Highly-Efficient Gallium-Interference Tumor Therapy Mediated by Gallium-Enriched Prussian Blue Nanomedicine.

Prussian blue (PB)-based nanomedicines constructed from metal ion coordination remain restricted due to their limited therapeutic properties, and their manifold evaluation complexity still needs to be unraveled. Owing to the high similarities of its ionic form to iron (Fe) and the resulting cellular homeostasis disruption performance, physiologically unstable and low-toxicity gallium (Ga) has garnered considerable attention clinically as an anti-carcinogen. Herein, Ga-based nanoparticles (NPs) with diverse Ga contents are fabricated in one step using PB with abundant Fe sites as a substrate for Ga substitution, which aims to overcome the deficiencies of both and develop an effective nanomedicine. A systematic comparison of their physicochemical properties effectively reveals the saturated Ga introduction state during the synthesis process, further identifying the most Ga-enriched PB NPs with a substitution content of >50% as a nanomedicine for subsequent exploration. It is verified that the Ga interference mechanisms mediated by the most Ga-enriched PB NPs are implicated in metabolic disorders, ionic homeostasis disruption, cellular structure dysfunction, apoptosis, autophagy, and target activation of the mammalian target of the rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways. This study provides significant guidance on exploiting clinically approved agents for Ga interference and lays the foundation for the next generation of PB-based theranostic agents.

TMM: A comprehensive CAD system for hepatic fibrosis 5-grade METAVIR staging based on liver MRI.

BACKGROUND: Precise staging of hepatic fibrosis with MRI is necessary as it can assist precision medicine. Computer aided diagnosis (CAD) system with distinguishing radiomics features and radiologists domain knowledge is expected to obtain 5-grade meta-analysis of histological data in viral hepatitis (METAVIR) staging. PURPOSE: This study aims to obtain the precise staging of hepatic fibrosis based on MRI as it predicts the risk of future liver-related morbidity and the need for treatment, monitoring and surveillance. Based on METAVIR score, fibrosis can be divided into five stages. Most previous researches focus on binary classification, such as cirrhosis versus non-cirrhosis, early versus advanced fibrosis, and substantial fibrosis or not. In this paper, a comprehensive CAD system TMM is proposed to precisely class hepatic fibrosis into five stages for precision medicine instead of the common binary classification. METHODS: We propose a novel hepatic fibrosis staging CAD system TMM which includes three modules, Two-level Image Statistical Radiomics Feature (TISRF), Monotonic Error Correcting Output Codes (MECOC) and Monotone Multiclassification with Deep Forest (MMDF). TISRF extracts radiomics features for distinguishing different hepatic fibrosis stages. MECOC is proposed to encode monotonic multiclass by making full use of the progressive severity of hepatic fibrosis and increase the fault tolerance and error correction ability. MMDF combines multiple Deep Forest network to ensure the final five-class classification, which can achieve more precise classification than the common binary classification. The performance of the proposed hepatic fibrosis CAD system is tested on the hepatic data collected from our rabbits models of fibrosis. RESULTS: A total of 140 regions of interest (ROI) are selected from MRI T1W of liver fibrosis models in 35 rabbits with F0(n = 16), F1(n = 28), F2(n = 29), F3(n = 44) and F4(n = 23). The performance is evaluated by five-fold cross-validation. TMM can achieve the highest total accuracy of 72.14% for five fibrosis stages compared with other popular classifications. To make a comprehensive comparison, a binary classification experiment have been carried out. CONCLUSIONS: T1WI can obtain precise staging of hepatic fibrosis with the help of comprehensive CAD including radiomics features extraction inspired by radiologists, monotonic multiclass according to the severity of hepatic fibrosis, and deep learning classification.

SET Domain Group 703 Regulates Planthopper Resistance by Suppressing the Expression of Defense-Related Genes.

