A plant-derived natural photosynthetic system for improving cell anabolism.

Insufficient intracellular anabolism is a crucial factor involved in many pathological processes in the body1,2. The anabolism of intracellular substances requires the consumption of sufficient intracellular energy and the production of reducing equivalents. ATP acts as an 'energy currency' for biological processes in cells3,4, and the reduced form of NADPH is a key electron donor that provides reducing power for anabolism5. Under pathological conditions, it is difficult to correct impaired anabolism and to increase insufficient levels of ATP and NADPH to optimum concentrations1,4,6-8. Here we develop an independent and controllable nanosized plant-derived photosynthetic system based on nanothylakoid units (NTUs). To enable cross-species applications, we use a specific mature cell membrane (the chondrocyte membrane (CM)) for camouflage encapsulation. As proof of concept, we demonstrate that these CM-NTUs enter chondrocytes through membrane fusion, avoid lysosome degradation and achieve rapid penetration. Moreover, the CM-NTUs increase intracellular ATP and NADPH levels in situ following exposure to light and improve anabolism in degenerated chondrocytes. They can also systemically correct energy imbalance and restore cellular metabolism to improve cartilage homeostasis and protect against pathological progression of osteoarthritis. Our therapeutic strategy for degenerative diseases is based on a natural photosynthetic system that can controllably enhance cell anabolism by independently providing key energy and metabolic carriers. This study also provides an enhanced understanding of the preparation and application of bioorganisms and composite biomaterials for the treatment of disease.

Neutralization of Intracellular pH Homeostasis to Inhibit Osteoclasts Based on a Spatiotemporally Selective Delivery System.

Osteoporosis is a global disease caused by abnormal overactivation of osteoclasts. The acidic environment in sealing zone of osteoclasts with H+ pumped from cytoplasm is critical to the maturation of osteoclasts. Therefore, reducing the intracellular H+ concentration can reduce the H+ secretion of osteoclasts from the source. In our study, we developed a novel nanovesicle which encapsulates Na2HPO4 with a liposome hybridizes with preosteoclast membrane (Na2HPO4@Lipo-pOCm). These nanovesicles release Na2HPO4 into the preosteoclast by targeting preosteoclasts and membrane fusion, reducing the intracellular H+ concentration, and achieve biological cascade regulation of osteoclasts through simple pH regulation. In vitro and in vivo experiments confirmed that these nanovesicles reduce mitochondrial membrane potential by decreasing intracellular H+ concentration, thereby reducing the ROS in osteoclasts as well as the expression of the upstream transcription factor FOXM1 of Acp5. In short, this nanovesicle can significantly inhibit the osteoclasts and ameliorate osteoporosis caused by OVX.

Deoxynivalenol (DON)-Triggered Dual-Color Composite Probe Based on Gold Nanoclusters for Simultaneous Imaging of DON and miR-34a in Living Cells.

Deoxynivalenol (DON) is a mycotoxin secreted by Fusarium species, posing great harm to food safety and human health. Therefore, it is of great significance to study its toxic effects and mechanism. miR-34a is a representative biomarker during the process of DON-induced apoptosis. Herein, a DON-triggered dual-color composite probe was constructed for simultaneous imaging of DON and miR-34a in living cells. The aptamer blocks the recognition sequence of miR-34a to realize DON-triggered cell imaging. The specific binding of DON with its aptamer and HCR induced by miR-34a resulted in the recovery of fluorescence of the dual-color Au NCs. Under the optimal conditions, the correlation between the relative fluorescence intensities of dual-color Au NCs showed good linear relationships with the logarithm of DON and miR-34a concentration, respectively. With the increase in DON concentration (0-20 µg/mL) and stimulation time (0-12 h), the fluorescence of dual-color Au NCs gradually recovered. This dual-color Au NCs composite probe can realize simultaneous detection of DON and miR-34a induced by DON, which is significant for verifying the cytotoxic mechanism of DON.

Hydrogel-integrated sensors for food safety and quality monitoring: Fabrication strategies and emerging applications.

