Review and prospect of immune checkpoint blockade therapy represented by PD-1/PD-L1 in the treatment of clear cell renal cell carcinoma.

As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma, accounting for approximately 75% of the total number of patients with renal cell carcinoma. Currently, the clinical treatment of ccRCC involves targeted therapy, immunotherapy, and a combination of the two. In immunotherapy, PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment. However, as treatment progresses, some patients gradually develop resistance to immunotherapy. Meanwhile, other patients experience great side effects after immunotherapy, resulting in a survival status far lower than the expected survival rate. Based on these clinical problems, many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results. We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.

Identification and functional characterization of AcMYB113 in anthocyanin metabolism of Aesculus chinensis Bunge var. chinensis leaves.

Anthocyanins can be induced by environmental factors such as low-temperature and play essential roles in plant color formation. In this study, leaves of Aesculus chinensis Bunge var. chinensis with different colors under natural low-temperature in autumn were collected and grouped into green leaf (GL) and red leaf (RL). To reveal the underlying mechanism of color formation in RL, a combined analysis of the metabolome and transcriptome was conducted with GL and RL. Metabolic analyses revealed that total anthocyanin content and primary anthocyanin components were increased RL relative to GL and cyanidin was the main anthocyanin compound in RL. Transcriptome analysis provided a total of 18720 differentially expressed genes (DEGs), of which 9150 DEGs were upregulated and 9570 DEGs were downregulated in RL relative to GL. KEGG analysis showed that DEGs were mainly enriched in flavonoid biosynthesis, phenylalanine metabolism, and phenylpropanoid biosynthesis. Furthermore, co-expression network analysis indicated that 56 AcMYB transcription factors were highly expressed in RL compared with GL, among which AcMYB113 (an R2R3-MYB TF) had a strong correlation with anthocyanins. Overexpression of AcMYB113 in apple resulted in dark-purple transgenic calluses. In addition, the transient expression experiment showed that AcMYB113 enhanced anthocyanin synthesis by activating pathways of anthocyanin biosynthesis in leaves of Aesculus chinensis Bunge var. chinensis. Taken together, our findings reveal new insights into the molecular mechanism of anthocyanin accumulation in RL and provide candidate genes for the breeding of anthocyanin-rich cultivars.

Analyzing the Treatment of Patients with Acute Exacerbation of COPD with the Aid of Intelligent Diagnosis Method.

To observe the clinical efficacy of heat clearing phlegm mixture combined with vibration sputum excretion instrument in the treatment of patients with acute exacerbation of COPD with phlegm-heat obstructing lung, 90 patients with acute exacerbation of COPD are selected and divided into three groups, namely, control group, traditional medicine group, and combined group: the control group (conventional western medicine treatment), traditional medicine group (heat clearing and phlegm mixture), and combined group (heat clearing and phlegm mixture + vibratory sputum excretion instrument) with 30 cases each. All the patients in the three groups were given conventional western medicine treatment. On this basis, the traditional medicine group was given the oral administration of the heat-clearing and phlegm-clearing mixture, and the combined group was given the oral administration of the heat-clearing and phlegm-clearing mixture and the vibratory sputum discharge apparatus. Machine learning is used to classify the patients into three groups based on the characteristics of their biomarkers, physical attributes, and medical history. The TCM syndrome score, blood gas analysis, lung function, and inflammatory indexes of the three groups were compared. TCM syndrome scores of the three groups were all lower than before; both the combined group and the TCM group were better than the control group (P < 0.05). Although the improvement degree of the combined group was better than that of the TCM group, the difference was not statistically significant (P > 0.05). TCM syndrome effect is seen to be 96.55% in the combined group, 89.29% in the TCM group, and 63.33% in the control group. Blood gas analysis is also performed; PO2 and PCO2 of the three groups were significantly improved after treatment. The combination group was superior to the traditional medicine group and the control group (P < 0.05), and the traditional medicine group was superior to the control group (P < 0.05). It is concluded that the combination of heat clearing phlegm mixture and vibration sputum excretion instrument can improve TCM syndrome score, CAT score, blood gas analysis, lung function, and inflammatory indicators in patients with acute exacerbation of COPD with phlegm-heat obstructing lung.

Expression of FKBP52 in the ovaries of PCOS rats.

The present study aimed to examine the expression of FK­506 binding protein 52 (FKBP52) in the ovary tissues of rats with polycystic ovarian syndrome (PCOS) and its action on mediating androgen receptor (AR) through the mitogen­activated protein kinase (MAPK)/extracellular signal­regulated kinase (ERK) pathway. PCOS model rats were established by dehydroepiandrosterone injection. Enzyme­linked immunosorbent assay (ELISA) measured serum sex hormones. Hematoxylin and eosin (H&E) staining was used to examine histological changes of the ovarian tissues. The expression levels of FKBP52 were detected by immunohistochemical (IHC) staining, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis and western blotting (WB). In addition, RT­qPCR analysis was used to detect the mRNA expression of AR, and WB was used to detect the protein expression levels of AR, ERK1/2 and phosphorylated (p­)ERK1/2. In granulosa cell (GC) experiments, primary GCs were extracted and cultured. FKBP4 is the FKBP52­encoding gene, therefore, adenovirus vectors Ad­Oe­FKBP4­EGFP and Ad­siRNA­FKBP4­EGFP were constructed to examine the association among the above factors using the RT­qPCR and WB methods. In the animal experiment, the vaginal smear, H&E staining and ELISA results showed that the PCOS model was successfully established. The IHC staining revealed that the expression of FKBP52 in the GCs of the PCOS model group was higher than the remaining groups (P<0.01). The mRNA and expression levels of FKBP52 and AR in the PCOS model rats were significantly increased, when compared with levels in the other rats (P<0.05). The expression level of p­ERK1/2 was also higher (P<0.05). In the GC experiment, following overexpression of the FKBP4 gene, the mRNA and expression levels of FKBP52 and AR were increased (P<0.05). The expression level of p­ERK1/2 was also increased (P<0.05). Following FKBP4 gene silencing, the mRNA and expression levels of FKBP52 and AR were decreased (P<0.05). The expression level of ERK1/2 was also decreased (P<0.05). However, the expression level of p­ERK1/2 was increased (P<0.05). In conclusion, the upregulation of co­chaperone FKBP52 may mediate the activation of AR through the MAPK/ERK pathway.

Indium-doped ZnO nanowires with infrequent growth orientation, rough surfaces and low-density surface traps.

Indium-doped ZnO nanowires have been prepared by vapor transport deposition. With increasing In content, the growth orientation of the nanowires switches from [101_0] to infrequent [022_3] and the surface becomes rough. No surface-related exciton emission is observed in these nanowires. The results indicate that large surface-to-volume ratio, high free electron concentration, and low density of surface traps can be achieved simultaneously in ZnO nanowires via In doping. These unique properties make In-doped ZnO nanowire a potential material for photocatalysis application, which is demonstrated by the enhanced photocatalytic degradation of Rhodamine B.