Polyphosphate promotes oxidation resistance of ppk-expressing transgenic rice in low phosphorus culture.

Phosphorus (P) plays a crucial role in plant growth. Insufficient availability of inorganic phosphate (Pi) can significantly impact crop yields. To address this, we previously developed transgenic rice expressing the low polyphosphate kinase gene (ppk) - known as ETRS - to enhance the efficiency of P resource utilization. Previous studies have shown that ETRS thrives and presents high yields in the low P culture. ETRS and wild-type rice (WT) were cultivated to the heading stage at 15 µM of P in the low P (LP) culture and 300 µM of P in the normal culture (CK) to identify the molecular pathways behind low P tolerance. Our findings revealed that polyphosphate (polyP) significantly enhanced the growth performance of ETRS in the LP culture. This enhanced tolerance can be attributed to polyP's capacity to mitigate oxidative damage induced by LP. This was evidenced by the reduction in levels of superoxide radicals, hydrogen peroxide, and malondialdehyde. PolyP also improved the antioxidant capacity of ETRS under LP stress by regulating enzymatic antioxidants viz., superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as non-enzymatic antioxidants such as ascorbate (AsA) and glutathione (GSH). In addition, transcriptomics analysis suggested that polyP synthesis positively promoted the expressions of SOD, POD, and CAT related genes and played an active role in regulating the expression of AsA-GSH cycle system related genes in ETRS in the LP culture. These results strongly support the notion that polyP within ETRS mitigates oxidative damage through enhancement of the antioxidant system, ultimately bolstering tolerance to LP conditions.

The ppk-expressing transgenic rice floating bed improves P removal in slightly polluted water.

With significant economic advantages, the plant floating bed has been widely utilized in the ecological remediation of eutrophic water because of the excessive phosphorus (P) and nitrogen discharge in China. Previous research has demonstrated that polyphosphate kinase (ppk)-expressing transgenic rice (Oryza sativa L. ssp. japonica) (ETR) can increase the P absorption capacity to support rice growth and boost rice yield. In this study, the floating beds of ETR with single copy line (ETRS) and double copy line (ETRD) are built to investigate their capacity to remove aqueous P in slightly polluted water. Compared with the wild type Nipponbare (WT) floating bed, the ETR floating beds greatly reduce the total P concentration in slightly polluted water though the ETR floating beds have the same removal rates of chlorophyll-a, NO3--N, and total nitrogen in slightly polluted water. The P uptake rate of ETRD on the floating bed is 72.37% in slightly polluted water, which is higher than that of ETRS and WT on the floating beds. Polyphosphate (polyP) synthesis is a critical factor for the excessive phosphate uptake of ETR on the floating beds. The synthesis of polyP decreases the level of free intracellular phosphate (Pi) in ETR on the floating beds, simulating the phosphate starvation signaling. The OsPHR2 expression in the shoot and root of ETR on the floating bed increased, and the corresponding P metabolism gene expression in ETR was changed, which promoted Pi uptake by ETR in slightly polluted water. The Pi accumulation further promoted the growth of ETR on the floating beds. These findings highlight that the ETR floating beds, especially ETRD floating bed, have significant potential for P removal and can be exploited as a novel method for phytoremediation in slightly polluted water.

Amplified cyanobacterial bloom is derived by polyphosphate accumulation triggered by ultraviolet light.

Cyanobacterial blooms appear more strongly, constantly and globally, yet the positive effect of surface solar ultraviolet radiation (UV) on cyanobacterial bloom in natural freshwater habitats is largely ignored. Here in-situ and laboratory studies were jointly designed to probe the mechanism of cyanobacterial bloom promoted by solar UV light. The results showed that solar UV light is a key trigger factor for the accumulation of total phosphorus, dissolved inorganic phosphorus and polyphosphate (polyP) in blooming cyanobacterial cells. The increase of UV dose induces polyP accumulation to result in the excessive phosphorus uptake of blooming cyanobacteria, which provides sufficient phosphorus for cyanobacterial growth in suitable environment. Solar UV light also can promote the contents of phycocyanin, allophycocyanin, and phycoerythrin, producing sufficient ATP by photosynthesis for polyP synthesis in cyanobacterial cells in lake enviroment. The frequent variations of UV irradiance exposure prompts cyanobacteria to absorb excessive phosphorus from suspended solid or sediment. Cyanobacterial intracellular phosphorus is accumulated for their growth. UV light promotes polyP accumulation in blooming cyanobacterial cells to avoid damage. The adsorption amount of phosphorus increases for exuberant growth and then more surface blooming cyanobacteria are exposed to UV light to absorb ample phosphorus. Thus, the positive feedback occurs in lake water bodies with abundant phosphorus. This amplified cycle of cyanobacterial density and phosphorus due to solar UV light in eutrophic water bodies is analogous to a triode to amplify visible photosynthesis by UV light as a base electric current in the energy flow process in lake environment, therefore, "Cyanobacterial Phosphorus Assimilation Ultraviolet Effect" is used to describe this phenomenon. A new explanation is provided for the continuing proliferating mechanism of cyanobacterial bloom. Besides, a new perspective appears on the outbreak of cyanobacterial blooms in natural eutrophic lake water bodies worldwide.

