Celastrol inhibits mouse B16-F10 melanoma cell survival by regulating the PI3K/AKT/mTOR signaling pathway and repressing HIF-1α expression.

OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.

Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy. RESULTS: A total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66-0.71) and 0.72 (0.69-0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70-0.78). CONCLUSIONS: Among the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.

Predicting Schistosomiasis Intensity in Africa: A Machine Learning Approach to Evaluate the Progress of WHO Roadmap 2030.

The World Health Organization (WHO) 2030 Roadmap aims to eliminate schistosomiasis as a public health issue, targeting reductions in the heavy intensity of infections. Previous studies, however, have predominantly used prevalence as the primary indicator of schistosomiasis. We introduce several machine learning (ML) algorithms to predict infection intensity categories, using morbidity prevalence, with the aim of assessing the elimination of schistosomiasis in Africa, as outlined by the WHO. We obtained morbidity prevalence and infection intensity data from the Expanded Special Project to Eliminate Neglected Tropical Diseases, which spans 12 countries in sub-Saharan Africa. We then used a series of ML algorithms to predict the prevalence of infection intensity categories for Schistosoma haematobium and Schistosoma mansoni, with morbidity prevalence and several relevant environmental and demographic covariates from remote-sensing sources. The optimal model had high accuracy and stability; it achieved a mean absolute error (MAE) of 0.02, a root mean square error (RMSE) of 0.05, and a coefficient of determination (R2) of 0.84 in predicting heavy-intensity prevalence for S. mansoni; and an MAE of 0.02, an RMSE of 0.04, and an R2 value of 0.81 for S. haematobium. Based on this optimal model, we found that most areas in the surveyed countries have not achieved the target of the WHO road map for 2030. The ML algorithms used in our analysis showed a high overall predictive power in estimating infection intensity for each species, and our methods provided a low-cost, effective approach to evaluating the disease target in Africa set in the WHO road map for 2030.

Klinefelter syndrome: Etiology and clinical considerations in male infertility.

Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics and clinical reproductive medicine.

Disulfiram Improves Fat Graft Retention by Modulating Macrophage Polarization Via Inhibition of NLRP3 Inflammasome-Mediated Pyroptosis.

BACKGROUND: Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates in inflammatory pathologies. OBJECTIVES: This study sought to determine whether macrophage pyroptosis is activated during the inflammatory phase after fat grafting and to investigate the efficacy of a pyroptosis inhibitor, disulfiram (DSF) in fat graft retention. METHODS: We established a C57BL/6 mice fat grafting model and then analyzed macrophage pyroptosis. DSF (50 mg/kg, every other day) was intraperitoneally injected started from 1 h prior to fat grafting and continued for 14 days. An in vitro co-culture system was established in which mouse RAW264.7 macrophages were co-cultured with apoptotic adipocytes to further validate the findings of the in vivo studies and to explore the underlying mechanisms. RESULTS: Here we reported that macrophage pyroptosis was activated in both fat grafts and in vitro co-culture models. DSF was found to be a potent pyroptosis inhibitor to promote M2 macrophage polarization. In addition, DSF was demonstrated to enhance vascularization and graft retention. CONCLUSIONS: Our results suggested that pyroptosis plays a crucial role in the inflammatory cascade within fat grafts. DSF, being a clinically available drug could be translated into a clinically effective drug for improving fat graft survival via inhibiting macrophage pyroptosis, thereby inducing M2 macrophage polarization and promoting neovascularization.

Correction: Fluorescence detection of three types of pollutants based on fluorescence resonance energy transfer and its comparison with colorimetric detection.

[This corrects the article DOI: 10.1039/D3RA02647G.].

Anti-ROS and NIR-II-Responsive Hyaluronic Acid Microneedle Loaded With Baicalin Nanoparticles for Treatment of Psoriasis.

