Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Abstract To select the optimal condition of 1064 nm Q-switched Nd:YAG laser irradiation and study the molecular mechanism of laser irradiation for skin rejuvenation. Sixty male, 6-week-old SKH-1 hairless mice were equally divided into 6 groups: 3d, 7d, 21d, 28d, 42d and 56d of 1064 nm laser irradiation at both 0 J/cm2 (left region) and 1.5 J/cm2 (right region) fluence. The basic skin performances were analysed via quantifying hydroxyproline content and skin hydration in the dermis and epidermis. The Collagen I, MMP2 and TIMP1, as well as ERK 1/2, p38MAPK, JNK and ERK5 signaling pathways levels were detected by qRT-PCR. Laser irradiation led to a marked increase in hydroxyproline content and skin hydration in the dermis and epidermis compared to the non-irradiated area. After laser irradiation, collagen I was markedly up-regulated, MMP2 was significantly decreased and TIMP1 was unchanged. Moreover, qRT-PCR results revealed ERK 1/2 and p38MAPK signaling pathways were activated after laser irradiation. we are firstly proves that 1064 nm laser irradiation can inhibit collagen degradation by stimulating the activation of ERK1/2 and p38MAPK signaling pathways. Additionally, the condition of laser irradiation lasting 21d at fluence of 1.5 J/cm2 displays the best effect of skin rejuvenation in our study.

ABSTRACT Target of rapamycin (TOR) is a very critical protein in plants, which connects with biological process, glycometabolism, life span, and photosynthesis. Here, the evolutionary relationship, conserved motif, gene structure and cis-acting elements of TOR were analyzed. Promoter cis-acting elements analysis indicated various cis-acting elements respond to light, auxin, ABA and multiple signal pathway. Transcriptome sequencing and the co-expression network of VvTOR, sugar and abscisic acid (ABA) related genes from Vitis vinifera L. Cabernet Sauvignon berries indicated that VvTOR might participate in sugar and ABA signaling. The expression of VvTOR in grape suspension cells analyzed by quantitative real-time PCR showed that VvTOR responded to ABA and glucose treatment. These results predicted the potential functions of VvTOR in glucose metabolism and ABA signal pathway.

Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Soil chemical and topographic properties are two important factors influencing available micronutrient distribution of soil in the horizontal dimension. The objective of this study was to explore the relative influence of soil chemistry (including soil pH, soil organic matter, total nitrogen, available phosphorus, and available potassium) and topography (including elevation, slope, aspect, and wetness index) on the availability of micronutrients (Fe, Mn, Cu, Zn, and B) using structural equation modeling (SEM) at the watershed scale. To do this, levels of soil micronutrients, pH, soil organic matter, total nitrogen, available phosphorus, available potassium, and topographic factors were measured at 523 sampling points of Fanshi County on the Chinese Loess Plateau, and the spatial distribution of soil available micronutrients were analyzed by geostatistical method. The results showed that topography had both direct effects and indirect effect on some soil micronutrients, while the indirect effect indicated effects from topography on soil chemistry and then further on micronutrient concentration. Soil chemistry had direct effects on levels of all soil micronutrients, and topography had direct effects on levels of all micronutrients except for Cu and B, and indirect effects on Fe, Zn, and B. The direct effect of soil chemistry on Fe levels was greater than the total effects (including both direct and indirect) of topography. Topography had a stronger direct effect on Mn than soil chemistry, and topography had less direct but stronger total effects on Zn than soil chemistry. Soil chemistry directly influenced both Cu and B, but topography only influenced B in an indirect manner. The semivariance indicated that the micronutrients had moderate spatial dependency except for B which had weak spatial dependency. Within the spatial distribution of the micronutrients, there was a zone in the middle of the watershed with lower values than in the northern and southern areas for Fe, Mn, Zn, and B, which were related to the characteristics of topography and soil chemistry. These results may guide the management of soil micronutrients of the Chinese Loess Plateau and other similar regions in the world.