Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

High-Throughput Screening of Functional Neo-Antigens and Their Specific T-Cell Receptors via the Jurkat Reporter System Combined with Droplet Microfluidics.

T-cell receptor (TCR)-engineered T cells can precisely recognize a broad repertoire of targets derived from both intracellular and surface proteins of tumor cells. TCR-T adoptive cell therapy has shown safety and promising efficacy in solid tumor immunotherapy. However, antigen-specific functional TCR screening is time-consuming and expensive, which limits its application clinically. Here, we developed a novel integrated antigen-TCR screening platform based on droplet microfluidic technology, enabling high-throughput peptide-major histocompatibility complex (pMHC)-to-TCR paired screening with a high sensitivity and low background signal. We introduced DNA barcoding technology to label peptide antigen candidate-loaded antigen-presenting cells and Jurkat reporter cells to check the specificity of pMHC-TCR candidates. Coupled with the next-generation sequencing pipeline, interpretation of the DNA barcodes and the gene expression level of the Jurkat T-cell activation pathway provided a clear peptide-MHC-TCR recognition relationship. Our proof-of-principle study demonstrates that the platform could achieve pMHC-TCR paired high-throughput screening, which is expected to be used in the cross-reactivity and off-target high-throughput paired testing of candidate pMHC-TCRs in clinical applications.

Integrated proteome and phosphoproteome analysis of gastric adenocarcinoma reveals molecular signatures capable of stratifying patient outcome.

Metastasis is one of the main causes of low survival rate of gastric cancer patients. Exploring key proteins in the progression of gastric adenocarcinoma (GAC) may provide new candidates for prognostic biomarker development and therapeutic intervention. We applied quantitative mass spectrometry to compare the proteome and phosphoproteome of primary tumor tissues between GAC patients with and without lymph node metastasis (LNM). We then performed an integrated analysis of the proteomic and transcriptomic data to reveal the molecular features. We quantified a total of 5536 proteins, and we found 218 upregulated and 49 downregulated proteins in tumor samples from patients with LNM compared to those without LNM. Clustering analysis identified a number of hub proteins that have been previously shown to play important roles in gastric cancer progression. We also found that two extracellular proteins, TNXB and SPON1, are overexpressed in patients with LNM, which correlates with poor survival of GAC patients. Overexpression of TNXB and SPON1 was validated by western blotting and immunohistochemistry. Furthermore, treating gastric cancer cells with anti-TNXB antibody significantly reduced cell migration. Finally, quantitative phosphoproteomic analysis combined with activity-based kinase capture revealed a number of activated kinases in primary tumor tissues from patients with LNM, among which GSK3 might be a new target that warrants further study. Our study provides a snapshot of the proteome and phosphoproteome of GAC tumor tissues that have metastatic potential, and identifies potential biomarkers for GAC progression.

Species-specific rewiring of definitive endoderm developmental gene activation via endogenous retroviruses through TET1-mediated demethylation.

Transposable elements (TEs) are the major sources of lineage-specific genomic innovation and comprise nearly half of the human genome, but most of their functions remain unclear. Here, we identify that a series of endogenous retroviruses (ERVs), a TE subclass, regulate the transcriptome at the definitive endoderm stage with in vitro differentiation model from human embryonic stem cell. Notably, these ERVs perform as enhancers containing binding sites for critical transcription factors for endoderm lineage specification. Genome-wide methylation analysis shows most of these ERVs are derepressed by TET1-mediated DNA demethylation. LTR6B, a representative definitive endoderm activating ERV, contains binding sites for FOXA2 and GATA4 and governs the primate-specific expression of its neighboring developmental genes such as ERBB4 in definitive endoderm. Together, our study proposes evidence that recently evolved ERVs represent potent de novo developmental regulatory elements, which, in turn, fine-tune species-specific transcriptomes during endoderm and embryonic development.

Piwi/piRNAs control food intake by promoting neuropeptide F expression in locusts.

Animal feeding, which directly affects growth and metabolism, is an important physiological process. However, the contribution of PIWI proteins and PIWI-interacting RNAs (piRNAs) to the regulatory mechanism of animal feeding is unknown. Here, we report a novel function of Piwi and piRNAs in regulating food intake in locusts. Our study shows that the locust can serve as a representative species for determining PIWI function in insects. Knockdown of Piwi1 expression suppresses anabolic processes and reduces food consumption and body weight. The reduction in food intake by knockdown of Piwi1 expression results from decreased expression of neuropeptide NPF1 in a piRNA-dependent manner. Mechanistically, intronic piRNAs might enhance RNA splicing of NPF1 by preventing hairpin formation at the branch point sites. These results suggest a novel nuclear PIWI/piRNA-mediated mechanism that controls food intake in the locust nervous system.

Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis.

Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. Methods: We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. Results: We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells in vitro and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Conclusion: Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.

The spatial network and its driving factors for sustainable total-factor ecology efficiency: the case of China.

