Palladium/Norbornene Cooperatively Catalyzed Modular Trifunctionalization of 2-Bromoaryl Ketone via a Decarbonylation Process.

Palladium/norbornene cooperatively catalyzed Catellani-type reactions were normally limited to aryl iodides as substrates. The employment of aryl bromides has remained challenging. Herein a Pd/NBE cooperatively catalyzed Catellani-type reaction of 2-bromoaryl ketone is described. The 2-bromoaryl ketone was employed as both substrates and arylation reagents with a Heck acceptor. A decarbonylation process of the ketones also occurred in the reaction, finishing the modular ispo-Heck/ortho,ortho-diarylation in one pot. It provided the functionalized m-triphenyl derivatives with three new C-C bonds in moderate to excellent yields which exhibited good regioselectivities and functional group tolerance.

Impact of DEHP on mitochondria-associated endoplasmic reticulum membranes and reproductive toxicity in ovary.

Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500 mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.

A serial mediation model reveals the association between parental over-protection and academic entitlement among nursing students.

The study aims to explore the influence of parental over-protection on academic entitlement of nursing students, and examine the mediating roles of external locus of control and psychological entitlement. The study sampled two medical universities in Guizhou and Yunnan provinces, China. Participants were nursing students in grades one to four (N = 1003; mean age = 19.51 years; 81.95% female). Using a structural equation model, we examined the mediating effect of external locus of control and psychological entitlement on parental over-protection and academic entitlement. The results show that there was a significant correlation between all variables, and external locus of control and psychological entitlement played a serial mediating role between parental over-protection and academic entitlement. Our findings suggest that academic entitlement of nursing students can be reduced by adjusting parental rearing behaviors, reducing students' psychological entitlement, and teaching them how to form a healthier attribution style.

[Effect of chronic periodontitis on quality of life and severity in patients with bronchiectasis].

PURPOSE: To investigate the effects of chronic periodontitis on the quality of life and severity of the disease in patients with bronchiectasis. METHODS: A total of 80 bronchiectasis patients admitted to The Fourth Hospital of Changsha between April 2021 and April 2023 were randomly selected. Patients were divided into two groups according to whether they had moderate to severe chronic periodontitis: bronchiectasis with periodontitis group (n=45) and bronchiectasis without periodontitis group (n=35). The Qualify of Life Questionnaire for Bronchiectasi(QoL-B) was used to assess patients' quality. The severity of the disease was assessed using the Bronchiectasis Severity Index (BSI), and serum levels of hypersensitive C-reactive protein (hsCRP), tumor necrosis factor alpha(TNF-alpha), and interleukin-6(IL-6) were detected. SPSS 20.0 software package was used for data analysis. RESULTS: The QoL-B score of bronchiectasis with periodontitis group was significantly lower than that of bronchiectasis without periodontitis group, and the BSI score was significantly higher than that of bronchiectasis without periodontitis group(P＜0.05). The levels of hs-CRP, TNF-alpha and IL-6 in bronchiectasis with periodontitis were significantly higher than those in bronchiectasis without periodontitis group(P＜0.05). CONCLUSIONS: Chronic periodontitis shows significant adverse effects on both quality of life and disease severity in patients with bronchiectasis, which may be related to the common mechanism of inflammatory response between the two kinds of diseases.

Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Recombination and amino acid point mutations in VP3 exhibit a synergistic effect on increased virulence of rMDPV.

Recombinant Muscovy duck parvovirus (rMDPV) is a product of genetic recombination between classical Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV). The recombination event took place within a 1.1-kb DNA segment located in the middle of the VP3 gene, and a 187-bp sequence extending from the P9 promoter to the 5' initiation region of the Rep1 ORF. This resulted in the alteration of five amino acids within VP3. Despite these genetic changes, the precise influence of recombination and amino acid mutations on the pathogenicity of rMDPV remains ambiguous. In this study, based on the rMDPV strain ZW and the classical MDPV strain YY, three chimeric viruses (rZW-mP9, rZW-mPR187, and rYY-rVP3) and the five amino acid mutations-introduced mutants (rZW-g5aa and rYY-5aa(ZW)) were generated using reverse genetic technology. When compared to the parental virus rZW, rZW-g5aa exhibited a prolonged mean death time (MDT) and a decreased median lethal dose (ELD50) in embryonated duck eggs. In contrast, rYY-5aa(ZW) did not display significant differences in MDT and ELD50 compared to rYY. In 2-day-old Muscovy ducklings, infection with rZW-g5aa and rYY-5aa(ZW) resulted in mortality rates of only 20% and 10%, respectively, while infections with the three chimeric viruses (rZW-mP9, rZW-mPR187, rYY-rVP3) and rZW still led to 100% mortality. Notably, rYY-rVP3, containing the VP3 region from strain ZW, exhibited 50% mortality in 6-day-old Muscovy ducklings and demonstrated significant horizontal transmission. Collectively, our findings indicate that recombination and consequent amino acid changes in VP3 have a synergistic impact on the heightened virulence of rMDPV in Muscovy ducklings.