Plant defense responses against insect pests are intricately regulated by highly complex regulatory networks. Post-translational modifications (PTMs) of histones modulate the expression of genes involved in various biological processes. However, the role of PTMs in conferring insect resistance remains unclear. Through the screening of a T-DNA insertion activation-tagged mutant collection in rice, we identified the mutant planthopper susceptible 1 (phs1), which exhibits heightened expression of SET domain group 703 (SDG703). This overexpression is associated with increased susceptibility to the small brown planthopper (SBPH), an economically significant insect pest affecting rice crops. SDG703 is constitutively expressed in multiple tissues and shows substantial upregulation in response to SBPH feeding. SDG703 demonstrates the activity of histone H3K9 methyltransferase. Transcriptomic analysis revealed the downregulation of genes involved in effector-triggered immunity (ETI) and pattern-triggered immunity (PTI) in plants overexpressing SDG703. Among the downregulated genes, the overexpression of SDG703 in plants resulted in a higher level of histone H3K9 methylation compared to control plants. Collectively, these findings indicate that SDG703 suppresses the expression of defense-related genes through the promotion of histone methylation, consequently leading to reduced resistance against SBPH. The defense-related genes regulated by histone methylation present valuable targets for developing effective pest management strategies in future studies. Furthermore, our study provides novel insight into the epigenetic regulation involved in plant-insect resistance.

Navigating zinc-involved nanomedicine in oncotherapy.

Zinc (Zn), extolled as "the flower of life" in modern medicine, has been extensively highlighted with its physiological functions to maintain growth, development, and metabolism homeostasis. Driven by the substantial advancement of nanotechnology and oncology, Zn-involved nanomedicines integrating the intrinsic bioactivity of Zn species and the physiochemical attributes of Zn-composed nanosystems have blazed a highly efficient and relatively biosafe antineoplastic path. In this review, we aim to highlight and discuss the recent representative modalities of emerging Zn-involved oncology nanomedicine, mainly emphasizing the rational design, biological effect and biosafety, and therapeutic strategies. In addition, we provide the underlying critical obstacles and future perspectives of Zn-involved oncology nanomedicines, primarily focusing on the chances and challenges of clinical translation. Furthermore, we hope the review can give rise to opportunities within oncology nanomedicine and other biomedical fields, promoting the prosperity and progress of the "Zincic Age".

Magnetomechanical force: an emerging paradigm for therapeutic applications.

Mechanical forces, which play a profound role in cell fate regulation, have prompted the rapid development and popularization of mechanobiology. More recently, magnetic fields in combination with intelligent materials featuring magnetic responsiveness have been identified as a spatially and time-controlled transducing paradigm to generate magnetomechanical forces and induce a therapeutic effect. Herein, recent magnetic materials and magnetic regulation systems are summarized, which offer opportunities for magnetomechanical force manipulation in a precise manner. Additionally, promising applications based on magnetomechanical force including drug controlled release, cancer therapy, and regenerative medicine are highlighted, with respect to both in vitro and in vivo. Furthermore, perspectives on the further development of magnetomechanical force are commented on, mainly emphasizing scientific restrictions and exploitation directions.

Modification of a new subclassification of Grade B postoperative pancreatic fistula: A bicenter retrospective cohort study.

AIM: To propose a modified subclassification of grade B postoperative pancreatic fistula (POPF) based on management approaches in Chinese patients. METHODS: Data of consecutive pancreatoduodenectomy at two hospitals in China from 2013 to 2018 were collected, and outcomes were compared across different groups of POPF. Subclassification of B-POPF was made based on intervention to B1: non-interventional subclass and B2: interventional subclass. RESULTS: A total of 142 of 522 patients had biochemical leaks (BLs) (27.2%), and POPFs developed in 106 of 522 patients (20.3%), with 81 B-POPFs (15.5%) and 25 C-POPFs (4.8%). BL did not differ from the non-fistula condition in almost all outcomes. The differences of outcomes among the non-fistula/BL, B-POPF and C-POPF groups were significant. The prevalence of subclass B1 and B2 was 56.8% (46/81) and 43.2% (35/81), respectively. Compared to the B1 group, patients in the B2 group had worse outcomes, such as post-pancreatectomy hemorrhage (15.2% vs 34.3%, P = .045), biliary fistula (13.0% vs 34.3%, P = .023), postoperative hospital stay (32 vs 39 days, P = .011), and cost ($US28 601.0 vs $US39 314.5, P < .001). CONCLUSION: The recently reported B-POPF subclassification method was modified in Chinese patients according to the intervention, and is more practical, simpler and fits Chinese patients.

