Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the second leading cause of cancer-related mortality worldwide. Processes involved in HCC progression and development, ...including cell transformation, proliferation, metastasis, and angiogenesis, are inflammation-associated carcinogenic processes because most cases of HCC develop from chronic liver damage and inflammation. Inflammation has been demonstrated to be a crucial factor inducing tumor development in various cancers, including HCC. Cytokines play critical roles in inflammation to accelerate tumor invasion and metastasis by mediating the migration of immune cells into damaged tissues in response to proinflammatory stimuli. Currently, surgical resection followed by chemotherapy is the most common curative therapeutic regimen for HCC. However, after chemotherapy, drug resistance is clearly observed, and cytokine secretion is dysregulated. Various chemotherapeutic agents, including cisplatin, etoposide, and 5-fluorouracil, demonstrate even lower efficacy in HCC than in other cancers. Tumor resistance to chemotherapeutic drugs is the key limitation of curative treatment and is responsible for treatment failure and recurrence, thus limiting the ability to treat patients with advanced HCC. Therefore, the capability to counteract drug resistance would be a major clinical advancement. In this review, we provide an overview of links between chemotherapeutic agents and inflammatory cytokine secretion in HCC. These links might provide insight into overcoming inflammatory reactions and cytokine secretion, ultimately counteracting chemotherapeutic resistance.
In this study, different influence mechanisms associated with temperatures and pH values were investigated through cemented paste backfill (CPB) systems. CPB samples were prepared with temperatures ...ranging from 10 to 50 °C in 10 °C increments and pH values of 3, 7, and 13. Then, the CPB mixture were subjected to rheological tests, thermogravimetric analysis (TG), derivative thermogravimetry analysis (DTG), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Results demonstrated that the temperatures had significant effects on the rheological properties of CPB, whereas the effects of pH values were relatively unapparent. Higher temperatures (over 20 °C) were prone to bring higher shear stress, yield stress, and apparent viscosity with the same pH value condition. However, an overly high temperature (50 °C) cannot raise the apparent viscosity. Non-neutral conditions, for pH values of 3 and 13, could strengthen the shear stress and apparent viscosity at the same temperature. Two different yield stress curves could be discovered by uprising pH values, which also led to apparent viscosity of two various curves under the same temperatures (under 50 °C). Microscopically, rheological properties of CPB were affected by temperatures and pH values which enhanced or reduced the cement hydration procedures, rates, products and space structures.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been ...reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants.
No consensus was reached on the efficacy of postoperative radiotherapy (PORT) in locally invasive thymomas because of the rarity of the thymic epithelial and the variations of study results. ...Therefore, we aimed to explore the efficacy of PORT in locally invasive thymomas using the Surveillance, Epidemiology, and End Results (SEER) database.
Patients diagnosed with thymomas from 2004 to 2016 were identified using the SEER database. Prognostic factors of cancer-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses.Propensity score matching (PSM) was performed to balance the baseline characteristics.
A total of 700 eligible patients were identified. After PSM, 262 paired patients were selected from the two groups, those who received or did not receive PORT. Receiving PORT improved CSS and OS before and after PSM. In the matched population, the multivariate analyses showed that tumour invasion into adjacent organs/structures and non-utilisation of PORT were independent poor prognostic factors for CSS, whereas age ≥62 years,tumour invasion into adjacent organs/structures, and non-utilisation of PORT were independently associated with poorer OS. The subgroup analysis revealed that PORT improved CSS and OS in Masaoka-Koga stage III thymoma, but showed no OS benefit in Masaoka-Koga stage IIB thymoma.
Based on the SEER database, we found that PORT provides a significant survival benefit in Masaoka-Koga stage III thymoma with complete or incomplete resection. The role of PORT in thymoma requires further evaluation.
With the rapid development in perovskite solar cell (PSC), high efficiency has been achieved, but the long‐term operational stability is still the most important challenges for the commercialization ...of this emerging photovoltaic technology. So far, bi‐dopants lithium bis(trifluoromethylsulfonyl)‐imide (Li‐TFSI)/4‐tert‐butylpyridine (t‐BP)‐doped hole‐transporting materials (HTM) have led to state‐of‐the art efficiency in PSCs. However, such dopants have several drawbacks in terms of stability, including the complex oxidation process, undesirable ion migration and ultra‐hygroscopic nature. Herein, a fluorine‐containing organic Lewis acid dopant bis(pentafluorophenyl)zinc (Zn‐FP) with hydrophobic property and high migration barrier has been employed as a potential alternative to widely employed bi‐dopants Li‐TFSI/t‐BP for polybis(4‐phenyl)(2,4,6‐trimethylphenyl)amine (PTAA). The resulting Zn‐FP‐based PSCs achieve a maximum PCE of 20.34 % with hysteresis‐free current density‐voltage (J‐V) scans. Specifically, the unencapsulated device exhibits a significantly advanced of operational stability under the International Summit on Organic Photovoltaic Stability protocols (ISOS−L‐1), maintaining over 90 % of the original efficiency after operation for 1000 h under continuous 1‐sun equivalent illumination in N2 atmosphere in both forward and reverse J‐V scan.
Superiorly operational stability: A fluorine‐containing hydrophobic Lewis acid dopant Zn‐FP as a potential alternative to widely employed bi‐dopant Li‐TFSI/t‐BP for PTAA, the resulting perovskite solar cells achieve high efficiency and superiorly operational stability.
Copper-to-copper (Cu-to-Cu) direct bonding is a promising approach to replace traditional solder joints in three-dimensional integrated circuits (3D ICs) packaging. It has been commonly conducted at ...a temperature over 300 °C, which is detrimental to integrated electronic devices. In this study, highly (111)-oriented nanotwinned (nt) Cu films were fabricated and polished using chemical mechanical planarization (CMP) and electropolishing. We successfully bonded and remained columnar nt-Cu microstructure at a low temperature of 150 °C thanks to the rapid diffusion of Cu on (111) surface. We employed a new microstructural method to characterize quantitatively the interfacial bonding quality using cross-sectional and plan-view microstructural analyses. We discovered that CMP nt-Cu bonding quality was greater than that of electropolished nt-Cu ones. The CMP nt-Cu films possessed extremely low surface roughness and were virtually free of pre-existing interface voids. Thus, the bonding time of such CMP nt-Cu films could be significantly shortened to 10 min. We expect that these findings may offer a pathway to reduce the thermal budget and manufacturing cost of the current 3D ICs packaging technology.
Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 ...regulates blood pressure is unknown.
To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.
In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.
RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
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