Direct synthesis of phthalimides via palladium-catalysed double carbonylation of o-dihaloarenes with nitroarenes.

The direct carbonylation of readily available nitro compounds is more attractive and straightforward than the use of traditional amines as nucleophiles. Herein, a practical palladium-catalysed double carbonylation of nitroarenes with o-dihaloarenes has been developed for the construction of various N-aryl phthalimides. Key to the success of this transformation is the use of Mo(CO)6, which acts as both a reducing agent and a solid carbonyl source. A wide range of nitroarenes and o-dihaloarenes as well as o-iodobenzoic acids reacted smoothly to give phthalimides in 27-94% yields.

Preparation and evaluation of sustained release pirfenidone-loaded microsphere dry powder inhalation for treatment of idiopathic pulmonary fibrosis.

Pirfenidone (PFND) is a recommended oral drug used to treat idiopathic pulmonary fibrosis, but have low bioavailability and high hepatotoxicity. The study, therefore, seeks to improve the therapeutic activities of the drug via increased bioavailability and reduced associated side effects by developing a novel drug delivery system. The electrostatic spray technology was used to prepare a sustained release pirfenidone-loaded microsphere dry powder inhalation with PEG-modified chitosan (PFND-mPEG-CS-MS). The entrapment efficiency, drug loading, and in vitro cumulative drug release rate (at 24 h and with a sustained release effect) of PFND-mPEG-CS-MS were 77.35±3.01%, 11.45±0.64%, and 90.4%, respectively. The Carr's index of PFND-mPEG-CS-MS powder was 17.074±2.163% with a theoretical mass median aerodynamic diameter (MMADt) of 0.99±0.07 µm, and a moisture absorption weight gain rate (Rw) of 4.61±0.72%. The emptying rate, pulmonary deposition rate (fine particle fraction) and actual mass median aerodynamic diameter (MMADa) were 90%∼95%, 48.72±7.04% and 3.10±0.16 µm, respectively. MTT bioassay showed that mPEG-CS-MS (200 µg/mL) had good biocompatibility (RGR = 90.25%) and PFND-mPEG-CS-MS (200 µg/mL) had significant inhibitory activity (RGR = 49.82%) on fibroblast growth. The pharmacokinetic data revealed that the t1/2 (5.02 h) and MRT (10.66 h) of PFND-mPEG-CS-MS were prolonged compared with the free PFND (t1/2, 1.67 h; MRT, 2.71 h). The pharmacodynamic results also showed that the formulated-drug group had slight pathological changes, lower lung hydroxyproline content, and reduced hepatotoxicity compared with the free-drug group. The PFND-mPEG-CS-MS further significantly down-regulated TGF-ß cytokines, Collagen I, and α-SMA protein expression levels compared with the free drug. The findings indicated that the PFND-mPEG-CS-MS had a good sustained release effect, enhanced bioavailability, decreased toxicity, and increased anti-fibrotic activities.

Revealing the coexistence of differentiation and communication in an endemic hare, Lepus yarkandensis (Mammalia, Leporidae) using specific-length amplified fragment sequencing.

BACKGROUND: The Yarkand hare (Lepus yarkandensis Günther, 1875) is endemic to oasis and desert areas around the Tarim Basin in the Xinjiang Uyghur Autonomous Region of northwest China; however, genome-wide information for this species remains limited. Moreover, the genetic variation, genetic structure, and phylogenetic relationships of Yarkand hare from the plateau mountain regions have not been reported. Thus, we used specific-length amplified fragment sequencing (SLAF-seq) technology to evaluate the genetic diversity of 76 Yarkand hares from seven geographic populations in the northern and southwestern parts of the Tarim Basin to investigate single-nucleotide polymorphism (SNP) marker-based population differentiation and evolutionary processes. Selective sweep analysis was conducted to identify genetic differences between populations. RESULTS: Using SLAF-seq, a total of 1,835,504 SNPs were initially obtained, of which 308,942 high-confidence SNPs were selected for further analysis. Yarkand hares exhibited a relatively high degree of genetic diversity at the SNP level. Based on pairwise FST estimates, the north and southwest groups showed a moderate level of genetic differentiation. Phylogenetic tree and population structure analyses demonstrated evident systematic phylogeographical structure patterns consistent with the geographical distribution of the hares. Hierarchical analysis of molecular variation further indicated that genetic variation was mainly observed within populations. Low to moderate genetic differentiation also occurred among populations despite a common genomic background, likely due to geographical barriers, genetic drift, and differential selection pressure of distinct environments. Nevertheless, the observed lineage-mixing pattern, as indicated by the evolutionary tree, principal component analysis, population structure, and TreeMix analyses, suggests a certain degree of gene flow between the north and southwest groups. This may be related to the migration of hares to high-altitude water sources southwest of the basin during glacial climatic oscillations, as well as river re-diffusion and oasis restoration in the basin following the glacial period. We also identified candidate genes, and their associated gene ontology terms and pathways, related to the adaptation of Yarkand hares to different environmental habitats. CONCLUSIONS: The identified genome-wide SNPs, genetic diversity, and population structure of Yarkand hares expand our understanding of the genetic background of this endemic species and provide valuable insights into its environmental adaptation, allowing for further exploration of the underlying mechanisms.

