Functional and Numerical Responses of Harmonia axyridis (Coleoptera: Coccinellidae) to Rhopalosiphum nymphaeae (Hemiptera: Aphididae) and Their Potential for Biological Control.

The water lily aphid (Rhopalosiphum nymphaeae) is a highly polyphagous herbivore that causes severe damage to many terrestrial and aquatic plants, especially lotus. Due to environmental concerns about water pollution and other issues caused by chemical control methods, there is an urgent need to develop effective and sustainable control methods. The harlequin ladybird (Harmonia axyridis) is a well-known aphid predator and may pose a potential threat to R. nymphaeae. To study the predation ability of H. axyridis at different developmental stages on R. nymphaeae, we assessed the functional response, attack rate, and search effect of H. axyridis larvae and adults preying on R. nymphaeae. The numerical response of this process was also evaluated under a constant ladybird-to-aphid ratio and constant aphid density conditions, respectively. Our results showed that all predator stages exhibited type II functional responses. The predation rate of individual H. axyridis on R. nymphaeae nymphs significantly increased as prey density increased. In contrast, the search effect of H. axyridis gradually decreased with an increase in prey density. Meanwhile, H. axyridis at different developmental stages possess varying predation abilities; fourth instar and adult H. axyridis were found to be highly efficient predators of R. nymphaeae. H. axyridis adults exhibited the highest predation ability and predation rate, while both the adult and fourth-instar larvae exhibited the highest attack rate. Moreover, fourth-instar larvae exhibited the highest search effect value at initially lower prey densities, although adults surpassed them at higher prey densities. Our results also indicated that H. axyridis exhibited varying degrees of intraspecific interference and self-interference influence as predator density increases. These results strongly support H. axyridis as an effective biocontrol agent for R. nymphaeae.

Engineering a conserved immune coreceptor into a primed state enhances fungal resistance in crops without growth penalty.

Plants must tactically balance immunity and growth when combating lethal pathogens like fungi. CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1), a conserved cell-surface co-receptor for the fungal elicitor chitin, enables plants to induce chitin-triggered immunity to counteract fungal invasion. Previously, we reported that bacterial infection can prime CERK1 through juxtamembrane (JM) phosphorylation to enhance fungal resistance, which only occurs in Arabidopsis (Arabidopsis thaliana) and its close relatives in Brassicaceae. Here, we aim to transfer the priming mechanism of Arabidopsis CERK1 (AtCERK1) to crop CERK1 via JM substitution. We revealed in protoplasts that the entire AtCERK1 JM variable region (AtJM) is essential for imparting the bacterial elicitor flg22-induced primed state to the Nicotiana benthamiana CERK1 (NbCERK1). The NbCERK1 chimera containing AtJM (NbCERK1AtJM) and similarly constructed rice (Oryza sativa) OsCERK1AtJM could undergo flg22-induced JM phosphorylation and confer enhanced antifungal immunity upon bacterial co-infection. Moreover, the NbCERK1AtJM+3D derivative with AtJM phosphomimetic mutations to mimic a constant primed state and similarly constructed OsCERK1AtJM+3D were sufficient to mediate strengthened chitin responses and fungal resistance in transgenic plants independent of bacterial infection. Importantly, no growth and reproduction defects were observed in these plants. Taken together, this study demonstrates that manipulating the primed state of a cell-surface immune receptor offers an effective approach to improve disease resistance in crops without compromising growth and yield and showcases how fundamental insights in plant biology can be translated into crop breeding applications.

Exosomal miR-4745-5p/3911 from N2-polarized tumor-associated neutrophils promotes gastric cancer metastasis by regulating SLIT2.

Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.

