A retrospective analysis of the safety and efficacy of low dose tacrolimus (FK506) for living donor liver transplant recipients

We sought to evaluate the efficacy and effects of low-dose tacrolimus （FK506） to recipients with living donor liver transplantation （LDLT）. A total of 66 patients who underwent LDLT between 2001 and 2007 were enrolled in this study. According to different doses of tacrolimus, the recipients were randomly divided into two groups： the low-dose tacrolimus group （group A） and the normal-dose tacrolimus group （group B）. The blood concentration of tacrolimus and its side effects including infection, hyperglycemia, hypertension, high blood creatinine and jaundice were monitored once a week at the perioperative period, and once a month thereafter. Besides, the survival rates of the recipients were analyzed at the 1and 3-year time point after operation. Among these patients, no significant acute rejection was detected after LDLT. The incidences of infection, hyperglycemia, liver dysfunction and renal impairment in group A were markedly lower than those in group B. However, no significant differences were detected in the incidence of hypertension between the two groups. Moreover, the recipients in each group had a similar survival rate according to the results of 1and 3-year follow-up. The incidence of side effects that associated with tacrolimus positively correlated with tacrolimus blood concentration. In conclusion, long-term and low-dose administration of tacrolimus is a safe and effective treatment for LDLT recipients.

Cryo-self-assembled silk fibroin sponge as a biodegradable platform for enzyme-responsive delivery of exosomes

Although advances in protein assembly preparation have provided a new platform for drug delivery during tissue engineering,achieving long-term controlled exosome delivery remains a significant challenge.Diffusion-dominated exosome release using protein hydrogels results in burst release of exosomes.Here,a fibroin-based cryo-sponge was developed to provide controlled exosome release.Fibroin chains can self-assemble into silk I structures under ice-cold conditions when annealed above the glass transition temperature.Exosome release is enzyme-responsive,with rates primarily determined by enzymatic degradation of the scaffolds.In vivo experiments have demonstrated that exosomes remain in undigested sponge material for two months,superior to their retention in fibrin glue,a commonly used biomaterial in clinical practice.Fibroin cryo-sponges were implanted subcutaneously in nude mice.The exosome-containing sponge group exhibited better neovascularization and tissue ingrowth effects,demonstrating the efficacy of this exosome-encapsulating strategy by realizing sustained release and maintaining exosome bioactivity.These silk fibroin cryo-sponges containing exosomes provide a new platform for future studies of exosome therapy.

LD-Pumped Random Fiber Laser Based on Erbium-Ytterbium Co-Doped Fiber

In this paper,a cladding-pumped erbium-ytterbium co-doped random fiber laser(EYRFL)operating at 1550 nm with high power laser diode(LD)is proposed and experimentally demonstrated for the first time.The laser cavity includes a 5-m-long erbium-ytterbium co-doped fiber that serves as the gain medium,as well as a 2-km-long single-mode fiber(SMF)to provide random distributed feedback.As a result,stable 2.14 W of 1550 nm random lasing at 9.80 W of 976 nm LD pump power and a linear output with the slope efficiency as 22.7%are generated.This simple and novel random fiber laser could provide a promising way to develop high power 1.5μm light sources.

Petrologic and geochemical characteristics of high-quality saline lacustrine source rocks in western Qaidam Basin

The main oil source in western Qaidam Basin is the Paleogene saline lacustrine source rocks.Traditionally,it was considered that these source rocks were characterized by low abundance and poor type of organic matter as well as limited oil generation potential,but this poor source rock condition was very inconsistent with good hydrocarbon exploration results.A previous study has just confirmed that this area develops high-quality source rocks,which is of great significance for recognizing potential of hydrocarbon resource and consolidating confidence to search large and medium-sized oil and gas fields in western Qaidam Basin.Based on fine geochemical analysis of source rocks,petrology,element geochemistry and organic geochemistry are applied to discuss development conditions of high-quality source rocks in this area.The results showed that the saline lacustrine sediments in western Qaidam Basin were deposited in relatively shallow and quiet water with relatively high salinity and low nutrient content;influenced by the drought and cold climate,the terrigenous supply of fresh water was limited,and few aquatic organisms were developed.Good preservation condition is favorable for rapid preservation of oil generating biomass(such as aquatic organisms),to form source rocks rich in hydrogen element with high soluble organic matter content;but relatively lower paleo-productivity makes organic matter abundance lower than that in the eastern saline lacustrine basins.The semi-deep lake,with relatively low salinity and abundant nutrients,is the most favorable are for development of high-quality source rocks;the source rocks have large thickness in the sedimentary depression areas,but due to high water salinity and far away from the provenance area,the water stratification was obvious,so it have moderate to high organic matter abundance.

Targeting RIP3 inhibits osteoarthritis development by restoring anabolic-catabolic balance in the bone-cartilage unit

Background:Osteoarthritis(OA)is a debilitating joint disorder characterized by pro-gressive cartilage degeneration.During OA,subchondral bone undergoes micro-structural and molecular changes that precede cartilage degradation.However,spe-cific mechanisms underlying metabolic dysregulation of the bone-cartilage unit remain unclear.This study aims to investigate the role of receptor-interacting protein kinase-3(RIP3)in OA progression,focusing on bone-cartilage metabolic homeostasis.Methods:RIP3-mediated pathological and metabolic alterations in chondrocytes,os-teoblasts,and bone marrow-derived macrophages(BMMs)were evaluated.RIP3-mediated OA manifestations in cartilage and,more importantly,subchondral bone were determined by intra-articular overexpression of RIP3 in rats.The protective effect of RIP3 deficiency on the bone-cartilage unit during OA was systematically investigated using Rip3 knockout mice.The CMap database was used to screen for compounds that abrogate RIP3-induced OA pathological changes.Results:RIP3 was upregulated in the cartilage and subchondral bone of OA patients and post-traumatic OA mouse model.RIP3 overexpression not only inhibited extra-cellular matrix(ECM)anabolism in chondrocytes but also attenuated osteoblast differentiation,whereas RIP3 deficiency blunted receptor activator of NF-kappaB ligand-mediated osteoclastogenesis of BMMs.Intra-articular RIP3 overexpression induced the imbalance of SP7+osteoblasts/tartrate-resistant acid phosphatase(TRAP)+osteoclasts within the subchondral bone in addition to cartilage degen-eration in rats,while Rip3 deletion significantly improved structural outcomes of the bone-cartilage unit,and achieved pain relief as well as functional improvement in surgery-induced and spontaneous OA mouse models.Mechanistically,RIP3 initiates OA by perturbing critical events,including cartilage metabolism,inflammatory re-sponses,senescence,and osteoclast differentiation.Clofibrate,a hypolipidemic drug,was identified as a novel RIP3 inhibitor that reverses ECM catabolism in OA.Conclusions:RIP3 is an essential governor of whole joint metabolic homeostasis by regulating both cartilage metabolism and subchondral bone remodeling.Reconstruction of the bone-cartilage unit by targeting RIP3 might provide a two-birds-one-stone approach for the development of future OA therapies.