Exogenous betaine enhances salt tolerance of Glycyrrhiza uralensis through multiple pathways.

BACKGROUND: Glycyrrhiza uralensis Fisch., a valuable medicinal plant, shows contrasting salt tolerance between seedlings and perennial individuals, and salt tolerance at seedling stage is very weak. Understanding this difference is crucial for optimizing cultivation practices and maximizing the plant's economic potential. Salt stress resistance at the seedling stage is the key to the cultivation of the plant using salinized land. This study investigated the physiological mechanism of the application of glycine betaine (0, 10, 20, 40, 80 mM) to seedling stages of G. uralensis under salt stress (160 mM NaCl). RESULTS: G. uralensis seedlings' growth was severely inhibited under NaCl stress conditions, but the addition of GB effectively mitigated its effects, with 20 mM GB had showing most significant alleviating effect. The application of 20 mM GB under NaCl stress conditions significantly increased total root length (80.38%), total root surface area (93.28%), and total root volume (175.61%), and significantly increased the GB content in its roots, stems, and leaves by 36.88%, 107.05%, and 21.63%, respectively. The activity of betaine aldehyde dehydrogenase 2 (BADH2) was increased by 74.10%, 249.38%, and 150.60%, respectively. The 20 mM GB-addition treatment significantly increased content of osmoregulatory substances (the contents of soluble protein, soluble sugar and proline increased by 7.05%, 70.52% and 661.06% in roots, and also increased by 30.74%, 47.11% and 26.88% in leaves, respectively.). Furthermore, it markedly enhanced the activity of antioxidant enzymes and the content of antioxidants (SOD, CAT, POD, APX and activities and ASA contents were elevated by 59.55%, 413.07%, 225.91%, 300.00% and 73.33% in the root, and increased by 877.51%, 359.89%, 199.15%, 144.35%, and 108.11% in leaves, respectively.), and obviously promoted salt secretion capacity of the leaves, which especially promoted the secretion of Na+ (1.37 times). CONCLUSIONS: In summary, the exogenous addition of GB significantly enhances the salt tolerance of G. uralensis seedlings, promoting osmoregulatory substances, antioxidant enzyme activities, excess salt discharge especially the significant promotion of the secretion of Na+Future studies should aim to elucidate the molecular mechanisms that operate when GB regulates saline stress tolerance.

Determination of PEGylation homogeneity of polyethylene glycol-modified canine uricase.

Polyethylene glycol-modified canine uricase (PEG-UHC) was prepared by modifying the ε-amino group of lysine residues on the canine uricase (UHC) protein to near-saturation with 5 kDa monomethoxyl-polyethylene glycol succinimide (mPEG-SPA-5k). In order to accurately determine the PEGylation uniformity of PEG-UHC, CZE, 3-8% gradient gel SDS-PAGE, and imaging CIEF (iCIEF) analyses were compared. CZE could not effectively separate PEG-UHC proteins with different degrees of modification, 3-8% gradient gel SDS-PAGE could separate PEG-UHC into seven gel bands; however, most of the gel bands were smeared or blurred, and the separation of PEG-UHC samples by iCIEF was significantly better than that by 3-8% gradient gel SDS-PAGE. Under denatured conditions, iCIEF separated 12 pI peaks, and could also accurately quantify the relative monomer PEG-UHC content. More than 85% of the total monomeric PEG-UHC was conjugated with 7-12 PEG molecules; of this 85%, approximately 40% was conjugated with 9-10 PEG molecules. These results demonstrated that iCIEF exhibits good potential for determining the PEGylation homogeneity of PEGylated protein drugs.

A Hierarchical Network of Four Regulatory Genes Controlling Production of the Polyene Antibiotic Candicidin in Streptomyces sp. Strain FR-008.