INTRODUCTION: Owing to the limited treatment options for hepatocellular carcinoma (HCC), interventions targeting pre-HCC stages have attracted increasing attention. In the pre-HCC stage, hepatic tumor-initiating cells (hTICs) proliferate abnormally and contribute to hepatocarcinogenesis. Numerous studies have investigated targeted senescence induction as an HCC intervention. However, it remains to be clarified whether senescence induction of hTICs could serve as a pre-HCC intervention. OBJECTIVES: This study was designed to investigate whether senescence induction of hTICs in the precancerous stage inhibit HCC initiation. METHODS AND RESULTS: HCC models developed from chronic liver injury (CLI) were established by using Fah-/- mice and N-Ras + AKT mice. PD-0332991, a selective CDK4/6 inhibitor that blocks the G1/S transition in proliferating cells, was used to induce senescence during the pre-HCC stage. Upon administration of PD-0332991, we observed a significant reduction in HCC incidence following selective senescence induction in hTICs, and an alleviation liver injury in the CLI-HCC models. PD-0332991 also induced senescence in vitro in cultured hTICs isolated from CLI-HCC models. Moreover, RNA sequencing (RNA-seq) analysis delineated that the "Cyclin D-CDK4/6-INK4-Rb" pathway was activated in both mouse and human liver samples during the pre-HCC stage, while PD-0332991 exhibited substantial inhibition of this pathway, thereby inducing cellular senescence in hTICs. Regarding the immune microenvironment, we demonstrated that senescent hTICs secrete key senescence-associated secretory phenotypic (SASP) factors, CXCL10 and CCL2, to activate and recruit macrophages, and contribute to immune surveillance. CONCLUSION: We found that hTICs can be targeted and induced into a senescent state during the pre-HCC stage. The SASP factors released by senescent hTICs further activate the immune response, facilitating the clearance of hTICs, and consequently suppressing HCC occurrence. We highlight the importance of pre-HCC interventions and propose that senescence-inducing drugs hold promise for preventing HCC initiation under CLI.

Association between preoperative sarcopenia and postoperative delirium in older patients undergoing gastrointestinal cancer surgery.

Background: Postoperative delirium (POD) is a usual neurological complication, often leading to poor prognoses. Early identification of high-risk patients is crucial for preventing POD. Sarcopenia is an age-related geriatric syndrome characterized by the loss of skeletal muscle mass and function, and previous studies indicated that preoperative low muscle mass might be a predictor for POD. However, the association between preoperative sarcopenia and POD remains to be fully elucidated. This study was to explore the correlation between preoperative sarcopenia and POD following gastrointestinal cancer surgery in older patients. Methods: Older patients (≥60 years) undergoing gastrointestinal cancer surgery were enrolled. Sarcopenia was defined based on the Special Interest Group on sarcopenia of the International Society of Physical and Rehabilitation Medicine (ISarcoPRM), which combined the loss of muscle mass (evaluated by ultrasound) and function (assessed by chair stand test and handgrip strength) before surgery. POD assessment was performed using the Confusion Assessment Method (CAM) or CAM for the intensive care unit (CAM-ICU) during the first 7 days after surgery or before discharge. Multivariate logistic regression analysis examined the correlation between preoperative sarcopenia and POD. Moreover, the receiver operator characteristic (ROC) curve was applied to analyze the predictive effect of the preoperative sarcopenia in POD. Results: One hundred and thirty patients were finally included, of which 43 patients presented with sarcopenia before surgery. Twenty-four patients ultimately developed POD, and the incidence was 18.5%. The results of the multivariate analyses demonstrated that preoperative sarcopenia was still independently associated with POD after adjusting for age ≥70 years, preoperative Mini-Mental State Examination score, and intraoperative blood transfusion. The area under the ROC curve of preoperative sarcopenia in predicting POD was 0.680 (95% confidence interval 0.557-0.804). Conclusion: Preoperative sarcopenia defined by ISarcoPRM criteria was independently associated with POD in geriatric patients after gastrointestinal cancer surgery.

Antihepatoma activity of Marsdenia tenacissima polysaccharide-decorated selenium nanoparticles by regulating the Bax/Bcl-2/caspases and p21/Akt/cyclin A2 signaling pathways.

