China's "coal-to-gas" policy had large impact on PM1.0 distribution during 2016-2019.

Particulate matter with an aerodynamic diameter of less than 1 µm (PM1.0) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM1.0 and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM1.0 concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations. The coefficient of determination (R2) of the model is 0.94, and the root-mean-square error (RMSE) is 8.49 µg/m3, mean absolute error (MAE) is 4.10 µg/m3, proving that the model has a very high performance. Based on the model, this study analyzed the PM1.0 concentration changes during the heating period (November and December) in the regions where the "coal-to-gas" policy was implemented in China, and found that the proposed "coal-to-gas" policy did reduce the PM1.0 concentration in the implemented regions. However, the lack of natural gas due to the unreasonable deployment of the policy in the early stage caused the increase of PM1.0 concentration. This study can provide a reference for the next step of urban air pollution policy development.

Organic photoelectrochemical transistor aptasensor for dual-mode detection of DEHP with CRISPR-Cas13a assisted signal amplification.

Emerging organic photoelectrochemical transistors (OPECTs) with inherent amplification capabilities, good biocompatibility and even self-powered operation have emerged as a promising detection tool, however, they are still not widely studied for pollutant detection. In this paper, a novel OPECT dual-mode aptasensor was constructed for the ultrasensitive detection of di(2-ethylhexyl) phthalate (DEHP). MXene/In2S3/In2O3 Z-scheme heterojunction was used as a light fuel for ion modulation in sensitive gated OPECT biosensing. A transistor system based on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) converted biological events associated with photosensitive gate achieving nearly a thousand-fold higher current gain at zero bias voltage. This work quantified the target DEHP by aptamer-specific induction of CRISPR-Cas13a trans-cutting activity with target-dependent rolling circle amplification as the signal amplification unit, and incorporated the signal changes strategy of biocatalytic precipitation and TMB color development. Combining OPECT with the auxiliary validation of colorimetry (CM), high sensitivity and accurate detection of DEHP were achieved with a linear range of 0.1 pM to 200 pM and a minimum detection limit of 0.02 pM. This study not only provides a new method for the detection of DEHP, but also offers a promising prospect for the gating and application of the unique OPECT.

Against all odds: The road to success in the development of human immune reconstitution mice.

The mouse genome has a high degree of homology with the human genome, and its physiological, biochemical, and developmental regulation mechanisms are similar to those of humans; therefore, mice are widely used as experimental animals. However, it is undeniable that interspecies differences between humans and mice can lead to experimental errors. The differences in the immune system have become an important factor limiting current immunological research. The application of immunodeficient mice provides a possible solution to these problems. By transplanting human immune cells or tissues, such as peripheral blood mononuclear cells or hematopoietic stem cells, into immunodeficient mice, a human immune system can be reconstituted in the mouse body, and the engrafted immune cells can elicit human-specific immune responses. Researchers have been actively exploring the development and differentiation conditions of host recipient animals and grafts in order to achieve better immune reconstitution. Through genetic engineering methods, immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts. From initially only being able to reconstruct single T lymphocyte lineages, it is now possible to reconstruct lymphoid and myeloid cells, providing important research tools for immunology-related studies. In this review, we compare the differences in immune systems of humans and mice, describe the development history of human immune reconstitution from the perspectives of immunodeficient mice and grafts, and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution, aiming to provide important references for immunological related researches.

Adipose stem cells control obesity-induced T cell infiltration into adipose tissue.

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.

Dibutyl phthalate exposure induced mitochondria-dependent ferroptosis by enhancing VDAC2 in zebrafish ZF4 cells.