The four regulatory genes fscR1 to fscR4 in Streptomyces sp. strain FR-008 form a genetic arrangement that is widely distributed in macrolide-producing bacteria. Our previous work has demonstrated that fscR1 and fscR4 are critical for production of the polyene antibiotic candicidin. In this study, we further characterized the roles of the other two regulatory genes, fscR2 and fscR3, focusing on the relationship between these four regulatory genes. Disruption of a single or multiple regulatory genes did not affect bacterial growth, but transcription of genes in the candicidin biosynthetic gene cluster decreased, and candicidin production was abolished, indicating a critical role for each of the four regulatory genes, including fscR2 and fscR3, in candicidin biosynthesis. We found that fscR1 to fscR4, although differentially expressed throughout the growth phase, displayed similar temporal expression patterns, with an abrupt increase in the early exponential phase, coincident with initial detection of antibiotic production in the same phase. Our data suggest that the four regulatory genes fscR1 to fscR4 have various degrees of control over structural genes in the biosynthetic cluster under the conditions examined. Extensive transcriptional analysis indicated that complex regulation exists between these four regulatory genes, forming a regulatory network, with fscR1 and fscR4 functioning at a lower level. Comprehensive cross-complementation analysis indicates that functional complementation is restricted among the four regulators and unidirectional, with fscR1 complementing the loss of fscR3 or -4 and fscR4 complementing loss of fscR2 Our study provides more insights into the roles of, and the regulatory network formed by, these four regulatory genes controlling production of an important pharmaceutical compound.IMPORTANCE The regulation of antibiotic biosynthesis by Streptomyces species is complex, especially for biosynthetic gene clusters with multiple regulatory genes. The biosynthetic gene cluster for the polyene antibiotic candicidin contains four consecutive regulatory genes, which encode regulatory proteins from different families and which form a subcluster within the larger biosynthetic gene cluster in Streptomyces sp. FR-008. Syntenic arrangements of these regulatory genes are widely distributed in polyene gene clusters, such as the amphotericin and nystatin gene clusters, suggesting a conserved regulatory mechanism controlling production of these clinically important medicines. However, the relationships between these multiple regulatory genes are unknown. In this study, we determined that each of these four regulatory genes is critical for candicidin production. Additionally, using transcriptional analyses, bioassays, high-performance liquid chromatography (HPLC) analysis, and genetic cross-complementation, we showed that FscR1 to FscR4 comprise a hierarchical regulatory network that controls candicidin production and is likely representative of how expression of other polyene biosynthetic gene clusters is controlled.

On the complexity measures of mutation hotspots in human TP53 protein.

The role of sequence complexity in 23 051 somatic missense mutations including 73 well-known mutation hotspots across 22 major cancers was studied in human TP53 proteins. A role for sequence complexity in TP53 protein mutations is suggested since (i) the mutation rate significantly increases in low amino acid pair bias complexity; (ii) probability distribution complexity increases following single point substitution mutations and strikingly increases after mutation at the mutation hotspots including six detectable hotspot mutations (R175, G245, R248, R249, R273, and R282); and (iii) the degree of increase in distribution complexity is significantly correlated with the frequency of missense mutations (r = -0.5758, P < 0.0001) across 20 major types of solid tumors. These results are consistent with the hypothesis that amino acid pair bias and distribution probability may be used as novel measures for protein sequence complexity, and the degree of complexity is related to its susceptibility to mutation, as such, it may be used as a predictor for modeling protein mutations in human cancers.

The ethanol extract of honeysuckle stem modulates the innate immunity of Chinese mitten crab Eriocheir sinensis against Aeromonas hydrophila.

Honeysuckle stem had been used as feed additives to modulate immunity in breeding industry, which was limited in the aquaculture field. In this study, the immunomodulation of honeysuckle stem ethanol extract (designed as HSE) on Chinese mitten crab Eriocheir sinensis was detected. The crabs fed with HSE diets for 30 days had higher level of the total haemocyte count (HTC), lysozyme activity and PO activity (P < 0.05), and had no obvious affect on the phagocytic activity, NO and TNF-α level. When challenged with Aeromonas hydrophila (1.0 × 107 colony-forming units), HSE exhibited weak antibacterial activity against A. hydrophila and increased survival rate of crabs. The decreasing of THC and the increasing of TNF-α concentration, EsCaspase and EsLITAF mRNA expression level were all inhibited significantly by HSE treatment (P < 0.05), when the crabs were challenged by A. hydrophila. Moreover, the following immune parameters of crabs were enhanced by HSE treatment after A. hydrophila infection, including the rising of phagocytosis index and phagocytic rate of haemocyte, the rising of lysozyme, PO, NOS activities and nitric oxide concentration (P < 0.05). Therefore, it was concluded that HSE had great potential to develop into feed additive of crabs, which could enhance the innate immunity of Chinese mitten crabs E. sinensis effectively after A. hydrophila infection.

