lipid digestion of oil-in-water emulsions using controlled aggregation and heteroaggregation of soybean protein isolate-peach gum microspheres.

There is a growing interest in developing highly viscous lipid foods using plant protein and polysaccharide gum-based emulsion technology. However, gaps remain in understanding the rheological, microstructural, and digestive properties of plant proteins like soybean protein isolate (SPI) in combination with various gums. This study investigates how combining SPI and peach gum (PG) affects rheology and lipolysis of oil-in-water (O/W) emulsions containing 20 wt% soybean oil. Emulsions with varying SPI and PG compositions including SPI-PG single and SPI/PG mixed droplet systems were prepared. Heating induced alterations in viscosity (e.g., SPI-PG from 14.88 to 90.27 Pa·s and SPI/PG from 9.66 to 85.32 Pa·s) and microstructure revealing aggregate formation at oil-water interface. The viscosity decreased significantly from the oral to intestinal phase (SPI-PG: 28.10 to 0.19 Pa·s, SPI/PG: 21.27 to 0.10 Pa·s). These changes affected lipid digestion, notably in SPI-PG and SPI/PG emulsions where a compact interface hindered lipolysis during digestion. Interestingly, free fatty acid (FFA) release during small intestinal phase followed a different order: SPI (82.51 %) > SPI-PG (70.77 %) > SPI/PG (63.60 %) > PG (56.09 %). This study provides insights into creating highly viscous O/W spreads with improved rheology, stability, and delayed lipid digestion, offering potential benefits in food product formulation.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway.

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells' viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells' viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway.

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Evolution Characterization and Pathogenicity of an NADC34-like PRRSV Isolated from Inner Mongolia, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.

Locationally activated PRP via an injectable dual-network hydrogel for endometrial regeneration.

Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.

Topological Nature of Radiation Asymmetry in Bilayer Metagratings.

Manipulating radiation asymmetry of photonic structures is of particular interest in many photonic applications such as directional optical antenna, high efficiency on-chip lasers, and coherent light control. Here, we proposed a term of pseudopolarization to reveal the topological nature of radiation asymmetry in bilayer metagratings. Robust pseudopolarization vortex with an integer topological charge exists in P-symmetry metagrating, allowing for tunable directionality ranging from -1 to 1 in synthetic parameter space. When P-symmetry breaking, such vortex becomes pairs of C points due to the conservation law of charge, leading to the phase difference of radiation asymmetry from π/2 to 3π/2. Furthermore, topologically enabled coherent perfect absorption is robust with customized phase difference at will between two counterpropagating external light sources. This Letter can not only enrich the understanding of two particular topological photonic behaviors, i.e., bound state in the continuum and unidirectional guided resonance, but also provide a topological view on radiation asymmetry, opening an unexplored avenue for asymmetric light manipulation in on-chip laser, light-light switch, and quantum emitters.

Esophageal cancer screening, early detection and treatment: Current insights and future directions.

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.