Lonicerin alleviates the progression of experimental rheumatoid arthritis by downregulating M1 macrophages through the NF-κB signaling pathway.

The present study aimed to evaluate anti-rheumatoid arthritis (RA) effect of Lonicerin (LON), a safe compound with anti-inflammatory and immunomodulatory properties. Nevertheless, the exact role of LON in RA remains elusive. In this test, the anti-RA effect of LON was evaluated in collagen-induced arthritis (CIA) mouse model. Relevant parameters were measured during the experiment; ankle tissue and serum were collected at the end of the experiment for radiology, histopathology, and inflammation analysis. ELISA, qRT-PCR, immunofluorescence, and western blot were used to explore the effect of LON on the polarization of macrophages and related signal pathways. It was discovered that LON treatment attenuated the disease progression of CIA mice with lower paw swelling, clinical score, mobility, and inflammatory response. LON treatment significantly decreased M1 marker levels in CIA mice and LPS/IFN-γ-induced RAW264.7 cells, while slightly increasing M2 marker levels in CIA mice and IL-4-induced RAW264.7 cells. Mechanistically, LON attenuated the activation of the NF-κB signaling pathway, which contributes to M1 macrophage polarization and inflammasome activation. In addition, LON inhibited NLRP3 inflammasome activation in M1 macrophages, thereby reducing inflammation by inhibiting IL-1ß and IL-18 release. These results indicated that LON might exert anti-RA effects by regulating the polarization of M1/M2 macrophage, especially by inhibiting macrophage polarization toward M1.

All-inside technique versus in situ transtendon repair for Ellman â ¢ partial articular supraspinatus tendon avulsion.

BACKGROUND: The current surgical techniques for repairing Ellman Ⅲ partial articular supraspinatus tendon avulsion (PASTA) is mainly tear completion followed by repair and in situ transtendon repair, and both techniques have been proven to have good clinical effects. In situ transtendon repair is more widely used because of its high performance in preserving the integrity of the bursal side supraspinatus tendon. However, there is still some scope for improvement. Our purpose was to compare the clinical outcomes of the all-inside repair technique and in situ transtendon repair for Ellman III PASTA. METHODS: A retrospective comparative study was conducted on 56 patients who suffered from Ellman Ⅲ PASTA and underwent rotator cuff repair; 28 patients were treated with the all-inside technique (group A), and 28 patients were treated with the transtendinous technique (group B). All patients were followed up for at least 2 years. The visual analog scale (VAS), Constant, and American Shoulder and Elbow Surgeons (ASES) scores were used to evaluate the patient's shoulder joint function before surgery, 1 month and 3 months after surgery, and at the last time of follow-up. RESULTS: Group A showed superiority in pain and functional improvement 1 month after the operation: the VAS score, 2.8 ± 0.3 in group A vs. 4.7 ± 0.4 in group B (P = .042); Constant score, 73 ± 5 in group A vs. 60 ± 6 in group B (P = .038); and ASES score, 75 ± 5 in group A vs. 58 ± 7 in group B (P = .043), whereas there was no statistical difference in group B. However, 3 months after surgery and at the last follow-up, the VAS, Constant, and ASES scores in both groups were significantly improved (P < .01), and there was no significant statistical difference between the groups (P > .05). Magnetic resonance imaging showed that the repaired rotator cuff tendon-bone healed well; at the last follow-up, all patients were in good function, the pain was completely relieved, and no revision was performed in both groups. CONCLUSION: Arthroscopic repair of Ellman Ⅲ PASTA provided satisfactory functional improvements and pain relief regardless of the all-inside and in situ transtendon repair techniques. However, the all-inside repair technique is more beneficial due to its dual function in preserving the intact bursa and avoidance of uneven tension of the articular side, which is advantageous to early postoperative rehabilitation.

Total Synthesis of the Potent and Broad-Spectrum Antibiotics Amycolamicin and Kibdelomycin.

The complex and intriguing structures of the antibiotics amycolamicin and kibdelomycin are herein confirmed through total synthesis. Careful titration of the synthetic products reveals that kibdelomycin is the salt form of amycolamicin. This synthesis employs a highly convergent strategy, which provides a modular approach for further SAR studies of this class of antibiotics.

Visible-Light Photoredox-Catalyzed and Copper-Promoted Trifluoromethoxylation of Arenediazonium Tetrafluoroborates.