Scutellarin Prevents Nonalcoholic Fatty Liver Disease (NAFLD) and Hyperlipidemia via PI3K/AKT-Dependent Activation of Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2) in Rats.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing. Enzyme activity assay, immunofluorescence, Western blot, and quantitative RT-PCR were performed to analyze the factors of the oxidant/antioxidant system and pathway. RESULTS After the high-fat diet and chronic stress administration for 12 weeks, serum and liver lipid metabolism of treatment groups with the different doses of SCU effectively improved and the degree of oxidative damage reduced. Using Western blot assay and immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins significantly increased after SCU treatment for 4 weeks (P<0.01). The hepatic mRNA expression of HO-1, NQO1, and Nrf2 in SCU treatment groups was upregulated significantly through quantitative RT-PCR assay (P<0.05). However, compared to the positive control group, no difference was detected in the SCU (100 or 300 mg/kg) groups (P>0.05). These results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress. CONCLUSIONS The antioxidant effects of SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2 nuclear translocation, which increases expression of HO-1 and NQO1. We therefore suggest that breviscapine may be a potentially useful therapeutic strategy for NAFLD and hyperlipidemia.

Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.

UNLABELLED: Genome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways. IMPORTANCE: Microbial genomes encode numerous cryptic biosynthetic gene clusters for unknown small metabolites with potential biological activities. Several genome mining approaches have been developed to activate and bring these cryptic metabolites to biological tests for future drug discovery. Previous sequence-guided procedures relied on bioinformatic analysis to predict potentially interesting biosynthetic gene clusters. In this study, we describe an efficient approach based on heterologous expression and functional screening of a whole-genome library for the mining of bioactive metabolites from Streptomyces The usefulness of this function-driven approach was demonstrated by the capture of four large biosynthetic gene clusters for metabolites of various chemical types, including streptothricins, borrelidin, two novel lipopeptides, and one unknown antibiotic from Streptomyces rochei Sal35. The transfer, expression, and screening of the library were all performed in a high-throughput way, so that this approach is scalable and adaptable to industrial automation for next-generation antibiotic discovery.

Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families.

In Streptomyces sp. FR-008, the biosynthetic gene cluster of the polyene antibiotic FR-008, also known as candicidin, consists of 21 genes, including four regulatory genes, fscRI-fscRIV. Our bioinformatics analyses indicate that FscRI has an N-terminal PAS domain, whereas the other three regulators have N-terminal AAA domains and are members of the LAL (large ATP-binding regulators of the LuxR type) family. Deletion of fscRI abolished the production of FR-008, with production restored in the complemented strain, supporting a critical role for FscRI in FR-008 biosynthesis. Consistent with these findings, transcription of genes involved in the biosynthesis and efflux of FR-008 was greatly downregulated in a ΔfscRI mutant. Interestingly, the regulatory gene fscRIV was also downregulated in the ΔfscRI mutant. Production of FR-008 was reduced, but not abrogated, in an fscRIV deletion mutant, and although structural genes were downregulated in ΔfscRIV, the changes were much less dramatic than in ΔfscRI, suggesting a stronger regulatory role for FscRI. Remarkably, transcription of fscRI was also decreased in ΔfscRIV. Expression of fscRI restored antibiotic production in a ΔfscRIV mutant, but not vice versa. Putative binding sequences for FscRI were identified upstream of fscRIV and the three structural genes fscA, fscB and fscD, which encode large modular polyketide synthases. Our findings suggest that fscRI and fscRIV are interregulatory, whereas expression of fscRII and fscRIII appears to be independent of fscRI and fscRIV. This study demonstrates that the regulation of polyene antibiotic synthesis can involve mutually regulated transcriptional activators that belong to different families.

Protective HSP70 Induction by Z-Ligustilide against Oxygen-Glucose Deprivation Injury via Activation of the MAPK Pathway but Not of HSF1.