A modified alternative fistula risk score (a-FRS) obtained from the computed tomography enhancement pattern of the pancreatic parenchyma predicts pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Alternative fistula risk score (a-FRS) is useful to predict clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). METHODS: Clinical data from 239 patients undergoing PD were collected. The CT value of the pancreatic parenchyma was measured in the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases. The A/N, A/P, P/L and A/L ratios were calculated and their correlation with CR-POPF were analyzed. By replacing pancreatic texture with the best CT attenuation ratio, a modified a-FRS was developed. RESULTS: Forty-seven patients developed CR-POPF. The A/P ratio (P < 0.001), P/L ratio (P = 0.002) and A/L ratio (P < 0.001) were significantly higher in the CR-POPF group. The A/L ratio performed best in predicting CR-POPF (AUC: 0.803) and the cut-off value is 1.36. A/L ratio >1.36 (P < 0.001), body mass index (P = 0.005) and duct diameter (P = 0.037) were independently associated with CR-POPF. By replacing soft texture with an A/L ratio >1.36, a modified a-FRS was developed and performed better than the a-FRS (AUC: 0.823 vs 0.748, P = 0.006) in predicting CR-POPF. CONCLUSIONS: The modified a-FRS is an objective and preoperative model for predicting the occurrence of CR-POPF after PD.

Excellent Adsorptive Behaviors of ZnO Nanoparticle-Deposited Activated Carbon Covered with Nano-Graphene Oxide.

In the paper, ZnO-deposited activated carbon composite (ZnO-AC) was firstly prepared in a simple two-step preparation process, and then covered with nano-graphene oxide to give the NGO-ZnOAC composite. The successful deposition of ZnO and NGO on the AC surface was demonstrated by various experiments, and the ZnO nanoparticles showed a mean diameter size mainly within about 10 nm. The specific surface area of the NGO-AC and NGO-ZnO-AC decreased from 67.74 m²/g of the parent AC to 32.54 and 11.43 m²/g, respectively. The fabricated NGO-ZnO-AC showed excellent adsorptive behaviors towards CrO2-4 and Cu2+ ions, outperforming both ZnO-AC and AC.

Effects of the different levels of dietary trace elements from organic or inorganic sources on growth performance, carcass traits, meat quality, and faecal mineral excretion of broilers.

This experiment was conducted to evaluate the effects of different sources and levels of trace elements on growth performance, carcass composition and mineral excretion levels of broilers. In a completely randomised experimental design, 900 one-day-old male Ross-308 broilers were assigned to 5 treatments, with 6 replicates of 30 birds each. The control group (CITE) was fed with a basal diet containing regular inclusion levels of inorganic trace elements. Treatment groups were supplied with reduced levels (30% and 50% of the regular level) of inorganic (ITE) or organic trace elements (OTE), respectively. Groups 50% ITE, 30% OTE and 50% OTE diets had equivalent average daily gain (ADG), average daily feed intake (ADFI), feed to gain ratio (F/G ratio) and mortality rate compared with group CITE in any phase. However, compared with group CITE chicks in group 30% ITE have lower ADG and ADFI and higher F/G ratio. The carcass yields were not affected by dietary treatments. Compared with group CITE, in groups 30% ITE, 50% ITE, 30% OTE and 50% OTE the shear force values of the breast muscle were only 71.8%, 83.4%, 63.5% and 59.4% (p < 0.05), respectively. Birds received diets containing reduced levels of trace elements had diminished excretions of Mn and Zn throughout the entire period (p < 0.01). In conclusion, the reduced supplementation of trace elements had no or slightly negative impact on growth performance, carcass yield and meat quality, but decreased faecal mineral excretion. Moreover, the trace element supply as OTE played a limited role on performance and excretion and was only partly beneficial for animal performance in case the trace element supply was reduced to 30%.