Dibutyl phthalate (DBP) contamination has raised global concern for decades, while its health risk with toxic mechanisms requires further elaboration. This study used zebrafish ZF4 cells to investigate the toxicity of ferroptosis with underlying mechanisms in response to DBP exposure. Results showed that DBP induced ferroptosis, characterized by accumulation of ferrous iron, lipid peroxidation, and decrease of glutathione peroxidase 4 levels in a time-dependent manner, subsequently reduced cell viability. Transcriptome analysis revealed that voltage-dependent anion-selective channel (VDAC) in mitochondrial outer membrane was upregulated in ferroptosis signaling pathways. Protecting mitochondria with a VDAC2 inhibitor or siRNAs attenuated the accumulation of mitochondrial superoxide and lipid peroxides, the opening of mitochondrial permeability transition pore (mPTP), and the overload of iron levels, suggesting VDAC2 oligomerization mediated the influx of iron into mitochondria that is predominant and responsible for mitochondria-dependent ferroptosis under DBP exposure. Furthermore, the pivotal role of activating transcription factor 4 (ATF4) was identified in the transcriptional regulation of vdac2 by ChIP assay. And the intervention of atf4b inhibited DBP-induced VDAC2 upregulation and oligomerization. Taken together, this study reveals that ATF4-VDAC2 signaling pathway is involved in the DBP-induced ferroptosis in zebrafish ZF4 cells, contributing to the in-depth understanding of biotoxicity and the ecological risk assessment of phthalates.

Dclre1c-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research.

Severe combined immunodeficient (SCID) mice serve as a critical model for human xenotransplantation studies, yet they often suffer from low engraftment rates and susceptibility to graft-versus-host disease (GVHD). Moreover, certain SCID strains demonstrate 'immune leakage', underscoring the need for novel model development. Here, we introduce an SCID mouse model with a targeted disruption of the dclre1c gene, encoding Artemis, which is essential for V(D)J recombination and DNA repair during T cell receptor (TCR) and B cell receptor (BCR) assembly. Artemis deficiency precipitates a profound immunodeficiency syndrome, marked by radiosensitivity and compromised T and B lymphocyte functionality. Utilizing CRISPR/Cas9-mediated gene editing, we generated dclre1c-deficient mice with an NOD genetic background. These mice exhibited a radiosensitive SCID phenotype, with pronounced DNA damage and defective thymic, splenic and lymph node development, culminating in reduced T and B lymphocyte populations. Notably, both cell lines and patient-derived tumor xenografts were successfully engrafted into these mice. Furthermore, the human immune system was effectively rebuilt following peripheral blood mononuclear cells (PBMCs) transplantation. The dclre1c-knockout NOD mice described herein represent a promising addition to the armamentarium of models for xenotransplantation, offering a valuable platform for advancing human immunobiological research.

Grape Seed Proanthocyanidins Protect Pancreatic ß Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.

Pancreatic ß cell damage is the primary contributor to type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains nebulous. This study explored the role of ferroptosis in pancreatic ß cell damage and the protective effects of grape seed proanthocyanidin extract (GSPE). In T2DM model rats, the blood glucose, water intake, urine volume, HbA1c, and homeostasis model assessment-insulin resistance were significantly increased, while the body weight and the insulin level were significantly decreased, indicating the successful establishment of the T2DM model. MIN6 mouse insulinoma ß cells were cultured in high glucose and sodium palmitate conditions to obtain a glycolipid damage model, which was administered with GSPE, ferrostatin-1 (Fer-1), or nuclear factor erythroid 2-related factor 2 (Nrf2) small interfering (si) RNA. GSPE and Fer-1 treatment significantly improved pancreatic ß-cell dysfunction and protected against cell death. Both treatments increased the superoxide dismutase and glutathione activity, reduced the malondialdehyde and reactive oxygen species levels, and improved iron metabolism. Furthermore, the treatments reversed the expression of ferroptosis markers cysteine/glutamate transporter (XCT) and glutathione peroxidase 4 (GPX4) caused by glycolipid toxicity. GSPE treatments activated the expression of Nrf2 and related proteins. These effects were reversed when co-transfected with si-Nrf2. GSPE inhibits ferroptosis by activating the Nrf2 signaling pathway, thus reducing ß-cell damage and dysfunction in T2DM. Therefore, GSPE is a potential treatment strategy against T2DM.

mRNA PROTACs: engineering PROTACs for high-efficiency targeted protein degradation.

