Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2.

BACKGROUND: G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. METHODS: Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K+ current (IK1) were recorded using whole-cell patch clamps. Isolated cardiomyocytes were stained with Fluo-3/AM dye, and intracellular Ca2+ handling was examined by CCD camera. A mouse model of AF was established by Ang-II (angiotensin II) infusion. RESULTS: Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile, IK1 current was increased and Ca2+ handling was impaired in isolated atrial myocytes of SPX-KO mice. GALR2-cKO mice, but not GALR1-cKO and GALR3-cKO mice, had a higher incidence of AF, which was associated with higher IK1 current and intracellular Ca2+ overload. The phosphorylation level of CREB (cyclic AMP responsive element binding protein 1) was upregulated in atrial tissues of SPX-KO and GALR2-cKO mice. Chromatin immunoprecipitation confirmed the recruitment of p-CREB to the proximal promoter regions of KCNJ2 and SLN. Finally, spexin treatment suppressed CREB signaling, decreased IK1 current and decreased intracellular Ca2+ overload, which thus reduced the inducibility of AF in Ang-II-infused mice. CONCLUSIONS: Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

Transcriptomics analysis of LINC02202/XBP1 axis in melanoma: Implications for drug targeting and PD-1 monoclonal antibody efficacy.

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.

Mitigation of respiratory syncytial virus epidemics by RSVpreF vaccines after the COVID-19 pandemic in the UK: a modelling study.

BACKGROUND: The RSVpreF vaccines have breakthrough progress. The respiratory syncytial virus (RSV) vaccine for older adults from GlaxoSmithKline was the first RSV vaccine approved by the US Food and Drug Administration (FDA) in early May 2023, followed by the subsequent FDA approval of Pfizer's RSV vaccines for older adults and pregnant women. We aimed to estimate the public health impact of the potential population-level administrations of the RSVpreF vaccine in the UK. METHODS: In this modelling study, we used national census and contact survey data to construct an individual-based mathematical model, with interpersonal connections characterising household structure, social settings, and age-specific contact patterns. We considered both within-host viral-load dynamics and between-host RSV transmission. We modelled the coverages of RSV vaccines for older people (age ≥60 years) and pregnant women, using influenza vaccination data from the 2018-19 season. We explored a range of possible transmissibility and estimated the health burden averted by RSVpreF vaccine over a 300-day period as compared with the control scenario without vaccines. FINDINGS: In a low-transmission scenario (Re=1·2), RSVpreF would avert a total population of 2·35 (95% credible interval [CrI] 1·24-3·77) million infections, 12.80 (95% CrI 8·60-17·06) thousand hospital admissions, and 0·93 (95% CrI 0·69-1·25) thousand deaths, with 1·82 (1·41-2·33) million infections, 12·44 (8·50-16·38) thousand hospital admissions, and 0·93 (0·67-1·23) thousand deaths averted for people aged 60 years and older. In a high-transmission scenario (Re=2·0), RSVpreF would avert 2·01 (1·37-2·68) million infections, 14·67 (10·05-18·33) thousand hospital admissions, and 1·12 (0·80-1·35) thousand deaths. The majority averted would still be among older adults. INTERPRETATION: Our mathematical models will help improve the vaccine schedules of RSVpreF. Future work will address several limitations when data become available, including the incorporation of population immunity, potential vaccine hesitancy, and other factors affecting vaccine uptake and effectiveness. FUNDING: Government of the Hong Kong Special Administrative Region, the European Research Council, and Ministry of Science and Technology of the People's Republic of China.

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.

OBJECTIVE: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. DESIGN: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. RESULTS: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. CONCLUSIONS: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

Insight into the Feasibility of Fatty Acyl Chlorides with 10-18 Carbons for the Ball-Milling Synthesis of Thermoplastic Cellulose Esters.

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures (Tf) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a Tf of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.

Screening Allergenic Potencies of Skin-Contact Products Using the Human-Derived THP-1 Cell Activation Test.

