Tumor cell vaccine combined with Newcastle disease virus promote immunotherapy of lung cancer.

Lung cancer is a fatal disease with the highest worldwide morbidity and mortality rates. Despite recent advances in targeted therapy and immune checkpoint inhibitors for cancer, their efficacy remained limited. Therefore, we designed a Newcastle disease virus (NDV)-modified tumor whole-cell vaccine as a therapeutic vaccine and identified its antigen presentation level to develop effective immunotherapy. Then, we calculated the therapeutic and immune-stimulating effects of NDV-modified lung cancer cell vaccine and intratumoral NDV injection combination on tumor-bearing mice. The results showed that the immunogenic cell death (ICD) expression in NDV-modified lung cancer cell vaccine stimulates dendritic cell maturation and T cell activation in vivo and in vitro. Moreover, NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could significantly inhibit tumor growth and enhance the differentiation of Th1 cells and Inflammatory cell infiltration in vivo, leading to an excellent immunotherapeutic effect. Therefore, our results revealed that NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could promote antigen presentation and induce a strong antitumor immune response, which provided a promising combined therapy strategy for tumor immunotherapy.

Dephosphorylation of ERK1/2 and DRP1 S585 regulates mitochondrial dynamics in glutamate toxicity of retinal neurons in vitro.

There are many theories surrounding the pathogenesis of glaucoma, and glutamate excitatory toxicity has been suggested to play an important role. Some studies have shown that glutamate excitatory toxicity is associated with mitochondrial dynamics; however, the relationship between glutamate excitatory toxicity and mitochondrial dynamics in the pathogenesis of glaucoma remains unclear. In this study, the glutamate transporter inhibitor, threohydroxyaspartate, was used to simulate the glutamate excitatory toxicity cell model of rat retinal neurons in vitro, and the changes in the level of proteins related to mitochondrial dynamics, mitochondrial morphology, and length of neuronal axons were measured. We found that in the glutamate excitotoxicity model, retinal neurons can promote mitochondrial fusion by reducing the phosphorylation of ERK1/2 and its downstream protein DRP1 S585, and enhance its ability to resist the excitotoxicity of glutamate. At the same time, the DRP1-specific inhibitor, Mdivi-1, could promote the mitochondrial fusion of retinal neurons.

Normal vitreous promotes angiogenesi via the epidermal growth factor receptor.

Vitreous, a transparent tissue in our body, contains anti-angiogenesis factors. Our previous work reported that vitreous activates the signaling pathway of epidermal growth factor receptor (EGFR), which plays a critical role in angiogenesis. The aim of this study was to determine the role of EGFR in vitreous-induced angiogenesis-related cellular responses in vitro. Using a pharmacologic and molecular approach, we found that vitreous increased proliferation and migration via EGFR in human umbilical vein endothelial cells (HUVECs). Furthermore, we demonstrated that vitreous promoted tube formation via EGFR in HUVECs. Subsequently, depletion of EGFR using CRISPR/Cas9 and blockage with EGFR inhibitor AG1478 suppressed vitreous-induced Akt activation and cell proliferation, migration, and tube formation in HUVECs. The significance of the angiogenic effect derived from vitreous demonstrates the importance of vitreous in the ocular physiology and the pathobiology of angiogenesis-related ophthalmic diseases, such as proliferative diabetic retinopathy.

Cross-talk between MYOC p. Y437H mutation and TGF-ß2 in the pathology of glaucoma.

Objective: To identify the interaction between the MYOC Y437H mutation and TGF-ß2 in a family with primary open-angle glaucoma (POAG). Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-ß2 found in the aqueous humor. Samples were taken both from normal controls and MYOC mutant carriers and cross-talk between MYOC Y437H and TGF-ß2 were evaluated in the trabecular meshwork (TM) cells. Results: Aqueous humor secreted myocilin protein levels were reduced while TGF-ß2 levels were increased in patients with the MYOC (c.1309T>C) mutation. This inverse relationship indicated that elevated TGF-ß2 may be an important pathogenic mechanism in the progression of myocilin-related POAG. In TM cells expressing the MYOC Y437H mutant, exogenous TGF-ß2 also significantly increased myocilin expression as well as the endoplasmic reticulum (ER) stress markers GRP94 and CHOP. This increase in TGF-ß2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation. Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-ß2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.