Complete mitochondrial genome sequence of Lepus yarkandensis Günther, 1875 (Lagomorpha, Leporidae): characterization and phylogenetic analysis.

Lepus yarkandensis is a national second-class protected animal endemic to China and distributed only in the hot and arid Tarim Basin in Xinjiang. We sequenced and described the complete mitogenome of L. yarkandensis to analyze its characteristics and phylogeny. The species' DNA is a 17,047 bp circular molecule that includes 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and one control region. The overall base composition was as follows: A, 31.50%; T, 29.40%; G, 13.30% and C, 25.80%, with a high A+T bias of 60.9%. In the PCGs, ND6 had deviation ranges for AT skew (-0.303) and GC skew (0.636). The Ka/Ks values of ND1 (1.067) and ND6 (1.352) genes were >1, indicating positive selection, which might play an important role in the adaptation of L. yarkandensis to arid and hot environments. The conserved sequence block, the central conserved domain, and the extended termination-associated sequences of the control region and their features were identified and described. The phylogenetic tree based on the complete mitogenome showed that L. yarkandensis was closely related to the sympatric Lepus tibetanus pamirensis. These novel datasets of L. yarkandensis can supply basic data for phylogenetic studies of Lepus spp., apart from providing essential and important resource for further genetic research and the protection of this species.

LIF in embryo culture medium is a predictive marker for clinical pregnancy following IVF-ET of patients with fallopian tube obstruction.

Leukemia inhibitory factor (LIF) has played a vital role in a series of reproductive events, including follicle growth, embryo growth and differentiation. However, it is unclear whether the level of LIF in embryo culture medium can be used as a marker for clinical pregnancy. In this study, we aimed to investigate whether LIF level in embryo culture medium can act as a predictive marker for pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET) in infertile women due to tubal problems. A total of 208 infertile women due to tubal problems underwent IVF-ET treatment. The women were divided into two groups according to whether they were clinically pregnant. The level of LIF in the embryo culture medium was measured, and the correlation between LIF level and embryo quality and clinical pregnancy outcome was analyzed. The embryo culture medium was collected on the day of blastocyst transplantation. Compared to non-pregnant group, LIF level in the embryo culture medium on the day of blastocyst transplantation was significantly higher in the pregnant group. LIF level in the embryo culture medium may be used as a non-invasive auxiliary biomarker for predictive clinical pregnancy in infertile women with tubal problems that using single blastocyst transfer method.

Body mass index (BMI) is associated with serum thyroid-stimulating hormone (TSH) level in infertile women: a cross-sectional study.

Studies suggest that there is a relationship between body mass index (BMI) and thyroid-stimulating hormone (TSH) levels. But conflicting evidence exists regarding the relationship between the two variables. Moreover, thyroid function is closely related to female fertility and has certain effects on infertility. Therefore, the present study will explore the relationship between BMI and TSH levels in patients with infertility in our center. We retrospectively analyzed relevant indicators of 2,789 in Tubal Factor Infertility patients undergoing assisted reproduction technology from January 2016 to December 2018 in our center in order to analyze the relationship between BMI and serum TSH level. The medical histories of patients were reviewed. The relationship between BMI and TSH was assessed using smooth curve fitting and multivariate regression model. The smoothing curve fitting between BMI and TSH exhibited a non-linear relationship, and the resulting curve exhibited a two-stage change and a breakpoint. By multivariate piecewise linear regression, we found that the TSH level was increased with the increase of BMI when the BMI was greater than 25.3 kg/m2 (ß 0.06, 95% CI 0.02, 0.01; p = 0.0028). In contrast, the TSH level was decreased with the increase of BMI when the BMI was less than 25.3 kg/m2 (ß -0.02, 95% CI -0.05, 0.00; p = 0.0573). Collectively, our study described a non-linear relationship between BMI and TSH level in infertile patients after adjustment of potential confounders. However, such causal relationship between BMI and TSH in infertile women still needs to be further clarified in future investigations.