Heat-shock protein 70 (HSP70) is known to function as a protective molecular chaperone that is massively induced in response to misfolded proteins following cerebral ischemia. The objective of this study was to characterize HSP70 induction by Z-ligustilide and explore its potential role in protection against cerebral ischemia-reperfusion injury. Our results demonstrated that the intranasal administration of Z-ligustilide reduced infarct volume and improved neurological function in a rat stroke model. Meanwhile, Z-ligustilide enhanced the cell viability of PC12 cells insulted by oxygen-glucose deprivation-reoxygenation (OGD-Reoxy) and decreased apoptotic and necrotic cell death. Importantly, Z-ligustilide induced HSP70 expression both in vitro and in vivo. Although heat-shock factor 1 (HSF1) nuclear translocation was promoted by Z-ligustilide, HSP70-based heat-shock element (HSE)-binding luciferase activity was not activated, and HSP70 expression responsive to Z-ligustilide was not attenuated by HSE decoy oligonucleotides. However, Z-ligustilide significantly activated the phosphorylation of mitogen-activated protein kinases (MAPKs). Further inhibition of MAPK activity by specific inhibitors attenuated HSP70 induction by Z-ligustilide. Meanwhile, downregulation of HSP70 using KNK437, an HSP70 synthesis inhibitor, or small hairpin RNA (shRNA) significantly attenuated the protection of Z-ligustilide against OGD-Reoxy-induced injury. Moreover, the application of specific inhibitors of MAPKs also achieved similar results. Finally, Z-ligustilide alleviated the accumulation of ubiquitinated proteins induced by OGD-Reoxy, which was inhibited by HSP70-shRNA. Taken together, our results demonstrated that Z-ligustilide may induce protective HSP70 expression via the activation of the MAPK pathway, but not canonical HSF1 transcription. HSP70 plays a key role in the protection of Z-ligustilide against OGD-Reoxy-induced injury.

Natriuretic peptide receptor A as a novel target for cancer.

The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPR-A), has been reported to be expressed in lung cancer, prostate cancer and ovarian cancer. NPR-A expression and signaling is important for tumor growth; its deficiency protects C57BL/6 mice from lung, skin and ovarian cancers. This suggests that NPR-A is a new marker and a new target for cancer therapy. Recently, NPR-A has been demonstrated to be expressed in pre-implantation embryos and in embryonic stem cells, which has a novel role in the maintenance of self-renewal and pluripotency of embryonic stem cells. A nanoparticle-formulated interfering RNA for NPR-A attenuated B16 melanoma tumors in mice. Ectopic expression of a plasmid encoding NP73-102, the NH2-terminal peptide of the ANP prohormone which downregulates NPR-A expression, also suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1 cells in immunocompetent BALB/c mice. These results suggest that NPR-A is involved in tumorigenesis and a new target for cancer therapy. This review focuses on structure, abnormal functions and carcinogenic mechanisms of NPR-A to investigate its role in tumorigenesis.

Expression of natriuretic peptide receptor-A in esophageal squamous cell carcinomas and the relationship with tumor invasion and migration.

BACKGROUND: The natriuretic peptide receptor-A (NPRA) has been investigated as a receptor of natriuretic peptides in the cardiovascular system. In this study, however, we analyze the expression status of NPRA and the relationship with tumor invasion in esophageal squamous cell carcinoma (ESCC) for the first time. METHODS: Western blots were used to examine the expression status of protein in human ESCC cell lines. Then, we used immunohistochemistry to detect the expression of NPRA in 45 ESCC specimens and 40 corresponding nontumor tissues. The clinical data were analyzed through statistical methods. Sh-RNA-NPRA was transfected into Eca109 cells to detect the relationship between NPRA and cell invasion through transwell assays. RESULTS: In esophageal squamous cells, the expression of NPRA was strongly detected in the cytoplasm, while undetectable or very weak in the nucleus. The positive rates of NPRA in cancer tissues are significantly higher than that in nontumor tissues (P<0.05). Clinicopathological analyses revealed that increased NPRA expression correlated with differentiation and TNM stage (P<0.05), while it showed no statistically significant association with age, gender, and lymph node metastasis. In analysis of prognosis, we found that highly.Transwell assays showed that NPRA promoted Eca109 cell migration and invasion in vitro and may be involved in MMP2 and MMP9 activation. CONCLUSIONS: NPRA protein is highly expressed in ESCC tissues and could promote Eca109 cell migration and invasion in vitro.

Triptolide inhibits proliferation and invasion of colorectal cancer cells by blocking Nrf2 expression.

