Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard.

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.

Gut Microbiota Analysis in Silkworms (Bombyx mori) Provides Insights into Identifying Key Bacterials for Inclusion in Artificial Diet Formulations.

The gut microbiome significantly influences the health and productivity of silkworms (Bombyx mori), the cornerstone of sericulture. With the increasing use of cost-effective artificial diets in sericulture, it is crucial to understand how these diets impact the silkworm gut microbiomes. Here we employed 16S rRNA sequencing to delineate the impact of three distinct dietary regimens on the silkworm gut microbiomes: exclusive mulberry leaf diet (SY), exclusive artificial feed diet (SL), and a sequential transition from artificial feed to mulberry leaves (ZS). Our results unveiled stark differences in microbial diversity across the groups, with the ZS group displaying an intermediary complexity. LefSe and random forest analyses identified Methylobacteriaceae, Microbacterium, and Rhodococcus as significantly enriched in the ZS group, suggesting their potential to facilitate silkworms' adaptation to dietary transitions. Functional profiling revealed differential pathway regulation, indicating a metabolic reconfiguration in response to dietary modulations. Notably, the enrichment of Lactobacillus and Weissella in both the SL and ZS groups highlights their potential as probiotics in artificial diets. Our findings provide insights into the diet adaptation mechanisms of silkworm gut microbiota, paving the way for harnessing the intestinal bacteria to enhance silkworm health and silk production through targeted microbial interventions in sericulture practices.

Polyhydroxy steroids isolated from starfish (Asterina pectinifera) and their embryotoxicity.

Many marine organisms possess an essential capacity to produce secondary metabolites that exhibit toxic characteristics. A new polyhydroxy steroid, 24-methyl-5α-cholestane-24(28)-ene-3ß, 4ß, 6α, 7α, 8, 15ß, 16ß, 26-octol-6-O-sodium sulphate (1) was isolated from starfish (Asterina pectinifera), along with five polar steroid compounds (2-6) that were previously identified. NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC, and NOESY) and HR-ESI-MS were employed for structure elucidations. The embryotoxicity and teratogenicity of the isolated compounds were assessed using embryos of marine medaka (Oryzias melastigma). Compound 5 exhibited moderate embryotoxicity (96h-LC50: 65 µM).

Erratum: A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.

[This corrects the article DOI: 10.1016/j.omtn.2017.07.005.].

Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.

AIMS: This study aims to investigate the pharmacological effects and the underlying mechanism of cannabidiol (CBD) on methamphetamine (METH)-induced relapse and behavioral sensitization in male mice. METHODS: The conditioned place preference (CPP) test with a biased paradigm and open-field test were used to assess the effects of CBD on METH-induced relapse and behavioral sensitization in male mice. RNA sequencing and bioinformatics analysis was employed to identify differential expressed (DE) circRNAs, miRNAs, and mRNAs in the nucleus accumbens (NAc) of mice, and the interaction among them was predicted using competing endogenous RNAs (ceRNAs) network analysis. RESULTS: Chronic administration of CBD (40 mg/kg) during the METH withdrawal phase alleviated METH (2 mg/kg)-induced CPP reinstatement and behavioral sensitization in mice, as well as mood and cognitive impairments following behavioral sensitization. Furthermore, 42 DEcircRNAs, 11 DEmiRNAs, and 40 DEmRNAs were identified in the NAc of mice. The circMeis2-miR-183-5p-Kcnj5 network in the NAc of mice is involved in the effects of CBD on METH-induced CPP reinstatement and behavioral sensitization. CONCLUSIONS: This study constructed the ceRNAs network for the first time, revealing the potential mechanism of CBD in treating METH-induced CPP reinstatement and behavioral sensitization, thus advancing the application of CBD in METH use disorders.

Meta-analysis of the relationship between ocular and peripheral serum IL-17A and diabetic retinopathy.

Purpose: A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. Results: A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Conclusion: Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.

Antimicrobial sesterterpenoids with a unique 5/8/6/5 tetracyclic carbon-ring-system and diepoxide polyketides from a deep sea-sediment-sourced fungus Chaetomium globosum SD-347.

Two new sesterterpenoids, sesterchaetins A and B (1 and 2), and two new diepoxide polyketides, chaetoketoics A and B (3 and 4), were characterized from the culture extract of Chaetomium globosum SD-347, a fungal strain derived from deep sea-sediment. Their structures and absolute configurations were unambiguously determined by detailed NMR, mass spectra, and X-ray crystallographic analysis. Compounds 1 and 2 contained a distinctive 5/8/6/5 tetracyclic carbon-ring-system, which represented a rarely occurring natural product framework. The new isolates 1-4 exhibited selective antimicrobial activities against human and aquatic pathogenic bacteria and plant-pathogenic fungi.

High-Performance Aluminum Fuels Induced by Monolayer Self-Assembly of Nano-Sized Energetic Fluoride Vesicles on the Surface.

