Nickel-Catalyzed Cross-Electrophile Coupling Reactions between Allylic Acetates and gem-Difluorovinyl Tosylate.

A nickel-catalyzed cross-electrophile coupling of allylic acetates and gem-difluorovinyl tosylate is presented, which first achieves allylic gem-difluoroolefins via C(sp3)-C(sp2) cross-electrophile coupling. In addition, this protocol was performed under mild reaction conditions, affording a variety of allylic gem-difluorovinyl arenes in moderate to good yields. Moreover, both linear and branched allylic acetate could produce a linear cross-coupling product exclusively. Mechanistic studies reveal that the reaction involves two different Ni(0)/Ni(II) catalytic cycles.

Palladium-catalysed difluoroolefination of benzyl tosylates toward the synthesis of gem-difluoro-2-trifluromethyl styrene derivatives.

We have presented an efficient method to access gem-difluoro-2-trifluromethyl styrene derivatives via palladium catalysis. This method features mild reaction conditions, broad substrate scope and good product yields. Moreover, gram-scale reactions demonstrated the robustness and potential of this method. Control experiments revealed that the -CF3 group was essential to the success of this transformation. Finally, the practicality of this method was successfully proven by three synthetic applications.

Eluting mode of photodynamic nanofibers without photosensitizer leakage for one-stop treatment of outdoor hemostasis and sterilizing superbacteria.

Bleeding in outdoor environments is often accompanied by bacterial infection. Due to poor outdoor conditions, it is essential to use the same materials to achieve one-stop treatment of fast hemostasis and simultaneously sterilizing bacteria, especially multidrug-resistant bacteria. Photodynamic therapy (PDT) can kill superbacteria, and local PDT through a nanofiber platform can effectively reduce damage to normal tissue. However, current photosensitizers whether in the interior or on the surface of fibers would leak into the wound and inhibit collagen regeneration. Herein, we use a battery-powered handheld electrospinning device that can work outdoors. It directly spins fibers onto the wound, which facilitates fast hemostasis due to its excellent adhesion to the wound. Eluting holes in the hydrophobic fibers by wound tissue fluid are also proposed to accelerate the escape of reactive oxygen species (ROS) from the interior of the fibers to the wound. After photosensitizers were coated on upconverting nanoparticles (UCNPs), they formed clusters whose size (∼55 nm) was much larger than the uniform elution hole (∼4 nm), which prevented photosensitizers from leaking out into the wound tissue. This cluster structure can also tailor the photosensitizers to be triggered by near infrared (NIR) light, whose deeper penetration depth in tissue can facilitate treating deep infections. Because of the combination of the in situ fiber deposition method with the designed elution mode, ROS is effectively poured out onto the fiber surface and is quickly delivered to the wound. Thus, after rapid hemostasis (<7 s), this one-stop treatment followed by photodynamic sterilizing of superbacteria can promote collagen regeneration and reduce wound healing time from 24 to 16 days.

Self-powered portable melt electrospinning for in situ wound dressing.

BACKGROUND: Electrospun (e-spun) nanofibers for wound dressing have attracted wide attention due to its large specific surface area, large porosity and breathability. Compared with solution electrospinning (e-spinning), melt e-spinning is more bio-friendly without toxic solvent participation, which provides the possibility of in situ e-spinning on wounds directly. However, previously reported melt e-spinning devices were usually bulky and cumbersome due to their necessary heating unit, and different components were separated to avoid electrostatic interference. RESULTS: In this article, we report on a self-powered hand-held melt e-spinning gun which can work without any external power supply (outdoors). The problem of electrostatic interference for this integrated device was solved by using a special high heat transfer insulation unit. The apparatus is easy and safe to operate by a single hand due to its small volume (24 × 6 × 13 cm3) and light weight (about 450 g). Some biodegradable polymers, for example, polycaprolactone (PCL) fibers were successful e-spun onto wounds directly by using this dressing gun. CONCLUSIONS: PCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.

Nickel-Catalyzed Intramolecular Desulfitative C-N Coupling: A Synthesis of Aromatic Amines.

A nickel-catalyzed intramolecular C-N coupling reaction via SO2 extrusion is presented. The use of a catalytic amount of BPh3 allows the transformation to take place under much milder conditions (60 °C) than previously reported C-N coupling reactions by CO or CO2 extrusion (160-180 °C). In addition, this method displays good functional group tolerance and versatility, as it can be applied to the synthesis of dialkyl aryl amines, alkyl diaryl amines, and triaryl amines. The robustness of the desulfitative C-N coupling is demonstrated by three high-yielding gram-scale reactions.

