Group-based trajectory modeling for fear of cancer recurrence in cancer survivors: a systematic review.

PURPOSE: We aimed to systematically review studies that used a group-based trajectory modeling approach to explore the categories of fear of cancer recurrence (FCR) trajectories and their predictors in cancer survivors. METHODS: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science were searched. Three authors independently reviewed the literature for predefined eligibility criteria. The Joanna Briggs Institute critical appraisal tools for Cohort Studies and the Guidelines for Reporting on Latent Trajectory Studies were used to assess the quality of included studies. A qualitative synthesis of the included studies was performed. RESULTS: Ninety-eight studies were retrieved after removing duplicates, and 11 studies met the criteria for inclusion. There are four types of FCR trajectories: stable, decreasing, increasing, and stable-then-decreasing-then-increasing. The following factors were considered significant predictors of FCR trajectory category in at least one of the included studies: age, race, income, education, employment, cancer stage, physical symptoms, depression, anxiety, satisfaction with medical care, and selected cognitive and behavioral factors. CONCLUSIONS: There was considerable heterogeneity among the studies included in study design and FCR trajectory results. Factors that significantly predicted FCR trajectory categories mostly focused on psychological characteristics. The correlation of sociodemographic and disease-related predictors with FCR trajectory categories was not consistent among the included studies. IMPLICATIONS FOR CANCER SURVIVORS: We suggest that future scholars should incorporate more psychological factors when identifying cancer survivors who persistently maintain a high level of FCR and developing FCR mitigation measures.

TIN2-mediated reduction of mitophagy induces RPE senescence under high glucose.

The telomere-associated protein TIN2 localizes to both telomeres and mitochondria. Nevertheless, the impact of TIN2 on retinal pigment epithelial (RPE) cells in diabetic retinopathy (DR) remains unclear. This research aims to examine the role of TIN2 in the senescence of RPE and its potential as a therapeutic target. Western blotting and immunofluorescence staining were utilized to identify TIN2 expression and mitophagy. RT-qPCR was employed to identify senescent associated secretory phenotype (SASP) in ARPE-19 cells infected with TIN2 overexpression. To examine mitochondria and the cellular senescence of RPE, TEM, SA-ß-gal staining, and cell cycle analysis were used. The impact of TIN2 was examined using OCT and immunohistochemistry in mice. DHE staining and ZO-1 immunofluorescence were applied to detect RPE oxidative stress and tight junctions. Our research revealed that increased mitochondria-localized TIN2 aggravated the cellular senescence of RPE cells both in vivo and in vitro under hyperglycemia. TIN2 overexpression stimulated the mTOR signaling pathway in ARPE-19 cells and exacerbated the inhibition of mitophagy levels under high glucose, which can be remedied through the mTOR inhibitor, rapamycin. Knockdown of TIN2 significantly reduced senescence and mitochondrial oxidative stress in ARPE-19 cells under high glucose and restored retinal thickness and RPE cell tight junctions in DR mice. Our study indicates that increased mitochondria-localized TIN2 induced cellular senescence in RPE via compromised mitophagy and activated mTOR signaling. These results propose that targeting TIN2 could potentially serve as a therapeutic strategy in the treatment of DR.

Effects of returning paddy field to wetland on composition and stability of soil aggregates in the Yellow River Delta.

The composition and stability of soil aggregates are important indicators for measuring soil quality, which would be affected by land use changes. Taking wetlands with different returning years (2 and 15 years) in the Yellow River Delta as the research object, paddy fields and natural wetlands as control, we analyzed the changes in soil physicochemical properties and soil aggregate composition. The results showed that soil water content, total organic carbon, dissolved organic carbon and total phosphorus of the returning soil (0-40 cm) showed an overall increasing trend with returning period, while soil pH and bulk density was in adverse. There was no significant change in clay content, electrical conductivity, and total nitrogen content. The contents of macro-aggregates and micro-aggregates showed overall increasing and decreasing trend with returning period, respectively. The stability of aggregates in the topsoil (0-10 cm) increased with returning years. Geometric mean diameter and mean weight diameter increased by 8.9% and 40.4% in the 15th year of returning, respectively, while the mass proportion of >2.5 mm fraction decreased by 10.5%. There was no effect of returning on aggregates in subsoil (10-40 cm). Our results indicated that returning paddy field to wetland in the Yellow River Delta would play a positive role in improving soil structure and aggregate stability.