Combining selenium nanoparticles (SeNPs) with bioactive polysaccharides is one of the effective ways to overcome the shortcomings of SeNPs and polysaccharides and obtain novel antitumor drug candidates. In this study, a heteropolysaccharide (MTP70) with moderate antihepatoma activity was isolated from the stems of Marsdenia tenacissima (Roxb.) Wight et Arn. To further improve the antihepatoma activity of MTP70 and the application of SeNPs, a novel stable nanoparticle (MTP-SeNP) was designed and fabricated. MTP-SeNPs (Se content of 8.25 %) were characterized as monodisperse spherical nanoparticles (50 nm) with MTP70 wrapped on the surface of the SeNPs by the formation of CO⋯Se bonds and possessed high stability and good dispersion in water for almost a month. In addition, MTP-SeNPs showed higher inhibitory effect compared with MTP70. MTP-SeNPs could effectively inhibit the proliferation, invasion, and metastasis of HepG2 cells by inducing apoptosis and arresting the cell cycle at the S phase, which were closely related to the activation of the Bax/Bcl-2/Caspases and p21/Akt/Cyclin A2 signaling pathways. Our results provide a theoretical basis for further development and application of M. tenacissima polysaccharide, and show that MTP-SeNPs could be explored as a promising anti-hepatoma agent in the pharmaceutical and biomedical industries.

[Effectiveness analysis of biplanar vertical fixation and inverted triangle fixation with hollow screw for Pauwels type â ¢ femoral neck fracture in young and middle-aged patients].

Objective: To compare the effectiveness of biplanar vertical fixation and inverted triangle fixation with hollow screw for Pauwels type Ⅲ femoral neck fracture in young and middle-aged patients. Methods: The clinical data of 55 young and middle-aged patients with Pauwels type Ⅲ femoral neck fracture between June 2021 and December 2022 was retrospectively analyzed. All patients were treated with closed reduction and internal fixation with hollow screws, 25 cases were treated with biplanar vertical fixation (study group), 30 cases with inverted triangle fixation (control group). There was no significant difference in gender, age, affected side, cause of injury, underlying diseases, and time from injury to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy times, guide needle puncture times, starting time of weight bearing, time of full weight bearing, time of fracture healing, and complications were recorded and compared between the two groups. The hip joint function was evaluated by Harris score at 1 day, 6 months, 12 months after operation, and at last follow-up, and the pain relief was evaluated by visual analogue scale (VAS) score. The femoral neck shortening was measured on the X-ray film at last follow-up. Results: All patients were followed up 12-31 months (mean, 22.0 months), and there was no significant difference in follow-up time between the two groups ( P>0.05). The operation time, intraoperative blood loss, and fluoroscopy times in the study group were higher than those in the control group, but the difference was not significant ( P>0.05). The guide needle puncture times in the study group was more than that in the control group, and the time of starting weight bearing and the time of full weight bearing in the study group were shorter than those in the control group, the differences were significant ( P<0.05). Bony healing was achieved in both groups, and there was no significant difference in fracture healing time between the two groups ( P>0.05). No osteonecrosis of the femoral head and incision-related complication was found in the two groups during follow-up, and the femoral neck shortening length in the study group was significantly shorter than that in the control group at last follow-up ( P<0.05). There was no significant difference in Harris score between the two groups at 1 day after operation ( P>0.05), and the Harris score of the study group was significantly better than that of the control group at other time points ( P<0.05); there was no significant difference in VAS score between the two groups at each time point after operation ( P>0.05). Conclusion: Compared with the inverted triangle fixation, the treatment of Pauwels type Ⅲ femoral neck fracture with biplanar vertical fixation can effectively reduce femoral neck shortening without affecting fracture healing, and improve hip joint function in early stage.

Autologous exosomes loaded with a rationally designed photosensitizer for enhanced photodynamic therapy.