Proteolysis-targeting chimeras (PROTACs) are essential bifunctional molecules that target proteins of interest (POIs) for degradation by cellular ubiquitination machinery. Despite significant progress made in understanding PROTACs' functions, their therapeutic potential remains largely untapped. As a result of the success of highly flexible, scalable, and low-cost mRNA therapies, as well as the advantages of the first generation of peptide PROTACs (p-PROTACs), we present for the first time an engineering mRNA PROTACs (m-PROTACs) strategy. This design combines von Hippel-Lindau (VHL) recruiting peptide encoding mRNA and POI-binding peptide encoding mRNA to form m-PROTAC and promote cellular POI degradation. We then performed proof-of-concept experiments using two m-PROTACs targeting two cancer-related proteins, estrogen receptor alpha and B-cell lymphoma-extra large protein. Our results demonstrated that m-PROTACs could successfully degrade the POIs in different cell lines and more effectively inhibit cell proliferation than the traditional p-PROTACs. Moreover, the in vivo experiment demonstrated that m-PROTAC led to significant tumor regression in the 4T1 mouse xenograft model. This finding highlights the enormous potential of m-PROTAC as a promising approach for targeted protein degradation therapy.

MXene-Enhanced Bi2S3/CdIn2S4 Heterojunction Photosensitive Gate for DEHP Detection in a Signal-On OPECT Aptamer Biosensor.

Organic electrochemical transistors with signal amplification and good stability are expected to play a more important role in the detection of environmental pollutants. However, the bias voltage at the gate may have an effect on the activity of vulnerable biomolecules. In this work, a novel organic photoelectrochemical transistor (OPECT) aptamer biosensor was developed for di(2-ethylhexyl) phthalate (DEHP) detection by combining photoelectrochemical analysis with an organic electrochemical transistor, where MXene/Bi2S3/CdIn2S4 was employed as a photoactive material, target-dependent DNA hybridization chain reaction was used as a signal amplification unit, and Ru(NH3)63+ was selected as a signal enhancement molecule. The poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)-based OPECT biosensor modulated by the MXene/Bi2S3/CdIn2S4 photosensitive material achieved a high current gain of nearly a thousand times at zero bias voltage. The developed signal-on OPECT sensing platform realized sensitive and specific detection of DEHP, with a detection range of 1-200 pM and a minimum detection limit of 0.24 pM under optimized experimental conditions, and its application to real water samples was also evaluated with satisfactory results. Hence, the construction of this OPECT biosensing platform not only provides a promising tool for the detection of DEHP but also reveals the great potential of the OPECT application for the detection of other environmental toxins.

Ascorbic Acid Induced the Improved Oxygen Vacancy Defects of Bi4O5Br2 and Its Application on Photoelectrochemical Detection of DNA Demethylase MBD2 with Improved Detection Sensitivity.

Oxygen vacancy defects (OVs) are one of the main strategies for nanomaterials modification to improve the photoactivity, but current methods for fabricating OVs are usually complicated and harsh. It is important to develop simple, rapid, safe, and mild methods to fabricate OVs. By studying the effects of different weak reducing agents, the concentration of the reducing agent and the reaction time on fabrication of OVs, it is found that L-ascorbic acid (AA) gently and rapidly induces the increase of OVs in Bi4O5Br2 at room temperature. The increased OVs not only improve the adsorption of visible light, but also enhance the photocurrent response. Based on this, the preparation of OVs in Bi4O5Br2 is employed to the development of a photoelectrochemical biosensor for the detection of DNA demethylase of methyl-CpG binding domain protein 2 (MBD2). The biosensor shows a wide linear range of 0.1-400 ng mL-1 and a detection limit as low as 0.03 ng mL-1 (3σ). In addition, the effect of plasticizers on MBD2 activity is evaluated using this sensor. This work not only provides a novel method to prepare OVs in bismuth rich materials, but also explores a new novel evaluation tool for studying the ecotoxicological effects of contaminants.