Construction of GPC3-modified Lipopolymer SiRNA Delivery System.

BACKGROUND: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared. METHODS: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining. RESULTS: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation. CONCLUSION: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

Biotransformation of Bioactive Metabolites in Cassiae Semen by Endogenous Enzymes and Probiotics.

The present study evaluated the potential of endogenous enzymes and probiotics in transforming bioactive metabolites to reduce the purgative effect and improve the functional activity of Cassiae Semen and verified and revealed the biotransformation effect of endogenous enzymes. Although probiotics, especially Lactobacillus rhamnosus, exerted the transformation effect, the endogenous enzymes proved to be more effective in transforming the components of Cassiae Semen. After biotransformation by endogenous enzymes for 12 h, the levels of six anthraquinones in Cassiae Semen increased by at least 2.98-fold, and free anthraquinones, total phenolics, and antioxidant activity also showed significant improvement, accompanied by an 82.2% reduction in combined anthraquinones responsible for the purgative effect of Cassiae Semen. Further metabolomic analysis revealed that the biotransformation effect of endogenous enzymes on the bioactive metabolites of Cassiae Semen was complex and diverse, and the biotransformation of quinones and flavonoids was particularly prominent and occurred by three primary mechanisms, hydrolyzation, methylation, and dimerization, might under the action of glycosyl hydrolases, SAM-dependent methyltransferases, and CYP450s. Accordingly, biotransformation by endogenous enzymes emerges as a mild, economical, food safety risk-free, and effective strategy to modify Cassiae Semen into an excellent functional food.

Gentulizumab, a novel anti-CD47 antibody with potent antitumor activity and demonstrates a favorable safety profile.

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. RESULTS: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. CONCLUSION: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.

SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.

BACKGROUND: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na+ overload, hypertrophy, and swelling. Therefore, in this study, we assessed the effect of SPAK inhibitor ZT-1a on pathogenesis and cognitive function in a mouse model of VCID induced by bilateral carotid artery stenosis (BCAS). METHODS: Following sham or BCAS surgery, mice were randomly assigned to receive either vehicle (DMSO) or SPAK inhibitor ZT-1a treatment regimen (days 14-35 post-surgery). Mice were then evaluated for cognitive functions by Morris water maze, WML by ex vivo MRI-DTI analysis, and astrogliosis/demyelination by immunofluorescence and immunoblotting. RESULTS: Compared to sham control mice, BCAS-Veh mice exhibited chronic cerebral hypoperfusion and memory impairments, accompanied by significant MRI DTI-detected WML and oligodendrocyte (OL) death. Increased activation of WNK-SPAK-NKCC1-signaling proteins was detected in white matter tissues and in C3d+ GFAP+ cytotoxic astrocytes but not in S100A10+ GFAP+ homeostatic astrocytes in BCAS-Veh mice. In contrast, ZT-1a-treated BCAS mice displayed reduced expression and phosphorylation of NKCC1, decreased astrogliosis, OL death, and WML, along with improved memory functions. CONCLUSION: BCAS-induced upregulation of WNK-SPAK-NKCC1 signaling contributes to white matter-reactive astrogliosis, OL death, and memory impairment. Pharmacological inhibition of the SPAK activity has therapeutic potential for alleviating pathogenesis and memory impairment in VCID.

Deletion of Slc9a1 in Cx3cr1+ cells stimulated microglial subcluster CREB1 signaling and microglia-oligodendrocyte crosstalk.

Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. To explore underlying mechanisms, we conducted single cell RNA-seq transcriptome analysis in conditional Slc9a1 knockout (cKO) and wild-type (WT) mouse white matter tissues at 3 days post-stroke. Compared to WT, Nhe1 cKO brains expanded a microglial subgroup with elevated transcription of white matter myelination genes including Spp1, Lgals3, Gpnmb, and Fabp5. This subgroup also exhibited more acidic pHi and significantly upregulated CREB signaling detected by ingenuity pathway analysis and flow cytometry. Moreover, the Nhe1 cKO white matter tissues showed enrichment of a corresponding oligodendrocyte subgroup, with pro-phagocytosis and lactate shuffling gene expression, where activated CREB signaling is a likely upstream regulator. These findings demonstrate that attenuation of NHE1-mediated H+ extrusion acidifies microglia/macrophage and may underlie the stimulation of CREB1 signaling, giving rise to restorative microglia-oligodendrocyte interactions for remyelination.