Food safety is a global issue in public hygiene. The accurate, sensitive, and on-site detection of various food contaminants performs significant implications. However, traditional methods suffer from the time-consuming and professional operation, restricting their on-site application. Hydrogels with the merits of highly porous structure, high biocompatibility, good shape-adaptability, and stimuli-responsiveness offer a promising biomaterial to design sensors for ensuring food safety. This review describes the emerging applications of hydrogel-based sensors in food safety inspection in recent years. In particular, this study elaborates on their fabrication strategies and unique sensing mechanisms depending on whether the hydrogel is stimuli-responsive or not. Stimuli-responsive hydrogels can be integrated with various functional ligands for sensitive and convenient detection via signal amplification and transduction; while non-stimuli-responsive hydrogels are mainly used as solid-state encapsulating carriers for signal probe, nanomaterial, or cell and as conductive media. In addition, their existing challenges, future perspectives, and application prospects are discussed. These practices greatly enrich the application scenarios and improve the detection performance of hydrogel-based sensors in food safety detection.

Demonstration of constant-cladding tapered-core Yb-doped fiber for mitigating thermally-induced mode instability in high-power monolithic fiber amplifiers.

In this work, a large-mode-area (LMA) step-index constant-cladding tapered-core (CCTC) Yb-doped fiber with a cladding diameter of ∼600 µm is successfully fabricated. The CCTC fiber has a small-core region (diameter of ∼20 µm) at both ends and a large-core region (diameter of ∼36 µm) in the middle. To prove the laser performance of the CCTC fiber, a detailed comparison experiment with conventional uniform fiber with the same effective core diameter is carried out in a multi-kW all-fiber MOPA configuration. The experimental results show that employing the CCTC fiber can effectively mitigate the thermally-induced transverse mode instability (TMI) in both co-pump and counter-pump schemes, and realize high slope efficiency and single-mode beam quality (M2∼1.30). Under the counter-pump scheme, the TMI threshold of the CCTC fiber is observed at ∼2.49 kW with a slope efficiency of 86.2%, while the uniform fiber amplifier exhibits a TMI threshold of ∼2.05 kW. The theoretical analysis based on a semi-analytical model indicates this CCTC fiber can effectively improve the TMI threshold owing to a stronger gain saturation. Our results verify the great potential of such an LMA CCTC fiber to mitigate thermal-induced TMI effect and achieve single-mode operation without sacrifice of laser efficiency in high power monolithic fiber lasers, and the further power scaling is expected by optimizing the fiber design.

Low-numerical aperture confined-doped long-tapered Yb-doped silica fiber for a single-mode high-power fiber amplifier.

A low-numerical aperture (NA) confined-doped long-tapered (LCT) Yb-doped fiber is proposed and fabricated by modified chemical vapor deposition combined with solution doping technique. The LCT fiber owns the core NA of ∼0.05 and the gain dopant doping diameter ratio of ∼77%, with a core/cladding diameter of 25/400 µm at both ends and 37.5/600 µm in the middle. The laser performance is demonstrated by a bidirectional pumping all-fiber amplifier, of which a 4.18-kW single-mode (M2 factor ∼1.3) laser output is achieved with a slope efficiency of ∼82.8%. Compared with the conventional fiber, the co-pumped and counter-pumped transverse mode instability thresholds and beam quality of the LCT fiber are remarkably enhanced. Throughout the continuous operation, the LCT fiber amplifier presents high power stability with fluctuation of < 1%. These results indicate that LCT fiber has great potential in power scaling remaining excellent beam quality.

Tapered Yb-doped fiber enabled a 4†kW near-single-mode monolithic fiber amplifier.

In this Letter, we demonstrate a monolithic high-power master oscillator power amplifier by using a home-made double-clad tapered Yb-doped fiber (T-YDF) with an input end of ∼20/400 µm and an output end of ∼30/600 µm. Thanks to perfect core/cladding matching with the fiber components at both ends of the T-YDF, the laser is pumped bidirectionally and an output power of over 4 kW with a high slope efficiency of 84.1% and excellent beam quality M2 ∼ 1.46 is achieved. In contrast to previous work on common fiber lasers, experimental results also reveal that the co-pump scheme has a higher transverse mode instability (TMI) threshold and power-boosting capability than that of a counter-pump scheme. To the best of our knowledge, this is the highest output power demonstrated to date from such a T-YDF with excellent beam quality. This work indicates the great potential of the T-YDF to realize further power scaling, high laser efficiency, and excellent beam quality in high-power fiber lasers.

