High-throughput nanopore targeted sequencing for efficient drug resistance assay of Mycobacterium tuberculosis.

Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is one of the urgent clinical problems and public health challenges. Culture-based phenotypic drug susceptibility testing (pDST) is time-consuming, and PCR-based assays are limited to hotspot mutations. In this study, we developed and validated a convenient and efficient approach based on high-throughput nanopore sequencing technology combined with multiplex PCR, namely nanopore targeted sequencing (NTS), to simultaneously sequence 18 genes associated with antibiotic resistance in Mycobacterium tuberculosis (MTB). The analytical performance of NTS was evaluated, and 99 clinical samples were collected to assess its clinical performance. The NTS results showed that MTB and its drug resistance were successfully identified in approximately 7.5 h. Furthermore, compared to the pDST and Xpert MTB/RIF assays, NTS provided much more drug resistance information, covering 14 anti-TB drugs, and it identified 20 clinical cases of drug-resistant MTB. The mutations underlying these drug-resistant cases were all verified using Sanger sequencing. Our approach for this TB drug resistance assay offers several advantages, including being culture-free, efficient, high-throughput, and highly accurate, which would be very helpful for clinical patient management and TB infection control.

Sulforaphane impaired immune checkpoint blockade therapy through activating ΔNP63α/PD-L1 axis in gastric cancer.

Sulforaphane (SFN) exerts anticancer effect on various cancers including gastric cancer. However, the regulatory effect of SFN on programmed death-ligand 1 (PD-L1) and checkpoint blockade therapy in gastric cancer have not been elucidated. Here we demonstrated that SFN suppressed gastric cancer cell growth both in vitro and in vivo study. SFN upregulated PD-L1 expression through activating ΔNP63α in gastric cancer cells. Further, we found that SFN impaired the anticancer effect of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) on gastric cancer cells. These results uncover a novel PD-L1 regulatory mechanism and the double-edged role of SFN in gastric cancer intervention.

Self-Perceptional Soft Robotics by a Dielectric Elastomer.

Soft robotics has been a rapidly growing field in recent decades due to its advantages of softness, deformability, and adaptability to various environments. However, the separation of perception and actuation in soft robot research hinders its progress toward compactness and flexibility. To address this limitation, we propose the use of a dielectric elastomer actuator (DEA), which exhibits both an actuation capability and perception stability. Specifically, we developed a DEA array to localize the 3D spatial position of objects. Subsequently, we integrate the actuation and sensing properties of DEA into soft robots to achieve self-perception. We have developed a system that integrates actuation and sensing and have proposed two modes to achieve this integration. Furthermore, we demonstrated the feasibility of this system for soft robots. When the robots detect an obstacle or an approaching object, they can swiftly respond by avoiding or escaping the obstacle. By eliminating the need for separate perception and motion considerations, self-perceptional soft robots can achieve an enhanced response performance and enable applications in a more compact and flexible field.

The combined effects of ultrasound and plasma-activated water on silkworm pupae:Physicochemical properties, microbiological diversity and ultrastructure.

A novel technique was proposed for processing silkworm pupae by combining plasma- activated water (PAW) with ultrasound (US). The microbial diversity and quality characteristics of the silkworm pupae were also evaluated. The results of the microbial diversity analysis indicated that PAW combined with US treatment significantly reduced the relative abundance of Streptococcaceae, Leuconostocaceae, and Acetobacteraceae from 32%, 18% and 16% to 27%, 11% and 11%, respectively. Microstructural analysis demonstrated that the collapse of the internal structure of chitin in silkworm pupae facilitated the release of nutrients and flavour compounds including fatty acids, water-soluble proteins (WSP), amino acids, phenolics, and volatile compounds. Furthermore, the increase in antioxidant capacity and the decrease in catalase activity and malondialdehyde content confirmed the mechanism of quality change. These findings provide new insights into the possible mechanism of PAW combined with US to improve the quality of edible insects.

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings.

BACKGROUND:  Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. METHODS: Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). RESULTS: The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. CONCLUSIONS:  NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Function-oriented mechanism discovery of coumarins from Psoralea corylifolia L. in the treatment of ovariectomy-induced osteoporosis based on multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

[Retrospective clinical study of hip replacement in the treatment of traumatic arthritis secondary to acetabular fracture].

