In the study, we used oil palm residues (empty fruit bunch, EFB) as raw material to produce cellulosic ethanol by pretreatment, enzymatic hydrolysis and fermentation. Firstly, the pretreatment of EFB with alkali, alkali/hydrogen peroxide and the effects on the components and enzymatic hydrolysis of cellulose were studied. The results show that dilute alkali was the suitable pretreatment method and the conditions were first to soak the substrate with 1% sodium hydroxide with a solid-liquid ratio of 1:10 at 40 degrees C for 24 h, and then subjected to 121 degrees C for 30 min. Under the conditions, EFB solid recovery was 74.09%, and glucan, xylan and lignin content were 44.08%, 25.74% and 13.89%, respectively. After separated with alkali solution, the pretreated EFB was washed and hydrolyzed for 72 h with 5% substrate concentration and 30 FPU/g dry mass (DM) enzyme loading, and the conversion of glucan and xylan reached 84.44% and 89.28%, respectively. We further investigated the effects of substrate concentration and enzyme loading on enzymatic hydrolysis and ethanol batch simultaneous saccharification and fermentation (SSF). The results show that when enzyme loading was 30 FPU/g DM and substrate concentration was increased from 5% to 25%, ethanol concentration were 9.76 g/L and 35.25 g/L after 72 h fermentation with Saccharomyces cerevisiae (inoculum size 5%, V/V), which was 79.09% and 56.96% of ethanol theory yield.
Alkalies ; chemistry ; Biofuels ; Ethanol ; metabolism ; Fermentation ; Lignin ; chemistry ; Palm Oil ; Plant Oils

As non-invasive drug delivery systems,transdermal patches can deliver drugs through the intact skin at a fixed dose and a adjustable rate in order to product a systemic or local therapeutic effect.Focused on the key quality attributes of transdermal patches,the article illustrated the testing methods and how to control key points.It also briefly described the testing methods and standards of some other characteristics referring to pharmacopoeia,current policies and regulations in various countries,which provided a reference for pharmaceutical industries and relevant departments to improve the quality control methods and standards.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

OBJECTIVETo investigate whether I-tetrahydropalmatine (I-THP), an alkaloid mainly present in Corydalis family, could ameliorate early vascular inflammatory responses in atherosclerotic processes.

METHODSFluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells (HUVECs), which were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the nuclear translocation of nuclear factor (NF)-κ B in HUVECs.

RESULTSL-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31% and 36% at 30 μ mol/L. L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated TNF-α-stimulated NF-κ B nuclear translocation.

CONCLUSIONThese results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-κ B.

Berberine Alkaloids ; pharmacology ; Cell Adhesion ; drug effects ; Cell Nucleus ; drug effects ; metabolism ; Down-Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Monocytes ; cytology ; drug effects ; metabolism ; NF-kappa B ; metabolism ; Protein Transport ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; drug effects ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Reports of tuberculosis (TB) outbreaks among schoolchildren have increased in recent years in countries across the Western Pacific Region. Cases from China, Japan, Mongolia and the Republic of Korea were studied to derive lessons from the challenges and responses to TB outbreaks in schools. Despite differences in the TB burden and outbreak preparedness, the four countries reported similar challenges. These included delayed diagnosis of index cases, lack of experienced health professionals and sustained financial support, and difficulty in responding to intensified media and community attention. Early detection of outbreaks, established resource mobilization networks, coordination among stakeholders and proactive communication were highlights of successful outbreak responses. These principles could be adapted to each context for responses to future TB outbreaks in schools.