Split ring resonator as a nanoscale optical transducer for heat-assisted magnetic recording.

Split ring resonators (SRR) are optical nanostructures that have received a lot of attention for their ability to support magnetic resonance and for their potential use as materials with negative dielectric constant. In this work, we design SRRs as near-field transducers (NFT) for generating a nanoscale hotspot in heat-assisted magnetic recording (HAMR), which is considered a candidate for the next-generation data storage technology. The underlying mechanisms for the generation of hotspot and the dependence on wavelength and geometry of the SRR structure are studied. Optical and thermal performance of SRRs functioning as NFTs in a HAMR device are evaluated. These structures were fabricated using focused ion beam milling. The focusing capability of the SRR is experimentally demonstrated using a scattering near field scanning optical microscope.

A porous silicon composite with irregular silver nano-dendritic particles: a rapid optical sensor for trace detection of malachite green in freshwater fish.

This study focused on creating a SERS composite particle specifically designed for detecting malachite green. We synthesized silver nano-dendritic structures on p-type porous silicon using an external electric field, separating them from the silicon wafer. Ultrasonic crushing yielded irregular silver nanodendrite-modified porous silicon composite particles. Upon being tested in an aqueous solution of malachite green, these composite particles demonstrated significant surface-enhanced Raman scattering effects. Our findings highlight the exceptional performance of the SERS substrate composed of porous silicon and irregular silver nano-dendritic particles. It exhibited high sensitivity, specificity, consistent signal strength, and reliability in detecting trace amounts of malachite green in water. Under ideal conditions, the substrate could detect malachite green at concentrations as low as 10-8 M. Moreover, its swift response to trace amounts of malachite green in fish underscores its potential as an effective Raman detector.

[Retracted] Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway.

Following the publication of the above paper, it has been drawn to the Editors' attention by a concerned reader that certain of the lumen formation assay data shown in Fig. 5A on p. 112 were strikingly similar to data appearing in different form in another article written by different authors at different research institute, which had already been published in the journal Biomedicine & Pharmacotherapy prior to the submission of this paper to International Journal of Molecular Medicine, and which has also subsequently been retracted. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 103­114, 2019; DOI: 10.3892/ijmm.2019.4183].

Terahertz quantitatively distinguishing gasoline mixtures using multiparameter-combined analysis.

Refined oil mixtures can be quantified using terahertz-absorption-coefficient spectra and dualistic linear regression fitting. However, when this method was used to quantify mixtures of 90# and 97# gasolines, the absolute error between the real and fitted value was large (25%), and this was due to the component similarity between 90# and 97# gasolines. To solve this problem, the present research addresses the possibility of developing a method that would allow direct, simple, and accurate determination of the 97# gasoline content in gasoline mixtures using a terahertz time-domain pulse coupled to a multiparameter-combined analysis. The multiparameter represents the time delay and amplitude of the first transmission dip and peak in the time-domain pulse. The relationship between these four parameters and the 97# gasoline content in gasoline mixtures was thoroughly investigated, and four distinct calibration models for quantifying gasoline mixtures were built using least square fitting. To enable the development of an informative and accurate calibration model, the four individual models were given proper weights and combined. The weight was determined by the cosine-optimal method, which aimed to determine the most proper weight under the condition of the cosine of the angle between the fitted content vector and the real content vector that reaches the maximum. This method allows the determination of 97# gasoline content in gasoline mixtures with a low absolute error (6%), resulting in predictions that are more accurate and precise than those obtained by the terahertz-absorption-coefficient spectra and dualistic linear regression fitting.

Pathologically high intraocular pressure induces mitochondrial dysfunction through Drp1 and leads to retinal ganglion cell PANoptosis in glaucoma.