ZIF-8 base-aptamer "gate-lock" probes enable the visualization of a cascade response between deoxynivalenol and cytochrome c inside living cells.

Zeolitic imidazolate framework (ZIF-8) base-aptamer "gate-lock" biomaterial probes have been synthesized for monitoring intracellular deoxynivalenol (DON) and cytochrome c (cyt c) levels. The aptamer and organic fluorescent dye were regarded as a recognition element and a sensing element, respectively. In the presence of DON, the aptamers of DON and cyt c were specifically bound with the DON and induced cyt c, leading to the dissociation of aptamers from the porous surface of the probes. The gate was subsequently opened to release methylene blue (MB) and Rhodamine 6G (Rh6G), and their fluorescence (emission of MB at 700 nm and Rh6G at 550 nm) significantly recovered within 6 h. Cell imaging successfully monitored the exposure of DON and the biological process of cyt c discharge triggered by the activation of the DON-induced apoptosis pathway. In addition, the response between DON and cyt c was observed during the apoptosis process, which is of high significance for the comprehensive and systematic development of mycotoxins cytotoxicity.

All-fiber pulsed laser generation of 25.5 mJ and solution of parasitic oscillation.

A Q-switched, high-energy pulsed master oscillator power amplifier fiber laser utilizing the lab-built 100/400 µm double-cladding Yb-doped fiber is demonstrated. After two-stage amplification, the pulse energy was boosted to 25.5 mJ, for an average power of 510 W at a repetition of 20 kHz, yielding a slope efficiency of approximately 72.8%; the pulse duration was approximately 140 ns, and corresponding peak power was 182.1 kW. What is more, the limitation of further promotion of pulse energy was proposed: the threshold-like parasitic oscillation, which was determined by the injecting power, repetition, and fiber length, was the main restriction on power scaling in ultra-high-energy systems. Efficient solutions were proposed to suppress the parasitic oscillation by experimentally studies.

Smart Nanosacrificial Layer on the Bone Surface Prevents Osteoporosis through Acid-Base Neutralization Regulated Biocascade Effects.

Osteoporosis is a global chronic disease characterized by severe bone loss and high susceptibility to fragile fracture. It is widely accepted that the origin acidified microenvironment created by excessive osteoclasts causes irreversible bone mineral dissolution and organic degradation during osteoclastic resorption. However, current clinically available approaches are mainly developed from the perspective of osteoclast biology rather than the critical acidified niche. Here, we developed a smart "nanosacrificial layer" consisting of sodium bicarbonate (NaHCO3)-containing and tetracycline-functionalized nanoliposomes (NaHCO3-TNLs) that can target bone surfaces and respond to external secreted acidification from osteoclasts, preventing osteoporosis. In vitro and in vivo results prove that this nanosacrificial layer precisely inhibits the initial acidification of osteoclasts and initiates a chemically regulated biocascade to remodel the bone microenvironment and realize bone protection: extracellular acid-base neutralization first inhibits osteoclast function and also promotes its apoptosis, in which the apoptosis-derived extracellular vesicles containing RANK (receptor activator of nuclear factor-κ B) further consume RANKL (RANK ligand) in serum, achieving comprehensive osteoclast inhibition. Our therapeutic strategy for osteoporosis is based on original and precise acid-base neutralization, aiming to reestablish bone homeostasis by using a smart nanosacrificial layer that is able to induce chemically regulated biocascade effects. This study also provides a novel understanding of osteoporosis therapy in biomedicine and clinical treatments.

Bleaching of photodarkening in Tm-doped silica fiber with deuterium loading.

