Enzyme-photo-coupled catalytic systems.

Efficient chemical transformation in a green, low-carbon way is crucial for the sustainable development of modern society. Enzyme-photo-coupled catalytic systems (EPCS) that integrate the exceptional selectivity of enzyme catalysis and the unique reactivity of photocatalysis hold great promise in solar-driven 'molecular editing'. However, the involvement of multiple components and catalytic processes challenged the design of efficient and stable EPCS. To show a clear picture of the complex catalytic system, in this review, we analyze EPCS from the perspective of system engineering. First, we disintegrate the complex system into four elementary components, and reorganize these components into biocatalytic and photocatalytic ensembles (BE and PE). By resolving current accessible systems, we identify that connectivity and compatibility between BE and PE are two crucial factors that govern the performance of EPCS. Then, we discuss the origin of undesirable connectivity and low compatibility, and deduce the possible solutions. Based on these understandings, we propose the designing principles of EPCS. Lastly, we provide a future perspective of EPCS.

Establishment of acute liver failure model in Tibetan miniature pig and verified by dual plasma molecular adsorption system.

BACKGROUND: Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality rates. Animal models are important for research on ALF. This study aimed to establish a reproducible, Tibetan miniature pig model of D-galactosamine-induced ALF and verify it using a dual plasma molecular adsorption system (DPMAS). METHODS: Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after catheterization. D-galactosamine (D-gal) at 0.45, 0.40, 0.35, and 0.35 g/kg body weight, respectively, was injected through the catheter. Group D was treated with DPMAS 48 h after D-gal administration. Vital signs and blood index values were recorded every 12 h after D-gal administration. H&E, TUNEL, Ki67, and Masson staining tests were performed. RESULTS: After D-gal administration, Tibetan miniature pigs developed different degrees of debilitation, loss of appetite, and jaundice. Survival times of groups A, B, C, and D were 39.7 ± 5.9, 53.0 ± 12.5,61.3 ± 8.1, and 61 ± 7 h, respectively. Blood levels of ALT, AST, TBIL, ammonia, PT, and inflammation factors significantly increased compared with baseline levels in the different groups (Ps < 0.05). Pathological results revealed a clear liver cell necrosis positive correlation with D-gal dose. However, DPMAS did not increase the survival time in ALF, ammonia, or liver cell necrosis. CONCLUSION: We successfully established a reproducible Tibetan miniature pig model of d-galactosamine-induced ALF, and we believe that a dosage of 0.35 g/kg is optimal.

A simple and efficient strategy for cell-based and cell-free-based therapies in acute liver failure: hUCMSCs bioartificial liver.

Acute liver failure (ALF) is a life-threatening condition. Cell-based and cell-free-based therapies have proven to be effective in treating ALF; however, their clinical application is limited by cell tumorigenicity and extracellular vesicle (EV) isolation in large doses. Here, we explored the effectiveness and mechanism of umbilical cord mesenchymal stem cells (hUCMSCs)-based bioartificial liver (hUCMSC-BAL), which is a simple and efficient strategy for ALF. D-galactosamine-based pig and mouse ALF models were used to explore the effectiveness of hUCMSC-BAL and hUCMSC-sEV therapies. Furthermore, high-throughput sequencing, miRNA transcriptome analysis, and western blot were performed to clarify whether the miR-139-5p/PDE4D axis plays a critical role in the ALF model in vivo and in vitro. hUCMSC-BAL significantly reduced inflammatory responses and cell apoptosis. hUCMSC-sEV significantly improved liver function in ALF mice and enhanced the regeneration of liver cells. Furthermore, hUCMSC-sEV miRNA transcriptome analysis showed that miR-139-5p had the highest expression and that PDE4D was one of its main target genes. The sEV miR-139-5p/PDE4D axis played a role in the treatment of ALF by inhibiting cell apoptosis. Our data indicate that hUCMSC-BAL can inhibit cytokine storms and cell apoptosis through the sEV miR-139-5p/PDE4D axis. Therefore, we propose hUCMSC-BAL as a therapeutic strategy for patients with early ALF.

Treatment Strategy and Safety of Eribulin in Advanced Breast Cancer.

