Development and validation of a predictive model for acute-on-chronic liver failure after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a cause of acute-on-chronic liver failure (ACLF). AIM: To investigate the risk factors of ACLF within 1 year after TIPS in patients with cirrhosis and construct a prediction model. METHODS: In total, 379 patients with decompensated cirrhosis treated with TIPS at Nanjing Drum Tower Hospital from 2017 to 2020 were selected as the training cohort, and 123 patients from Nanfang Hospital were included in the external validation cohort. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. The prediction model was established based on the Akaike information criterion. Internal and external validation were conducted to assess the performance of the model. RESULTS: Age and total bilirubin (TBil) were independent risk factors for the incidence of ACLF within 1 year after TIPS. We developed a prediction model comprising age, TBil, and serum sodium, which demonstrated good discrimination and calibration in both the training cohort and the external validation cohort. CONCLUSION: Age and TBil are independent risk factors for the incidence of ACLF within 1 year after TIPS in patients with decompensated cirrhosis. Our model showed satisfying predictive value.

Structure and functional divergence of PIP peptide family revealed by functional studies on PIP1 and PIP2 in Arabidopsis thaliana.

PAMP-induced secreted peptide (PIP), one of the small post-translationally modified peptides (PTMPs), plays a crucial role in plant development and stress tolerance. However, little is known about functional divergence among this peptide family. Here, we studied the evolution of the PIP family in 23 plant species (10 monocotyledons and 13 dicotyledons from 7 families) and their functional divergence in Arabidopsis. A total of 128 putative PIP precursors were identified and classified into two subfamilies through phylogenetic analysis. Functional studies on AtPIP1 which represents Clade I family and AtPIP2 which represents Clade II family have shown that AtPIP2 displayed stronger immunity induction activity but weaker root growth inhibition than AtPIP1 in Arabidopsis. Transcriptome analysis of Arabidopsis seedlings treated with AtPIP1 and AtPIP2 showed that differential genes for both polypeptides were significantly enriched in similar plant defense pathways. However, Co-expression and Protein-protein interaction (PPI) analysis showed that the functions of AtprePIP2 co-expressed genes were more enriched in plant defense pathways than AtprePIP1. Molecular docking results show that AtPIP1 binds to RLK7 receptor with a more stable free energy and less binding area than AtPIP2, while hydrogen bond transfer occurs at the SGP motif position. The above results suggest that the PIP family have undergone functional divergence during evolution. Collectively, this work illustrates the relationship between PIP structure and function using Arabidopsis PIP as an example, and provides new insights into the current understanding between growth inhibition and immune responses which may be correlated but not fully coupled.

Space Squeeze Reasoning and Low-Rank Bilinear Feature Fusion for Surgical Image Segmentation.

Surgical image segmentation is critical for surgical robot control and computer-assisted surgery. In the surgical scene, the local features of objects are highly similar, and the illumination interference is strong, which makes surgical image segmentation challenging. To address the above issues, a bilinear squeeze reasoning network is proposed for surgical image segmentation. In it, the space squeeze reasoning module is proposed, which adopts height pooling and width pooling to squeeze global contexts in the vertical and horizontal directions, respectively. The similarity between each horizontal position and each vertical position is calculated to encode long-range semantic dependencies and establish the affinity matrix. The feature maps are also squeezed from both the vertical and horizontal directions to model channel relations. Guided by channel relations, the affinity matrix is expanded to the same size as the input features. It captures long-range semantic dependencies from different directions, helping address the local similarity issue. Besides, a low-rank bilinear fusion module is proposed to enhance the model's ability to recognize similar features. This module is based on the low-rank bilinear model to capture the inter-layer feature relations. It integrates the location details from low-level features and semantic information from high-level features. Various semantics can be represented more accurately, which effectively improves feature representation. The proposed network achieves state-of-the-art performance on cataract image segmentation dataset CataSeg and robotic image segmentation dataset EndoVis 2018.

One-Pot Preparation of Peptide-Doped Metal-Amino Acid Framework for General Encapsulation and Targeted Delivery.

Metal-organic frameworks (MOFs), especially those made by biological molecules (bio-MOFs), have been proved to be prospective candidates for biomedical applications. However, a simple and universal bio-MOF to load different substances for precise targeting is still lacking. In this work, we propose a facile one-pot method to prepare a peptide-doped bio-MOF for general encapsulation and targeted delivery. This bio-MOF is constructed by 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-His) as a bridging linker that coordinates with Zn2+ ions, denoted as ZFH. The Fmoc-His-Asp-Gly-Arg peptide (Fmoc-HDGR) can be easily doped into the ZFH structure with different ratios to modulate the targeting ability of ZFH-DGR. Containing both hydrophobic Fmoc and hydrophilic His moieties, this framework is compatible with encapsulating various types of payloads, including hydrophobic chemotherapeutic, hydrophilic protein, and positively/negatively charged inorganic nanoparticles. It has also been proved to be highly biocompatible and stable in circulation, exhibit the capabilities to target ανß3 integrin overexpressed on tumor cells, and trigger drug release in a low pH microenvironment at the tumor site. As a proof of concept, Doxorubicin (Dox)-loaded ZFH-DGR (ZFH-DGR/Dox) demonstrated high cell selectivity between liver hepatocellular carcinoma (HepG2) cells and normal liver (L02) cells, which express high and low ανß3 integrin, respectively. This selectivity endows ZFH-DGR/Dox precise treatment and low toxicity in Heps-bearing liver cancer mice. This work develops a de novo approach to construct a peptide-doped bio-MOF system for universal load, precise delivery, and peptide drug combination therapy in the future.

[Analysis of factors related to oil-spilling and establishment of limit standards of Asparagi Radix].