The interaction of regional ecological efficiency is important for promoting ecological efficiency. Using a gravity model and social network analysis, this study investigated the spatial network characteristics of the sustainable total-factor ecology efficiency (STFEcE) in 30 provinces of China from 2005 to 2016 for the first time. The quadratic assignment procedure (QAP) was also used to analyze the factors affecting the network. The results are as follows. (1) The STFEcE between regions exhibited a spatial network relationship. (2) Jiangsu, Guangdong, Shandong, Ningxia, and other provinces were in the center of the network, whereas Guangxi, Anhui, and other provinces were on the edge. (3) The 30 provinces were divided into four plates, and the connections in the network were primarily based on the relationship between plates. (4) The difference between urban population, energy structure, and technical advancement negatively impacted the network relationship. The provinces should fully understand the value of the STFEcE network and implement appropriate measures to achieve collaborative improvement of regional ecological efficiency according to their roles in the network.

Exploring the differential stages of the pigment metabolism by pre-harvest bagging and post-harvest ethylene de-greening of Eureka lemon peel.

Pre-harvest bagging or post-harvest ethylene treatments on lemons are commonly applied to change the surface color from green to favorable yellow. In this study, the differential mechanisms of the pigment metabolism by the two treatments were investigated by pigments contents and related genetic expression. The results showed that both treatments reduced the number of chloroplasts and the content of chlorophyll. The differential expression of PSY1 and PSY2 were observed, causing the different accumulation of the main carotenoid phytoene content. The differential expression of NYC resulted in altered contents of chlorophyll a and chlorophyll b, and further led to the difference in a* value. More interestingly, the degradation of chlorophyll uncovered the color of carotenoids, leading to the color changed from green to yellow.

Effects of Vertical Water Mass Segregation on Bacterial Community Structure in the Beaufort Sea.

The Arctic Ocean is one of the least well-studied marine microbial ecosystems. Its low-temperature and low-salinity conditions are expected to result in distinct bacterial communities, in comparison to lower latitude oceans. However, this is an ocean currently in flux, with climate change exerting pronounced effects on sea-ice coverage and freshwater inputs. How such changes will affect this ecosystem are poorly constrained. In this study, we characterized the bacterial community compositions at different depths in both coastal, freshwater-influenced, and pelagic, sea-ice-covered locations in the Beaufort Sea in the western Canadian Arctic Ocean. The environmental factors controlling the bacterial community composition and diversity were investigated. Alphaproteobacteria dominated the bacterial communities in samples from all depths and stations. The Pelagibacterales and Rhodobacterales groups were the predominant taxonomic representatives within the Alphaproteobacteria. Bacterial communities in coastal and offshore samples differed significantly, and vertical water mass segregation was the controlling factor of community composition among the offshore samples, regardless of the taxonomic level considered. These data provide an important baseline view of the bacterial community in this ocean system that will be of value for future studies investigating possible changes in the Arctic Ocean in response to global change and/or anthropogenic disturbance.

Water mass and depth determine the distribution and diversity of Rhodobacterales in an Arctic marine system.

Marine Rhodobacterales are recognized as a widespread, abundant, and metabolically versatile bacterial group in the world's oceans. They also show a nearly universal conservation of the genes for production of gene transfer agents (GTAs), virus-like particles that mediate genetic exchange between cells. It is not yet clear what factors determine the distribution of the various taxonomic subgroups of this order. To address this question, we analyzed the Rhodobacterales communities in 10 seawater samples from northern Baffin Bay collected during September 2008. A conserved gene from the GTA gene cluster was used to characterize the Rhodobacterales community structure. A total of 320 clones from 10 clone libraries were sequenced, and 22 operational taxonomic units representing putative species and 13 clusters representing putative genera were identified. A cluster related to Octadecabacter comprised 59% of total clones from the northern Baffin Bay. Phylogenetic analysis of the clones showed that the Rhodobacterales communities had distinct compositions in the different water masses that were sampled. A change in community structure related to depth was also observed. Therefore, in northern Baffin Bay where two ocean currents meet and mix, the Rhodobacterales community structures were primarily determined by water mass and depth.

Isolation and characterization of the heavy metal resistant bacteria CCNWRS33-2 isolated from root nodule of Lespedeza cuneata in gold mine tailings in China.

A total of 108 strains of bacteria were isolated from root nodules of wild legumes growing in gold mine tailings in northwest of China and were tested for heavy metal resistance. The results showed that the bacterial strain CCNWRS33-2 isolated from Lespedeza cuneata was highly resistant to copper, cadmium, lead and zinc. The strain had a relatively high mean specific growth rate under each heavy metal stress test and exhibited a high degree of bioaccumulation ability. The partial sequence of the copper resistance gene copA was amplified from the strain and a sequence comparison with our Cu-resistant PCR fragment showed a high homology with Cu-resistant genes from other bacteria. Phylogenetic analysis based on the 16S rRNA gene sequence showed that CCNWRS33-2 belongs to the Rhizobium-Agrobacterium branch and it had 98.9% similarity to Agrobactrium tumefaciens LMG196.

Rhizobialide: a new stearolactone produced by Mesorhizobium sp. CCNWGX022, a rhizobial endophyte from Glycyrrhiza uralensis.

The endophytic strain Mesorhizobium sp. CCNWGX022 was isolated from licorice (Glycyrrhiza uralensis Fisch.) grown in the arid and semi-arid regions of Northwest China. The new stearic acid derived gamma-lactone 1, named rhizobialide (= (5S)-4,5-dihydro-5-(8-oxotetradecyl)furan-2(3H)-one), was isolated from the petroleum-ether extract of the fermentation broth of this strain. The structure of 1 was elucidated on the basis of spectroscopic and mass-spectrometric analysis. This is the first report of this type of compound from rhizobia.