We present generalizing statistical surrogate models to select an optimized photosensitizer, TPP, which is subsequently loaded into autologous exosomes by ultrasonic mixing to achieve tumor targeting with enhanced therapeutic efficacy by photodynamic therapy (PDT). This work contributes to the exploration of PDT enhancement strategies, and provides new prospects for using autologous exosomes as a delivery system.

Association of visceral adiposity index with phenotypic age acceleration: insight from NHANES 1999-2010.

BACKGROUND: Obesity correlates with accelerated aging. This study aims to investigate the association between the visceral adiposity index (VAI) and accelerated aging. METHODS: Biological aging was evaluated by phenotypic age acceleration (PhenoAgeAccel). Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010, we employed weighted multivariable logistic regression models, along with subgroup analysis, to examine the association between VAI and PhenoAgeAccel. Moreover, smooth curve fitting was utilized to identify potential nonlinear association, complemented by a two-piece linear regression model to investigate threshold effects. RESULTS: Of the included 11,340 participants aged 20 years and older, the mean (95% CI) age was 46.569 (45.946, 47.191) years, and 49.189% were male. The mean (95% CI) VAI for all participants was 2.176 (2.114, 2.238), and the mean (95% CI) PhenoAgeAccel was -6.306 (-6.618, -5.994) years. In the fully adjusted model, each incremental unit increase of VAI was associated with a 0.312-year increase in PhenoAgeAccel (ß = 0.312, 95% CI: 0.217, 0.408). This positive association was more statistically significant among individuals with cancer. Furthermore, a segmented association was observed between VAI and PhenoAgeAccel, with a turning point identified at 10.543. Below this threshold, VAI exhibited a positive correlation with PhenoAgeAccel (ß = 0.617, 95% CI: 0.499, 0.735), while beyond it, the association became nonsignificant. CONCLUSION: This study demonstrated a positive association between VAI and accelerated aging within a nationally representative population. The findings suggest that controlling adiposity may exert anti-aging effects and help prevent aging-related diseases.

Effects of Haskap (Lonicera caerulea L.) Extracts against Oxidative Stress and Inflammation in RAW 264.7 Cells.

This study aimed to evaluate the antioxidant and anti-inflammatory activities of Lonicera caerulea L. ethanol extract (LCEE) and water extract (LCWE) in vitro. We primarily evaluated the improvement effect of LCWE and LCEE on hydrogen peroxide (H2O2)-induced oxidative damage and lipopolysaccharide (LPS)-induced inflammatory damage in RAW 264.7 cells by detecting oxidation-related indicators and inflammatory factors, respectively. Cellular studies showed that LCWE and LCEE increased superoxide dismutase and catalase antioxidant enzyme levels and decreased malondialdehyde and nitric oxide peroxide levels in H2O2-induced RAW 264.7 cells. Moreover, LCWE and LCEE decreased the secretion of inflammatory factors [e.g., interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α] in LPS-induced RAW 264.7 cells. In conclusion, LCWE and LCEE demonstrated excellent antioxidant and anti-inflammatory effects in vitro. However, LCWE was superior to LCEE, which may be related to its chemical composition and requires further research.

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy.

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment, the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging population. The relationships between these disorders and cancer are intricate, bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of malignancies. Herein, we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario, with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities, as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

Osteoblast-specific down-regulation of NLRP3 inflammasome by aptamer-functionalized liposome nanoparticles improves bone quality in postmenopausal osteoporosis rats.