In this work, a natural medicine, baicalin, is designed for the treatment of psoriasis with the aid of hyaluronic acid (HA)-based MNs patches. This is also to improve the solubility of baicalin and increase its residence time in infected part, which is made into nanoparticles by complexation with humic acid and Eu2+. The baicalin nanoparticles loaded-MNs exhibit satisfactory rigidity, minimum injury, and controlled drug delivery. The anti-reactive oxygen species (anti-ROS) and anti-inflammatory action are verified by the effective scavenging oxygen and nitrogen radicals. In addition, the loading of baicalin nanoparticles brings remarkable photothermic effect to the MNs, enabling the device to release a controlled drug under near-infrared region II (NIR-II) laser irradiation. With the aid of NIR-II laser, the baicalin-mediated treatment of psoriasis is significantly improved by expediting radical scavenging and suppressing inflammation. The design of baicalin MNs provides a new idea for the treatment of chronic disease.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Vaginal microbiota molecular profiling and diagnostic performance of artificial intelligence-assisted multiplex PCR testing in women with bacterial vaginosis: a single-center experience.

Background: Bacterial vaginosis (BV) is a most common microbiological syndrome. The use of molecular methods, such as multiplex real-time PCR (mPCR) and next-generation sequencing, has revolutionized our understanding of microbial communities. Here, we aimed to use a novel multiplex PCR test to evaluate the microbial composition and dominant lactobacilli in non-pregnant women with BV, and combined with machine learning algorithms to determine its diagnostic significance. Methods: Residual material of 288 samples of vaginal secretions derived from the vagina from healthy women and BV patients that were sent for routine diagnostics was collected and subjected to the mPCR test. Subsequently, Decision tree (DT), random forest (RF), and support vector machine (SVM) hybrid diagnostic models were constructed and validated in a cohort of 99 women that included 74 BV patients and 25 healthy controls, and a separate cohort of 189 women comprising 75 BV patients, 30 intermediate vaginal microbiota subjects and 84 healthy controls, respectively. Results: The rate or abundance of Lactobacillus crispatus and Lactobacillus jensenii were significantly reduced in BV-affected patients when compared with healthy women, while Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, BVAB2, Megasphaera type 2, Prevotella bivia, and Mycoplasma hominis were significantly increased. Then the hybrid diagnostic models were constructed and validated by an independent cohort. The model constructed with support vector machine algorithm achieved excellent prediction performance (Area under curve: 0.969, sensitivity: 90.4%, specificity: 96.1%). Moreover, for subjects with a Nugent score of 4 to 6, the SVM-BV model might be more robust and sensitive than the Nugent scoring method. Conclusion: The application of this mPCR test can be effectively used in key vaginal microbiota evaluation in women with BV, intermediate vaginal microbiota, and healthy women. In addition, this test may be used as an alternative to the clinical examination and Nugent scoring method in diagnosing BV.

Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

A Dual-Gene Reporter-Amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange.

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co-expression of a dual-gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1-driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3-expressing cells with access to a larger water pool compared with exchange-limited conditions. We further show that our methodology allows cells to be detected using approximately 10-fold lower concentrations of gadolinium than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell cultures containing a low fraction of Oatp1b3-labeled cells that are undetectable on the basis of Oatp1b3 expression alone.

Corrosion Behavior of Carbon Steel in Diethylenetriamine Solution for Post-combustion CO2 Capture.

In the realm of postcombustion carbon capture, diethylenetriamine (DETA), recognized for its substantial CO2 absorption capacity, presents a formidable challenge due to its corrosive impact on equipment. This study delves into the corrosion behavior of 20# carbon steel immersed in DETA solutions under varying conditions, employing weight loss and electrochemical methods. The investigation incorporates scanning electron microscopy/energy-dispersive spectroscopy and X-ray diffraction analyses for characterization. Corrosion experiments were also conducted in monoethanolamine (MEA) solutions for a comparative analysis. Results from the corrosion tests in DETA solutions mirror the temperature-dependent corrosion rate (CR) observed in MEA. However, a distinctive trend emerges as the CO2 loading of DETA increases from 0.2 mol CO2/mol amine to 1.2 mol CO2/mol amine, leading to a continuous decrease in the CR of carbon steel-contrary to MEA solutions. This anomaly is attributed to DETA's robust complexing ability with metal ions and its elevated solubility of Fe2+ in solution. Additionally, an examination of the corrosion mechanism in the presence of oxygen was conducted through characterizing the specimen surface and solution precipitates postexperiment. The absence of a protective FeCO3 layer can be attributed to insufficient concentrations of free Fe2+ and CO32- in the solution, failing to achieve the minimum saturation required for protective film formation. The insights gained from studying the corrosion behavior of carbon steel in DETA solutions lay the groundwork for subsequent developments in corrosion inhibitors.