With the prevalence of allergic contact dermatitis (ACD) from the usage of skin-contact products, like wearable, skin care, and hair care products, screening their skin sensitizing potential is necessary, for the sake of alleviating the consequent public health impact. In the present study, a total of 77 skin-contact products classified by four categories, watch bands (WBs), skin care products (SCPs), hair care products (HCPs), and rubber gloves (RGs), were investigated, using an optimized in vitro assay of human cell line activation test (h-CLAT). Extracting the products using neutral artificial sweat simulated well the practical usage scenarios, and testing the extracts showed that 26 of them were allergy test positive, including nine WBs, six SCPs, two HCPs, and nine RGs. The allergenic response was mainly characterized by the induction of CD54 expression, and diverse paradigms of CD54 and CD86 levels were observed by analyzing dose-response curves, which could also be influenced by the compromised viability of the THP-1 cells. The data implicated the intricate regulation by different contributors to suspicious ingredients in the test samples. Altogether, a promising methodology for testing skin allergy potential was well established for commonly used commodities by neutral artificial sweat extraction coupled with h-CLAT screening. The findings would be of great help in tracing the potential allergens in practical products and improving their qualities.

AhR Agonistic Components in Urban Particulate Matter Regulate Astrocytic Activation and Function.

Exposure to atmospheric particulate matter (PM) has been found to accelerate the onset of neurological disorders via the induction of detrimental neuroinflammatory responses. To reveal how astrocytes respond to urban atmospheric PM stimulation, a commercially available standard reference material (SRM1648a) was tested in this study on the activation of rat cortical astrocytes. The results showed that SRM1648a stimulation induced both A1 and A2 phenotypes in astrocytes, as characterized by the exposure concentration-dependent increases in Fkbp5, Sphk1, S100a10, and Il6 mRNA levels. Studying the functional alterations of astrocytes indicated that the neurotrophic factors of Gdnf and Ngf were transcriptionally upregulated due to astrocytic A2-type activation. SRM1648a also promoted autonomous motility of astrocytes and elevated the expressions of chemokines. The aryl hydrocarbon receptor (AhR) agonistic components, such as polycyclic aromatic hydrocarbons (PAHs), were recognized to greatly contribute to SRM1648a-induced effects on astrocytes, which was confirmed by the attenuation of PM-disturbed astrocytic effects via AhR blockage. This study, for the first time, uncovered the direct regulation of urban atmospheric PM on astrocytic activation and function and traced the containing bioactive components (e.g., PAHs) with AhR agonistic activity. The findings provided new knowledge on understanding the ambiguous neurological disturbance from ambient fine PM pollution.

A scoring system to predict the technical difficulty of endoscopic resection for cardial submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

Survival and disease burden analyses of occupational pneumoconiosis during 1958-2021 in Huangshi city, China: a retrospective cohort study.

BACKGROUND: Pneumoconiosis, a chronic disease stemming from prolonged inhalation of dust particles, stands as a significant global burden of occupational diseases. This study aims to investigate the survival outcomes of pneumoconiosis patients in Huangshi city, China, while also evaluating the disease burden on afflicted patients. METHODS: Data for this study were sourced from the Huangshi Center for Disease Control and Prevention. Survival analyses of pneumoconiosis patients were conducted employing life tables and the Kaplan-Meier method. The Cox proportional hazards models were deployed to identify factors influencing pneumoconiosis patients' survival duration. Competing risks models were employed to confirm the validity of the model outcomes. Additionally, in the disease burden assessment, disability-adjusted life years (DALYs) were computed for various demographic groups and time frames. RESULTS: A total of 5,641 pneumoconiosis cases, diagnosed in Huangshi City, Hubei Province between 1958 and 2021, were incorporated into the cohort analysis. The probability of mortality and the risk ratio increased with advancing age. Notably, the median survival time of stage III pneumoconiosis patients was significantly shorter compared with those in stages I and II. The Cox proportional hazards model and competing risks analyses underscored several significant factors influencing survival time, including dust exposure duration (HR = 1.197, 95% CI: 1.104-1.298), age at first diagnosis (HR = 3.149, 95% CI: 2.961-3.349), presence of silicosis (HR = 1.378, 95% CI: 1.254-1.515), and stage II-III pneumoconiosis (HR = 1.456, 95% CI: 1.148-1.848). Cumulatively, DALYs amounted to 7,974.35 person-years, with an average of 1.41 person-years. The period between 2000 and 2019 witnessed the highest disease burden. CONCLUSION: Our findings highlight the urgent need for improved prevention, earlier detection, and more effective management strategies for the occupational pneumoconiosis population. This study not only underscores the persistent issue of pneumoconiosis in industrial environments but also serves as a crucial call to action for policymakers and healthcare providers.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Muscular injury as an independent risk factor for esophageal stenosis after endoscopic submucosal dissection of esophageal squamous cell cancer.

BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

3-tert-Butyl-4-hydroxyanisole Perturbs Differentiation of C3H10T1/2 Mesenchymal Stem Cells into Brown Adipocytes through Regulating Smad Signaling.

3-tert-Butyl-4-hydroxyanisole (3-BHA), one of the most commonly used antioxidants in foodstuffs, has been identified as an environmental endocrine disruptor (EED) with obesogenic activity. Given the increasing concern on EED-caused dysfunction in lipid metabolism, whether 3-BHA could influence the development of brown adipocytes is worthy of being explored. In this study, the effect of 3-BHA on the differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) into brown adipocytes was investigated. Exposure to 3-BHA promoted lipogenesis of the differentiated cells, as evidenced by the increased intracellular lipid accumulation and elevated expressions of adipogenic biomarkers, including peroxisome proliferator-activated receptor γ (PPARγ), Perilipin, Adiponectin, and fatty acid binding protein 4 (FABP4). Surprisingly, the thermogenic capacity of the differentiated cells was compromised as a result of 3-BHA exposure, because neither intracellular mitochondrial contents nor expressions of thermogenic biomarkers, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), cell-death-inducing DNA fragmentation factor α subunit-like effector A (CIDEA), and PR domain containing 16 (PRDM16), were increased by this chemical. The underlying molecular mechanism exploration revealed that, in contrast to p38 MAPK, 3-BHA stimulation induced phosphorylation of Smad1/5/8 in an exposure time-dependent manner, suggesting that this chemical-triggered Smad signaling was responsible for the shift of C3H10T1/2 MSC differentiation from a brown to white-like phenotype. The finding herein, for the first time, revealed the perturbation of 3-BHA in the development of brown adipocytes, uncovering new knowledge about the obesogenic potential of this emerging chemical of concern.

Risk factors for complications and incomplete resection after endoscopic resection for duodenal submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection (ER) has been used to remove submucosal tumors (SMTs) in recent years; however, duodenal ER is associated with high rates of immediate or delayed bleeding and perforation. Whether ER can be recommended for the treatment of duodenal SMTs remains controversial. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SMTs and to assess possible predictive factors for complications and incomplete resection. METHODS: This retrospective study included 141 patients with duodenal SMTs. The therapeutic outcomes from ER and procedure-related complications were analyzed. RESULTS: Of the 141 patients, 78.7% achieved complete resection and nine (6.4%) developed complications. The multivariate analysis suggested that location near the duodenal papilla (P = 0.010) and diameter exceeding 15 mm (P = 0.091) of duodenal SMTs were independent risk factors for complications in ER. Besides, submucosal fibrosis (P = 0.042), location near the duodenal papilla (P = 0.049), and irregular morphology (P = 0.067) were independent risk factors for incomplete resection. CONCLUSIONS: ER can be recommended as an effective and minimally invasive treatment for duodenal SMTs.

Endoscopic resection and suturing methods for non-ampullary duodenal submucosal tumors: "mini-invasive" treatments that should never be underestimated.