NAD+ mediated photoelectrochemical biosensor for histone deacetylase Sirt1 detection based on CuO-BiVO4-AgNCs heterojunction and hybridization chain reaction amplification.

BACKGROUND: Histone deacetylate Sirt1 has been involved in many important biological processes and is closely related to the occurrence and development of many diseases. Therefore, the accurate detection of Sirt1 is of great significance for the diagnosis and treatment of diseases caused by Sirt1 and the development of related drugs. RESULTS: In this work, a photoelectrochemical biosensor was developed for Sirt1 detection based on the NAD + mediated Sirt1 recognition and E. Coli DNA ligase activity. CuO-BiVO4p-n heterojunction was employed as the photoactive material, rolling circle amplification (RCA), hybridization chain reaction (HCR) and AgNCs were used as triple signal amplifications. As a bifunctional cofactor, NAD+ played a crucial role for Sirt1 detection, where the peptide deacetylation catalyzed by Sirt1 consumed NAD+, and the decreased amount of NAD + inhibited the activity of E. Coli DNA ligase, leading to the failure on RCA reaction, and improving the HCR reaction. Finally, AgNCs were generated using C-rich DNA as carrier. The surface plasmon effect of AgNCs and its heterojunction with CuO and BiVO4 accelerated the transfer rate of photogenerated carriers and improved the photocurrent signal. When the detection range was 0.001-200 nM, the detection limit of the biosensor was 0.76 pM (S/N = 3). SIGNIFICANCE: The applicability of the method was evaluated by studying the effects of known inhibitors nicotinamide and environmental pollutant halogenated carbazole on Sirt1 enzyme activity. The results showed that this method can be used as a new platform for screening Sirt1 enzyme inhibitors, and also provided a new biomarker for evaluating the ecotoxicological effects of environmental pollutants.

[Model construction and software design of computed tomography radiation system based on visualization].

The Monte Carlo N-Particle (MCNP) is often used to calculate the radiation dose during computed tomography (CT) scans. However, the physical calculation process of the model is complicated, the input file structure of the program is complex, and the three-dimensional (3D) display of the geometric model is not supported, so that the researchers cannot establish an accurate CT radiation system model, which affects the accuracy of the dose calculation results. Aiming at these two problems, this study designed a software that visualized CT modeling and automatically generated input files. In terms of model calculation, the theoretical basis was based on the integration of CT modeling improvement schemes of major researchers. For 3D model visualization, LabVIEW was used as the new development platform, constructive solid geometry (CSG) was used as the algorithm principle, and the introduction of editing of MCNP input files was used to visualize CT geometry modeling. Compared with a CT model established by a recent study, the root mean square error between the results simulated by this visual CT modeling software and the actual measurement was smaller. In conclusion, the proposed CT visualization modeling software can not only help researchers to obtain an accurate CT radiation system model, but also provide a new research idea for the geometric modeling visualization method of MCNP.

[A comprehensive review on photon-counting computed tomography: Principles, technical hurdles and analysis of clinical applications].

In recent years, photon-counting computed tomography (PCD-CT) based on photon-counting detectors (PCDs) has become increasingly utilized in clinical practice. Compared with conventional CT, PCD-CT has the potential to achieve micron-level spatial resolution, lower radiation dose, negligible electronic noise, multi-energy imaging, and material identification, etc. This advancement facilitates the promotion of ultra-low dose scans in clinical scenarios, potentially detecting minimal and hidden lesions, thus significantly improving image quality. However, the current state of the art is limited and issues such as charge sharing, pulse pileup, K-escape and count rate drift remain unresolved. These issues could lead to a decrease in image resolution and energy resolution, while an increasing in image noise and ring artifact and so on. This article systematically reviewed the physical principles of PCD-CT, and outlined the structural differences between PCDs and energy integration detectors (EIDs), and the current challenges in the development of PCD-CT. In addition, the advantages and disadvantages of three detector materials were analysed. Then, the clinical benefits of PCD-CT were presented through the clinical application of PCD-CT in the three diseases with the highest mortality rate in China (cardiovascular disease, tumour and respiratory disease). The overall aim of the article is to comprehensively assist medical professionals in understanding the technological innovations and current technical limitations of PCD-CT, while highlighting the urgent problems that PCD-CT needs to address in the coming years.