Novel thawing method of ultrasound-assisted slightly basic electrolyzed water improves the processing quality of frozen shrimp compared with traditional thawing approaches.

Thawing is the primary step in handling frozen aquatic products, which directly determines their end-product quality. This study firstly constructed a novel thawing method of ultrasound-assisted slightly basic electrolyzed water (UST), and its influences on the physicochemical and histological properties of shrimp, as well as the structural of myofibrillar proteins (MPs) in shrimp were evaluated. Results indicated that the UST treatment greatly reduced 48.9 % thawing time of frozen shrimp compared to traditional thawing approaches. Meanwhile, the UST effectively decreased the generation of malondialdehyde (MDA), total volatile basic nitrogen (TVB-N), and carbonyl compounds in the thawed shrimps. In addition, it significantly preserved the elasticity and integrity of muscle fiber. Notably, the UST reduced the damage of thawing to the spatial structures of MPs, thereby greatly keeping the stability of protein. All these favorable changes maintained the water holding capacity (WHC) and quality of shrimp. Therefore, the UST is a promising non-thermal thawing technology for aquatic products.

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain.

INTRODUCTION: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group. CONCLUSIONS: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04094662.

Prospective Evaluation of Artificial Intelligence Triage of Incidental Pulmonary Emboli on Contrast-Enhanced CT Examinations of the Chest or Abdomen.

Background: Artificial intelligence (AI) algorithms improved detection of incidental pulmonary embolism (IPE) on contrast-enhanced CT (CECT) examinations in retrospective studies; however, prospective validation studies are lacking. Objective: To assess the effect on radiologists' real-world diagnostic performance and report turnaround times of a radiology department's clinical implementation of an AI triage system for detecting IPE on CECT examinations of the chest or abdomen. Methods: This prospective single-center study included consecutive adult patients who underwent CECT of the chest or abdomen for reasons other than PE detection from May 12, 2021 to June 30, 2021 (phase 1) or from July 1, 2021 to September 29, 2021 (phase 2). Before phase 1, the radiology department installed a commercially available AI triage algorithm for IPE detection that automatically processed CT examinations and notified radiologists of positive results through an interactive floating widget. In phase 1, the widget was inactive, and radiologists interpreted examinations without AI assistance. In phase 2, the widget was activated, and radiologists interpreted examinations with AI assistance. A review process involving a panel of radiologists was implemented to establish the reference standard for the presence of IPE. Diagnostic performance and report turnaround times were compared using Pearson Chi-square test and Wilcoxon rank-sum test, respectively. Results: Phase 1 included 1467 examinations in 1434 patients (mean age, 53.8±18.5 years; 753 male, 681 female); phase 2 included 3182 examinations in 2886 patients (mean age, 55.4±18.2 years; 1520 male, 1366 female). The frequency of IPE was 1.4% (20/1467) in phase 1 and 1.6% (52/3182) in phase 2. Radiologists without AI, in comparison with radiologists with AI, showed significantly lower sensitivity (80.0% vs 96.2%, P=.03), without a significant difference in specificity (99.1% vs 99.9%, P=.58), for detection of IPE. The mean report turnaround time for IPE-positive examinations was not significantly different between radiologists without AI and radiologists with AI (78.3 vs 64.6 min, P=.26). Conclusion: An AI triage system improved radiologists' sensitivity for IPE detection on CECT examinations of the chest or abdomen without significant change in report turnaround times. Clinical Impact: This prospective real-world study supports the use of AI assistance for maximizing IPE detection.

DBP Exposure Affects Oocyte Fertilization Via Extracellular Vesicles-Derived miR-116-5p in Ovarian Granulosa Cells Through Downregulating FOXO3a Expression.