OBJECTIVE: To investigate the clinical effect of total hip replacement (THA) in the treatment of traumatic arthritis secondary to acetabular fracture. METHODS: From October 2019 to June 2022, 15 patients with secondary traumatic arthritis of acetabulum fracture were treated with THA. There were 8 males and 7 females, aged from 40 to 76 years old with an average of (59.20±9.46) years old. Prosthesis loosening, dislocation of hip joint, range of motion of hip joint, nerve injury and other conditions were recorded before and after surgery. Harris score, visual analogue scale (VAS) and imaging were used to evaluate hip joint function and surgical effect. RESULTS: Follow-up time ranged 6 to 39 months with an average of (18.33±9.27) months. All the 15 patients successfully completed the operation, no nerve and blood vessel injury during the operation, postoperative wound healing was stageⅠ, no infection, one case of acetabular side prosthesis loosening at half a year after operation, and recovered well after revision surgery, one case of hip dislocation was cured after open reduction treatment, no adverse consequences. Harris score at the last postoperative follow-up was (88.60±4.01) points, compared with the preoperative (47.20±11.77) points, the difference was statistically significant (P<0.05), and VAS at the lateat postoperative follow-up was 1 (1) points, compared with the preoperative 8 (2) points, the difference was statistically significant (P<0.05). At the last follow-up, the pain symptoms were relieved or disappeared, and the joint function was satisfactory. The imaging data of the latest follow-up showed joint was well pseudoradiated, no abnormal ossification occurred, and the prosthesis was not loose. CONCLUSION: THA is effective in the treatment of traumatic arthritis secondary to acetabular fracture and can effectively improve the quality of life of patients. Preoperative comprehensive evaluation and bone defect evaluation of patients, and intraoperative management of acetabulum, femur, internal fixation and bone defect are key factors for the success of surgery.

Robust Fuzzy Neural Network With an Adaptive Inference Engine.

Fuzzy neural networks (FNNs) have been very successful at handling uncertainty in data using fuzzy mappings and if-then rules. However, they suffer from generalization and dimensionality issues. Although deep neural networks (DNNs) represent a step toward processing high-dimensional data, their capacity to address data uncertainty is limited. Furthermore, deep learning algorithms designed to improve robustness are either time consuming or yield unsatisfactory performance. In this article, we propose a robust fuzzy neural network (RFNN) to overcome these problems. The network contains an adaptive inference engine that is capable of handling samples with high-level uncertainty and high dimensions. Unlike traditional FNNs that use a fuzzy AND operation to calculate the firing strength for each rule, our inference engine is able to learn the firing strength adaptively. It also further processes the uncertainty in membership function values. Taking advantage of the learning ability of neural networks, the acquired fuzzy sets can be learned from training inputs automatically to cover the input space well. Furthermore, the consequent layer uses neural network structures to enhance the reasoning ability of the fuzzy rules when dealing with complex inputs. Experiments on a range of datasets show that RFNN delivers state-of-the-art accuracy even at very high levels of uncertainty. Our code is available online. https://github.com/leijiezhang/RFNN.

A solid phase extraction column based on SiO2@ZIF-8 for efficient analysis of domoic acid toxins in the seawater environment: experiments and DFT calculations on adsorption behaviour.

Algal toxins are important metabolites of toxic harmful algal blooms (HABs), and their qualitative and qualitative detection can serve as early warning indicators for toxic HABs, complementing traditional HAB monitoring and improving the accuracy of early warning. Therefore, this work took the detection of domoic acid (DA) as an example and prepared zeolitic imidazolate framework-8 (ZIF-8) with high enrichment performance and high water stability and its core-shell composite material SiO2@ZIF-8 as an adsorbent filler. Density functional theory (DFT) calculations and interference experiments verified that Zn2+ on SiO2@ZIF-8 played a crucial role in enriching DA on SiO2@ZIF-8. By using it as a solid-phase extraction (SPE) filler, it showed excellent performance compared with other SPE columns (C18/HLB/SAX/ZIF-8). Therefore, the SiO2@ZIF-8 column was coupled to high-performance liquid chromatography-mass spectrometry (SPE-HPLC-MS/MS) to establish a highly sensitive detection method for algal toxins in seawater, which had a wide linear range (12.0-5000.0 ng L-1), good reproducibility (RSD) and low limit of detection (4.0 ng L-1), and realized the monitoring of trace DA in the Pingtan sea area of Fujian Province from 2021 to 2022. By comparing other HAB early warning indicators such as salinity and pH and combining them with the information released by the Fujian Provincial Ocean and Fisheries Bureau, the content of DA in seawater measured by the established SPE-HPLC-MS/MS method can provide reference information for HAB monitoring and early warning.

Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK/mTORC1 pathway switching glycolytic reprogramming.

Dysfunction of macrophage polarization majorly contributes to the progression of rheumatoid arthritis (RA). Polarization and functions of activated macrophages are closely associated with the reprogramming of intracellular metabolisms. Previously, we demonstrated that the anti-arthritis effect of berberine (BBR) in rats with adjuvant-induced arthritis (AA) may be related to AMP-activated protein kinase (AMPK) activation (a key regulator in the biological energy metabolism), and balanced macrophage polarization. However, the specific molecular mechanism of BBR in macrophage metabolism is yet to be elucidated. In this study, we clarified that BBR ameliorated articular inflammation and restored M1/M2 ratio in collagen-induced arthritis (CIA) mice in an AMPK-dependent manner. Mechanistically, BBR reversed the effects of mTORC1 agonist leucine (Leu) on regulating macrophage polarization through activation of AMPK to switch glycolytic reprogramming. Furthermore, BBR inhibition of mTORC1 rely on activation of AMPK to phosphorylate raptor and TSC2 instead of destroying its structure. Our study revealed that the activation of AMPK is required for the BBR-mediated anti-arthritis effect by downregulating mTORC1/HIF-1α and inhibiting the glycolysis in M1 macrophages.

A new anti-neuroinflammation labdane diterpenoid from Salvia tricuspis.

One new labdane diterpenoid, tricuspion A (1), as well as five known triterpenoids (2-6) were isolated from Salvia tricuspis Franch (family Labiatae). The structure of tricuspion A was identified by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 1-6 were evaluated for their inhibitory effects on the NO production in LPS-stimulated BV-2 microglia cells, and 1 exhibited potent inhibitory activity with IC50 value of 14.92 ± 0.51 µM. Compound 1 might exert anti-neuroinflammatory activity through inhibiting the excessive production of NO and down-regulating the protein expression of iNOS and COX-2. As such, labdane diterpenoid (tricuspion A) could provide promising anti-neuroinflammatory lead compound for further structural modification.

FedTP: Federated Learning by Transformer Personalization.

Federated learning is an emerging learning paradigm where multiple clients collaboratively train a machine learning model in a privacy-preserving manner. Personalized federated learning extends this paradigm to overcome heterogeneity across clients by learning personalized models. Recently, there have been some initial attempts to apply transformers to federated learning. However, the impacts of federated learning algorithms on self-attention have not yet been studied. In this article, we investigate this relationship and reveal that federated averaging (FedAvg) algorithms actually have a negative impact on self-attention in cases of data heterogeneity, which limits the capabilities of the transformer model in federated learning settings. To address this issue, we propose FedTP, a novel transformer-based federated learning framework that learns personalized self-attention for each client while aggregating the other parameters among the clients. Instead of using a vanilla personalization mechanism that maintains personalized self-attention layers of each client locally, we develop a learn-to-personalize mechanism to further encourage the cooperation among clients and to increase the scalability and generalization of FedTP. Specifically, we achieve this by learning a hypernetwork on the server that outputs the personalized projection matrices of self-attention layers to generate clientwise queries, keys, and values. Furthermore, we present the generalization bound for FedTP with the learn-to-personalize mechanism. Extensive experiments verify that FedTP with the learn-to-personalize mechanism yields state-of-the-art performance in the non-IID scenarios. Our code is available online https://github.com/zhyczy/FedTP.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