Triptolide (TPL), the main active ingredient of Tripterygium wilfordii, has anti-inflammatory, immunomodulatory, and antitumor actions. It can also inhibit cell proliferation and metastasis while promoting apoptosis of several tumors, such as colorectal cancer (CRC). However, the mechanism of TPL against CRC is not clear. This study was designed to investigate the effects and molecular mechanisms of TPL on the proliferation and invasion ability of CRC cells. A human CRC cell line (HT29 cell line) cultured in vitro was treated with different concentrations of TPL (0, 25, 50, and 100 nmol/L). The proliferation of cells was detected by MTT, the invasion ability of cells by Transwell, and the apoptosis level by flow cytometry. The protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), matrix metalloproteinase (MMP)-2, and MMP-9 were detected by western blotting. After transfection with sh-Nrf2, HT29 cells were divided into NC group, NC + TPL group and sh-Nrf2 + TPL group, and the above assays were repeated for each group. TPL significantly inhibited the proliferation and invasion ability of HT29 cells and promoted apoptosis (p < .05). Notably, its inhibitory or promotional effects were concentration-dependent, which were enhanced with increasing drug concentration (p < .05). After silencing Nrf2 expression, the proliferation, and invasion ability of HT29 cells were further significantly inhibited while cells apoptosis was further promoted (p < .05). Besides, the decreased Nrf2 expression reduced the protein expression levels of MMP-2 and MMP-9 (p < .05). TPL can effectively inhibit the proliferation and invasion while promoting apoptosis of HT29 cells. And its mechanism of action may be related to the inhibition of Nrf2 signaling expression.

Long-term outcome of uniport vs. multiport video-assisted thoracoscopic lobectomy for lung cancer.

This study aims to compare the perioperative outcomes and long-term survival of U-VATS lobectomy for NSCLC with multiportal VATS (M-VATS, involving two ports or more) lobectomy. A total of 339 patients who underwent intentional VATS lobectomy for lung cancer between 2012 and 2017 were included in the analysis. Perioperative outcomes and long-term survival were evaluated. Propensity score matching was utilized to minimize baseline characteristic differences between the two groups. Out of the total cases, 17 (5.01%) were converted to open thoracotomy. The conversion rates were 4.96% (7/141) in the U-VATS group and 5.05% (10/198) in the M-VATS group. A total of 322 consecutive patients underwent VATS lobectomy and mediastinal lymphadenectomy. After propensity matching, 106 pairs were obtained, consisting of 83 males and 129 females. Intraoperative bleeding volume, number of retrieved lymph nodes, explored nodal stations, drainage time and volume, and postoperative hospital stay were similar between the two groups. Both groups exhibited comparable morbidity and mortality rates. From the multivariable analysis, there was no significant difference observed in terms of overall survival (OS) and disease-free survival (DFS) between the two patient cohorts. U-VATS demonstrated comparable perioperative outcomes and long-term efficacy to M-VATS. However, further confirmation of these findings is required.

Increased dominance of terrestrial component in dissolved organic matter in Chinese lakes.

The source composition of chromophoric dissolved organic matter (CDOM) in lakes is closely related to regional environmental changes, human activities, and the carbon cycle. The spectral slope ratio (SR) is an important parameter of CDOM optical components, and combined with remote sensing technology, the source composition of CDOM can be tracked comprehensively and efficiently in large regions. Here, we proposed a CDOM source tracking remote sensing model (CDOM-SR) based on the hue angle (α) to assess the spatial pattern and long-term trend of the CDOM source composition in Chinese lakes (surface area ≥ 1 km2) from 1986 to 2021. Validation results show that the CDOM-SR model has a good SR estimation performance with a median absolute percentage difference, root mean square deviation, median ratio, and median deviation of 17.91 %, 0.23, 1.02, and 0.03, respectively. We found that the average SR of Chinese lakes presents an obvious spatial pattern of high in the west and low in the east due to the difference in human activity intensity and the natural geographical environment. Additionally, we found that the average SR of Chinese lakes from 1986 to 2021 decreased at a rate of - 0.06/10 years, of which 64.37 % of lakes decreased significantly, 15.42 % of lakes had no significant change, and only 20.20 % of lakes increased. The widespread decrease in the average SR indicates that the increasing human activity discharge of terrestrial organic matter has had an important impact on the source composition of the CDOM in Chinese lakes. Our results provide a new resource for remote sensing monitoring of CDOM sources and important insights into lake carbon cycling under the influence of ongoing human activities.