We report the development of photoredox-catalyzed and copper-promoted trifluoromethoxylation of arenediazonium tetrafluoroborates, with trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxylation reagent. This new method takes advantage of visible-light photoredox catalysis to generate the aryl radical under mild conditions, combined with copper-promoted selective trifluoromethoxylation. The reaction is scalable, tolerates a wide range of functional groups, and proceeds regioselectively under mild reaction conditions. Furthermore, mechanistic studies suggested that a Cs[Cu(OCF3 )2 ] intermediate might be generated during the reaction.

Large Areal Mass, Mechanically Tough and Freestanding Electrode Based on Heteroatom-doped Carbon Nanofibers for Flexible Supercapacitors.

A flexible and freestanding supercapacitor electrode with a N,P-co-doped carbon nanofiber network (N,P-CNFs)/graphene (GN) composite loaded on bacterial cellulose (BC) is first designed and fabricated in a simple, low-cost, and effective approach. The porous structure and excellent mechanical properties make the BC paper an ideal substrate that shows a large areal mass of 8 mg cm-2 . As a result, the flexible N,P-CNFs/GN/BC paper electrode shows appreciable areal capacitance (1990 mF cm-2 in KOH and 2588 mF cm-2 in H2 SO4 electrolytes) without sacrificing gravimetric capacitance (248.8 F g-1 and 323.5 F g-1 ), exhibits excellent cycling ability (without capacity loss after 20 000 cycles), and remarkable tensile strength (42.8 MPa). By direct coupling of two membrane electrodes, the symmetric supercapacitor delivers a prominent areal capacitance of 690 mF cm-2 in KOH and 898 mF cm-2 in H2 SO4 , and remarkable power/energy density (19.98 mW cm-2 /0.096 mW h cm-2 in KOH and 35.01 mW cm-2 /0.244 mW h cm-2 in H2 SO4 ). Additionally, it shows stable behavior in both bent and flat states. These results promote new opportunities for N,P-CNFs/GN/BC paper electrodes as high areal performance, freestanding electrodes for flexible supercapacitors.

Synthesis and biological evaluation of Aspergillomarasmine A derivatives as novel NDM-1 inhibitor to overcome antibiotics resistance.

The ß-lactam antibiotic resistance of Gram-negative bacteria has shown to be a critical global health problem. One of the primary reasons for the drug resistance is the existence of ß-lactamases especially metallo-ß-lactamases such as New Delhi metallo-ß-lactamase (NDM-1) and Verona Integron-encoded metallo-ß-lactamase (VIM-2). The fungal natural product Aspergillomarasmine A (AMA) has proven to be a promising inhibitor of NDM-1 and VIM-2 both in vitro and in vivo. Seven new analogues of AMA were synthesized by utilizing different strategies. The biological evaluation of these analogues was performed to study the structure-activity relationship of AMA both in vitro and in vivo. Remarkably, the lead compound 4 showed synergistic effect in combination with Meropenem to overcome the antibiotic resistance of the Gram-negative bacteria such as K. pneumoniae (BAA-2146) expressing NDM-1.

Total Synthesis and Structural Reassignment of Aspergillomarasmine†A.

The increase and spread of Gram-negative bacteria that resistant are to almost all currently available ß-lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo-ß-lactamases such as metallo-ß-lactamase-1 (NDM-1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM-1-expressing Gram-negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo-ß-lactamase inhibitors to potentiate ß-lactam antibiotics.

Total syntheses of (-)-macrocalyxoformins A and B and (-)-ludongnin C.

The complex and diverse molecular architectures along with broad biological activities of ent-kauranoids natural products make them an excellent testing ground for the invention of synthetic methods and strategies. Recent efforts notwithstanding, synthetic access to the highly oxidized enmein-type ent-kauranoids still presents considerable challenges to synthetic chemists. Here, we report the enantioselective total syntheses of C-19 oxygenated enmein-type ent-kauranoids, including (-)-macrocalyxoformins A and B and (-)-ludongnin C, along with discussion and study of synthetic strategies. The enabling feature in our synthesis is a devised Ni-catalyzed decarboxylative cyclization/radical-polar crossover/C-acylation cascade that forges a THF ring concomitantly with the ß-keto ester group. Mechanistic studies reveal that the C-acylation process in this cascade reaction is achieved through a carboxylation followed by an in situ esterification. Biological evaluation of these synthetic natural products reveals the indispensable role of the ketone on the D ring in their anti-tumor efficacy.