Glaucoma is a common neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) loss and visual field defects. Pathologically high intraocular pressure (ph-IOP) is an important risk factor for glaucoma, and it triggers molecularly distinct cascades that control RGC death and axonal degeneration. Dynamin-related protein 1 (Drp1)-mediated abnormalities in mitochondrial dynamics are involved in glaucoma pathogenesis; however, little is known about the precise pathways that regulate RGC injury and death. Here, we aimed to investigate the role of the ERK1/2-Drp1-reactive oxygen species (ROS) axis in RGC death and the relationship between Drp1-mediated mitochondrial dynamics and PANoptosis in ph-IOP injury. Our results suggest that inhibiting the ERK1/2-Drp1-ROS pathway is a potential therapeutic strategy for treating ph-IOP-induced injuries. Furthermore, inhibiting Drp1 can regulate RGC PANoptosis by modulating caspase3-dependent, nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3(NLRP3)-dependent, and receptor-interacting protein (RIP)-dependent pathways in the ph-IOP model. Overall, our findings provide new insights into possible protective interventions that could regulate mitochondrial dynamics to improve RGC survival.

Review of Aging Evaluation Methods for Silicone Rubber Composite Insulators.

Silicone rubber insulation material is widely used for the external insulation of power systems. During the continuous service of a power grid, it will be seriously aged due to the influence of high voltage electric fields and harsh climate environments, which will reduce its insulation performance and service life and cause transmission line failure. How to evaluate the aging performance of silicone rubber insulation materials scientifically and accurately is a hot and difficult issue in the industry. Starting from the composite insulator, which is the most widely used insulating device of silicone rubber insulation materials, this paper expounds the aging mechanism of silicone rubber materials, analyzes the applicability and effectiveness of various existing aging tests and evaluation methods, especially discusses the magnetic resonance detection methods emerging in recent years, and finally summarizes the characterization and evaluation technology of the aging state of silicone rubber insulation materials.

Integrated analysis of long non-coding RNAs and mRNAs associated with glaucoma in vitro.

Introduction: In recent years, the biological functions and important roles of long non-coding RNAs (lncRNAs) have been widely reported in many diseases. Although glaucoma is the leading cause of blindness worldwide, the specific mechanisms of lncRNAs in the pathogenesis and progression of glaucoma remain unclear. Our research aims to elucidate the differentially expressed lncRNAs and mRNAs in glaucoma and to provide a basis for further exploration of the specific mechanism of action of lncRNAs in the progression of glaucoma. Methods: We performed RNA sequencing on samples from a pressurized model of R28 cells and performed bioinformatics analyses on the sequencing results. The expression consistency of lncRNAs in clinical samples from patients with glaucoma or cataracts was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Results: RNA sequencing results showed that lncRNAs in cluster 5 were upregulated with increasing stress after typing all significantly altered lncRNAs using k-means in a cellular stress model. KEGG analysis indicated that they were associated with neurodegenerative diseases. Differentially expressed lncRNAs were verified by RT-qPCR, and the lncRNA expression levels of AC120246.2 and XLOC_006247 were significantly higher in the aqueous humor (AH) of patients with glaucoma than in those with cataracts. For LOC102551819, there was almost no expression in the AH and trabecular meshwork in patients with glaucoma but high expression was observed in the iris. Conclusion: Our research proposes potential diagnostic or intervention targets for clinical applications as well as a theoretical basis for more in-depth research on the function of lncRNAs in glaucoma.

Translocator protein 18 kDa regulates retinal neuron apoptosis and pyroptosis in glaucoma.