Metastasis-associated 1 localizes to the sarcomeric Z-disc and is implicated in skeletal muscle pathology.

Metastasis-associated 1 (MTA1), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) corepressor complex, was reported to be expressed in the cytoplasm of skeletal muscles. However, the exact subcellular localization and the functional implications of MTA1 in skeletal muscles have not been examined. This study aims to demonstrate the subcellular localization of MTA1 in skeletal muscles and reveal its possible roles in skeletal muscle pathogenesis. Striated muscles (skeletal and cardiac) from C57BL/6 mice of 4-5 weeks were collected to examine the expression of MTA1 by Western blotting and immunohistochemistry. Immunofluorescence and immunoelectron microscopy were performed for MTA1, α-actinin (a Z-disc marker protein), and SMN (survival of motor neuron) proteins. Gene Expression Omnibus (GEO) data sets were analyzed using the GEO2R online tool to explore the functional implications of MTA1 in skeletal muscles. MTA1 expression was detected by Western blotting and immunohistochemistry in skeletal and cardiac muscles. Subcellular localization of MTA1 was found in the Z-disc of sarcomeres, where α-actinin and SMN were expressed. Data mining of GEO profiles suggested that MTA1 dysregulation is associated with multiple skeletal muscle defects, such as Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, nemaline myopathy, and dermatomyositis. The GEO analysis also showed that MTA1 expression gradually decreased with age in mouse skeletal muscle precursor cells. The subcellular localization of MTA1 in sarcomeres of skeletal muscles implies its biological roles in sarcomere structures and its possible contribution to skeletal muscle pathology.

ANP-NPRA signaling pathway--a potential therapeutic target for the treatment of malignancy.

It was well established that the atrial natriuretic peptide (ANP)/natriuretic peptide receptor-A (NPRA) signaling pathway controls natriuretic, diuretic, vasorelaxant, and anti-proliferative responses in the regulation of the human cardiovascular system by previous studies. Yet in recent years, more and more evidence has shown that the ANP/NPRA signaling pathway plays an important role in human cancer. For example, NPRA is abundantly expressed on tumorigenic mouse and human prostate cancer (PCa) cells, but not in nontumorigenic prostate epithelial cells and down-regulation of NPRA-induced apoptosis in PCa cells. Dexamethasone can increase the expression of ANP markedly, and that is the reason why dexamethasone is the cornerstone in the treatment of multiple myeloma. NPRA deficiency can substantially protect C57BL/6 mice from lung, skin, and ovarian cancers. These results strongly suggest ANP and NPRA may play an anti-cancer and carcinogenesis role, respectively, and this signaling pathway could be a more potent target for cancer therapy. In light of these new insights, this review will summarize the structures, functions, and their regulation by cell signaling, and their different impacts on tumors.

Efficacy of conversion surgery on stage IV gastric cancer and its prognosis analysis.

BACKGROUND: The aim of this study was to explore the clinical efficacy and safety of conversion surgery in the treatment of stage IV gastric cancer, and to analyze the influencing factors for the prognosis of patients. METHODS: The clinical data of 84 patients with stage IV gastric cancer treated in our hospital from September 2014 to March 2016 were collected. All patients were treated with S-1 + oxaliplatin or S-1 + docetaxel chemotherapy, among which 42 patients had surgical indications after chemotherapy and received gastrectomy (R0 resection or R1 resection) (conversion surgery group); the remaining 42 patients had no surgical indications after chemotherapy (simple chemotherapy group). The patients in both groups were followed-up to record the survival status; moreover, the possible influencing factors for the prognosis were analyzed. RESULTS: In the conversion surgery group, the median chemotherapy cycle was 4.3, and the objective response rate (ORR) was 73.8% (31/42). During chemotherapy in the two groups, there were 22 cases (52.3%) and 24 cases (57.1%) of hematological toxicity, and 28 cases (66.7%) and 32 cases (76.2%) of non-hematological toxicity, mainly in grade I-II, which could be relieved after symptomatic treatment, and chemotherapy was successfully completed. After chemotherapy, 42 out of 84 patients met the surgical indications. All patients were followed-up for 6-36 months. The 3-year overall survival was 35.7% (15/42) and 9.5% (4/42), respectively, in the two groups, and the difference was statistically significant according to the log-rank test (P<0.05). The results of multivariate analysis showed that whether the surgical margin was R0 was an independent influencing factor for the prognosis of patients (HR=8.012, 95% CI: 2.522-14.384, P=0.027). CONCLUSIONS: Radical surgery after conversion therapy can raise the survival rate of patients, with tolerable adverse reactions. Whether the surgical margin is R0 in conversion therapy it is an independent influencing factor for the prognosis of patients with stage IV gastric cancer.