Rationale: NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. Methods: We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR. Lastly, we accessed the effect of decreased NLRP3 levels on ovariectomized (OVX) rats. To specifically deliver NLRP3 siRNA to osteoblasts, we constructed NLRP3 siRNA wrapping osteoblast-specific aptamer (CH6)-functionalized lipid nanoparticles (termed as CH6-LNPs-siNLRP3). Results: We found that the levels of NLRP3 inflammasome were significantly increased in patients with PMOP, and were negatively correlated with estradiol levels. NLRP3 knock-down influenced signal pathways including immune system process, interferon signal pathway. Notably, of the top ten up-regulated genes in NLRP3-reduced osteoblasts, nine genes (except Mx2) were enriched in immune system process, and five genes were related to interferon signal pathway. The in vitro results showed that CH6-LNPs-siNLRP3 was relatively uniform with a dimeter of 96.64 ± 16.83 nm and zeta potential of 38.37 ± 1.86 mV. CH6-LNPs-siNLRP3 did not show obvious cytotoxicity and selectively delivered siRNA to bone tissue. Moreover, CH6-LNPs-siNLRP3 stimulated osteoblast differentiation by activating ALP and enhancing osteoblast matrix mineralization. When administrated to OVX rats, CH6-LNPs-siNLRP3 promoted bone formation and bone mass, improved bone microarchitecture and mechanical properties by decreasing the levels of NLRP3, IL-1ß and IL-18 and increasing the levels of OCN and Runx2. Conclusion: NLRP3 inflammasome may be a new biomarker for PMOP diagnosis and plays a key role in the pathology of PMOP. CH6-LNPs-siNLRP3 has potential application for the treatment of PMOP.

Association between systemic inflammatory response index and bone turnover markers in Chinese patients with osteoporotic fractures: a retrospective cross-sectional study.

Background: The systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings. Methods: A retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People's Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, ß-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed. Results: The results revealed a negative correlation between baseline SIRI values and both ß-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 (ß = -0.04; 95% confidence interval [CI], -0.05 to -0.03; with p-value <0.001) in ß-CTX levels and a decrease of 3.77 (ß = 3.77; 95% CI, 5.07 to 2.47; with p-value <0.001) in P1NP levels. Furthermore, a curvilinear relationship and threshold effect were also identified. Turning points were identified at SIRI values of 1.41 and 1.63 on the adjusted smooth curve. Conclusion: The results showed a negative correlation between the baseline SIRI value and ß-CTX level, as well as the level of P1NP. This suggests a possible link between the systemic inflammatory response and reduced bone metabolism. If these findings are verified, SIRI has the potential to function as a predictive indicator for BTMs. Nevertheless, additional research is necessary to verify these findings.

Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.

Label-free electrochemical biosensor based on dual amplification of gold nanoparticles and polycaprolactones for CEA detection.

Carcinoembryonic Antigen (CEA), an acidic glycoprotein with human embryonic antigen properties, is found on the surface of cancer cells that have differentiated from endodermal cells. This paper presents a label-free electrochemical immunoassay for the dual amplification detection of CEA using gold nanoparticles loaded with polypyrrole polydopamine (Au/PPy-PDA) and polymerized polycaprolactone (Ng-PCL) prepared by ring-opening polymerization (ROP). First, the composite Au/PPy-PDA was adhered to the electrode surface. Then, gold nanoparticles form a Au-S bond with the sulfhydryl group in Apt1 to secure it on the electrode surface. Subsequently, the non-specific binding sites on the electrodes surface are closed by bovine serum albumin (BSA). Next, CEA is dropped onto the electrode surface, which is immobilized by antigen-antibody specific recognition, and the carboxyl-functionalized Apt2 forms a "sandwich structure" of antibody-antigen-antibody by specific recognition. Polymeric Ng-PCL is adhered to the electrode surface, leading to an increase in the electrochemical impedance signal, resulting in a complete chain of signal analysis. Finally, the response signal is detected by electrochemical impedance spectroscopy (EIS). Under optimal experimental conditions, the method has the advantages of high sensitivity and wide linear range (1 pg mL-1∼100 ng mL-1), and the lower limit of detection (LOD) is 0.234 pg mL-1. And it has the same high sensitivity, selectivity and interference resistance for the real samples detection. Thus, it provides a new way of thinking about biomedical and clinical diagnosis.

