Understanding distribution and transport of carbon assimilates and photosynthesis contribution to grain yield in wheat spike is important in assessing the photosynthetic process under stress conditions. In this study, photosynthetic characteristics were evaluated in a pot experiment. Transport of spike photosynthates to grain was demonstrated using 14 C isotope tracer technique. Yield and key enzyme activities of C 3 and C 4 pathways were examined after anthesis in wheat cultivars of different drought resistance. The ear net photosynthetic rate, chlorophyll content of the spike bracts (glume, lemma, and palea), and relative water content slightly decreased under water deficit in drought resistant variety Pubing 143 (Pub) during the grain filling stage, whereas all parameters decreased significantly in drought sensitive variety Zhengyin 1 (Zhe). Grain 14 C-photosynthate distribution rate fell by 3.8% in Pub and increased by 3.9% in Zhe. After harvest, the water-use efficiency of Zhe dropped by 18.7% under water deficit. Rubisco activity in ear organs declined significantly under water deficit, whereas activity of C 4 pathway enzymes was significantly enhanced, especially that of phosphoenolpyruvate carboxylase and NADP-malate dehydrogenase. Water deficit exerted lesser influence on spike photosynthesis in Pub. Ear organs exhibited delayed senescence. Accumulation of photosynthetic carbon assimilates in ear bracts occurred mainly during the early grain filling and photosynthates were transported in the middle of grain filling. C 4 pathway enzymes seem to play an important function in ear photosynthesis. We speculate that the high enzyme activity of the C 4 pathway and the increased capacity of photosynthetic carbon assimilate transport were the reasons for the drought tolerance characteristics of ears. Additional key words:14 C-labelling; harvest index; malic enzyme; spike assimilate transport; Triticum aestivum L.

The relative importance of fallopian tube (FT) compared with ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. A collection of transcriptome data of 80 FTs, 89 OSEs, and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors. A molecular signature was developed for identifying tissue origin of SOC and then was used to reevaluate the prognostic genes and therapeutic biomarkers of SOC of different tissue origins. IHC staining of tissue array and functional experiments on a panel of ovarian cancer cell lines were used to further validate the key findings. The expression patterns of tissue-specific genes, prognostic genes, and molecular markers all support a dualistic tissue origin of SOC, from either FT or OSE. A molecular signature was established to identify the tissue identity of SOCs. Surprisingly, the signature showed a strong association with overall survival (OSE-like vs. FT-like, HR = 4.16; 95% CI, 2.67-6.48; < 10). The pharmacogenomic approach revealed AXL to be a therapeutic target of the aggressive OSE-derived SOC. SOC has two subtypes originated from either FT or OSE, which show different clinical and pathologic features. .

DNA methylation is a key epigenetic mark that is critical for gene regulation in multicellular eukaryotes. Although various human cell types may have the same genome, these cells have different methylomes. The systematic identification and characterization of methylation marks across cell types are crucial to understand the complex regulatory network for cell fate determination. In this study, we proposed an entropy-based framework termed SMART to integrate the whole genome bisulfite sequencing methylomes across 42 human tissues/cells and identified 757 887 genome segments. Nearly 75% of the segments showed uniform methylation across all cell types. From the remaining 25% of the segments, we identified cell type-specific hypo/hypermethylation marks that were specifically hypo/hypermethylated in a minority of cell types using a statistical approach and presented an atlas of the human methylation marks. Further analysis revealed that the cell type-specific hypomethylation marks were enriched through H3K27ac and transcription factor binding sites in cell type-specific manner. In particular, we observed that the cell type-specific hypomethylation marks are associated with the cell type-specific super-enhancers that drive the expression of cell identity genes. This framework provides a complementary, functional annotation of the human genome and helps to elucidate the critical features and functions of cell type-specific hypomethylation.

Torreya grandis Fort. ex Lindl. is a plant belonging to the Taxaceae family and Torreya grandis cv. Merrillii is the only grafted and thoroughbred species belonging to this species. In this study, we extracted five different seed oils, including T. grandis seed oil (TGSO), T. grandis “Xiangyafei” seed oil (XYSO), T. grandis “Zhimafei” seed oil (ZMSO), T. grandis “Majus”seed oil (TGMSO), and T. grandis “cunguangfei” seed oil (CGSO) using physical pressure. The resulting extracts were analyzed to determine their fatty acid composition, antioxidant activity, and inhibitory activity towards tyrosinase. The results of the antioxidant activity assays revealed that XYSO and ZMSO exhibited much greater DPPH radical scavenging activity and ferric reducing power than TGSO. Notably, all five of the seed oils showed dose-dependent inhibitory activity towards tyrosinase. XYSO and TGSO gave the highest activities of all of the seed oils tested in the current study against monophenolase and diphenolase, with IC50 values of 227.0 and 817.5μg/mL, respectively. The results of this study show that wild TGSOs exhibit strong antioxidant and tyrosinase inhibition activities. These results therefore suggest that wild TGSOs could be used as a potential source of natural antioxidant agents and tyrosinase inhibitors.

Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) often exhibit fatigued or inefficient upper airway dilator muscle activity. It has been shown that estrogen may have some impact on upper airway contractility under normoxic conditions. Chronic intermittent hypoxia (CIH) is a frequent feature of OSAHS, and it may alter muscle susceptibility to oxidative stress, a characteristic of a fatigable nature. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that is responsible for the regulation of oxygen homeostasis under hypoxic conditions. We examined the effects of estrogen on the contractility of the genioglossus by exposing rats to alternating cycles of 6-8% O(2) every 15 s for a total duration of 35 d. The results showed that muscle fatigue resistance was significantly decreased after CIH but was partially reversed after estrogen treatment. Compared with the control group, real-time reverse transcription-polymerase chain reaction and western blotting showed higher levels of HIF-1alpha messenger RNA and protein in the CIH group, but estrogen treatment reduced, in a dose-independent manner, the levels of HIF-1alpha messenger RNA and protein in rats exposed to CIH. We conclude that CIH induced the expression of HIF-1alpha in the genioglossus and altered the physical properties towards a more fatigable phenotype, whereas estrogen inhibited the over-expression of HIF-1alpha, and this may account for the improvement of upper airway muscle endurance in CIH rats.