This study sought to investigate the efficacy and safety of eribulin in advanced breast cancer patients. Eighteen patients with advanced breast cancer were retrospectively included. The previous use of taxanes, and the use of eribulin in subsequent treatment was reviewed. Progression- free survival（PFS）and the efficacy of eribulin, influencing factors, and adverse reactions were analysed. For patients who were previously treated with taxanes were more resistant, subsequent eribulin treatment chemotherapy PFS was generally for two months. However, for patients who chose eribulin combined with anlotinib for the latter-line regimen, PFS reached for five months, and these patients were in continuous remission. Among the 18 patients, 17 patients (94.4%) had different degrees of bone marrow suppression. Patients who have not been treated with taxanes or who have been treated with taxanes for a long response time, experience better effects when eribulin was used as subsequent treatment. Eribulin combined with anlotinib is the preferred combination therapy. Key Words: Breast cancer, Eribulin, Efficacy, Safety.

Non-SMC condensin I complex subunit H promotes the malignant progression and cisplatin resistance of breast cancer MCF-7 cells.

Breast cancer is one of the most frequently diagnosed types of cancer worldwide. The present study aimed to investigate the role and underlying regulatory mechanism of non-structural maintenance of chromosome condensin I complex subunit H (NCAPH) in the malignant progression and cisplatin (DDP) resistance of breast cancer cells. Therefore, the mRNA and protein expression levels of NCAPH were first determined in breast cancer cells via reverse transcription-quantitative PCR and western blotting. Furthermore, following transfection of NCAPH interference plasmids, the effect of NCAPH knockdown on cell proliferation, migration, invasion were also assessed using CCK-8, wound healing and Transwell assays. Apoptosis was evaluated using TUNEL assay, and western blotting was performed in breast cancer cells and DDP-resistant breast cancer cells. The association between NCAPH and its downstream target, aurora kinase B (AURKB), was verified using bioinformatic analysis and the co-immunoprecipitation assay. Furthermore, the effect of AURKB overexpression on the aforementioned processes and the Akt/mTOR signaling pathway were also assessed. The results demonstrated that NCAPH mRNA and protein expression levels were significantly upregulated in breast cancer cells, whereas NCAPH knockdown significantly attenuated the proliferation, migration and invasion of breast cancer cells. NCAPH silencing also exacerbated the apoptosis of DDP-resistant breast cancer cells. AURKB mRNA and protein expression levels were also significantly upregulated in MCF-7 cells, whereas its overexpression significantly reversed the effects of NCAPH knockdown on breast cancer cells and the Akt/mTOR signaling pathway. Overall, NCAPH knockdown significantly downregulated AURKB mRNA and protein expression levels to block the Akt/mTOR signaling pathway and inhibited breast cancer cell proliferation, migration, invasion, and aggravate DDP-resistant breast cancer cell apoptosis, indicating that NCAPH may serve as a promising therapeutic target for breast cancer.

In vitro safety and efficacy evaluation of a novel hybrid bioartificial liver system with simulated liver failure serum.

BACKGROUND: Acute liver failure (ALF), which can potentially be treated with an artificial liver, is a fatal condition. The purpose of this study was to evaluate the safety and effectiveness of a novel hybrid bioartificial liver system (NHBLS) using simulated liver failure serum in vitro. METHODS: The bioreactor in experimental group was cultivated with primary porcine hepatocytes, whereas in control group was not. Next, the simulated liver failure serum was treated using the NHBLS for 10 h. Changes in albumin (ALB), total bilirubin (TBIL), ammonia (Amm), total bile acid (TBA), creatinine (Cr), and blood urea nitrogen (BUN) were measured before treatment (0 h) and every 2 h during treatment. In addition, changes in NHBLS pressures, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lidocaine metabolism were also recorded. RESULTS: The NHBLS worked steadily without unexpected occurrences during the treatment. Blood culture showed no bacterial growth after 7 days, and the endotoxin level was less than 0.5 EU. The TBIL, TBA, Cr, and BUN levels in both groups were markedly lower than those at 0 h (p < 0.05). The Amm level in experimental group was significantly lower than that in control group (p < 0.05). NHBLS pressures were also stable, and the hepatocytes in the bioreactor functioned well. CONCLUSIONS: The preparation method for the simulated liver failure serum was optimized successfully, and the safety and effectiveness of the NHBLS in vitro were verified. Furthermore, the NHBLS significantly reduced the levels of Amm which can lead to hepatic encephalopathy.