Long Noncoding RNA SERTAD2-3 Inhibits Osteosarcoma Proliferation and Migration by Competitively Binding miR-29c.

Background: Osteosarcoma (OS) is a malignant tumor disease with high morbidity and mortality in children and adolescents. Recently, attention has been focused on the effects of long noncoding RNAs (lncRNAs) on tumor biology. In this study, we identified the role of lnc-SERTAD2-3 in the development of OS. Materials and Methods: Sixty OS samples and adjacent tissues were collected to determine the relationship between lnc-SERTAD2-3 levels and clinicopathological characteristics. Quantitative real-time PCR (qPCR) was used to measure gene expression levels. A transwell invasion assay, a Cell Counting Kit-8 assay, and flow cytometry were used to measure cell migration, growth, and apoptosis, respectively. The binding site between the lnc-SERTAD2-3 and miR-29c RNAs was evaluated using a luciferase reporter assay. Results: The expression of the lnc-SERTAD2-3 was significantly downregulated in OS samples and three OS cell lines (MG-63, U2OS, and Saos-2) compared to normal tissue. Patients with lower levels of lnc-SERTAD2-3 expression had a more unfavorable prognosis (larger OS size, distant metastasis, and recurrence). Overexpression of lnc-SERTAD2-3 inhibited proliferation and migration, and promoted apoptosis in OS cells. Moreover, we found that lnc-SERTAD2-3 could suppress miR-29c by direct binding. Moreover, reexpression of miR-29c reversed the effect of lnc-SERTAD2-3 on OS cells. Conclusion: Overall, lnc-SERTAD2-3, an OS suppressor, is involved in the inhibition of OS proliferation and migration by targeting miR-29c.

T Cell Receptor Immune Repertoires Are Promptly Reconstituted After Methicillin-Resistant Staphylococcus aureus Infection.

T cells represent a subset of lymphocytes characterized by immunosurveillance and immunoregulation function. Peripheral blood mononuclear cells (PBMCs) are enriched in T cells, which exert critical antimicrobial roles in infectious diseases. High-throughput sequencing of the T cell receptor (TCR) provides deep insight into monitoring the immune microenvironment. Flow cytometry was used to analyse the distribution of αß/γδ T cells and their CD69, IFN-γ/IL-17 expression from PBMCs. Here, we utilized next-generation sequencing (NGS) to detect the complementarity determining region 3 (CDR3) of TCRß (TRB) and TCRδ (TRD) chain after methicillin-resistant Staphylococcus aureus (MRSA) infection. Our data demonstrated a significant increase in the activation of αß and γδ T cells after MRSA infection. Simultaneously, significantly high CDR3 amino acid (AA) diversity and markedly reconstituted TCR immune repertoires were observed after MRSA infection. Finally, we identified several MRSA-specific initial CDR3 AA motifs after MRSA infection. Our work reveals the profiles of TRB and TRD immune repertoires in response to MRSA and demonstrates a reconstitution of the TCR immune repertoire after MRSA infection.

In situ accurate deposition of electrospun medical glue fibers on kidney with auxiliary electrode method for fast hemostasis.

An auxiliary electrode electrospinning method is proposed to deposit N-octyl-2-cyanoacrylate (NOCA) medical glue fibrous membrane on kidney for in-situ fast hemostasis. A metal electrode equipped to the spinning needle is used to confine the divergence angle of jet. Compared to the conventional electrospinning method, the fiber deposition area has reduced by 2.5 times, and it can achieve in-situ accurate deposition. Moreover, it reduces both the external dimension and over-reliance on electricity, which is superior to previous air-flow assisted electrospinning method. In addition, in situ accurate deposition of NOCA on the kidney exhibits fast hemostasis within 10 s, confirming that this auxiliary electrode method can be applied in outdoors for fast hemostasis. Further pathological studies indicate that this auxiliary electrode method can reduce the inflammatory response of tissues due to the better accurate deposition. This portable hand-held device with the auxiliary electrode method may have potential application in fast hemostasis for outdoors due to its accurate deposition and portability characteristics.

Dual antibacterial behavior of a curcumin-upconversion photodynamic nanosystem for efficient eradication of drug-resistant bacteria in a deep joint infection.