High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear DNAbinding protein, functions as a potent proinflammatory factor. In this study, we evaluated the effects of HMGB1 inhibition on murine lupus using the lupusprone model. We treated male BXSB mice with neutralizing anti-HMGB1 monoclonal antibody (HMGB1 mAb) from age 16 weeks to 26 weeks. The control group received the same amount of control IgG. Lupus-prone male BXSB mice treated with HMGB1mAb showed attenuated proteinuria, glomerulonephritis, circulating anti-dsDNA and immune complex deposition. Levels of serum IL-1b, IL-6, IL-17 and IL-18 were also significantly decreased by administration of HMGB1mAb in lupus-prone BXSB mice. HMGB1mAb treatment also decreased the caspase-1 activity in the kidneys of BXSB mice and reduced the mouse mortality. Our study supports that HMGB1 inhibition alleviates lupus-like disease in BXSB mice and might be a potential treatment option for human SLE.

Yinzhihuang granules (YZHG) is a patented Chinese medicine for the treatment of hepatitis B. This study aimed to investigate the intrinsic mechanisms of YZHG in the treatment of hepatitis B and to provide new evidence and insights for its clinical application. The chemical compounds of YZHG were searched in the CNKI and PUBMED databases, and their putative targets were then predicted through a search of the SuperPred and Swiss Target Prediction databases. In addition, the targets of hepatitis B were obtained from TTD, PharmGKB and DisGeNET. The abovementioned data were visualized using Cytoscape 3.7.1, and network construction identified a total of 13 potential targets of YZHG in the treatment of hepatitis B. Molecular docking verification showed that CDK6, CDK2, TP53 and BRCA1 might be strongly correlated with hepatitis B treatment. Furthermore, GO and KEGG analyses indicated that the treatment of hepatitis B by YZHG might be related to positive regulation of transcription, positive regulation of gene expression, the hepatitis B pathway and the viral carcinogenesis pathway. Network pharmacology intuitively shows the multicomponent, multitarget and multichannel pharmacological effects of YZHG in the treatment of hepatitis B and provides a scientific basis for its mechanism of action. The cause of hepatitis B is hepatitis B virus (HBV), which is a double-stranded, circular, incompletely closed DNA virus 1-3. Antiviral therapy involving pegylated interferon or nucleoside analogs (lamivudine, adefovir, entecavir, tenofovir disoproxil, or tenofovir alafenamide) is currently provided clinically to patients with hepatitis B to inhibit HBV DNA replication and improve liver inflammation and fibrosis 4,5 , but this treatment protocol requires patients to be treated indefinitely and has a relatively low cure rate. Researchers are constantly searching for more effective drugs. In addition, the long-term use of nucleos(t)ide analogs (NAs) might lead to drug resistance and renal damage and cannot reverse liver fibrosis. Therefore, an increasing number of people have begun to focus on Chinese herbal medicines and seek safer and more cost-effective supplementary drugs for hepatitis B 6-8. Chinese herbal medicines have a long history of use in China. In recent years, researchers have continuously found effective pharmaceutical ingredients and targets for the treatment of diseases from Chinese herbal medicines. These results show that Chinese herbal medicines constitute extremely rich resources, and the discovery of new medicine sources from Chinese herbal medicine is becoming a major method of drug development. Yinzhihuang granules (YZHG) can clear away heat and toxic materials, promote diuresis and eliminate jaundice. The prescription is composed of "Yinchenhao Decoction" (Han, Zhongjing Zhang, "Treatise on Febrile Diseases") and "Huanglianjiedu Decoction" (Tang, Tao Wang, "Essential Secrets from Outside the Metropolis"). The YZHG

compound Kushen injection (cKi), a medicine in widespread clinical use in china, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment. Esophageal cancer (ESCA) is widespread worldwide. According to Global Cancer Statistics 2018, it ranks seventh in incidence and sixth in mortality 1. The 5-year survival rate of ESCA is between 12 and 20% and differs substantially by sex 2. China is a high-risk area for ESCA, especially in some rural areas, where the incidence rate far exceeds that of urban areas due to lifestyle and environmental reasons 3. ESCA can be divided into esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) according to histological classification. In recent decades, the incidence of EAC in Western countries has increased several times, and the proportion of ESCC has exceeded 90% throughout China 4,5. The introduction of chemo(radio)therapy and surgical therapy led to increased survival rates and reduced the incidence of recurrence 6. Because conventional methods do not adequately improve patient survival of ESCA, however, scientists are seeking more effective treatments. Recently, traditional Chinese medicine (TCM) has taken the world stage as complementary and alternative medicine 7. Compound Kushen Injection (CKI) consists of two herbs, Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Smilacis Glabrae). CKI mainly contains various anticancer ingredients, such as matrine and oxymatrine, which can inhibit the growth of tumour cells, overcome resistance to metastasis and multidrug resistance, and protect human immunity 8. CKI has been utilized in clinical practice for decades to treat various solid tumour types, including liver cancer, breast cancer, gastric cancer, and other cancer types 8,9. The analysis of medical data on 2,550 ESCA patients from 22 large-scale hospitals in China confirmed that CKI has been ...