The rat as a novel model for chronic rotator cuff injuries.

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1ß and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1ß, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.

Pathologic mechanism of hidden blood loss after total knee arthroplasty: oxidative stress induced by free fatty acids.

BACKGROUND: Hidden blood loss (HBL) often occurs after joint replacement; however, the mechanism of HBL is not clear. We conducted a prospective study to analyze the correlation between high-level free fatty acids (FFA) and erythrocyte injury, and explore the pathologic mechanism of hidden blood loss (HBL) after total knee arthroplasty (TKA). METHODS: Perioperative blood indexes were tested in 120 patients who underwent unilateral total knee replacement for end-stage knee osteoarthritis. The changes in FFA, reactive oxygen species (ROS), hemoglobin (Hb), and red blood cells (RBC) in the blood samples were detected. The activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and hydrogen peroxide (H2O2) levels were measured. Morphologic changes of blood cells were analyzed under a microscope. RESULTS: HBL occurred in all patients after TKA. The Hb and RBC decreased significantly 24 h after surgery (P <0.05), while FFA and ROS concentration were substantially elevated, and heteromorphic red blood cells appeared under the microscope. The hemoglobin content decreased to its lowest level at 48 h after the operation (P<0.01). With the increase of FFA and ROS levels, HBL appeared more obvious (P<0.01). GSH-PX activity, T-SOD activity, and H2O2 levels significantly decreased compared to preoperative tested samples (P<0.01). Microscopically, atypical erythrocytes increased significantly with cellular rupture and lysis identified. CONCLUSIONS: High levels of FFA in blood can induce oxidative stress and damage red blood cells, leading to the occurrence of HBL after surgery. TRIAL REGISTRATION: Chinese Clinical Trials Registry (the trial number: ChiCTR17010681, URL: http://www.chictr.org.cn).

Access to the 2H-Tetrahydro-4,6-dioxo-1,2-oxazine Ring System from Nitrone via a Tandem Nucleophilic Addition and Transesterification Reaction.

A general and efficient synthesis of the 2H-tetrahydro-4,6-dioxo-1,2-oxazine ring system through a tandem nucleophilic addition and transesterification reaction is described. The reaction is highly functional-group-tolerant and proceeds under mild conditions, affording the corresponding products in good to excellent yields. This method represents the first general synthetic route to access this heterocyclic scaffold, which exists in the complex natural products alchivemycin A and B with significant antibiotic activities.

Epitaxial growth route to crystalline TiO2 nanobelts with optimizable electrochemical performance.

Anatase TiO(2) nanobelts with 13 nm in thickness have been successfully synthesized via an epitaxial growth chemical transformation, in which the primary H(2)Ti(3)O(7) nanobelt frameworks can be preserved. The phases, crystal structures, morphologies, and growth behavior of both the precursory (Na(2)Ti(3)O(7) and H(2)Ti(3)O(7)) and resultant products (TiO(2)) are characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). Detailed investigation of the formation mechanism of the TiO(2) nanobelts indicates epitaxial nucleation and oriented growth of textured TiO(2) inside the nanobelts. TiO(2) nanocrystals prefer certain epitaxial growth direction due to the structural matching of (110)(H2Ti3O7)//(101)(TiO2). We demonstrated that the initial reversible capacity of these TiO(2) nanobelts attained 225 mA h/g. Furthermore, the nanobelts exhibit high power density along with excellent cycling stability in their application as hybrid electrochemical cells.

Effects of the Pt loading side and cathode-biofilm on the performance of a membrane-less and single-chamber microbial fuel cell.

In order to analyze the effect of cathode's Pt loading side on the performance of single-chamber microbial fuel cells (MFCs), power generation of a bamboo charcoal membrane-less air-cathode MFC was examined. The maximum power outputs obtained were 0.144 and 1.16 mW, while the maximum voltage outputs were 0.400 and 0.500 V (external resistance was 500 Omega), respectively, when the Pt loading side facing to the air and to the anode chamber solution; after a long time of operation with the side of cathode loaded Pt facing to anode chamber solution, a biofilm was developed on the inner side of cathode. With the formation of this biofilm, the power outputs of MFC increased first, and then decreased to 0.8 mW; oxidation-reduction potentials (ORP) dropped first, and then achieved the level of stability. Coulombic efficiency (CE) increased at a certain extent. In addition, the impact of cathode-biofilm on the loss of water in anode chamber solution was determined.