Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.

New insights into multi-strategies of sludge granulation in up-flow anaerobic sludge blanket reactors from community succession and interaction.

This study aimed to elucidate the multiple strategies employed by anaerobes during granulation in a laboratory upflow anaerobic sludge blanket reactor, based on microbial succession and interactions. The anaerobic granulation process featured staged dominance of microbial genera, corresponding well with the environmental traits. Across the stages (selection, seeding, expansion, and maturation), chemotaxis attraction of nitrogen and/or carbon sources and flagellar motion were the primary strategy of microbial assembly. The second messengers - cyclic adenosine and guanosine monophosphates - partially regulated the agglomeration of filamentous Euryachaeota and Chloroflexi as the inner cores, while quorum sensing mediated the expansion of granules prior to maturation. Antagonism or competition governed the interactions within the phylogenetic molecular ecological network during sludge granulation, which were largely driven by the low-abundance (<1%) taxa. These new insights suggest that better engineering solutions to enhance chemotaxis attraction and species selection could achieve more efficient anaerobic granular sludge processes.

The state-of-the-art application of functional bacterial cellulose-based materials in biomedical fields.

Bacterial cellulose (BC) is a significant polysaccharide that bacteria create under specific growth conditions that exhibits high purity, high water-holding capacity, high crystallinity, strong mechanical capabilities, and high biocompatibility. Pure BC has been studied, marketed, and frequently combined with other materials to provide additional potential effects. Additionally, because of the abundance of hydroxyl groups in BC, it can be readily changed to yield derivatives or composites with improved physicochemical and functional characteristics for a variety of applications such as artificial blood vessel manufacturing, soft tissue engineering, and bone tissue engineering. In this review, state-of-the-art manufacturing, structural traits, and applications of BC are summarized, along with in situ and ex situ modification techniques and their biomedical applications. Finally, the future growth opportunities and obstacles for BC and its composites in the biological sector are anticipated.

Application of lignin and lignin-based composites in different tissue engineering fields.

Lignin is a major phenolic polymer from the plant biomass. Due to its abundant functional groups (carboxyl and hydroxyl groups), lignin could act as an antioxidant, antimicrobial as well as an immune modulator. These remarkable biological properties render lignin a highly potential bioactive candidate in the biomedical applications including tissue engineering. Although several effective applications of lignin-based composites have been reported in tissues repairing and organ regeneration, a systematic review to summarize the recent utilization of lignin-based composites in different tissue engineering fields is still lacking. Hence, the aim of this review is to delineate the biological functions of lignin and to highlight the latest applications of lignin-based composites in different tissue engineering fields, such as bone regeneration, organ regeneration and wound dressing. This review will serve as an illuminating resource to direct and promote the biomedical applications of lignin and lignin-based composites.

Sustainable lignin and lignin-derived compounds as potential therapeutic agents for degenerative orthopaedic diseases: A systemic review.

Lignin, the most abundant natural and sustainable phenolic compound in biomass, has exhibited medicinal values due to its biological activities decided by physicochemical properties. Recently, the lignin and its derivatives (such as lignosulfonates and lignosulfonate) have been proven efficient in regulating cellular process and the extracellular microenvironment, which has been regarded as the key factor in disease progression. In orthopaedic diseases, especially the degenerative diseases represented by osteoarthritis and osteoporosis, excessive activated inflammation has been proven as a key stage in the pathological process. Due to the excellent biocompatibility, antibacterial and antioxidative activities of lignin and its derivatives, they have been applied to stimulate cells and restore the uncoupling bone remodeling in the degenerative orthopaedic diseases. However, there is a lack of a systemic review to state the current research actuality of lignin and lignin-derived compounds in treating degenerative orthopaedic diseases. Herein, we summarized the current application of lignin and lignin-derived compounds in orthopaedic diseases and proposed their possible therapeutic mechanism in treating degenerative orthopaedic diseases. It is hoped this work could guide the future preparation of lignin/lignin-derived drugs and implants as available therapeutic strategies for clinically degenerative orthopaedic diseases.

Preparing printable bacterial cellulose based gelatin gel to promote in vivo bone regeneration.