Mono-butyl phthalate (MBP), the metabolite of dibutyl phthalate (DBP), is the most abundant phthalate metabolite found in Chinese women. Extracellular vesicles (EVs) are nanoscale lipid bilayer particles produced by extensive kinds of cells, serving a key role in intercellular communication. Extracellular vesicle miRNAs (EV-miRNAs) in follicular fluid (FF) have been evidenced to be associated with female reproductive health. The objective of this study was to investigate the associations of EV-miRNAs expressed profile with DBP exposure in FF of female participants and expose its potential mechanism in impaired oocyte development. Based on participants' FF MBP concentrations and fertilization status, we compared the miRNA expression between the FF-EVs of group A (high DBP exposure and impaired fertilization) and group B (low DBP exposure and normal fertilization). Compared with group B, miR-1246, miR-3679-5p, miR-423-5p, miR-5585-3p, miR-116-5p, miR-172-5p were upregulated, while miR-34b-3p was downregulated in group A. Target genes of the differently expressed miRNAs were predicted, and the functional analysis was performed. Furthermore, we exposed human ovarian granulosa tumor cell line (KGN) to MBP (4ug/L) to isolate the EVs from the culture medium and validated the expression levels of different miRNAs. We found that MBP exposure was significantly associated with increased levels of miR-116-5p (P = 0.01). In addition, we demonstrated that the most different miRNA, miR-116-5p regulated oocyte fertilization by inhibiting FOXO3a. Our findings suggested that EV-miRNAs in the FF might mediate MBP toxicity in oocytes.

Optimization of the structure, morphology and luminescent properties of NaYF4 upconversion nanoparticles.

We designed and constructed rare earth doped upconversion nanoparticles ß-Na(Y0.78Yb0.18Er0.04)F4, sensitizing layer encapsulated ß-Na(Y0.9Er0.1)F4@ß-NaYbF4 and inert layer encapsulated ß-Na(Y0.9Er0.1)F4@ß-NaYbF4@ß-NaYF4. Compared with the mononuclear material, the luminescence intensity of the particles encapsulated with double shells in the three main bands of blue, green and red emissions increased by 346, 22, and 54 times respectively. While improving the upconversion luminescence performance, the underlying reasons for this improvement were analyzed in detail. The effects of shell coating on the fluorescence lifetime, thermal stability and energy level transition are discussed. On this basis, the composite film material was constructed by combining the shell coating strategy and the plasma resonance interaction strategy, which further improved the upconversion efficiency. In addition, by combining performance optimized upconversion particles with information coding, we explored its potential as an anti-counterfeiting material.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Association of High apoB/apoA1 Ratio with Increased Erythrocytes, Platelet/Lymphocyte Ratio, D-dimer, Uric Acid and Cardiac Remodeling in Elderly Heart Failure Patients: A Retrospective Study.

Background: Previous studies have confirmed that high apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio was associated with increased mortality from heart failure (HF). Furthermore, the association of plasma apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling is still limited in chronic HF with mildly reduced ejection fraction (HFmrEF) elderly patients. Therefore, this study investigated the association of apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling in chronic HFmrEF elderly patients. Methods: A total of 587 Chinese elderly (≥65 years) with coronary heart disease (CHD), HFmrEF (EF 40-50%) and related blood biochemical data were collected retrospectively. The cross-sectional data of echocardiographic and blood parameters were compared between binary apoB/apoA1 groups. Results: In the elderly CHD patients with chronic HFmrEF, the univariate correlation analysis showed that apoB/apoA1 was correlated with younger age, increased prevalence of type 2 diabetes, erythrocytes, platelet/lymphocyte ratio (PLR), D-dimer, fibrinogen, high sensitivity C-reactive protein and uric acid, and adverse cardiac remodeling (All P < 0.05). However, multivariate logistic binary regression analysis found that high apoB/apoA1 ratio (≥0.62) was independently correlated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling (All P < 0.05). Conclusion: In this retrospective study, the high apoB/apoA1 ratio is found to be associated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling in Chinese CHD elderly with chronic HFmrEF.

Automatic segmentation of dura for quantitative analysis of lumbar stenosis: A deep learning study with 518 CT myelograms.

BACKGROUND: The diagnosis of lumbar spinal stenosis (LSS) can be challenging because radicular pain is not often present in the culprit-level localization. Accurate segmentation and quantitative analysis of the lumbar dura on radiographic images are key to the accurate differential diagnosis of LSS. The aim of this study is to develop an automatic dura-contouring tool for radiographic quantification on computed tomography myelogram (CTM) for patients with LSS. METHODS: A total of 518 CTM cases with or without lumbar stenosis were included in this study. A deep learning (DL) segmentation algorithm 3-dimensional (3D) U-Net was deployed. A total of 210 labeled cases were used to develop the dura-contouring tool, with the ratio of the training, independent testing, and external validation datasets being 150:30:30. The Dice score (DCS) was the primary measure to evaluate the segmentation performance of the 3D U-Net, which was subsequently developed as the dura-contouring tool to segment another unlabeled 308 CTM cases with LSS. Automatic masks of 446 slices on the stenotic levels were then meticulously reviewed and revised by human experts, and the cross-sectional area (CSA) of the dura was compared. RESULTS: The mean DCS of the 3D U-Net were 0.905 ± 0.080, 0.933 ± 0.018, and 0.928 ± 0.034 in the five-fold cross-validation, the independent testing, and the external validation datasets, respectively. The segmentation performance of the dura-contouring tool was also comparable to that of the second observer (the human expert). With the dura-contouring tool, only 59.0% (263/446) of the automatic masks of the stenotic slices needed to be revised. In the revised cases, there were no significant differences in the dura CSA between automatic masks and corresponding revised masks (p = 0.652). Additionally, a strong correlation of dura CSA was found between the automatic masks and corresponding revised masks (r = 0.805). CONCLUSIONS: A dura-contouring tool was developed that could automatically segment the dural sac on CTM, and it demonstrated high accuracy and generalization ability. Additionally, the dura-contouring tool has the potential to be applied in patients with LSS because it facilitates the quantification of the dural CSA on stenotic slices.