Energy and social factor decomposition to identify drivers impeding sustainable environmental transition in emerging countries: SDGs-2030 progress assessment using LMDI analysis.

The balance between human growth, economic prosperity, and the consumption of hydrocarbon energy factors has become a prerequisite for environmental sustainability. However, the complexities of these factors force researchers to work for more viable combinations of such a balance. Therefore, this study attempted to determine the factors driving environmental sustainability in leading populated economies. For this purpose, the Logarithmic Mean Division Index (LMDI) utilized to decompose critical factors such as activity, economy, real density, energy intensity, and suburban effects for the period 1999-2022. Both population and its consequences (economic activity) have been found to be the leading factors behind environmental fluctuations, and energy has a negative impact on hydrocarbon forms, while contributing positively to environmental sustainability with high efficiency and low intensity. Therefore, sustainable demographic and energy transitions can be leading pathways for environmental sustainability in developing economies.

Ion imprinted differential modulation system based on enhanced optic-fiber evanescent wave for sensitive and label-free detection of trace nickel ions.

An optical system with low cost monitoring, high sensitivity, strong selectivity and much lower nickel ion (Ni2+) content in tap water than the World Health Organization (WHO) standard (1.19 µM) has been prepared by a simple strategy. This proposed ion-imprinted differential modulation system is based on the Bragg grating (FBG) and microfiber interferometer structure, and the interferometer sensing surface is coated with a polydopamine (PDA)/graphene oxide (GO) film to enhance its sensitivity. Combined with the ion imprinting technique, the microfiber interferometer sensor sensitivity can reach 0.32 nm/nM with the detection limit of 0.66 nM in the low concentration range (Ni2+ concentration range is 0 nM-100 nM). The experiment not only studies the principle of microfiber interferometer and FBG and their refractive index and temperature performance, but also shows that the FBG power change has a good fitting relationship with wavelength change. In addition, this system performance by the amount of power difference rather than the amount of wavelength shift, which significantly saves on the high cost weight, and size associated with the use of spectral analyzers in traditional inspection systems. This study provides a novel and easy method to develop new sensors with higher comprehensive performance.

Loss of mitogen-activated protein kinase phosphate-5 aggravates islet dysfunction in mice with type 1 and type 2 diabetes.

Impaired functionality and loss of islet ß-cells are the primary abnormalities underlying the pathogenesis of both type 1 and 2 diabetes (T1DM and T2DM). However, specific therapeutic and preventive mechanisms underlying these conditions remain unclear. Mitogen-activated protein kinase phosphatase-5 (MKP-5) has been implicated in carcinogenesis, lipid metabolism regulation, and immune cell activation. In a previous study, we demonstrated the involvement of exogenous MKP-5 in the regulation of obesity-induced T2DM. However, the role of endogenous MKP-5 in the T1DM and T2DM processes is unclear. Thus, mice with MKP-5 knockout (KO) were generated and used to establish mouse models of both T1DM and T2DM. Our results showed that MKP-5 KO exacerbated diabetes-related symptoms in mice with both T1DM and T2DM. Given that most phenotypic studies on islet dysfunction have focused on mice with T2DM rather than T1DM, we specifically aimed to investigate the role of endoplasmic reticulum stress (ERS) and autophagy in T2DM KO islets. To accomplish this, we performed RNA sequence analysis to gain comprehensive insight into the molecular mechanisms associated with ERS and autophagy in T2DM KO islets. The results showed that the islets from mice with MKP-5 KO triggered 5' adenosine monophosphate-activated protein kinase (AMPK)-mediated autophagy inhibition and glucose-regulated protein 78 (GRP-78)-dominated ERS. Hence, we concluded that the autophagy impairment, resulting in islet dysfunction in mice with MKP-5 KO, is mediated through GRP-78 involvement. These findings provide valuable insights into the molecular pathogenesis of diabetes and highlight the significant role of MKP-5. Moreover, this knowledge holds promise for novel therapeutic strategies targeting MKP-5 for diabetes management.

PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.