We demonstrate the rapid photodarkening (PD) phenomenon in Tm-doped fiber (TDF) core pumped by a laser at 1080 nm and the bleaching effect of deuterium (${{\rm D}_2}$D2) on PD TDF. By ${{\rm D}_2}$D2 loading for seven days, the PD-induced excess loss (PIEL) in the visible (VIS) and near-infrared (NIR) region have been largely eliminated, and no degradation was observed within 30 days. PD resistance of the ${{\rm D}_2}$D2 pretreated TDF has been investigated as well. The formation of color centers based on defects and precursors in the silica matrix and the mechanism of ${{\rm D}_2}$D2 bleaching are discussed.

532†nm pump induced photo-darkening inhibition and photo-bleaching in high power Yb-doped fiber amplifiers.

A novel method for mitigating photo-darkening and the effective photo-bleaching phenomenon by 532 nm cladding pump in Yb-doped fiber were herein reported. Compared with the pristine fiber, beyond 30% of photo-darkening induced excess loss was suppressed by 532 nm pretreatment. Moreover, the excess loss in the photo-darkened fiber was completely bleached with 532 nm pump. Additionally, the bleached fiber exhibited better photo-darkening resistance. Therefore, for high power application, a 20/400 gamma irradiated fiber was bleached in situ by 532 nm pump and the laser properties were explored. The output power restored to 421W accounting for 82% of the pristine fiber, with the mode instability threshold rising to over 2.6 times and the efficiency increasing from 37% to 63%. The results indicate 532 nm pump has bright prospects for the stable operation of high power fiber lasers.

Gain-tailored Yb/Ce codoped aluminosilicate fiber for laser stability improvement at high output power.

A gain-tailored Ge-free Yb/Ce codoped aluminosilicate fiber is fabricated by MCVD combined with solution doping technique. Through regulating the temperature in the tube and designing the solution doping process, the refractive index profile of this fiber is close to a step-index without any center dip. The laser performance of this fiber is proved through contrast experiments with conventional fiber in a kW-level MOPA setup. The gain-tailored fiber amplifier presents a beam quality of M2 ~1.43 at 1.2 kW. Its MI threshold is 1.25 kW, about 1.74 times as much as that of the conventional fiber amplifier. The laser slope efficiency of the gain-tailored fiber amplifier is 86.75%. Stabilized at an output power of 1.1 kW for 15 hours, the MI threshold does not decrease after this long-term operation, demonstrating a strong resistance to photodarkening effect. These results have confirmed that MCVD-fabricated gain-tailored Yb/Ce codoped aluminosilicate fibers have great potential in power scaling and output stability of high-power fiber lasers and amplifiers.

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway.

BACKGROUND/AIMS: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. METHODS: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. RESULTS: In CEP cells, Interleukin (IL)-1ß upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1ß-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. CONCLUSION: LY could serve as a potential drug for treating IVD disease.

Single transverse mode laser in a center-sunken and cladding-trenched Yb-doped fiber.

We report a novel center-sunken and cladding-trenched Yb-doped fiber, which was fabricated by a modified chemical vapor deposition process with a solution-doping technique. The simulation results showed that the fiber with a core diameter of 40 µm and a numerical aperture of 0.043 has a 1217 µm2 effective mode area at 1080 nm. It is also disclosed that the leakage loss can be reduced lower than 0.01 dB/m for the LP01 mode, while over 80 dB/m for the LP11 mode by optimizing the bending radius as 14 cm. A 456 W laser output was observed in a MOPA structure. The laser slope efficiency was measured to be 79% and the M2 was less than 1.1, which confirmed the single mode operation of the large mode area center-sunken cladding-trenched Yb-doped fiber.

Current advances in the development of natural meniscus scaffolds: innovative approaches to decellularization and recellularization.

The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.

Application of postoperative autotransfusion in total joint arthroplasty reduces allogeneic blood requirements: a meta-analysis of randomized controlled trials.