A network pharmacological-based study of the mechanism of Liuwei Dihuang pill in the treatment of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disease that poses a huge economic burden to society. Liuwei Dihuanng pill is an effective treatment for chronic kidney disease, but its treatment mechanism is unclear. The rapid development of network pharmacology has provided new strategies for studying Chinese medicine. METHOD: The traditional Chinese medicine systems pharmacology database and analysis platform was used to obtain the bioactive components and targets of Liuwei Dihuanng pill. The sources for the CKD-related targets were then obtained from the Genecards, OMIM, TTD, and DisGeNET databases. R was used to identify the intersecting genes for Liuwei Dihuang pill and CKD-related targets. Analysis of protein-protein interactions (PPI) was performed using STRING, and PPI networks and drug-component-target networks were constructed using Cytoscape software. Kyoto encyclopedia of genes and genomes pathway and gene ontology enrichment analyses were performed using R. Finally, molecular docking was performed to determine the binding activity between bioactive components and the targets. RESULT: After screening and data de-duplication of 74 active components, 209 drug targets, and 14,794 disease targets, a total of 204 drug-disease targets were acquired. Subsequently, a drug-component-target network and PPI network were established. The primary components of Liuwei Dihuang pill included quercetin, stigmasterol, kaempferol, beta-sitosterol, tetrahydroalstonine, kadsurenone, hederagenin, hancinone C, diosgenin, and sitosterol. In addition, JUN, AKT1, TP53, RELA, MAPK1, FOS, TNF, IL6, ESR1, and RXRA were identified as the main targets. Gene ontology function enrichment analysis revealed that these targets were involved in reactive oxygen species metabolic processes, responses to metal ions and to chemical stimuli, G protein-coupled amine receptor activity, and nuclear factor receptor activity. Kyoto encyclopedia of genes and genomes enrichment analysis showed that these targets were involved in the AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. Molecular docking results indicated good binding activity between the core targets and core components. CONCLUSION: The potential mechanism of Liuwei Dihuanng pill in the treatment of CKD was preliminarily discussed in this study, providing a theoretical basis and evidence for further experimental research.

A Hybrid Method Fusing Frequency Recognition With Attention Detection to Enhance an Asynchronous Brain-Computer Interface.

OBJECTIVE: One critical problem in controlling an asynchronous brain-computer interface (BCI) system is to discriminate between control and idle states. This paper proposes a hybrid attention detection and frequency recognition method based on weighted Dempster-Shafer theory (ADFR-DS), which integrates information of different aspects of the task from two brain regions, to enhance asynchronous control performance of a steady-state visual evoked potential (SSVEP)-based BCI system. METHODS: The ADFR-DS method utilizes a hybrid architecture to process electroencephalogram (EEG) data from different channels simultaneously: an individualized frequency band based optimized complex network (IFBOCN) algorithm processes neural activity from the prefrontal area for attention detection, and an ensemble task-related component analysis (eTRCA) algorithm processes data from the occipital area for frequency recognition. The ADFR-DS method then fuses their classification results at decision level to generate the final output of the BCI system. A novel weighted Dempster-Shafer fusion method was proposed to enhance the fusion performance. This study evaluated the proposed method using a 40-target dataset recorded from 35 participants. MAIN RESULTS: The proposed method outperformed the eTRCA algorithm in the true positive rate (TPR), true negative rate (TNR), accuracy (ACC) and information transfer rate (ITR). Specifically, ADFR-DS improved the average ACC of eTRCA from 62.71% to 69.30%, and improved the average ITR from 184.28 bits/min to 216.89 bits/min (data length 0.3 s). CONCLUSION: The results suggest that the proposed ADFR-DS method can enhance asynchronous SSVEP-based BCI systems.

Discrete Element Simulation of the Relationship betweenComposition, ITZ Property, and Tensile Behavior ofEco-Friendly UHPC Matrix.

To combat global warming, the development of eco-friendly ultra-high performance concrete (UHPC) has become one of the current research hotspots. Understanding the relationship between composition and performance of eco-friendly UHPC from a meso-mechanical point will be of great significance in proposing a more scientific and effective mix design theory. In this paper, the 3D discrete element model (DEM) of an eco-friendly UHPC matrix was constructed. The mechanism of the effect of the interface transition zone (ITZ) properties on the tensile behavior of an eco-friendly UHPC matrix was studied. The relationship between composition, ITZ property, and tensile behavior of eco-friendly UHPC matrix was analyzed. The results show that ITZ strength influences the tensile strength and cracking behavior of eco-friendly UHPC matrix. The effect of ITZ on the tensile properties of eco-friendly UHPC matrix is more significant than that of normal concrete. The tensile strength of UHPC will be increased by 48% when the ITZ property is changed from normal condition to perfect. Improving the reactivity of the binder system of UHPC will improve the performance of ITZ. The cement content in UHPC was reduced from 80% to 35%, and the σITZ/σPaste was reduced from 0.7 to 0.32. Both nanomaterials and chemical activators can promote the hydration reaction of the binder material, which in turn leads to better ITZ strength and tensile properties for an eco-friendly UHPC matrix.

