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The programmed cell death 1 (PD-1) immune checkpoint of co-inhibitory signaling plays crucial roles in controlling the magnitude and duration of T cell activation to limit tissue damage and maintain self-tolerance. Cancer cells hijack the co-inhibitory pathway and escape immune surveillance by overexpressing the PD-1 ligand PD-L1. Immune checkpoint inhibitors, such as PD-1 blocking antibody have been approved for tumor immunotherapy. However, not all patients can benefit from PD-1 monotherapy. Combination immunotherapy based on PD-1 axis blockade substantially improves clinical anti-tumor efficacy. In this review, we briefly summarize the current progress on the mechanisms of PD-1-mediated inhibition of T cell activation and strategies for cancer combination immunotherapy.

Premature ovarian insufficiency is a multi-factor gynecological disease that has become a major global health problem. In recent years, several trials have explored the treatment of premature ovarian insufficiency using Chinese herbal medicine and acupuncture, but the efficacy and safety of this combination remains controversial. This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of combining Chinese herbal medicine with acupuncture to treat premature ovarian insufficiency. From eight different databases, we retrieved randomized controlled trials wherein Chinese herbal medicine and acupuncture had been compared with western medicine in the treatment of premature ovarian insufficiency. The bias risk assessment stipulated by the Cochrane Collaboration's tool was utilized to evaluate the quality of the chosen randomized controlled trials. This meta-analysis was executed with the help of Review Manager 5.3 and Stata 10.0. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A total of 10 randomized controlled trials involving 594 premature ovarian insufficiency patients were included in the analysis. Compared with western medicine, co-treatment with acupuncture and Chinese herbal medicine exhibited a significantly higher total effective rate (relative risk: 1.21; 95% confidence interval: 1.12–1.31; P

Aims: Shenghua Decoction (SHD) is a well-known classic herbal formula documented in traditional Chinese medicine (TCM) that has been widely applied during the postpartum period in Chinese communities for several years. We conducted this systematic review and meta-analysis to explore the influence of SHD as an adjuvant treatment for early medical abortion using a combination of mifepristone followed by misoprostol. Methods: This systematic review and meta-analysis was reported using 2020 PRISMA guidelines. Eight databases were searched from their establishment to February 28, 2022, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, the Chinese BioMedical database, the Chinese Scientific Journal Database, and the Wanfang database. The Grading of Recommendations Assessment, Development, and Evaluation estimated the quality of evidence. Results: Sixteen RCTs involving 3016 patients were included in the meta-analysis. Overall, compared with no treatment as the control group after early medical abortion, patients treated with SHD were associated with a higher complete abortion rate (RR: 1.14; 95% CI: 1.10 – 1.18; P

Calcineurin (Cn or CaN) is implicated in the control of skeletal muscle fiber phenotype and hypertrophy. However, little information is available concerning the expression of Cn in chickens. In the present study, the expression of two Cn subunit genes (CnAα and CnB1) was quantified by qPCR in the lateral gastrocnemius (LG, mainly composing of red fast-twitch myofibers), the soleus (mainly composing of red slow-twitch myofibers) and the extensor digitorum longus (EDL, mainly composing of white fast-twitch myofibers) from Qingyuan partridge chickens (QY, slow-growing chicken breed) and Recessive White chickens (RW, fast-growing chicken breed) on different days (1, 8, 22, 36, 50 and 64 days post-hatching). Although CnAα and CnB1 gene expressions were variable with different trends in different skeletal muscles in the two chicken breeds during postnatal growth, it is highly muscle phenotype and breed specific. In general, the levels of CnAα and CnB1 gene expressions of the soleus were lower than those of EDL and LG in both chicken breeds at the same stages. Compared between the two chicken breeds, the levels of CnAα gene expression of the three skeletal muscles in QY chickens were higher than those in RW chickens on days 1 and 22. However, on day 64, the levels of both CnAα and CnB1 gene expressions of the three skeletal muscles were lower in QY chickens than those in RW chickens. Correlation analysis of the levels of CnAα and CnB1 gene expressions of the same skeletal muscle showed that there were positive correlations for all three skeletal muscle tissues in two chicken breeds. These results provide some valuable clues to understand the role of Cn in the development of chicken skeletal muscles, with a function that may be related to meat quality.

Abstract: Little is known about the muscle developmental patterns during embryonic to neonatal development in ducks. We investigated the developmental patterns in the lateral gastrocnemius muscles of Gaoyou and Jinding ducks differing in their muscle growth rates during the final stages of egg incubation and the first week after hatching. Expression of the MyoD gene was quantified by quantitative real-time PCR (qRT-PCR). The average cross-sectional area and diameter of the fibers increased from embryonic day 21 (E21), peaking at E27, and then declining slightly 7 d after hatching. The density of the fibers decreased initially but increased after hatching in both breeds and sexes. The within-breed variation in muscle fiber-type composition was greater than the average variation between the breeds. Overall, the percentage of type I fibers increased and that of type IIb fibers decreased consistently. However, the percentage of type IIa fibers was almost constant as development proceeded in both duck breeds. The profiles of MyoD mRNA expression were similar in both breeds, and a significantly positive relationship was observed between the expression of MyoD and the percentage of type IIb fibers. This study firstly revealed the characteristics of duck muscle development and differences between the two breeds differing in growth rates. Moreover, type IIb fibers might convert to type I fibers in the lateral gastrocnemius, while MyoD may potentially function in controlling the muscle fiber phenotype during the secondary myogenesis of muscle development.

Summary: RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases.

The uneven distribution of solar radiation is one of the main reasons for the variations in the yield gap between different regions in China and other countries of the world. In this study, different solar radiation levels were created by shading and the yield gaps induced by those levels were analyzed by measuring the aboveground and underground growth of maize. The experiments were conducted in Qitai, Xinjiang, China, in 2018 and 2019. The maize cultivars Xianyu 335 (XY335) and Zhengdan 958 (ZD958) were used with planting density of 12×104 plants ha–1 under either high solar radiation (HSR) or low solar radiation (LSR, 70% of HSR). The results showed that variation in the solar radiation resulted in a yield gap and different cultivars behaved differently. The yield gaps of XY335 and ZD958 were 8.9 and 5.8 t ha–1 induced by the decreased total intercepted photosynthetically active radiation (TIPAR) of 323.1 and 403.9 MJ m-2 from emergence to the maturity stage, respectively. The average yield of XY335 was higher than that of ZD958 under HSR, while the average yield of ZD958 was higher than that of XY335 under LSR. The light intercepted by the canopy and the photosynthetic rates both decreased with decreasing solar radiation. The aboveground dry matter decreased by 11.1% at silking and 21% at maturity, and the dry matter of vegetative organs and reproductive organs decreased by 9.8 and 20.9% at silking and by 12.1 and 25.5% at physiological maturity, respectively. Compared to the HSR, the root weights of XY335 and ZD958 decreased by 54.6 and 45.5%, respectively, in the 0–60 cm soil layer under LSR at silking stage. The aboveground and underground growth responses to different solar radiation levels explained the difference in yield gap. Selecting suitable cultivars can increase maize yield and reduce the yield gaps induced by variation of the solar radiation levels in different regions or under climate change.