Comparison of the Visual Outcomes of Enhanced and Standard Monofocal Intraocular Lens Implantations in Eyes with Early Glaucoma.

This study aimed to compare the efficacies and safety of enhanced and standard monofocal intraocular lenses (IOLs) in eyes with early glaucoma. Patients with concurrent cataracts and open-angle glaucoma (OAG) were enrolled. They underwent cataract surgery with IOL implantation. The comprehensive preoperative ophthalmic examination included the manifest refraction; monocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA); visual field (VF); and contrast sensitivity (CS); defocus curves and questionnaires were assessed three months postoperatively. Totals of 34 and 38 patients had enhanced and standard monofocal IOLs, respectively. The enhanced monofocal IOL provided better UIVA than the standard monofocal IOL (p = 0.003) but similar UDVA, CDVA, and UNVA. The enhanced monofocal IOL had more consistent defocus curves than the standard monofocal IOL, especially at -1 (p = 0.042) and -1.5 (p = 0.026) diopters. The enhanced monofocal IOL provided better satisfaction (p = 0.019) and lower spectacle dependence (p = 0.004) than the standard monofocal IOL for intermediate vision, with similar VF and CS outcomes. In conclusion, enhanced monofocal IOLs are recommended for patients with OAG because they provide better intermediate vision, higher satisfaction, and lower dependence on spectacles than standard monofocal IOLs, without worsening other visual outcomes.

[Automatic sleep staging model based on single channel electroencephalogram signal].

Sleep staging is the basis for solving sleep problems. There's an upper limit for the classification accuracy of sleep staging models based on single-channel electroencephalogram (EEG) data and features. To address this problem, this paper proposed an automatic sleep staging model that mixes deep convolutional neural network (DCNN) and bi-directional long short-term memory network (BiLSTM). The model used DCNN to automatically learn the time-frequency domain features of EEG signals, and used BiLSTM to extract the temporal features between the data, fully exploiting the feature information contained in the data to improve the accuracy of automatic sleep staging. At the same time, noise reduction techniques and adaptive synthetic sampling were used to reduce the impact of signal noise and unbalanced data sets on model performance. In this paper, experiments were conducted using the Sleep-European Data Format Database Expanded and the Shanghai Mental Health Center Sleep Database, and achieved an overall accuracy rate of 86.9% and 88.9% respectively. When compared with the basic network model, all the experimental results outperformed the basic network, further demonstrating the validity of this paper's model, which can provide a reference for the construction of a home sleep monitoring system based on single-channel EEG signals.

Mechanical Properties, Microstructure, and In Vitro Digestion of Transglutaminase-Crosslinked Whey Protein and Potato Protein Hydrolysate Composite Gels.