Surface modification is frequently used to solve the problems of low combustion properties and agglomeration for aluminum-based fuels. However, due to the intrinsic incompatibility between the aluminum powder and the organic modifiers, the surface coating is usually uneven and disordered, which significantly deteriorates the uniformity and performances of the Al-based fuels. Herein, a new approach of monolayer nano-vesicular self-assembly is proposed to prepare high-performance Al fuels. Triblock copolymer G-F-G is produced by glycidyl azide polymer (GAP) and 2,2'-(2,2,3,3,4,5,5-Octafluorohexane-1,6-diyl) bis (oxirane) (fluoride) ring-open addition reaction. By utilizing G-F-G vesicular self-assembly in a special solvent, the nano-sized vesicles are firmly adhered to the surface of Al powder through the long-range attraction between the fluorine segments and Al. Meanwhile, the electrostatic repulsion between vesicles ensures an extremely thin coating thickness (≈15 nm), maintaining the monolayer coating structure. Nice ignition, combustion, anti-agglomeration, and water-proof properties of Al@G-F-G(DMF) are achieved, which are superior among the existing Al-based fuels. The derived Al-based fuel has excellent comprehensive properties, which can not only inspire the development of new-generation energetic materials but also provide facile but exquisite strategies for exquisite surface nanostructure construction via ordered self-assembly for many other applications.

Repair effect of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles on ovarian injury induced by cisplatin.

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)-derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC-sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC-sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle-stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti-mullerian hormone (AMH) increased significantly with the treatment of huMSC-sEVs. Meanwhile, huMSC-sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p-PI3K and p-Akt. Therefore, treatment with huMSC-sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over-atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC-sEVs restore ovarian tissue function.

Clinical observation of laparoscopic sleeve gastrectomy and metformin treatment in obese PCOS patients.

Background: To observe the basic metabolic characteristics of obese patients with polycystic ovarian syndrome (PCOS), and observe and compare the effect of laparoscopic sleeve gastrectomy and metformin treatment after 3 months. Methods: In January to December 2018, the Second Hospital of Hebei Medical University selected 104 women who were classified as obese with a body mass index (BMI) of 28 kg/cm2 or higher and had PCOS. They were divided into obese PCOS group (53 cases) and obese non-PCOS group (51 cases). Results: 1. There was no significant difference in waist circumference and WHR between patients who are obese with PCOS and patients who are obese without PCOS (P > 0.05). Obese PCOS patients were significantly higher in anti-Müllerian hormone (AMH), LH/FSH, T, FAI, homa-ir, triglyceride (TG), low density lipoprotein (LDL), Apo-B and uric acid than the group of non-PCOS patients who were obese. (P<0.05). The SHBG levels of obese patients with PCOS were obviously lower when contrasted with the levels in obese patients without PCOS (P < 0.05). 2. Body weight, BMI, INS, homa-ir and TG of obese PCOS patients were significantly decreased 3 months after laparoscopic sleeve gastrectomy compared with that before surgery (P < 0.05). After three months of medical treatment with metformin, the patients' homeostatic model assessment of insulin resistance (HOMA-IR) was obviously reduced when contrasted with the pre-treatment HOMA-IR levels (P < 0.05), and there was no significant difference in the improvement degree of homa-ir between the two groups (P > 0.05). Conclusions: 1. Obese patients with PCOS demonstrated higher expression of AMH, LH/FSH, T, SHBG, and FAI when contrasted with the control group. Additionally, they experienced more severe insulin resistance and lipid metabolism disorders. 2. The weight and BMI of obese PCOS patients were significantly decreased after weight loss, while IR and blood lipid were significantly improved, while IR was improved in metformin group, and no significant discrepancy was observed in the degree of improvement of insulin resistance between both groups.

Accuracy of artificial intelligence-assisted endoscopy in the diagnosis of gastric intestinal metaplasia: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric intestinal metaplasia is a precancerous disease, and a timely diagnosis is essential to delay or halt cancer progression. Artificial intelligence (AI) has found widespread application in the field of disease diagnosis. This study aimed to conduct a comprehensive evaluation of AI's diagnostic accuracy in detecting gastric intestinal metaplasia in endoscopy, compare it to endoscopists' ability, and explore the main factors affecting AI's performance. METHODS: The study followed the PRISMA-DTA guidelines, and the PubMed, Embase, Web of Science, Cochrane, and IEEE Xplore databases were searched to include relevant studies published by October 2023. We extracted the key features and experimental data of each study and combined the sensitivity and specificity metrics by meta-analysis. We then compared the diagnostic ability of the AI versus the endoscopists using the same test data. RESULTS: Twelve studies with 11,173 patients were included, demonstrating AI models' efficacy in diagnosing gastric intestinal metaplasia. The meta-analysis yielded a pooled sensitivity of 94% (95% confidence interval: 0.92-0.96) and specificity of 93% (95% confidence interval: 0.89-0.95). The combined area under the receiver operating characteristics curve was 0.97. The results of meta-regression and subgroup analysis showed that factors such as study design, endoscopy type, number of training images, and algorithm had a significant effect on the diagnostic performance of AI. The AI exhibited a higher diagnostic capacity than endoscopists (sensitivity: 95% vs. 79%). CONCLUSIONS: AI-aided diagnosis of gastric intestinal metaplasia using endoscopy showed high performance and clinical diagnostic value. However, further prospective studies are required to validate these findings.