Microcystin-leucine arginine (MC-LR) induces mouse ovarian inflammation by promoting granulosa cells to produce inflammatory cytokine via activation of cGAS-STING signaling.

Early experimental studies have demonstrated that microcystin-leucine arginine (MC-LR) is able to induce multiple organ damage. Female reproductive disorders caused by MC-LR have attracted increased attention in recent years. However, the underlying mechanisms of female reproductive malfunctions are not yet fully understood. Our previous study confirmed that MC-LR could enter mice ovary, induce apoptosis of ovarian granulosa cell and lead to follicular atresia. Research shows that ovary inflammation is positively related to the decline of female reproductive function. This study was aimed to find out the relationship between inflammation response and ovarian injury caused by MC-LR. MC-LR were administrated at 0, 7.5, 22.5 and 45 µg/kg for two weeks by intraperitoneal injection in female BALB/c mice. Histopathological analysis of ovary was performed. We found that MC-LR exposure induced inflammation response and fibrosis in ovary. In the present study, we observed that MC-LR could enter ovary and was mainly distributed in mGCs (mouse ovarian granulosa cells), but not in the theca-interstitial cells. We isolated and cultured mGCs with different concentrations of MC-LR at 0, 0.01, 0.1, 1 and 10 µM. MC-LR exposure caused mitochondrial DNA (mtDNA) leakage which was detected by qPCR andimmunofluorescence staining. Subsequently, mtDNA leakage activated cGAS-STING signaling, leading to elevated production of inflammatory cytokines TNF-α in mGCs.Diffusion of TNF-α in ovary resulted in inflammatory cell infiltration and interstitial cell proliferation. Ovarian inflammation provides a new perspective to explore the underlying mechanisms associated with MC-LR-induced female reproductive dysfunction.

Prognostic Worth of Epidermal Growth Factor Receptor (EGFR) in Patients with Head and Neck Tumors.

INTRODUCTION: Head and neck tumors (HNT) are tumors that normally occur at the head and neck region of the body. Epidermal growth factor receptor (EGFR) has been found to be highly expressed in breast and other tumors; therefore, there is the need to investigate the level of EGFR expression among patients with head and neck tumors in Ghana. METHOD: The level of EGFR expression was determined in head and neck tumor and control head and neck tissues with quantitative real-time PCR and immunohistochemistry analysis. RESULTS: The level of EGFR expressions was high in tumor tissues than in the control tissues. There was a significant difference of p value 0.025 among the ages >40 and ≤ 40 when the high and low level of EGFR was compared in the head and neck malignant tumor. The area under the curve for the high expression of EGFR among the malignant head and neck tumors was 0.901 with a specificity of 86.4%. CONCLUSION: EGFR can serve as a prognostic marker in monitoring patients with HNT as well as a molecular therapeutic target.

Prenatal diagnosis of skeletal dysplasias using whole exome sequencing in China.

BACKGROUND: Skeletal dysplasias account for nearly 10% of fetal structural malformations detected by ultrasonography. This clinically heterogeneous group of genetic anomaly includes at least 461 genetic skeletal disorders with extreme clinical, phenotypic, and genetic heterogeneities, thus, significantly complicates accurate diagnosis. Researches have used whole exome sequencing (WES) for prenatal molecular diagnoses of skeletal dysplasias, however, data are still limited. METHODS: DNA extracted from umbilical cord blood or amniocytes from fetuses suspected of skeletal dysplasias based on ultrasound evaluations were analyzed by WES. Blood samples were taken from the parents of the positive fetuses for co-segregation analysis using Sanger sequencing. RESULT: Definitive molecular diagnosis was made in 6/8 (75%) cases, comprised of 5 de novo disease-causing changes in 3 genes (FGFR3, COL2A1, and COL1A2) and one proband with a biallelic deficiency for Lamin B Receptor(LBR),and including 3 novel variants. All fetuses had no detectable copy number variation (CNV) from sequencing results. CONCLUSIONS: Our study suggests that WES is an efficient approach for prenatal diagnosis of fetuses suspected of skeletal abnormalities and contributes to parental genetics counseling and pregnancy management.

MC-LR induced overproduction of progesterone via inhibiting miR-3473g: in vitro and in vivo evidence.

Health risk of human exposure to microcystin-leucine arginine (MC-LR) has drawn more and more attention in recent years. In the present study, MC-LR inhibited miR-3473g expression of mouse granulosa cells both in vitro and in vivo. By dual-luciferase reporter assay, we confirmed miR-3473g is able to bind the 3'-UTR of StAR protein (StAR) mRNA and suppress StAR expression. Thus, downregulation of miR-3473g after MC-LR exposure led to StAR overexpression. Excessive StAR probably transported much more cholesterol into the inner membrane of the mitochondria and finally resulted in overproduction of progesterone. Our results revealed that MC-LR exposure was associated with premature luteinization of granulosa cells and may adversely affect women's fertility.