Space-specific flux estimation of atmospheric chemicals from point sources to soil.

Predicting chemical flux to soil from industrial point sources accurately at a regional scale has been a significant challenge due to high uncertainty in spatial heterogeneity and quantification. To address this challenge, we developed an innovative approach by combining California Air Resources Board Puff (CALPUFF) and mass balance models, leveraging their complementary strengths in quantitative accuracy and spatial precision. Specifically, CALPUFF was used to predict the polycyclic aromatic hydrocarbons (PAHs) flux to soil due to industrial sources. Additionally, the spatial distribution coefficient of PAHs flux (e.g., si for spatial unit i) was calculated by neural network and combined with the mass balance model to obtain the results of total PAHs fluxes, which were then combined with the results predicted by CALPUFF to effectively estimate the contribution of industrial sources to soil PAHs flux. Taking a petrochemical industry region located in Zhejiang province, China as a case study, results showed the input Phenanthrene (Phe) and Benzo(a)pyrene (BaP) fluxes predicted by CALPUFF were generally lower than those by the mass balance model, with slightly different distribution patterns. CALPUFF results, based on 36 industrial sources, partially represent those of the mass balance model, which includes all sources and pathways. It was suggested that industrial sources contributed 49%-89% and 65%-100% of soil Phe and BaP, respectively across the study area. The average Phe flux from point sources by deposition averaged 2.68 mg m-2∙a-1 in 2021, accounting for approximately 60% of the total Phe flux to soil. The average BaP flux from point sources by deposition averaged 0.0755 mg m-2∙a-1, accounting for only 0.1%-3.65% of the total BaP flux to soil. Thereby, our approach fills up a gap between the relevance to point sources and the accuracy of deposition quantification in estimating chemical flux from specific point sources to soil at a regional scale.

Protective Effects of Inulin on Stress-Recurrent Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the digestive tract and is closely associated with the homeostasis of the gut microbiota. Inulin, as a natural prebiotic, displays anti-inflammatory activity and maintains equilibrium of the intestinal microbiota. In this study, our research aimed to explore the potential of inulin in enhancing intestinal immunity and reducing inflammation in stress-recurrent IBD. In this study, a co-culture intestinal epithelium model and a stress-recurrent IBD mouse model was used to examine the protective effects of inulin. It was observed that inulin digesta significantly reduced pro-inflammatory cytokine expression (CXCL8/IL8 and TNFA) and increased MUC2 expression in intestinal epithelial cells. In vivo, our findings showed that Inulin intake significantly prevented IBD symptoms. This was substantiated by a decrease in serum inflammatory markers (IL-6, CALP) and a downregulation of inflammatory cytokine (Il6) in colon samples. Additionally, inulin intake led to an increase in short-chain fatty acids (SCFAs) in cecal contents and a reduction in the expression of endoplasmic reticulum (ER) stress markers (CHOP, BiP). Our results highlight that inulin can improve stress-recurrent IBD symptoms by modulating microbiota composition, reducing inflammation, and alleviating ER stress. These findings suggested the therapeutic potential of inulin as a dietary intervention for ameliorating stress-recurrent IBD.

Inoculation of Pan02 cells produces tumor nodules in mouse pancreas: Characterization of a novel orthotopic pancreatic ductal adenocarcinoma tumor model for interventional studies.