Glaucoma is the leading cause of blindness worldwide. However, our insufficient understanding of the pathogenesis of glaucoma has limited the development of effective treatments. Because recent research has highlighted the importance of non-coding RNAs (ncRNAs) in various diseases, we investigated their roles in glaucoma. Specifically, we detected expression changes of ncRNAs in cell and animal models of acute glaucoma. Further analysis revealed that the Ier2/miR-1839/TSPO axis was critical to cell loss and retinal damage. The knockdown of Ier2, the overexpression of miR-1839, and the silencing of TSPO effectively prevented retinal damage and cell loss. Furthermore, we found that the Ier2/miR-1839/TSPO axis regulated the pyroptosis and apoptosis of retinal neurons through the NLRP3/caspase1/GSDMD, cleaved-caspase3 pathways. In addition to high expression in the retina, TSPO expression was found to be significantly higher in the dorsal lateral geniculate nucleus (DLG) of the brain in the pathologically high intraocular pressure (ph-IOP) rat model, as well as in the peripheral blood mononuclear cells (PBMCs) of glaucoma patients with high IOP. These results indicate that TSPO, which is regulated by Ier2/miR-1839, plays an important role in the pathogenesis of glaucoma, and this study provides a theoretical basis and a new target for the diagnosis and treatment of glaucoma.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Terahertz spectroscopy for quantifying refined oil mixtures.

In this paper, the absorption coefficient spectra of samples prepared as mixtures of gasoline and diesel in different proportions are obtained by terahertz time-domain spectroscopy. To quantify the components of refined oil mixtures, a method is proposed to evaluate the best frequency band for regression analysis. With the data in this frequency band, dualistic linear regression fitting is used to determine the volume fraction of gasoline and diesel in the mixture based on the Beer-Lambert law. The minimum of regression fitting R-Square is 0.99967, and the mean error of fitted volume fraction of 97# gasoline is 4.3%. Results show that refined oil mixtures can be quantitatively analyzed through absorption coefficient spectra in terahertz frequency, which it has bright application prospects in the storage and transportation field for refined oil.

Bis[(2-chloro-4-fluoro-benz-yl)triphenyl-phospho-nium] bis-(1,2,5-thia-diazole-3,4-dithiol-ato)nickelate(II).

The title ion-pair complex, (C(25)H(20)ClFP)(2)[Ni(C(2)N(2)S(3))(2)], was obtained by the direct reaction of (4-F,2-ClBzTPP)(+)·Br(-) [4-F,2-ClBzTPP(+) is (2-chloro-4-fluoro-benz-yl)triphenyl-phos-pho-nium], NiCl(2)·6H(2)O and Na(2)tdas (tdas(2-) is 1,2,5-thia-diazole-3,4-dithiol-ate) in methanol. The asymmetric unit of the title structure comprises one (4-F,2-ClBzTPP)(+) cation and half of an [Ni(tdas)(2)](2-) complex anion, with the Ni(II) ion situated on a center of symmetry, leading to a slightly distorted square-planar coordination of the latter. In the cation, the tetra-hedral angles around the P atom are nearly undistorted. In the crystal, the cations and anions are linked by C-H⋯S, C-H⋯N and C-H⋯Cl hydrogen bonds.

The Relationship between Expression of Nuclear Factor I and the Progressive Occurrence of Diabetic Retinopathy.

The loss of nuclear factor I (NFI) function can lead to defects in Muller's glial differentiation, abnormalities of retinal morphology, and changes in retinal neurons numbers, which are highly involved in diabetic retinopathy (DR). In this study, we addressed the roles of NFIA and NFIB gene expression in the development of DR by using diabetes mellitus (DM) rat models. Retinal histologies were examined, and the expression of NFIA and NFIB at mRNA and protein levels was detected. The results showed that retinal edema and disordered cell arrangement frequently occurred in DR rats. The expressions of NFIA and NFIB in retinal tissue were significantly decreased in DM rats with DR complications. After further inhibiting the expression of NFIA gene in DM rats by using RNA-silencing, majority of DM rats occurred retinopathy and lens fibrosis, which indicated the relationship between decreased expression of NFI and occurrence of retinopathy in DM.

Targeting Cell Membranes, Depleting ROS by Dithiane and Thioketal-Containing Polymers with Pendant Cholesterols Delivering Necrostatin-1 for Glaucoma Treatment.