The naturally tight entanglement of fibers in bacterial cellulose (BC) results in low printability when BC is used as a bioink for printing scaffolds. In this study, neat BC was treated by TEMPO-mediated oxidation (TO-BC) and maleic acid (MA-BC) to prepare homogeneous BC dispersions to fabricate scaffolds for bone regeneration. Results showed that the treatments released individual fibrils in the corresponding uniform dispersions without impairing inherent crystalline properties. Compared with TO-BC, MA-BC hybridized with gelatin could endow the gel with improved rheological properties and compression modulus for 3D printing. Both TO-BC and MA-BC dispersions showed good osteoblast viability. However, MA-BC possessed more pronounced ability to express osteogenic marker genes and formation of mineralized nodules in vitro. Compared with TO-BC-based gelatin scaffolds, MA-BC-based gelatin scaffolds showed a better ability to stimulate the regeneration of rat calvaria, demonstrating a higher bone mineral density of newly formed bone and trabecular thickness in vivo.

Palladium-Catalyzed Enantioselective Heck Carbonylation with a Monodentate Phosphoramidite Ligand: Asymmetric Synthesis of (+)-Physostigmine, (+)-Physovenine, and (+)-Folicanthine.

Reported herein is the development of the first enantioselective monodentate ligand assisted Pd-catalyzed domino Heck carbonylation reaction with CO. The highly enantioselective domino Heck carbonylation of N-aryl acrylamides and various nucleophiles, including arylboronic acids, anilines, and alcohols, in the presence of CO was achieved. A novel monodentate phosphoramidite ligand, Xida-Phos, has been developed for this reaction and it displays excellent reactivity and enantioselectivity. The reaction employs readily available starting materials, tolerates a wide range of functional groups, and provides straightforward access to a diverse array of enantioenriched oxindoles having ß-carbonyl-substituted all-carbon quaternary stereocenters, thus providing a facile and complementary method for the asymmetric synthesis of bioactive hexahydropyrroloindole and its dimeric alkaloids.

A sustainable process for procuring biologically active fractions of high-purity xylooligosaccharides and water-soluble lignin from Moso bamboo prehydrolyzate.

BACKGROUND: Prehydrolyzate, which is from the prehydrolysis process in dissolving pulps industry, contains various sugar-derived and lignin compounds such as xylooligosaccharides (XOS), gluco-oligosaccharides, xylose, glucose, and soluble lignin (S-L). The XOS has several beneficial effects on human physiology. XOS and S-L in prehydrolyzate are difficult to efficiently fractionate due to their similar molecular weights and water solubility. In this work, we proposed a sustainable and green process using polystyrene divinylbenzene (PS-DVB) resin to simultaneously separate and recover XOS and S-L. Enzymatic hydrolysis with endo-1,4-ß-xylanase and fermentation with P. stipites were sequentially applied to purify XOS to minimize xylose content as well as amplify contents of xylobiose and xylotriose. In addition, 2D-HSQC NMR was used to analyze the structural characteristics of XOS and S-L. Furthermore, the biological abilities of antioxidants and prebiotics of these fractions were investigated by scavenging radicals and cultivating intestinally beneficial bacterias, respectively. RESULTS: Results showed that PS-DVB resin could simultaneously separate XOS and solubilized lignin with excellent yields of 93.2% and 85.3%, respectively. The obtained XOS after being purified by enzymatic hydrolysis and fermentation contained 57.7% of xylobiose and xylotriose. 10.4% amount of inherent xylan was found in the S-L fraction obtained by PS-DVB resin separation. 2D-HSQC NMR revealed that lignin carbohydrate complexes existed in both XOS and S-L as covalent linkages between lignin and 4-O-methylglucuronoarabinoxylan. The biological application results showed that the antioxidant capacity of S-L was stronger than XOS, while XOS was superior in promoting growth of intestinal Bifidobacteria adolescentis and stimulating production of short-chain fatty acids by Lactobacillus acidophilus. CONCLUSIONS: The proposed strategy of sequentially combining hydrophobic resin separation, enzymatic hydrolysis, and fermentation was successfully demonstrated and resulted in simultaneous production of high-quality XOS and solubilized lignin. These biomass-derived products in prehydrolyzate can be regarded as value-adding prebiotics and antioxidants.

Modular 2,3-diaryl-2H-azirine synthesis from ketoxime acetates via Cs2CO3-mediated cyclization.

