1-Methyl-3-trifluoro­methyl-1H-pyrazol-5-ol

In the title compound, C5H5F3N2O, the F atoms are disordered over two sets of sites in a 0.64 (3):0.36 (3) ratio. In the crystal structure, O—H⋯N hydrogen bonds link the mol­ecules into chains and a short C—H⋯F contact also occurs

Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA

Long-term survival with a combination of immunotherapy, anti-angiogenesis, and traditional radiotherapy in brain metastatic small cell lung cancer: a case report

PurposeBrain metastases (BMs) are common in Small Cell Lung Cancer (SCLC), but the prognosis is very poor. Currently, there is no standard of care on what constitutes optimal treatment, and there is no consensus regarding maintenance therapy in SCLC.Case descriptionWe report the case of a 55-year-old man with advanced SCLC. After the initial diagnosis, he received routine chemotherapy and chest radiotherapy but developed brain metastases with 2 lesions seven months later. We used an effective combination therapy consisting of the antiangiogenic inhibitor, Anlotinib and whole-brain radiotherapy. We then administered anti-PD-L1 immunotherapy Atezolizumab in combination with Anlotinib as long-term maintenance therapy. Twelve months later, there was a progression in one of the brain metastases. The patient underwent further stereotactic radiotherapy (SRT) for the lesion. However, after four months of treatment with SRT, the lesion began to gradually grow in size. The patient underwent surgical resection of the lesion, which confirmed radioactive brain necrosis. After a full 3-year course of anti-PD-L1 therapy, the patient discontinued immunotherapy and was administered only Anlotinib as maintenance. At the time of writing up this report, the patient was alive and the overall survival reached 41 months after the onset of BM.ConclusionThis indicated a potential synergistic effect of combined immunotherapy and antiangiogenic targeted therapy with local radiotherapy in patients with BM-SCLC and can provide directions for future clinical decisions

6-Amino-3-methyl-4-(4-nitro­phen­yl)-1-phenyl­pyrazolo[3,4-b]pyridine-5-carbonitrile

The title compound, C20H14N6O2, contains four rings. The dihedral angle between the pyridine ring and the pyrazole ring is 1.9 (1)°, i.e. almost coplanar, which gives rise to a conjugated structure. The dihedral angle between the nitro-substituted phenyl ring and the pyridine ring is 76.3 (1)° and that between the pyrazole ring and the non-substituted phenyl ring is 40.5 (1)°. In the crystal structure, symmetry-related mol­ecules are linked by N—H⋯O and C—H⋯N hydrogen bonds

Photometric observations of flares on AD Leo from GWAC-F30 and TESS

We observed active M dwarf star AD Leo for 146 hr in photometry by GWAC-F30 and also analyzed 528-hr photometric data of the star from TESS. A total of 9 and 70 flares are detected from GWAC-F30 and TESS, respectively. Flare durations, amplitudes and energies are calculated. The distributions of the three properties and FFDs are given. Within the same energy range of flares, the FFDs of AD Leo obtained in this research and the previous study are basically consistent, which suggests that the magnetic activity of this star has not significantly changed compared to that decades ago. Comparing with the average FFD of M-type stars, AD Leo's FFD is twice higher, indicating that its magnetic activity is more active than that of the average level of the M-type. Based on TESS light curve, AD Leo's rotation period is calculated as 2.21${+0.01 \choose -0.01}$ day , supporting the result given in previous research. During the decay phase of the most energetic flare from TESS, we identified QPPs and determined a 26.5-min oscillation period, which is currently the longest period for AD Leo, suggesting that long periodic physical process existed during flare of this star

Ring structure amino acids affect the suppressor activity of melon aphid-borne yellows virus P0 protein

AbstractMelon aphid-borne yellows virus (MABYV) is a newly identified polerovirus occurring in China. Here, we demonstrate that the MABYV encoded P0 (P0MA) protein is a strong suppressor of post-transcriptional gene silencing (PTGS) with activity comparable to tobacco etch virus (TEV) HC-Pro. In addition we have shown that the LP F-box motif present at the N-terminus of P0MA is required for suppressor activity. Detailed mutational analyses on P0MA revealed that changing the conserved Trp 212 with non-ring structured amino acids altered silencing suppressor functions. Ala substitutions at positions 12 and 211 for Phe had no effect on P0 suppression-activity, whereas Arg and Glu substitutions had greatly decreased suppressor activity. Furthermore, substitutions targeting Phe at position 30 also resulted in reduced P0 suppression-activity. Altogether, these results suggest that ring structured Trp/Phe residues in P0 have important roles in suppressor activity

Alendronate versus Raloxifene for Postmenopausal Women: A Meta-Analysis of Seven Head-to-Head Randomized Controlled Trials

Purpose. The aim of this study was to directly compare the efficacy and the safety of the two agents for postmenopausal women. Methods/Principal Findings. Electronic databases were searched for relevant articles that met our predefined inclusion criteria. Seven randomized controlled trials (RCTs) involving 4054 women were identified and included. Although Aln was more effective than Rlx in increasing bone mineral density (BMD), no statistical differences were observed in reducing the risk of neither vertebral fractures (P=0.45) nor nonvertebral fractures (P=0.87) up to two-year followup. Aln reduced the risk of vasomotor (P=0.006) but increased the risk of diarrhea compared to Rlx (P=0.01). Our subgroup analysis further indicated the difference between Aln and Rlx in fracture risk and was not materially altered by the administration pattern, the age. The weekly strategy of Aln would further reduce the upper gastrointestinal (GI) disorders and might gain more bone mass increment at lumbar spine compared to its daily treatment. Conclusion. There was no evidence of difference of fracture risk reduction between Aln and Rlx. In addition, age did not obviously influence their relative antifracture efficacy. For Aln the weekly strategy would further reduce the upper GI disorders and gain more bone mass increment compared to the daily treatment. During clinical decision making, the patients’ adherence and the related side-effects associated with both drugs should also be taken into account