BACKGROUND: Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. MAIN BODY: In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. CONCLUSION: Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.

UCP2-SIRT3 Signaling Relieved Hyperglycemia-Induced Oxidative Stress and Senescence in Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) is one of the most common reasons for blindness. uncoupling protein 2 (UCP2), an uncoupling protein located in mitochondria, has been reported to be related to metabolic and vascular diseases. This research aimed to illustrate the function and mechanism of UCP2 in the pathogenesis of DR. Methods: Human epiretinal membranes were collected to investigate the expression of UCP2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence. Primary human retinal microvascular endothelial cells (HRECs) were cultured in high glucose (HG) to establish an in vitro cell model for DR. Flow cytometry analysis was used to measure intracellular reactive oxygen species (ROS). Senescence levels were evaluated by the senescence-associated beta-galactosidase (SA-ß-gal) assay, the expression of senescence marker P21, and cell-cycle analysis. Adenovirus-mediated UCP2 overexpression or knockdown and specific inhibitors were administered to investigate the underlying regulatory mechanism. Results: Proliferative fibrovascular membranes from patients with DR illustrated the downregulation of UCP2 and sirtuin 3 (SIRT3) by qRT-PCR and immunofluorescence. Persistent hyperglycemia-induced UCP2 downregulation in the progress of DR and adenovirus-mediated UCP2 overexpression protected endothelial cells from hyperglycemia-induced oxidative stress and senescence. Under hyperglycemic conditions, UCP2 overexpression attenuated NAD+ downregulation; hence, it promoted the expression and activity of SIRT3, an NAD+-dependent deacetylase regulating mitochondrial function. 3-TYP, a selective SIRT3 inhibitor, abolished the UCP2-mediated protective effect against oxidative stress and senescence. Conclusions: UCP2 overexpression relieved oxidative stress and senescence based on a novel mechanism whereby UCP2 can regulate the NAD+-SIRT3 axis. Targeting oxidative stress and senescence amelioration, UCP2-SIRT3 signaling may serve as a method for the prevention and treatment of DR and other diabetic vascular diseases.

Steroid profiling in adrenal disease.

The measurement of steroid hormones in blood and urine, which reflects steroid biosynthesis and metabolism, has been recognized as a valuable tool for identifying and distinguishing steroidogenic disorders. The application of mass spectrometry enables the reliable and simultaneous analysis of large panels of steroids, ushering in a new era for diagnosing adrenal diseases. However, the interpretation of complex hormone results necessitates the expertise and experience of skilled clinicians. In this scenario, machine learning techniques are gaining worldwide attention within healthcare fields. The clinical values of combining mass spectrometry-based steroid profiles analysis with machine learning models, also known as steroid metabolomics, have been investigated for identifying and discriminating adrenal disorders such as adrenocortical carcinomas, adrenocortical adenomas, and congenital adrenal hyperplasia. This promising approach is expected to lead to enhanced clinical decision-making in the field of adrenal diseases. This review will focus on the clinical performances of steroid profiling, which is measured using mass spectrometry and analyzed by machine learning techniques, in the realm of decision-making for adrenal diseases.

An overview of mild traumatic brain injuries and emerging therapeutic targets.

The majority of traumatic brain injuries (TBIs), approximately 90%, are classified as mild (mTBIs). Globally, an estimated 4 million injuries occur each year from concussions or mTBIs, highlighting their significance as a public health crisis. TBIs can lead to substantial long-term health consequences, including an increased risk of developing Alzheimer's Disease, Parkinson's Disease (PD), chronic traumatic encephalopathy (CTE), and nearly doubling one's risk of suicide. However, the current management of mTBIs in clinical practice and the available treatment options are limited. There exists an unmet need for effective therapy. This review addresses various aspects of mTBIs based on the most up-to-date literature review, with the goal of stimulating translational research to identify new therapeutic targets and improve our understanding of pathogenic mechanisms. First, we provide a summary of mTBI symptomatology and current diagnostic parameters such as the Glasgow Coma Scale (GCS) for classifying mTBIs or concussions, as well as the utility of alternative diagnostic parameters, including imaging techniques like MRI with diffusion tensor imaging (DTI) and serum biomarkers such as S100B, NSE, GFAP, UCH-L1, NFL, and t-tau. Our review highlights several pre-clinical concussion models employed in the study of mTBIs and the underlying cellular mechanisms involved in mTBI-related pathogenesis, including axonal damage, demyelination, inflammation, and oxidative stress. Finally, we examine a selection of new therapeutic targets currently under investigation in pre-clinical models. These targets may hold promise for clinical translation and address the pressing need for more effective treatments for mTBIs.