Regulatory feedback loop between circ-EIF4A3 and EIF4A3 Enhances autophagy and growth in colorectal cancer cells.

Recent studies indicate that circular RNAs (circRNAs) are crucial in the progression of colorectal cancer (CRC). Eukaryotic translation initiation factor 4A3 (EIF4A3) has been identified as a promoter of circRNA production. The biological roles and mechanisms of EIF4A3-derived circRNA (circEIF4A3) in CRC cell autophagy remain poorly understood. This study explores the effects of circEIF4A3 on CRC cell growth and autophagy, aiming to elucidate the underlying molecular mechanisms. We discovered that EIF4A3 and circEIF4A3 synergistically enhance CRC cell growth. CircEIF4A3 sequesters miR-3126-5p, consequently upregulating EIF4A3. Further, circEIF4A3 increases EIF4A3 expression, which promotes autophagy by stabilizing ATG5 mRNA and enhances ATG7 protein stability through the stabilization of USP14 mRNA, a deubiquitinating enzyme. Upregulation of ATG5 and ATG7 counteracts the growth-inhibitory effects of EIF4A3 knockdown on CRC cells. Moreover, our findings demonstrate that EIF4A3 induces the formation of circEIF4A3 in CRC cells. In conclusion, a positive feedback loop between circEIF4A3 and EIF4A3 supports CRC cell growth by facilitating autophagy.

Higher LDL-C/HDL-C Ratio Is Associated with Elevated HbA1c and Decreased eGFR Levels and Cardiac Remodeling in Elderly with Hypercholesterolemia.

Background: This study aims to explore the relationship of the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein (HDL-C) ratio with glycated hemoglobin (HbA1c), renal dysfunction, coronary heart disease (CHD) and cardiac structure and function in elderly patients with hypercholesterolemia. Methods: A total of 1129 hospitalized Chinese elderly (aged ≥ 65 years) with hypercholesterolemia were collected retrospectively. The patients were divided into low (<2.63), moderate (≥2.63 to <3.33) and high (≥3.33) LDL-C/HDL-C ratio groups according to the tertiles of LDL-C/HDL-C. Results: Regression analysis of the LDL-C/HDL-C ratio with metabolic and echocardiographic parameters revealed that a high LDL-C/HDL-C ratio (≥3.33) was associated independently with male gender, elevated HbA1c, decreased estimated glomerular filtration rate (eGFR), prevalent CHD and left ventricular dilatation (all p < 0.05). Conclusions: A high LDL-C/HDL-C ratio was associated with male gender, increased HbA1c, decreased eGFR, CHD and enlarged left ventricle in elderly with hypercholesterolemia.

Metadata-Private Resource Allocation in Edge Computing Withstands Semi-Malicious Edge Nodes.

Edge computing provides higher computational power and lower transmission latency by offloading tasks to nearby edge nodes with available computational resources to meet the requirements of time-sensitive tasks and computationally complex tasks. Resource allocation schemes are essential to this process. To allocate resources effectively, it is necessary to attach metadata to a task to indicate what kind of resources are needed and how many computation resources are required. However, these metadata are sensitive and can be exposed to eavesdroppers, which can lead to privacy breaches. In addition, edge nodes are vulnerable to corruption because of their limited cybersecurity defenses. Attackers can easily obtain end-device privacy through unprotected metadata or corrupted edge nodes. To address this problem, we propose a metadata privacy resource allocation scheme that uses searchable encryption to protect metadata privacy and zero-knowledge proofs to resist semi-malicious edge nodes. We have formally proven that our proposed scheme satisfies the required security concepts and experimentally demonstrated the effectiveness of the scheme.

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology.

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.