The production of animal protein usually leads to higher carbon emissions than that of plant protein. To reduce carbon emissions, the partial replacement of animal protein with plant protein has attracted extensive attention; however, little is known about using plant protein hydrolysates as a substitute. The potential application of 2 h-alcalase hydrolyzed potato protein hydrolysate (PPH) to displace whey protein isolate (WPI) during gel formation was demonstrated in this study. The effect of the ratios (8/5, 9/4, 10/3, 11/2, 12/1, and 13/0) of WPI to PPH on the mechanical properties, microstructure, and digestibility of composite WPI/PPH gels was investigated. Increasing the WPI ratio could improve the storage modulus (G') and loss modulus (G″) of composite gels. The springiness of gels with the WPH/PPH ratio of 10/3 and 8/5 was 0.82 and 0.36 times higher than that of the control (WPH/PPH ratio of 13/0) (p < 0.05). In contrast, the hardness of the control samples was 1.82 and 2.38 times higher than that of gels with the WPH/PPH ratio of 10/3 and 8/5 (p < 0.05). According to the International Organization for Standardization of Dysphagia Diet (IDDSI) testing, the composite gels belonged to food level 4 in the IDDSI framework. This suggested that composite gels could be acceptable to people with swallowing difficulties. Confocal laser scanning microscopy and scanning electron microscopy images illustrated that composite gels with a higher ratio of PPH displayed thicker gel skeletons and porous networks in the matrix. The water-holding capacity and swelling ratio of gels with the WPH/PPH ratio of 8/5 decreased by 12.4% and 40.8% when compared with the control (p < 0.05). Analysis of the swelling rate with the power law model indicated that water diffusion in composite gels belonged to non-Fickian transport. The results of amino acid release suggested that PPH improved the digestion of composite gels during the intestinal stage. The free amino group content of gels with the WPH/PPH ratio of 8/5 increased by 29.5% compared with the control (p < 0.05). Our results suggested that replacing WPI with PPH at the ratio of 8/5 could be the optimal selection for composite gels. The findings indicated that PPH could be used as a substitute for whey protein to develop new products for different consumers. Composite gels could deliver nutrients such as vitamins and minerals to develop snack foods for elders and children.

Photoelectrochemical biosensor for DNA demethylase detection based on enzymatically induced double-stranded DNA digestion by endonuclease-exonuclease system and Bi4O5Br2-Au/CdS photoactive material.

A novel photoelectrochemical (PEC) biosensor for the detection of DNA demethylase MBD2 was developed based on Bi4O5Br2-Au/CdS photosensitive material. Bi4O5Br2 was firstly modified with gold nanoparticles (AuNPs), following with the modification onto the ITO electrode with CdS to realize the strong photocurrent response as a result of AuNPs had good conductibility and the matched energy between CdS and Bi4O5Br2. In the presence of MBD2, double-stranded DNA (dsDNA) on the electrode surface was demethylated, which triggered the digestion activity of endonuclease HpaII to cleave dsDNA and induced the further cleavage of the dsDNA fragment by exonuclease III (Exo III), causing the release of biotin labeled dsDNA and inhibiting the immobilization of streptavidin (SA) onto the electrode surface. As a results, the photocurrent was increased greatly. However, in the absence of MBD2, HpaII digestion activity was inhibited by DNA methylation modification, which further caused the failure in the release of biotin, leading to the successful immobilization of SA onto the electrode to realize a low photocurrent. The sensor had a detection of 0.3-200 ng/mL and a detection limit was 0.09 ng/mL (3σ). The applicability of this PEC strategy was assessed by studying the effect of environmental pollutants on MBD2 activity.

P53 Deficiency Accelerate Esophageal Epithelium Intestinal Metaplasia Malignancy.

Barrett's esophagus (BE) is a precancerous lesion of esophageal adenocarcinoma (EAC). It is a pathological change in which the squamous epithelium distal esophagus is replaced by columnar epithelium. Loss of P53 is involved in the development of BE and is taken as a risk factor for the progression. We established a HET1A cell line with P53 stably knockdown by adenovirus vector infection, followed by 30 days of successive acidic bile salt treatment. MTT, transwell assay, and wound closure assay were applied to assess cell proliferation and migration ability. The expression of key factors was analyzed by RT-qPCR, western blotting and immunohistochemical staining. Our data show that the protein expression level of P53 reduced after exposure to acidic bile salt treatment, and the P53 deficiency favors the survival of esophageal epithelial cells to accommodate the stimulation of acidic bile salts. Furthermore, exposure to acidic bile salt decreases cell adhesions by repressing the JAK/STAT signaling pathway and activating VEGFR/AKT in P53-deficient esophageal cells. In EAC clinical samples, P53 protein expression is positively correlated with that of ICAM1 and STAT3 and negatively correlated with VEGFR protein expression levels. These findings elucidate the role of P53 in the formation of BE, explain the mechanism of P53 deficiency as a higher risk of progression for BE formation, and provide potential therapeutic targets for EAC.