TRIM25 inhibition attenuates inflammation, senescence, and oxidative stress in microvascular endothelial cells induced by hyperglycemia.

PURPOSES: This work aimed to assess the possible role of TRIM25 in regulating hyperglycemia-induced inflammation, senescence, and oxidative stress in retinal microvascular endothelial cells, all of which exert critical roles in the pathological process of diabetic retinopathy. METHODS: The effects of TRIM25 were investigated using streptozotocin-induced diabetic mice, human primary retinal microvascular endothelial cells cultured in high glucose, and adenoviruses for TRIM25 knockdown and overexpression. TRIM25 expression was evaluated by western blot and immunofluorescence staining. Inflammatory cytokines were detected by western blot and quantitative real-time PCR. Cellular senescence level was assessed by detecting senescent marker p21 and senescence-associated-ß-galactosidase activity. The oxidative stress state was accessed by detecting reactive oxygen species and mitochondrial superoxide dismutase. RESULTS: TRIM25 expression is elevated in the endothelial cells of the retinal fibrovascular membrane from diabetic patients compared with that of the macular epiretinal membrane from non-diabetic patients. Moreover, we have also observed a significant increase in TRIM25 expression in diabetic mouse retina and retinal microvascular endothelial cells under hyperglycemia. TRIM25 knockdown suppressed hyperglycemia-induced inflammation, senescence, and oxidative stress in human primary retinal microvascular endothelial cells while TRIM25 overexpression further aggregates those injuries. Further investigation revealed that TRIM25 promoted the inflammatory responses mediated by the TNF-α/NF-κB pathway and TRIM25 knockdown improved cellular senescence by increasing SIRT3. However, TRIM25 knockdown alleviated the oxidative stress independent of both SIRT3 and mitochondrial biogenesis. CONCLUSION: Our study proposed TRIM25 as a potential therapeutic target for the protection of microvascular function during the progression of diabetic retinopathy.

An all-fiber system biosensor for trace ß-lactam antibiotics detection enhanced by functionalized microfiber and fiber bragg grating.

An all-fiber-optic system for rapid detection of antibiotic concentration, based on an optical enzyme biosensor with microfiber interferometer (MFI) and fiber gratings (FBGs) power variation, is proposed and experimentally validated. During the experiment, ß-lactamase(ß-LS) is fixed on the polyaniline (PANI)-coated optical fiber by cross-linking through glutaraldehyde (GA) covalent bonding. ß-LS can hydrolyze ß-lactam antibiotics to generate acidic by-products that transform polyaniline from the form of the emerald base to emerald salt, which results in the surface refractive index (RI) variation of MFI, to convert MFI wavelength and FBGs power macroscopic change for feedbackingly detecting the concentration of ß-lactam antibiotics. The detection of amoxicillin (AMX) in deionized water at concentrations in the range of 0.01-100 nM resulted in a wavelength change sensitivity of 0.6 nm/nM, and FBGs power difference change sensitivity of 1.3 dB/nM, with a detection limit LOD = 0.04 nM in real food and urine samples. The sensing system by the same calibration technique can detect antibiotic concentrations in different substances (tap water, milk and artificial urine). This developed all-fiber-optic system can be used as a rapid solution for the measurement of ß-lactam antibiotic residues in food and the environment.

Transcriptional regulatory mechanism of NR2F2 and ZNF423 in avian preadipocyte differentiation.