A curcumin-loaded biopolymeric nanocomposite alleviates dextran sulfate sodium induced ulcerative colitis via suppression of inflammation and oxidative stress.

Functional drugs nano delivery systems manufactured from natural active products are promising for the field of biomedicines. In this study, an anti-ulcerative colitis (UC) curcumin loaded biopolymeric nanocomposite (CZNH) was fabricated and investigated. CZNH nanocomposite was obtained using the anti-solvent precipitation method, wherein curcumin-loaded zein colloidal particles served as the core, while sodium casein (NaCas) and hyaluronic acid (HA) formed the outermost layer of CZNH nanocomposite. Fourier transform infrared (FT-IR) spectrum and transmission electron microscopy (TEM) findings demonstrated that CZNH nanocomposite was a double-layer spherical micelle (250 nm) resulting from the hydrogen bond interactions and electrostatic adsorptions between zein, NaCas, and HA. Furthermore, CZNH nanocomposite exhibited prominent resuspension and storage stability in aqueous solution, which can be stored at 4 °C for approximately 30 days. In vivo anti-UC studies showed that CZNH nanocomposite could effectively alleviate UC symptoms via mediating inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6], myeloperoxidase (MPO), and oxidative stress factor [malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)]. This study suggested that the CZNH nanocomposite showed great promise as an efficient curcumin nanocarrier for UC therapy.

Relationship between jejunum ATPase activity and antioxidant function on the growth performance, feed conversion efficiency, and jejunum microbiota in Hu sheep (Ovis aries).

BACKGROUND: ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. RESULTS: This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. CONCLUSIONS: The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.

Enhancing early breast cancer diagnosis through automated microcalcification detection using an optimized ensemble deep learning framework.

Background: Breast cancer remains a pressing global health concern, necessitating accurate diagnostics for effective interventions. Deep learning models (AlexNet, ResNet-50, VGG16, GoogLeNet) show remarkable microcalcification identification (>90%). However, distinct architectures and methodologies pose challenges. We propose an ensemble model, merging unique perspectives, enhancing precision, and understanding critical factors for breast cancer intervention. Evaluation favors GoogleNet and ResNet-50, driving their selection for combined functionalities, ensuring improved precision, and dependability in microcalcification detection in clinical settings. Methods: This study presents a comprehensive mammogram preprocessing framework using an optimized deep learning ensemble approach. The proposed framework begins with artifact removal using Otsu Segmentation and morphological operation. Subsequent steps include image resizing, adaptive median filtering, and deep convolutional neural network (D-CNN) development via transfer learning with ResNet-50 model. Hyperparameters are optimized, and ensemble optimization (AlexNet, GoogLeNet, VGG16, ResNet-50) are constructed to identify the localized area of microcalcification. Rigorous evaluation protocol validates the efficacy of individual models, culminating in the ensemble model demonstrating superior predictive accuracy. Results: Based on our analysis, the proposed ensemble model exhibited exceptional performance in the classification of microcalcifications. This was evidenced by the model's average confidence score, which indicated a high degree of dependability and certainty in differentiating these critical characteristics. The proposed model demonstrated a noteworthy average confidence level of 0.9305 in the classification of microcalcification, outperforming alternative models and providing substantial insights into the dependability of the model. The average confidence of the ensemble model in classifying normal cases was 0.8859, which strengthened the model's consistent and dependable predictions. In addition, the ensemble models attained remarkably high performances in terms of accuracy, precision, recall, F1-score, and area under the curve (AUC). Conclusion: The proposed model's thorough dataset integration and focus on average confidence ratings within classes improve clinical diagnosis accuracy and effectiveness for breast cancer. This study introduces a novel methodology that takes advantage of an ensemble model and rigorous evaluation standards to substantially improve the accuracy and dependability of breast cancer diagnostics, specifically in the detection of microcalcifications.

Self-Assembled Micelles Based on Ginsenoside Rg5 for the Targeted Treatment of PTX-Resistant Tumors.

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.