Some samples of Asparagi Radix were collected from medical markets.Colors of Asparagi Radix were observed by human vision and recorded to judge whether samples were degenerative.Water content of Asparagi Radix was determined by a drying method.The chroma value and color difference were determined and calculated by a colorimeter.With the deepening of color,the L*value was decreased and a*and ΔE*values were increased.It showed that the results determined by colorimeter can replace the results of visual observation.An HPLC method was established and used to determine the contents of 5-hydroxymethylfurfural(5-HMF) in Asparagi Radix.The results showed the 5-HMF contents were from 0.002 255 to 0.049 14 mg·g-1 in some samples with yellowish-white or yellowish-brown color,significantly increased from 0.080 80 to 0.105 1 mg·g-1 in some samples with brown color,and up to 1.033 mg·g-1 in an oil-spilling sample with dark brown color.This result demonstrated that the 5-HMF contents were significantly increased by accompanied with the deepening of color.There were the significant negatively correlation between the 5-HMF content and the L*value(P<0.01) and positively correlation between the 5-HMF content and the a*or ΔE*value(P<0.01) by the spearman analysis.The oil-spilling and qualified samples were clustered into two alone categories by the cluster analysis.That the limited standards of the 5-HMF content is not higher than 0.02% by HPLC method and of the L*value is not less than 50 by colorimeter method were suggested for Asparagi Radix.It is firstly reported the multiple-factor analysis about oil-spilling and discoloration and the establishment of limited standard of Asparagi Radix.

Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway.

Osteosarcoma is the most common cause of cancer-associated mortality and the prognosis is yet to be fully elucidated due to the paucity of effective therapeutic targets that significantly influence the quality of life and mean survival rates of patients with osteosarcoma. Studies have showed that tripartite motif-containing (TRIM)-14 is a member of the TRIM protein family that has a vital role in tumor progression and metastasis and promotes angiogenesis, invasion and apoptotic resistance of bone cancer. In this study, a chimeric antibody targeting TRIM-14 (Chanti-TRIM) was constructed and the molecular mechanism of target therapy for TRIM-14 was investigated in osteosarcoma cells and xenograft mice. The growth, migration and invasion properties of U-2OS cells were analyzed following incubation with 10-160 mg/ml Chanti-TRIM. Apoptosis of U-2OS cells was detected after Chanti-TRIM treatment. Matrix metalloproteinase (MMP)-9-mediated nuclear factor-κB (NF-κB) signal pathway was analyzed in U-2OS cells treated with Chanti-TRIM. The inhibitory efficacy of Chanti-TRIM was studied in U-2OS-bearing xenograft mice. Our results demonstrated that neutralizing TRIM-14 expression markedly inhibited the growth, migration and invasion of osteosarcoma cells, in vitro and in vivo. We found that TRIM-14 depletion decreased cell viability and induced cells apoptosis in vitro. In addition, we identified Chanti-TRIM inhibited growth and promoted apoptosis induced by cisplatin through MMP-9-mediated NF-κB signal pathway. Furthermore, we observed that Chanti-TRIM treatment inhibited osteosarcoma growth in vivo. Histological analysis indicated that apoptotic bodies were increased and NF-κB nuclear translocation factors, including Ikkß, p65 and IkBα, were decreased in tumors treated by Chanti-TRIM. In conclusion, these results showed that Chanti-TRIM markedly inhibited the progression of osteosarcoma, suggesting Chanti-TRIM may be a potential anti-cancer agent that functions via the activation of the NF-κB pathway for osteosarcoma.

Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury.

Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 days after injury. Results showed that Radix Ilicis Pubescentis total flavonoids could reduce pathological injury in rats with cerebral ischemia/reperfusion injury. The number of Nissl bodies increased, Bax protein expression decreased, Bcl-2 protein expression increased and the number of CD34-positive cells increased. Therefore, Radix Ilicis Pubescentis total flavonoids can improve the bone marrow stem cell mobilization effect, enhance the anti-apoptotic ability of nerve cells, and have a neuroprotective effect on cerebral ischemia/reperfusion injury in rats.

Integrated fossil and molecular data reveal the biogeographic diversification of the eastern Asian-eastern North American disjunct hickory genus (Carya Nutt.).

The hickory genus (Carya) contains ca. 17 species distributed in subtropical and tropical regions of eastern Asia and subtropical to temperate regions of eastern North America. Previously, the phylogenetic relationships between eastern Asian and eastern North American species of Carya were not fully confirmed even with an extensive sampling, biogeographic and diversification patterns had thus never been investigated in a phylogenetic context. We sampled 17 species of Carya and 15 species representing all other genera of the Juglandaceae as outgroups, with eight nuclear and plastid loci to reconstruct the phylogeny of Carya. The phylogenetic positions of seven extinct genera of the Juglandaceae were inferred using morphological characters and the molecular phylogeny as a backbone constraint. Divergence times within Carya were estimated with relaxed Bayesian dating. Biogeographic analyses were performed in DIVA and LAGRANGE. Diversification rates were inferred by LASER and APE packages. Our results support two major clades within Carya, corresponding to the lineages of eastern Asia and eastern North America. The split between the two disjunct clades is estimated to be 21.58 (95% HPD 11.07-35.51) Ma. Genus-level DIVA and LAGRANGE analyses incorporating both extant and extinct genera of the Juglandaceae suggested that Carya originated in North America, and migrated to Eurasia during the early Tertiary via the North Atlantic land bridge. Fragmentation of the distribution caused by global cooling in the late Tertiary resulted in the current disjunction. The diversification rate of hickories in eastern North America appeared to be higher than that in eastern Asia, which is ascribed to greater ecological opportunities, key morphological innovations, and polyploidy.