A periprosthetic joint infection (PJI) with methicillin-resistant Staphylococcus aureus (MRSA) is a catastrophic deep joint infection for patients who have had joint replacement surgery. To efficiently eradicate the MRSA, curcumin-upconversion nanoparticles (curcumin-UCNPs) were synthesized by binding the curcumin onto UCNPs, which could produce singlet oxygen under near infrared (NIR) irradiation. Dual antibacterial behavior induced by the curcumin-UCNP itself and induced by photodynamic therapy were demonstrated. Nearly 100% MRSA was eradicated using curcumin-UCNPs under the NIR irradiation because of the dual antibacterial behavior in vitro. Furthermore, a MRSA-induced PJI model was constructed using Sprague Dawley rats. The NIR could penetrate the rats' knee joint tissue well and activated the curcumin-UCNPs to perform photodynamic therapy, which exhibited a good antibacterial effect in the deep joint tissue (1 cm) and about 80% of MRSA was eradicated in vivo. Blood tests and histopathological examinations revealed that the inflammation was also significantly relieved because of the eradication of MRSA in the curcumin-UCNPs-NIR group. Compared with traditional treatments, this research may provide a new therapy for PJI.

Celecoxib-induced inhibition of neurogenesis in fetal frontal cortex is attenuated by curcumin via Wnt/ß-catenin pathway.

Celecoxib is widely used in pregnant women but its influence on fetal brain neurogenesis is largely unknown. The objective of the present study was to examine the influence of celecoxib to fetal brain development and to investigate whether curcumin could ameliorate celecoxib-induced neurotoxicity. Pregnant mice, cultured neurons and cultured neural progenitor cells were all treated with celecoxib with or without curcumin. The change in proliferation, differentiation and the activity of Wnt/ß-catenin signaling pathway were then assessed. Here, we report that prenatal celecoxib exposure inhibited the activity of Wnt/ß-catenin pathway and disrupted the proliferation of neuronal progenitor cells, leading to a decrease of newborn neurons in fetal frontal cortex. Treatment with curcumin significantly could attenuate the celecoxib-induced deficits in proliferation through activating the Wnt/ß-Catenin pathway. Our study for the first time showed that maternal celecoxib administration caused detrimental effects to fetal brain development and provided an evidence of the therapeutic role of curcumin in celecoxib-induced neurotoxicity.

Minimally invasive unicompartmental knee replacement: Midterm clinical outcome.

OBJECTIVE: The purpose of this study was to explore the midterm clinical outcomes of unicompartmental knee replacement (UKR) for medial knee arthropathy through a minimally invasive approach (MIA). METHODS: From January 2006 to June 2010, 442 consecutive patients (485 knees) were included in the study. All patients underwent MIA-UKR with the mobile bearing Oxford phrase III prosthesis. The incision was made starting 1 cm medial to the medial pole of the patella and extending distally to the tibial tubercle. Radiographic evaluations include femorotibial angle (FTA) from coronal x-rays and rectified varus deformity angle, while clinical evaluations included Knee Society Score (KSS, clinical score and function score), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis index and visual analog scale (VAS) for pain. Patients followed-up at 1, 3, 6, 12 months after surgery and each year thereafter. RESULTS: Four hundreds and two patients completed the entire follow-up, 40 patients (45 knees) were lost to follow-up. The average follow-up time was 73.0 ± 1.9 months. The mean length of the incisions was 5.0 ± 0.2 cm. The average FTA decreased from 183.6° ± 5.1° preoperatively to 174.3° ± 4.2° postoperatively, and the mean rectified varus deformity angle was 9.3° ± 1.2°. The KSS clinical score improved from 42.4 ± 2.9 to 92.9 ± 3.8, and the function score improved from 53.5 ± 3.8 to 93.5 ± 4.0. The WOMAC score improved from 47.5 ± 3.1 preoperatively to 12.3 ± 1.5 at the last evaluation. The VAS dropped from 7.8 ± 1.9 preoperatively to 1.6 ± 0.2 postoperatively. All clinical evaluations (KSS, WOMAC, VAS) were significantly different (p < 0.05) from pre and post-operative evaluations. The survival rate was 99.1% at 73 months, and the revision rate was 0.9%. CONCLUSION: The midterm clinical outcomes of MIA-UKR are satisfactory in a Chinese patient population, which is a good surgical option for patients with medial arthropathy of the knee. However, longer-term follow-up studies should be performed in these patients.

[Comparison of early effectiveness between SuperPATH approach and Hardinge approach in total hip arthroplasty].