OBJECTIVE: To evaluate the effectiveness and safety of endoscopic resection and various suturing methods to treat non-ampullary duodenal submucosal tumors (NAD-SMTs). DESIGN: We performed a retrospective observational study of patients with NAD-SMTs who underwent endoscopic resection at Zhongshan Hospital, Fudan University, China, between June 2017 and December 2020. Data on patient characteristics, treatments and follow-up results were collected. The association between clinicopathologic characteristics and different suturing methods or adverse events were analyzed. RESULTS: Of 128 patients analyzed, 26 underwent endoscopic mucosal resection (EMR), 64 underwent endoscopic submucosal excavation (ESE), and 38 underwent endoscopic full-thickness resection (EFTR). EMR and ESR are both appropriate for non-full-thickness lesions, whereas ESE is more appropriate for tumors located in the bulb or descending duodenum. Gastric tube drainage is more strongly recommended after ESE. Satisfactory suturing is also vital endoscopic resection of NAD-SMTs. Metallic clips are often used in EMR or ESE of non-full-thickness lesions. The pathological findings revealed that the full-thickness lesions were predominantly gastrointestinal stromal tumors (GIST), Brunner's tumor or lipoma, and the surgeons usually used purse-string sutures to close the wounds. The operation time was longer for purse-string suture closure than metallic clip closure. Eleven patients had complications. Risk factors for adverse events included large-diameter tumor (≥ 2 cm), location in the descending part of the duodenum, involvement of the fourth layer of the duodenal wall, EFTR, and GIST. CONCLUSIONS: Endoscopic resection of NAD-SMTs is effective but is associated with a high incidence of complications due to their anatomical peculiarities. Preoperative diagnosis is quite important. Careful selection of treatment and suturing methods are necessary to reduce the risk of adverse effects. Given the increased frequency of severe complications during or following duodenal endoscopic resection, this procedure should be performed by experienced endoscopists.

Reducing scan time in 177 Lu planar scintigraphy using convolutional neural network: A Monte Carlo simulation study.

PURPOSE: The aim of this study was to reduce scan time in 177 Lu planar scintigraphy through the use of convolutional neural network (CNN) to facilitate personalized dosimetry for 177 Lu-based peptide receptor radionuclide therapy. METHODS: The CNN model used in this work was based on DenseNet, and the training and testing datasets were generated from Monte Carlo simulation. The CNN input images (IMGinput ) consisted of 177 Lu planar scintigraphy that contained 10-90% of the total photon counts, while the corresponding full-count images (IMG100% ) were used as the CNN label images. Two-sample t-test was conducted to compare the difference in pixel intensities within region of interest between IMG100% and CNN output images (IMGoutput ). RESULTS: No difference was found in IMGoutput for rods with diameters ranging from 13 to 33 mm in the Derenzo phantom with a target-to-background ratio of 20:1, while statistically significant differences were found in IMGoutput for the 10-mm diameter rods when IMGinput containing 10% to 60% of the total photon counts were denoised. Statistically significant differences were found in IMGoutput for both right and left kidneys in the NCAT phantom when IMGinput containing 10% of the total photon counts were denoised. No statistically significant differences were found in IMGoutput for any other source organs in the NCAT phantom. CONCLUSION: Our results showed that the proposed method can reduce scan time by up to 70% for objects larger than 13 mm, making it a useful tool for personalized dosimetry in 177 Lu-based peptide receptor radionuclide therapy in clinical practice.

Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway.

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinß6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.

[Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics].

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

[Anti-depression mechanism of Zuojin Pills:based on UHPLC-TOF-MS, network pharmacology, and experimental verification].

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.

Lithography-free tunable absorber at visible region via one-dimensional photonic crystals consisting of an α-MoO3 layer.

Flexible control of light absorption within the lithography-free nanostructure is crucial for many polarization-dependent optical devices. Herein, we demonstrated that the lithography-free tunable absorber (LTA) can be realized by using two one-dimensional (1D) photonic crystals (PCs) consisting of an α-MoO3 layer at visible region. The two 1D PCs have different bulk band properties, and the topological interface state-induced light absorption enhancement of α-MoO3 can be realized as the α-MoO3 thin film is inserted at the interface between the two 1D PCs. The resonant cavity model is proposed to evaluate the anisotropic absorption performances of the LTA, and the results are in good agreement with those of the transfer matrix method (TMM). The absorption efficiency of the LTA can be tailored by the number of the period of the two PCs, and the larger peak absorption is the direct consequence of the larger field enhancement factor (FEF) within the α-MoO3 layer. In addition, near-perfect absorption can be achieved as the LTA is operated at the over-coupled resonance. By varying the polarization angle, the absorption channels can be selected and the reflection response can be effectively modulated due to the excellent in-plane anisotropy of α-MoO3.