BACKGROUND: Total joint arthroplasty is associated with significant blood loss and often requires blood transfusion. However, allogeneic blood transfusion (ABT) may lead to severe problems, such as immunoreaction and infection. Postoperative autotransfusion, an alternative to ABT, is controversial. We conducted a meta-analysis to evaluate the ability of postoperative autotransfusion to reduce the need for ABT following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Systematic literature searches for randomized controlled trials were performed using PubMed, Embase, and the Cochrane Library until February 2016. Relative risks (RRs) and weighted mean differences with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models; we also evaluated publication bias and heterogeneity. RESULTS: Seventeen trials with a total of 2314 patients were included in the meta-analysis. The pooled RRs of ABT rate between autotransfusion and the regular drainage/no drainage groups for TKA and THA were 0.446 (95% CI = 0.287, 0.693; p < 0.001) and 0.757 (95% CI = 0.599, 0.958; p = 0.020), respectively. In the subgroup analysis performed in TKA patients according to control interventions, the pooled RRs were 0.377 (95% CI = 0.224, 0.634; p < 0.001) (compared with regular drainage) and 0.804 (95% CI = 0.453, 1.426, p = 0.456) (compared with no drainage). In the subgroup analysis performed for THA, the pooled RRs were 0.536 (95% CI = 0.379, 0.757, p < 0.001) (compared with regular drainage) and 1.020 (95% CI = 0.740, 1.405, p = 0.904) (compared with no drainage). CONCLUSIONS: Compared to regular drainage, autotransfusion reduces the need for ABT following TKA and THA. This reduction is not present when comparing autotransfusion to no drainage. However, the reliability of the meta-analytic results concerning TKA was limited by significant heterogeneity in methods among the included studies.

Functional characterization of the gene FoOCH1 encoding a putative α-1,6-mannosyltransferase in Fusarium oxysporum f. sp. cubense.

Fusarium oxysporum f. sp. cubense (FOC) is the causal agent of banana Fusarium wilt and has become one of the most destructive pathogens threatening the banana production worldwide. However, few genes related to morphogenesis and pathogenicity of this fungal pathogen have been functionally characterized. In this study, we identified and characterized the disrupted gene in a T-DNA insertional mutant (L953) of FOC with significantly reduced virulence on banana plants. The gene disrupted by T-DNA insertion in L953 harbors an open reading frame, which encodes a protein with homology to α-1,6-mannosyltransferase (OCH1) in fungi. The deletion mutants (ΔFoOCH1) of the OCH1 orthologue (FoOCH1) in FOC were impaired in fungal growth, exhibited brighter staining with fluorescein isothiocyanate (FITC)-Concanavalin A, had less cell wall proteins and secreted more proteins into liquid media than the wild type. Furthermore, the mutation or deletion of FoOCH1 led to loss of ability to penetrate cellophane membrane and decline in hyphal attachment and colonization as well as virulence to the banana host. The mutant phenotypes were fully restored by complementation with the wild type FoOCH1 gene. Our data provide a first evidence for the critical role of FoOCH1 in maintenance of cell wall integrity and virulence of F. oxysporum f. sp. cubense.

Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries.

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan-Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5%. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0%, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95% confidence intervals: 1.285-5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3%, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0%, P = 0.404). Kaplan-Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.

Increased risk of colorectal malignant neoplasm in patients with nonalcoholic fatty liver disease: a large study.

Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk factor of colorectal benign adenomas and advanced neoplasms. The aim of this large cohort study was to further investigate the prevalence of colorectal malignant neoplasm (CRMN) in patients with NAFLD and determine whether association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males and 945 females) who underwent a routine colonoscopy according to international colorectal cancer screening guideline were recruited. Nature of colorectal lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary logistic regression analysis was applied to explore the related associations. Prevalence of CRMN was 29.3% (77/263) in patients with NAFLD, which was significantly higher than 18.0% (369/2,052) in the control group (P<0.05). In addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid colon than in control group (14.3 vs. 11.9%). The incidence of highly-differentiated colorectal adenocarcinoma in NAFLD group was significantly higher than control group (62.3 vs. 9.8%). Univariate analysis showed that NAFLD had strong association with CRMN (OR 2.043; 95% CI 1.512-2.761; P<0.05). After adjusting for metabolic and other confounding factors, NAFLD remained as an independent risk factor for CRMN (OR 1.868; 95% CI 1.360-2.567; P<0.05). NAFLD was an independent risk factor for CRMN. Sigmoid carcinoma and highly differentiated colorectal adenocarcinoma were more commonly found in NAFLD. (ClinicalTrials.gov number, NCT01657773, website: http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1 ).