Glaucoma is the leading cause of irreversible blindness worldwide, characterized by progressive vision loss due to the selective damage to retinal ganglion cells (RGCs) and their axons. Oxidative stress is generally believed as one key factor of RGCs death. Recently, necroptosis was identified to play a key role in glaucomatous injury. Therefore, depletion of reactive oxygen species (ROS) and inhibition of necroptosis in RGCs has become one of treatment strategies for glaucoma. However, existing drugs without efficient drug enter into the retina and have controlled release due to a short drug retention. Herein, we designed a glaucomatous microenvironment-responsive drug carrier polymer, which is characterized by the presence of thioketal bonds and 1,4-dithiane unit in the main chain for depleting ROS as well as the pendant cholesterols for targeting cell membranes. This polymer was adopted to encapsulate an inhibitor of necroptosis, necrostatin-1, into nanoparticles (designated as NP1). NP1 with superior biosafety could scavenge ROS in RGCs both in vitro and in vivo of an acute pathological glaucomatous injury model. Further, NP1 was found to effectively inhibit the upregulation of the necroptosis pathway, reducing the death of RGCs. The findings in this study exemplified the use of nanomaterials as potential strategies to treat glaucoma.

The roles of mitochondrial dynamics and NLRP3 inflammasomes in the pathogenesis of retinal light damage.

With the widespread popularity of electronic products and the diversification of lighting equipment, ocular photochemical damage caused by light has attracted research attention. Although such equipment mainly cause damage to the retina, the specific pathogenesis has not been systematically elucidated. Thus, the goal of this study was to explore the relationship between mitochondrial dysfunction and the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in retinal cell death caused by light damage. We used a white light-emitting diode source to establish a mouse model of retinal light damage and observed significant changes of retinal structure and an impairment of visual function. Further experiments revealed that dynamin-related protein 1 (Drp1)-mediated excessive mitochondrial fission induced overproduction of reactive oxygen species in the retinal cells, leading to apoptosis, activation of microglia, and formation of the NLRP3 inflammasome. This, in turn, triggered a series of inflammatory cascade reactions, leading to pyroptosis. We also carried out red light and Drp1 inhibitor treatment and found that retinal damage and the decline in visual function caused by white light could be partially ameliorated. In conclusion, this study clarified the association between mitochondrial dynamics and the NLRP3 inflammasome in retinal light damage and provides opportunities for therapeutic intervention.

Cross-species opsonic activity of zebrafish fish-egg lectin on mouse macrophages.

Zebrafish Fish-egg lectin (zFEL) has been identified and proved to be a maternal factor with antibacterial and opsonic ability in fishes. In this study, we found that zFEL was capable of enhancing the phagocytosis of the bacteria by macrophages of mouse (RAW264.7 and mouse peritoneal macrophages), suggesting a cross-species function of zFEL in higher animals. Further studies showed that zFEL can active the antigen presentation ability by up-regulating the expression of CD80, CD86 and MHC II. Meanwhile, zFEL also promoted the polarization of macrophages to M1-type, which was confirmed by the increase of cytokines TNF-α and IL-6. The expression of p38 gene was up-regulated in macrophages preincubated with zFEL. Taken together, zFEL appears opsonic function in mammal macrophages and has potential application in immunomodulation.

Astrogliosis in aging and Parkinson's disease dementia: a new clinical study with 11C-BU99008 PET.

The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an imidazoline-2 binding sites-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls and patients with established Parkinson's disease dementia. Eighteen healthy controls (age: 45-78 years) and six patients with Parkinson's disease dementia (age: 64-77 years) had one 11C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3 T MRI brain scan to facilitate the analysis of the PET data and to capture individual cerebral atrophy. Regional 11C-BU99008 volumes of distribution were calculated for each subject by the two-tissue compartmental modelling. Positive correlations between 11C-BU99008 volumes of distribution values and age were found for all tested regions across the brain within healthy controls (P < 0.05); furthermore, multiple regression indicated that aging affects 11C-BU99008 volumes of distribution values in a region-specific manner. Independent samples t-test indicated that there was no significant group difference in 11C-BU99008 volumes of distribution values between Parkinson's disease dementia (n = 6; mean age = 71.97 ± 4.66 years) and older healthy controls (n = 9; mean age = 71.90 ± 5.51 years). Our data set shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, 11C-BU99008 PET cannot differentiate patients with Parkinson's disease dementia from healthy controls of similar age.