Construction and application of a new cell electrochemical detecting system based on the hyposmotic principle.

A new cell electrochemical detecting system has been constructed based on the hyposmotic principle, in which the electrochemical signals have been strengthened by about 109.75% for the signal at about +0.70 V and 532.94% for the signal at about +1.03 V. The electrochemical detection limits of the cells have been improved by one order of magnitude. The individual concentrations of intracellular purines have been obtained.

Liver Metastasis from Colorectal Cancer in the Elderly: Is Surgery Justified?

BACKGROUND: The elderly population with liver metastasis from colorectal cancer has been increasing. As the potentially curative treatment, the role of liver resection in the elderly remains undetermined. AIMS: This study provides a meta-analysis on the outcome of liver resection of colorectal liver metastasis in patients aged over 70. METHODS: PubMed, Embase, Ovid, Web of Science, and Cochrane databases from the years 2000 to 2015 were searched for eligible studies. Data on perioperative mortality, postoperative complications, and survival were collected. RESULTS: Twelve retrospective studies with a total of 11,285 patients (2498 elderly patients and 8787 younger patients) were identified. The elderly (>70 years old) were associated with a similar overall complication rate (30.5 vs. 28.0%; OR 1.08; 95% CI 0.91-1.28; p = 0.39) and a higher 30-day mortality (OR 1.92; 95% CI 1.12-3.31; p = 0.02) after liver resection of colorectal liver metastasis (CRLM). The overall survival showed a significant difference in favor of the younger patients (HR 0.76; 95% CI 0.65-0.89; p = 0.0007). However, with regard to disease-free survival, there was no significant difference between elderly and younger patients (HR 0.93; 95% CI 0.82-1.06; p = 0.30). CONCLUSION: Liver resection of CRLM is relatively safe in carefully selected elderly patients. Liver resection should be offered to selected elderly patients with CRLM.

[Experimental study of adipose-derived mesenchymal stem cells in the treatment of Crohn's disease].

OBJECTIVE: To explore the efficacy of adipose-derived mesenchymal stem cells (ADMSCs) in a murine model of inflammatory bowel disease, and its potential mechanism. METHODS: Murine colitis mouse model of Crohn's disease(CD) was created by trinitrobenzene sulfonic acid(TNBS)-induced colitis. Seventy-five 6-8 weeks female BALB/c mice were randomly divided into 3 groups: control group, TNBS group and ADMSC group. To verify the therapeutic effect of ADMSC, real-time PCR and immunohistochemical staining were performed to measure inflammatory cytokines levels in colon tissues. The 10-day survival statuses were recorded after the infusion of ADMSCs. RESULTS: Intraperitoneal injection of ADMSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and increased survival(60% vs. 30%, P<0.05) in the TNBS-induced mouse model of CD. Compared with TNBS group, proinflammatory cytokines, including TNF-α, IL-12 and VEGF of ADMSC group were significantly reduced, with significant increase of IL-10 expression. CONCLUSION: ADMSCs can effectively repair the injury of colonitis through down-regulation of proinflammatory cytokines TNF-α, IL-12 and VEGF expression, and up-regulation of anti-inflammatory cytokine IL-10 expression, which may be a potential new alternative of cell-based therapy for CD.

Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival.

Obesity increases both the risk and mortality associated with many types of cancer including that of the breast. In mice, obesity increases both incidence of spontaneous tumors and burden of transplanted tumors. Our findings identify leptin, an adipose secreted cytokine, in promoting increased mammary tumor burden in obese mice and provide a link between this adipokine and cancer. Using a transplantable tumor that develops spontaneously in the murine mammary tumor virus-Wnt-1 transgenic mice, we show that tumors transplanted into obese leptin receptor (LepRb)-deficient (db/db) mice grow to eight times the volume of tumors transplanted into lean wild-type (WT) mice. However, tumor outgrowth and overall tumor burden is reduced in obese, leptin-deficient (ob/ob) mice. The residual tumors in ob/ob mice contain fewer undifferentiated tumor cells (keratin 6 immunopositive) compared with WT or db/db mice. Furthermore, tumors in ob/ob mice contain fewer cells expressing phosphorylated Akt, a growth promoting kinase activated by the LepRb, compared with WT and db/db mice. In vivo limiting dilution analysis of residual tumors from ob/ob mice indicated reduced tumor initiating activity suggesting fewer cancer stem cells (CSCs). The tumor cell populations reduced by leptin deficiency were identified by fluorescence-activated cell sorting and found to express LepRb. Finally, LepRb expressing tumor cells exhibit stem cell characteristics based on the ability to form tumorspheres in vitro and leptin promotes their survival. These studies provide critical new insight on the role of leptin in tumor growth and implicate LepRb as a CSC target.