Antibody-free photoelectrochemical biosensor for DNA carboxylation detection based on SnS2@Ti3C2 heterojunction.

As an important epigenetic modification, 5-carboxycytosine (5caC) played an important role in gene regulation, cell differentiation and growth. 5caC existed in many cells and tissues, but it was highly similar to the structure of other cytosine derivatives and had less content in the genome. Therefore, it was urgent to develop a sensitive and highly selective trace biosensor to detect 5caC. A novel photoelectrochemical biosensor was fabricated for 5-carboxy-2'-deoxycytidine-5'-triphosphate (5cadCTP) detection, where SnS2@Ti3C2 nanocomposite was employed as photoactive material, polyethyleneimine was used as 5cadCTP recognition and capture reagent, and Ru(NH3)63+ was used as photosensitizer for signal amplification. Due the good conductivity of Ti3C2 MXene and the matched energy band between Ti3C2 MXene and SnS2, SnS2@Ti3C2 nanocomposite presented strong photoactivity, which was beneficial to the high detection sensitivity. For specific recognition of 5cadCTP, the covalent interaction of -NH2 in 5cadCTP with -COOH on the substrate electrode was used, which was beneficial to the high detection selectivity. A broad linear relationship between photocurrent and 5cadCTP concentration was observed ranging from 1 pM to 0.2 µM. The low detection limit of 260 fM was achieved. The developed method has high detection specificity and can even distinguish 5caC with its derivatives. In addition, the applicability was evaluated by detecting the content change of 5caC in the genomic DNA of rice seedlings after cultured with environmental pollutants. This work provides a novel platform for 5cadCTP detection, and it can also be applied to detect other cytosine derivatives with suitable recognition strategies.

Association Between Parapapillary Microvasculature Dropout and Central Retinal Vessel Trunk in Primary Open Angle Glaucoma.

PRCIS: Central retinal vessel trunk displacement is an important factor in the generation and development of deep-layer microvasculature dropout in primary open angle glaucoma. PURPOSE: To investigate the association between the microvasculature dropout and the central retinal vessel trunk in primary open angle glaucoma eyes. METHODS: In total, 112 eyes from 112 patients with primary open-angle glaucoma were included. Matched 26 no microvasculature dropout eyes and 26 microvasculature dropout eyes, they had similar axial length and global retinal nerve fiber layer thickness. Central retinal vessel trunk shift index was calculated as the distance of the central retinal vessel trunk from the Bruch membrane opening center relative to that of the Bruch membrane opening border. The correlation of the presence, extent, and location of microvasculature dropout and the displacement extent and location of the central retina vessel trunk was analyzed. RESULTS: The central retinal vessel trunk shift index differed significantly between the 2 matched groups. Multivariate logistic analyses showed that in 112 eyes from 112 patients, eyes with microvasculature dropout was significantly associated with larger shift index than eyes without microvasculature dropout. The angular circumference of microvasculature dropout was significantly associated with adjusted shift index (a linear mixed model was constructed, exclude the influence of axial length and global retinal nerve fiber layer thickness on shift index). The location of the microvasculature dropout and central retinal vessel trunk contralateral were significantly correlated. CONCLUSIONS: In primary open angle glaucoma eyes, microvasculature dropout and the central retinal vessel trunk were significantly correlated. Because the central retinal vessel trunk represents the structural stability of the lamina cribrosa, microvasculature dropout seems to correlate with lamina cribrosa's structural stability.