Callicarpayongshunensis (Lamiaceae): A new species from Hunan, China.

This study provides detailed description of a newly-discovered Callicarpayongshunensis Wen B. Xu, Xiao D. Li & Yan Ling Liu (Lamiaceae) species from Hunan, China. The species shares similarities in the inflorescence, glandular colour and leaf shape features with C.luteopunctata H. T. Chang and C.giraldii Hesse ex Rehd., while its white fruits are similar to those of C.longifolia Lamk. However, its procumbent, evergreen shrub and white fruits are distinctly different from those of C.luteopunctata and C.giraldii, while its procumbent, scarless nodes and stellate pubescence free fruits distinguishes it from C.longifolia. Images, distribution, morphological features, molecular phylogenetic classification and conservation assessment of this new Callicarpa species are explored.

PPARδ agonist protects against osteoarthritis by activating AKT/mTOR signaling pathway-mediated autophagy.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and PPARs are involved in its pathogenesis; however, the specific mechanisms by which changes in PPARδ impact the OA pathogenesis yet to be discovered. The purpose of this study was to ascertain how PPARδ affects the onset and development of OA. In vitro, we found that PPARδ activation ameliorated apoptosis and extracellular matrix (ECM) degradation in OA chondrocytes stimulated by IL-1ß. In addition, PPARδ activation may modulate AKT/mTOR signaling to partially regulate chondrocyte autophagy and apoptosis. In vivo, injection of PPARδ agonist into the articular cavity improved ECM degradation, apoptosis and autophagy in rats OA models generated by destabilization medial meniscus (DMM), eventually delayed degeneration of articular cartilage. Thus, targeting PPARδ for OA treatment may be a possibility.

[Effectiveness of transverse double "8"-shaped tension band technique for Lawrence zone â fracture of the fifth metatarsal base].

Objective: To explore the effectiveness of transverse double "8"-shaped tension band technique in the treatment of Lawrence zoneⅠfracture of the 5th metatarsal base. Methods: Between February 2019 and October 2021, 15 patients with Lawrence zoneⅠfracture of the 5th metatarsal base were treated with transverse double "8"-shaped tension band technique. There were 8 males and 7 females, with a median age of 40 years (range, 23-59 years). The fractures were caused by sprains. The time from injury to operation was 3-7 days (mean, 4.1 days). X-ray films were taken to observe the fracture healing and the anchor looseness and detachment. The foot function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) score, and the eversion angle of the calcaneal talus joint. Results: The incisions healed by first intention after operation in 14 cases and the incision healed poorly in 1 case. All patients were followed up 8-12 months (median, 10 months). The imaging examination showed that all fractures healed well, with a healing time of 10-14 weeks (mean, 11.7 weeks). At last follow-up, AOFAS score was 82-100 (median, 98); 13 cases were excellent and 2 cases were good, with an excellent and good rate of 100%. VAS score was 0-3 (median, 1). Three cases had mild limited ankle joint range of motion, while 12 cases had normal range of motion. The eversion angle of the calcaneal talus joint was 25°-32° (median, 30°). Conclusion: The application of transverse double "8"-shaped tension band technique for Lawrence zone Ⅰ fracture of the 5th metatarsal base has advantages such as simple operation, avoidance of secondary operation, and reduction of foreign body sensation, with definite effectiveness.

Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

MiR-98-5p plays suppressive effects on IL-1ß-induced chondrocyte injury associated with osteoarthritis by targeting CASP3.

BACKGROUND: This study aims to explore how miR-98-5p affects osteoarthritis, focusing on its role in chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation. METHODS: Quantitative real-time PCR was used to measure miR-98-5p and CASP3 mRNA levels in OA cartilage tissues and IL-1ß-treated CHON-001 cells. We predicted miR-98-5p and CASP3 binding sites using TargetScan and confirmed them via luciferase reporter assays. Chondrocyte viability was analyzed using CCK-8 assays, while pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) were quantified via ELISA. Caspase-3 activity was examined to assess apoptosis, and Western blotting was conducted for protein marker quantification. RESULTS: Our results showed lower miR-98-5p levels in both OA cartilage and IL-1ß-stimulated cells. Increasing miR-98-5p resulted in reduced pro-inflammatory cytokines, decreased caspase-3 activity, and improved cell viability. Furthermore, miR-98-5p overexpression hindered IL-1ß-induced ECM degradation, evident from the decline in MMP-13 and ß-catenin levels, and an increase in COL2A1 expression. MiR-98-5p's impact on CASP3 mRNA directly influenced its expression. Mimicking miR-98-5p's effects, CASP3 knockdown also inhibited IL-1ß-induced inflammation, apoptosis, and ECM degradation. In contrast, CASP3 overexpression negated the suppressive effects of miR-98-5p. CONCLUSIONS: In conclusion, our data collectively suggest that miR-98-5p plays a protective role against IL-1ß-induced damage in chondrocytes by targeting CASP3, highlighting its potential as a therapeutic target for OA.

KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma.

Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors.

Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.