In the poultry industry, excessive abdominal fat deposition is not conducive to meat quality. Therefore, selection for optimal fat content levels in poultry has become a major breeding goal. We previously constructed NR2F2 overexpression (NR2F2OE) and knockout (NR2F2Δ/Δ/83-125aa) cell lines using Piggybac and CRISPR/Cas9 techniques, and confirmed that the transcription factor NR2F2 can significantly inhibit the differentiation of avian preadipocytes. In this study, we identified a downstream gene ZNF423 regulated by NR2F2, which is also involved in regulating avian fat deposition. First, we performed transcriptome analysis of the NR2F2-edited lines, which has been proven to be an inhibitor of avian fat deposition in our previous studies. Our findings revealed that NR2F2 affects a series of candidate regulators related to adipogenesis. Among these, we focused on ZNF423, which was significantly down-regulated in the NR2F2OE cell line and up-regulated in the NR2F2Δ/Δ/83-125aa cell line. Next, dual luciferase reporter assay results showed that the DNA-binding domain (DBDΔ72-143aa) of transcription factor NR2F2 may negatively affect the expression of downstream target gene ZNF423 by binding to its distal promoter region (-2356 to -2346). Moreover, we constructed a function analytical model and found that overexpression of ZNF423 significantly facilitated the differentiation of adipocytes in immortalized chicken preadipocytes (ICP1). Consistent with these findings, global transcriptome analysis of the ZNF423-overexpressed cell line (ZNF423OE) further demonstrated that the process of adipogenesis was significantly enriched. These results indicate that ZNF423 is a positive regulator of avian adipocyte differentiation. Overexpression of ZNF423 in the NR2F2OE cell line compensated for the inhibition of fat deposition phenotype, further suggesting that ZNF423 is a downstream target gene of NR2F2. These findings uncover a novel function of ZNF423 in avian adipocyte differentiation and analyzed the transcriptional regulation by its upstream transcription factor NR2F2. Additionally, we identified a list of functional candidate genes, providing important insights for further research on the mechanism of avian fat deposition.

Dual contrast CEST MRI for pH-weighted imaging in stroke.

PURPOSE: pH enhanced (pHenh ) CEST imaging combines the pH sensitivity from amide and guanidino signals, but the saturation parameters have not been optimized. We propose pHdual as a variant of pHenh that suppresses background signal variations, while enhancing pH sensitivity and potential for imaging ischemic brain injury of stroke. METHODS: Simulation and in vivo rodent stroke experiments of pHenh MRI were performed with varied RF saturation powers for both amide and guanidino protons to optimize the contrast between lesion/normal tissues, while simultaneously minimizing signal variations across different types of normal tissues. In acute stroke, contrast and volume ratio measured by pHdual imaging were compared with an amide-CEST approach, and perfusion and diffusion MRI. RESULTS: Simulation experiments indicated that amide and guanidino CEST signals exhibit unique sensitivities across different pH ranges, with pHenh producing greater sensitivity over a broader pH regime. The pHenh data of rodent stroke brain demonstrated that the lesion/normal tissue contrast was maximized for an RF saturation power pair of 0.5 µT at 2.0 ppm and 1.0 µT at 3.6 ppm, whereas an optimal contrast-to-variation ratio (CVR) was obtained with a 0.7 µT saturation at 2.0 ppm and 0.8 µT at 3.6 ppm. In acute stroke, CVR optimized pHenh (i.e., pHdual ) achieved a higher sensitivity than the three-point amide-CEST approach, and distinct patterns of lesion tissue compared to diffusion and perfusion MRI. CONCLUSION: pHdual MRI improves the sensitivity of pH-weighted imaging and will be a valuable tool for assessing tissue viability in stroke.

Graph Convolution and Self-attention Enhanced CNN with Domain Adaptation for Multi-site COVID-19 Diagnosis.

In 2019, coronavirus disease (COVID-19) is an acute disease that can rapidly develop into a very serious state. Therefore, it is of great significance to realize automatic COVID-19 diagnosis. However, due to the small difference in the characteristics of computed tomography (CT) between community acquire pneumonia (CP) and COVID-19, the existing model is unsuitable for the three-class classifications of healthy control, CP and COVID-19. The current model rarely optimizes the data from multiple centers. Therefore, we propose a diagnosis model for COVID-19 patients based on graph enhanced 3D convolution neural network (CNN) and cross-center domain feature adaptation. Specifically, we first design a 3D CNN with graph convolution module to enhance the global feature extraction capability of the CNN. Meanwhile, we use the domain adaptive feature alignment method to optimize the feature distance between different centers, which can effectively realize multi-center COVID-19 diagnosis. Our experimental results achieve quite promising COVID-19 diagnosis results, which show that the accuracy in the mixed dataset is 98.05%, and the accuracy in cross-center tasks are 85.29% and 87.53%.