Clinicopathological features and prognosis of male breast cancer.

OBJECTIVE: We aimed to describe the differences in clinicopathological characteristics and overall survival (OS) between male and female breast cancer patients, and to develop a prognostic nomogram to predict survival in patients with male breast cancer (MBC). METHODS: Using the Surveillance, Epidemiology, and End Results database, we compared age, race, histological type, histological grade, tumor size, lymph node status, metastases, estrogen/progesterone receptor (ER/PR) and HER-2 status between male and female patients, and analyzed their relationships with OS. We established a nomogram and produced a calibration curve to observe its predictive effect. RESULTS: Age, race, T stage, N stage, bone and lung metastases, and histological type and grade differed between male and female patients. OS in male patients was related to age, tumor size, metastatic site, ER/PR status, and histological grade, but not to race or lymph node status. A nomogram was established, which showed good predictive performance for survival in MBC patients (area under the curve = 0.7). CONCLUSION: MBC has a worse prognosis than female breast cancer, mainly characterized by late onset age, late staging, high proportion of invasive non-specific histological types, high histological grade, and luminal breast cancer.

Fiber scaffold bioartificial liver therapy relieves acute liver failure and extrahepatic organ injury in pigs.

Rationale: Acute liver failure (ALF) causes severe liver injury and a systemic inflammatory response, leading to multiorgan failure with a high short-term mortality. Bioartificial liver (BAL) therapy is a promising approach that is hampered by the lack of appropriate bioreactors and carriers to retain hepatic cell function and poor understanding of BAL treatment mechanisms in ALF and extrahepatic organ injury. Recently, we used a fiber scaffold bioreactor (FSB) for the high-density, three-dimensional (3D) culture of primary porcine hepatocytes (PPHs) combined with an absorption component to construct a BAL and verified its function in a D-galactosamine (D-gal)-induced ALF porcine model to evaluate its protective effects on the liver and extrahepatic organs. Methods: Male pigs were randomized into standard/supportive therapy (ST), ST+no-cell BAL (ST+Sham BAL) and ST+BAL groups and received treatment 48 h after receiving a D-gal injection. Changes in blood chemistry and clinical symptoms were monitored for 120 h. Tissues and plasma were collected for analysis by pathological examination, immunoblotting, quantitative PCR and immunoassays. Results: PPHs cultured in the FSB obtained sufficient aeration and nutrition for high-density, 3D culture and maintained superior viability and functionality (biosynthesis and detoxification) compared with those cultured in flasks. All the animals developed ALF, acute kidney injury (AKI) and hepatic encephalopathy (HE) 48 h after D-gal infusion and received corresponding therapies. Animals in the BAL group showed markedly improved survival (4/5; 80%) compared with those in the ST+Sham BAL (0/5; p < 0.001) and ST (0/5; p < 0.001) groups. The levels of blood ammonia and biochemical and inflammatory indices were alleviated after BAL treatment. Increased liver regeneration and attenuations in the occurrence and severity of ALF, AKI and HE were observed in the ST+BAL group compared with the ST (p = 0.0009; p = 0.038) and ST+Sham BAL (p = 0.011; p = 0.031) groups. Gut leakage, the plasma endotoxin level, bacterial translocation, and peripheral and neuroinflammation were alleviated in the ST+BAL group compared with those in the other groups. Conclusions: BAL treatment enhanced liver regeneration and alleviated the systemic inflammatory response and extrahepatic organ injury to prolong survival in the ALF model and has potential as a therapeutic approach for ALF patients.

Treatment of chronic renal failure by supplementing the kidney and invigorating blood flow.

OBJECTIVE: To evaluate the effectiveness of treatment of chronic renal failure by supplementing the kidney and invigorating blood flow. METHOD: The eligible patients were assigned to a treatment group (N = 120) treated with the above principle and a control group (N = 128) treated with western drugs, and the effectiveness was evaluated when the study was completed in one year. RESULTS: The total effective rate of 92.5% was achieved in the treatment group, better than that in the control group (49.2%); the difference was significant (P<0.01), especially in patients of stage I and II. CONCLUSION: The treatment of chronic renal failure by supplementing the kidney and invigorating blood flow proved to be very effective.