A modular 2H-azirine synthesis from ketoxime acetates via Cs2CO3-mediated cyclization has been developed. The reaction utilizes easily available starting materials and provides a general synthetic route to 2,3-diaryl-2H-azirines in good to excellent yields under mild conditions, which is complementary to the conventional approaches for the synthesis of 2H-azirines. A gram-scale reaction was performed to demonstrate the scale-up applicability of this synthetic method. Importantly, 2H-azirines can be efficiently converted to various azaheterocycles.

(18)F-FDG PET/CT imaging in systemic lupus erythematosus related autoimmune haemolytic anaemia and lymphadenopathy.

OBJECTIVE: We present a case of systemic lupus erythematosus (SLE) related autoimmune haemolytic anaemia (AIHA) and lymphadenopathy. AIHA as a serious complication of SLE, requiring urgent appropriate management. The timely differential diagnosis between SLE with lymphadenopathy and lymphoma, primary and SLE-related AIHA often looms as practical challenge under clinical scenario. Fluorine-18 fluorodeoxyglucose position emission tomography/computed tomography ((18)F-FDG PET/CT) performed for fever of a known origin and for possible malignancy, showed increased (18)F-FDG uptake in lymph nodes, as well as increased spleen uptake, which was probably due to lymphoma. CONCLUSIONS: A symmetrically increased (18)F-FDG uptake in small lymph nodes with multiple serous cavity effusion helped the differential diagnosis between SLE related AIHA and lymphoma. In addition, PET/CT can visualize not only the degree of disease activity or the "burden of inflammation" but also the distribution of the disease in the entire body.

Roles of XRCC1/XPD/ERCC1 Polymorphisms in Predicting Prognosis of Hepatocellular Carcinoma in Patients Receiving Transcatheter Arterial Chemoembolization.

OBJECTIVE: To investigate the potential prognostic roles of polymorphisms in the X-ray repair cross-complementing group 1 (XPCC1), xeroderma pigmentosum group D (XPD) and excision repair cross-complementing group 1 (ERCC1) genes for patients with hepatocellular carcinoma (HCC) receiving transcatheter arterial chemoembolization (TACE). METHODS: Clinical data and blood samples from 308 HCC patients receiving TACE were collected between January 2010 and December 2013. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) analyses was used to determine the genotypes of the XPCC1 (rs25487), XPD (rs13181) and ERCC1 (rs11615) genes. The relationships between the genotypes and the efficacy of TACE treatment were analyzed. RESULTS: The XRCCI rs25487 polymorphism was associated with a favorable prognosis in HCC patients receiving TACE (p = 0.006), and patients carrying variant genotypes (A/A + G/A) were associated with significantly reduced risk of death compared with those with the wild genotype (G/G) (HR = 0.556; 95% CI = 0.354-0.874). These findings were supported by Kaplan-Meier survival curve analysis showing that median survival time for patients with A/A + G/A genotypes was significantly longer compared with those with the G/G genotype (11.2 month vs. 8.0 months; log rank p = 0.006). Stratified analyses revealed that A/A + G/A genotypes of XRCC1 rs25487 are associated with significantly reduced risk of death compared with the G/G genotype in patients grouped by tumor size, portal vein tumor thrombus (PVTT), alpha-fetoprotein (AFP) and TNM stage (all p < 0.05). The ERCC1 rs13181 and XPD rs11615 polymorphisms were not predictive of clinical outcome for HCC patients receiving TACE (both p > 0.05). CONCLUSION: The XRCC1 rs25487 polymorphisms are prognostic for HCC patients receiving TACE. The ERCC1 and XPD polymorphisms had no relationship to the clinical outcomes.

Is it practical and cost effective to detect differentiated thyroid carcinoma metastases by (18)F-FDG PET/CT, by (18)F-FDG SPET/CT or by (131)I SPET/CT?

Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography/computerized tomography ((18)F-FDG PET/CT) plays an important role in detecting differentiated thyroid carcinoma (DTC) metastases with elevated thyroglobulin (Tg) and negative radioiodine ((131)I) uptake. In conclusion, (18)F-FDG PET/CT may fail to detect all DTC metastases, while (131)I WBS combined with (131)I SPET/CT may be a better cheaper and diagnostic tool as suggested by the case we presented here. Positive metastases in both (131)I and (18)F-FDG SPET/CT may indicate worse prognosis. Future research may add more evidence as to which is the best diagnostic imaging modality and relate it to the molecular mechanism of the uptake of the radionuclide used.