Objective: To compare the early effectiveness between SuperPATH approach and traditional Hardinge approach in total hip arthroplasty (THA). Methods: Between May 2015 and March 2016, 154 patients (173 hips) undergoing initial THA were included. THA was performed by SuperPATH approach in 64 cases (70 hips) in group A and by traditional Hardinge approach in 90 cases (103 hips) in group B. There was no significant difference in gender, age, body mass index, type of disease, and Harris hip score (HHS) between 2 groups ( P>0.05). The incision length, operation time, intraoperative blood loss, postoperative drainage volume, transfusion rate, ambulation time, length of stay, and complications were recorded. The HHS and visual analogue scale (VAS) were compared between 2 groups before operation and at 1 day, 3 days, 1 week, 3 weeks, 6 weeks, 12 weeks, and 24 weeks after operation. And the relative parameters were measured for imaging evaluation of prosthesis position. In addition, the stratification analysis was performed on 92 patients (100 hips) who received the SuperPATH technology. Results: The incision length, ambulation time, and length of stay in group A were significantly less than those in group B ( P<0.05); the operation time, transfusion rate, and intraoperative blood loss of group A were significantly higher than those of group B ( P<0.05); and there was no significant difference in postoperative drainage volume between 2 groups ( t=1.901, P=0.071). The follow-up period was 6 to 15 months (mean, 9 months). The VAS scores at 1 day, 3 days, and 1 week after operation in group A were significantly lower than those in group B ( P<0.05), but the HHS scores at 1 day, 3 days, 1 week, and 3 weeks after operation in group A were significantly higher than those in group B ( P<0.05). At 24 weeks after operation, the acetabular cup abduction and the proportion within the safe zone showed no significant difference between 2 groups ( P>0.05); the anteversion angle and limb length difference in group A were significantly greater than those in group B ( P<0.05), and the proportion of anteversion angle within the safe zone and eccentricity and recovery rate were significantly lower than those in group B ( P<0.05). In the stratification analysis, the operation time, incision length, intraoperative blood loss, transfusion rate, and VAS score at 1 day after operation in the former 30 hips were significantly higher than those in the latter 70 hips ( P<0.05). Great trochantern fracture and dislocation of the hip joint occurred in 1 and 2 of the former 30 hips, but no complications occurred in the latter 70 hips. No injury of nerve or blood vessel, deep vein thrombosis, infection, and prosthetic loosening were observed in the 2 groups. Conclusion: Compared with the Hardinge approach, the SuperPATH approach shows the advantages in little trauma, fast recovery, satisfactory effectiveness, and slight early postoperative pain, but it shows the disadvantages of much intraoperative blood loss and long operation time. In addition, SuperPATH approach needs a more anteverted angle, a smaller eccentricity, and a learning curve, so the mid-term and long-term outcomes still need further follow-up study.

[ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION IN TREATMENT OF OSTEOARTHRITIS AND ANTERIOR CRUCIATE LIGAMENT INJURY].

OBJECTIVE: To explore the short- and mid-term effectivenesses of combined unicompartmental knee arthroplasty (UKA) and anterior cruciate ligament (ACL) reconstruction for osteoarthritis (OA) and ACL injury. METHODS: Between January 2006 and January 2014, 32 patients with knee OA and ACL injury were treated by combined UKA and ACL reconstruction. There were 12 males and 20 females, aged 41-63 years (mean, 50 years); 17 left knees and 15 right knees were involved. The causes of ACL injury were sports injury (25 cases) and traffic accident injury (7 cases), including 27 cases of old injury and 5 cases of acute injury. Pain of the medial compartment of the knee and unstable knee joint were the main clinical symptoms. Preoperative X-ray films showed (3.1 ± 0.6)° of varus deformity. RESULTS: All incisions healed by first intention, without complication. The patients were followed up 16-112 months (mean, 55 months). Mobile bearing dislocation occurred in 2 cases after operation, and was cured after replacing much thicker mobile bearings. X-ray films showed (4.0 ± 0.7)° of valgus at last follow-up. There was no loosening of the prosthesis. Physiological radiolucent line (< 1 mm) was observed around the tibial component in 10 patients. The Oxford Knee Score (OKS), Knee Society Score (KSS) clinical score, KSS functional score, and Tegner activity score at last follow-up were improved significantly (P < 0.05). The range of motion (ROM) of the operated knee was (123.5 ± 2.8)°, and the posterior slope of the tibial component was (3.9 ± 1.2)° at last follow-up; a significant correlation was found between ROM and posterior slope according to the Pearson's correlation (r = 0.392, P = 0.031). CONCLUSION: Combined UKA and ACL reconstruction has good short- and mid-term effectivenesses for OA and ACL injury.