Laparoscopic and open liver resection for hepatocellular carcinoma with type 2 diabetes mellitus: multicenter propensity score-matched study.

PURPOSE: This study aimed at analyzing and comparing the perioperative results and long-term oncological outcomes of hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) treated with laparoscopic (LLR) versus open liver resection (OLR). METHODS: Clinicopathological data of HCC patients with T2DM who underwent LLR or OLR as initial treatment from four medical centers were retrospectively reviewed. The survival outcomes of patients who underwent laparoscopic liver resection (LLR) were compared with those of patients who underwent open liver resection (OLR). Using the Kaplan-Meier method, survival curves for the two groups of patients were generated, and the log-rank test was used to compare survival differences. Propensity score matching (PSM) analysis was used to match patients of the LLR and OLR groups in a 1:1 ratio. RESULTS: 230 HCC patients with T2DM were enrolled, including 101 patients in the LLR group and 129 patients in the OLR group. After PSM, 90 patients were matched in each of the study group. Compared with the OLR group, the LLR group had less blood loss, a shorter hospitalization and fewer postoperative complications. The LLR group had a significantly better overall survival (OS) and recurrence-free survival (RFS) than the OLR group before and after PSM. Subgroup analysis demonstrated that HCC patients with T2DM had survival benefits from LLR regardless of the course of T2DM. CONCLUSIONS: Laparoscopic liver resection for HCC patients with T2DM can be safely performed with favorable perioperative and long-term oncological outcomes at high-volume liver cancer centers, regardless of the course of T2DM.

Alkali exposure induces autophagy through activation of the MAPKpathway by ROS and inhibition of mTOR in Eriocheir sinensis.

Saline-alkali water is widely distributed around the world, and salinization of water ecosystems has occurred in some areas of the world, comprising approximately one-third of the total land area, which has drawn much attention to the conservation of water ecosystems and aquatic animals. However, due to the complex composition of saline-alkaline water, many aquatic animals are unable to survive, which greatly limits the development and utilization of saline-alkaline waters. Carbonate alkalinity is an important stress factor for aquatic animals in saline-alkaline water. Exposure to highly alkaline carbonate can induce oxidative stress. For this study, we used Eriocheir sinensis as a model organism to evaluate the effects of alkaline stress on oxidative stress and autophagy. The trial was divided into five alkali level treatment groups (control, 4.375 mmol/L, 8.75 mmol/L, 17.5 mmol/L, and 35 mmol/L, respectively), and liver tissues were assessed by antioxidant enzyme kits, real-time quantitative PCR assays and ultrastructural observations at 3 time points (24 h, 48 h, 96 h). Compared with the control group, the activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione reductase (GSH), glutathione peroxidase (GSH-PX) and total antioxidant capacity (T-AOC)) in the alkali stress group increased and then decreased with increasing time, while the content of malondialdehyde (MDA) increased. At the molecular level, the expression of MAPK pathway-related genes (P38, MAPK, JNK) in the alkaline stress group showed a dose-dependent increase at 48 and 96 h and was significantly higher than that in the control group. The expression of autophagy-related genes (ATG5, ATG12, ATG7 and GABARAP) increased dose-dependently at 24, 48, and 96 h and was significantly higher than that in the control group. In contrast, mTOR expression was always in a suppressed state. These results suggest that alkaline stress induces activation of the MAPK pathway via ROS and inhibits mTOR expression, thereby inducing autophagy in the liver tissue of Eriocheir sinensis. This study investigated the stress mechanism of carbonate on Eriocheir sinensis and provided a theoretical basis for the continued exploitation of saline-alkaline water aquaculture.