Spatial-temporal evolution of production-living-ecological space and layout optimization strategy in eco-sensitive areas: a case study of typical area on the Qinghai-Tibetan Plateau, China.

To achieve sustainable development goals and to solve environmental problems, land resources in eco-sensitive areas should be used and optimized. Qinghai, which is an important eco-sensitive area in China, represents a typical ecological vulnerable region on the Qinghai-Tibetan Plateau. Using land use/cover data for 2000, 2010 and 2020, this study applied a series of quantitative methods to analyze the spatial pattern and structure of the production-living-ecological space (PLES) in Qinghai. The results indicated that the spatial pattern of the PLES in Qinghai was stable over time, but the spatial distribution was very different. The structure of the PLES in Qinghai was stable, and the proportion of each space from high to low was ecological (81.01%), production (18.13%) and living (0.86%). We found that the proportion of ecological space in both the Qilian Mountains and the Three River Headwaters Region was lower than the rest of the study area, except for the Yellow River-Huangshui River Valley. Our study objectively and credibly presented the characteristics of the PLES in an important eco-sensitive area in China. This study further formulated targeted policy suggestions to provide a basis for regional sustainable development, ecological environment protection, and land and space optimization in Qinghai.

A hybrid remote sensing approach for estimating chemical oxygen demand concentration in optically complex waters: A case study in inland lake waters in eastern China.

Chemical oxygen demand concentration (CCOD) is widely used to indicate the degree of organic pollution of lakes, reservoirs and rivers. Mastering the spatiotemporal distribution of CCOD is imperative for understanding the variation mechanism and controlling of organic pollution in water. In this study, a hybrid approach suitable for Sentinel 3A/Ocean and Land Colour Instrument (OLCI) data was developed to estimate CCOD in inland optically complex waters embedding the interaction between CCOD and the absorption coefficients of optically active constituents (OACs). Based on in-situ sampling in different waters, the independent validations of the proposed model performed satisfactorily in Lake Taihu (MAPE = 23.52 %, RMSE = 0.95 mg/L, and R2 = 0.81), Lake Qiandaohu (MAPE = 21.63 %, RMSE = 0.50 mg/L and R2 = 0.69), and Yangtze River (MAPE = 29.34 %, RMSE = 0.83 mg/L, and R2 = 0.64). In addition, the approach not only showed significant superiority compared with previous algorithms, but also was suitable for other common satellite sensors equipped same or similar bands. The hybrid approach was applied to OLCI images to retrieve CCOD of Lake Taihu from 2016 to 2020 and reveals substantial interannual and seasonal variations. The above results indicate that the proposed approach is effective and stable for studying spatiotemporal dynamic of CCOD in optically complex waters, and that satellite-derived products can provide reliable information for lake water quality management.

Correlation between Antistress and Hepatoprotective Effects of Schisandra Lignans Was Related with Its Antioxidative Actions in Liver Cells.

The present study was conducted to investigate the relationship between the anti-stress and hepato-protective effects of Schisandra Lignans Extract (SLE) on stress-induced liver damage. Seven weeks old male mice were fixed in a restraint tube for 18 h to induce liver damage. SLE was orally administered to animals for 5 days at dosages of 100 and 200 mg/kg/day before exposed to restraint stress. Oral administration of SLE significantly reduced restraint-induced liver damage in experimental animal. SLE was further found to significantly alleviate the provocation of corticosterone in stressed mice. SLE also significantly decreased oxidative damage and increased anti-oxidative capability of liver cells by preventing the over production and accumulation of free radicals. In conclusion, the protective effects of SLE on stress-induced liver damage were confirmed, and the correlation between hepatoprotective and anti-stress effects of schisandra lignans was possible related to its alleviation on the malignant effects of stressors for bio-homeostasis, such as balance of oxidation and reduction in cells.