Preclinical models of cancer are vital for assessing and predicting efficacies and toxicities of novel treatments prior to testing in human subjects. Current pancreatic tumor models exhibit variable growth rates, unpredictable tumor size after implantation in non-native tissues, or require surgical implantation. Surgical implantation in the pancreas may produce not only unpredictable tumor uptake but could also elicit additional inflammatory responses. In searching for a pancreatic carcinoma cell that can be introduced into a mouse via simple injection, we found that Pan02, a murine ductal pancreatic adenocarcinoma derived from a pancreatic lesion of a C57BL/6 mouse, inoculated peritoneally can consistently produce pancreatic tumors. This intraperitoneal, but not intravenous, introduction of Pan02 cells leads to the attachment and growth of Pan02 in the pancreas before spreading to other tissues. Time-course tissue analysis indicates that the Pan02 cells first find, infiltrate, and grow within the pancreas, producing a pancreatic tumor model. This model appears to mimic pancreatic cancer development in humans and is the first reported use of Pan02 cells to produce orthotopic pancreatic and metastatic neoplasms in a mouse model without the need for tumor implantation within matrices or survival surgeries. This orthotopic pancreatic tumor model, with consistent tumor uptake, synchronized tumor development and survival, and predictable outcomes may enable and accelerate the preclinical evaluation of treatment candidates for pancreatic cancer.

The Brown Sugar Mediated Carbon Quantum Dots as a Novel Fluorescence Sensor for Sensitive Detection of Gentamicin and Its Application in Foods.

In this work, a novel fluorescence sensing strategy was proposed for the detection of gentamicin based on fluorescent carbon quantum dots (CQDs) and gold nanoparticles (AuNPs). Herein, the CQDs were green-synthesized for the first time via a one-step hydrothermal method utilizing brown sugar as the precursor. In the presence of citrate-stabilized AuNPs, the fluorescence of CQDs was quenched efficiently. Gentamicin, on the other hand, had a higher affinity for AuNPs and was able to compete with CQDs for a preferential binding to AuNPs, which ultimately led to the aggregation of AuNPs and freeing of CQDs in solution, causing the fluorescence recovery of CQDs. Based on the above phenomenon, the concentrations of gentamicin could be ascertained by detecting the variations in fluorescence intensity of CQDs. This sensing strategy exhibited excellent selectivity in various antibiotics. At the same time, the method displayed outstanding sensitivity for gentamicin, which was successfully applied to real samples detection.

A dual-gene reporter-amplifier architecture for enhancing the sensitivity of molecular MRI by water exchange.

The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in intact animals. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small percentage of cells express the reporter. To overcome this limitation, we developed an approach that amplifies signals by co-expressing an MRI reporter gene, Oatp1b3, with a water channel, aquaporin-1 (Aqp1). We first show that the expression of Aqp1 amplifies the paramagnetic relaxation effect of Oatp1b3 by facilitating transmembrane water exchange. This mechanism provides Oatp1b3-expressing cells with access to a larger water pool compared with typical exchange-limited conditions. We further demonstrated that our methodology allows dual-labeled cells to be detected using approximately 10-fold lower concentrations of contrast agent than that in the Aqp1-free scenario. Finally, we show that our approach enables the imaging of mixed-cell populations containing a low fraction of Oatp1b3-labeled cells that are otherwise undetectable based on Oatp1b3 expression alone.

Prediction Model for the Clearance of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B before Interferon Therapy: A Prospective Case-Control Study.

To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.

High lipoprotein(a) concentration is associated with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology. METHODS: Data for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted. RESULTS: A cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6-37.8) mg/dL vs. 14.9 (7.8-30.5) mg/dL, P < 0.001]. The odds ratios and 95% confidence intervals for Lp(a) were calculated in three models: unadjusted model, model 1 (adjusted for body mass index and systolic blood pressure), and model 2 (adjusted for model 1 plus triglyceride, C-reactive protein, homocysteine, and low-density lipoprotein cholesterol). Results were [1.613 (1.299-2.002), P < 0.001], [1.598 (1.286-1.986), P < 0.001], and [1.661 (1.330-2.074), P < 0.001], respectively. Furthermore, age, sex, or hypertension status had nothing to do with this relationship. CONCLUSIONS: Positive relationship exists between Lp(a) and MMD.