Meeting investors’ demands in PPP project to improve enthusiasm for participating in green and low-carbon

The use of PPP scheme to guide private investors to actively participate in green and low-carbon development is conducive to filling the funding gap of domestic green and low-carbon transformation. It is important to meet the demands of investors to ensure that investors can permanently participate in PPP low-carbon projects. Due to the high financing leverage, wide coverage, and government’s right to initiate in PPP project, the investors’ demands also include the enhancement of social reputation, and the acquisition of future project market resources besides investment income. To fully understand the purpose of the investors’ participation in PPP projects and provide guidance for further analysis of behavioural influence path, the study systematically analyzes the demands of investors and develops a demand measurement scale. Firstly, based on the characteristics of PPP scheme, six investor’s demands were identified. Secondly, through theoretical analysis, the measurement items of investors’ demand were constructed, and 269 valid data were collected through questionnaire. Finally, carrying out factor analysis, reliability and validity test, the items were revised to get the formal investor demand scale. The research provides guidance for improving the demand satisfaction of investors, which is conducive to attracting private capital to participate in the green low-carbon development strategy of PPP projects, and provides financial guarantee for achieving the ‘double carbon’ goal

Sugar alcohols-induced oxidative metabolism in cotton callus culture

Sugar alcohols (mannitol and sorbitol) may cause oxidative damage in plants if used in higher concentration. Our present experiment was undertaken to study physiological and metabolic responses in cotton (Gossypium hirsutum L.) callus against mannitol and sorbitol higher doses. Both markedly declined mean values of relative fresh weight growth rates with the increase in their concentration intensities. The overall protein and malonaldehyde (MDA) contents increased in the stressed-shocked cells. Also, the mean values of various antioxidants such as superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX) and calalase (CAT) quantitatively improved over their respective controls. As a whole, MDA contents were higher in magnitude than that of different antioxidant enzymes. Also values of relative increase in case of POD were higher as compared to SOD showing the ability of cotton callus culture to scavenge H2O2 produced as a result of the activity of SOD. Our results show that both agents caused greater damage to the membranous structure in comparison to less activation of the antioxidants. As a whole, the overall change regarding fresh weight growth rates was less after 14-day stress regime, while the mean values of the antioxidant enzymes activities were lower after the 28-day stress period. Such decrease conveys the message that less reactive oxygen species (ROS) might have been produced.Keywords: Antioxidants, callus culture, Gossypium hirsutum L., osmotic stress, sugar alcoholsAfrican Journal of Biotechnology Vol. 12(17), pp. 2191-220

Species-Specific Expansion and Molecular Evolution of the 3-hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Plants

Kazakh dandelion (Taraxacum kok-saghyz, Tk) is a rubber-producing plant currently being investigated as a source of natural rubber for industrial applications. Like many other isoprenoids, rubber is a downstream product of the mevalonate pathway. The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid, a key regulatory step in the MVA pathway. Such regulated steps provide targets for increases in isoprenoid and rubber contents via genetic engineering to increase enzyme activities. In this study, we identify a TkHMGR1 gene that is highly expressed in the roots of Kazakh dandelion, the main tissue where rubber is synthesized and stored. This finding paves the way for further molecular and genetic studies of the TkHMGR1 gene, and its role in rubber biosynthesis in Tk and other rubber-producing plants

Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for patients with unresectable hepatocellular carcinoma: a cost–utility analysis in China and the United States

ObjectiveCamrelizumab plus rivoceranib (camr-rivo) has been shown to significantly improve overall survival (OS) in patients with unresectable or advanced hepatocellular carcinoma (HCC) in the CARES-310 trial. However, the cost-utility of this treatment remains unclear. Therefore, this study evaluated the cost–utility of camr-rivo versus sorafenib as a first-line systemic therapy for patients with unresectable or advanced HCC from the perspectives of the Chinese healthcare system and the United States (US) payers.MethodsBased on the CARES-310 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes over a 10-year lifetime horizon. Drug costs were obtained from the public database, Red Book, and relevant literature. Health utility values were derived from the literature. One-way and probabilistic sensitivity analyses were performed. The willingness-to-pay (WTP) threshold was $36,627.25/QALY in China and$150,000.00/QALY in the United States.ResultsCamr-rivo yielded an additional 0.34 quality-adjusted life years (QALY) compared to sorafenib for patients with unresectable or advanced HCC. The incremental costs in China and the United States were $4,762.10 and$92,700.49, respectively, and the incremental cost–utility ratios (ICURs) were $14,174.40/QALY and$272,852.59/QALY, respectively. Sensitivity analyses indicated that the cost of rivoceranib and camrelizumab had the greatest impact on the ICUR in China and the United States. Scenario analyses showed that a price reduction of approximately 30% for camrelizumab and rivoceranib could make camr-rivo a cost-utility option in the United States.ConclusionAt the set WTP threshold, camr-rivo is a cost–utility treatment strategy compared to sorafenib as a first-line therapy for patients with unresectable or advanced HCC in China but not in the United States

Developing a predictive nomogram and web-based survival calculator for locally advanced hypopharyngeal cancer: A propensity score-adjusted, population-based study

Understanding the clinical features and accurately predicting the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) is important for patient centered decision-making. This study aimed to create a multi-factor nomogram predictive model and a web-based calculator to predict post-therapy survival for patients with LA-HPSCC. A retrospective cohort study analyzing Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for patients diagnosed with LA-HPSCC was conducted and randomly divided into a training and a validation group (7:3 ratio). The external validation cohort included 276 patients from Sichuan Cancer Hospital, China. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was used to identify independent factors associated with overall survival (OS) and cancer-specific survival (CSS), and nomogram models and web-based survival calculators were constructed. Propensity score matching (PSM) was used to compare survival with different treatment options. A total of 2526 patients were included in the prognostic model. The median OS and CSS for the entire cohort were 20 (18.6-21.3) months and 24 (21.7-26.2) months, respectively. Nomogram models integrating the seven factors demonstrated high predictive accuracy for 3-year and 5-year survival. PSM found that patients who received surgery-based curative therapy had better OS and CSS than those who received radiotherapy-based treatment (median survival times: 33 months vs 18 months and 40 months vs 22 months, respectively). The nomogram model accurately predicted patient survival from LA-HPSCC. Surgery with adjuvant therapy yielded significantly better survival than definitive radiotherapy. and should be prioritized over definitive radiotherapy

Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria

BACKGROUND: Induction of delta aminolevulinic acid synthase 1 ( ALAS1) gene expression and accumulation of neurotoxic intermediates result in neurovisceral attacks and disease manifestations in patients with acute intermittent porphyria, a rare inherited disease of heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.METHODS: We conducted a phase 1 trial of givosiran in patients with acute intermittent porphyria. In part A of the trial, patients without recent porphyria attacks (i.e., no attacks in the 6 months before baseline) were randomly assigned to receive a single subcutaneous injection of one of five ascending doses of givosiran (0.035, 0.10, 0.35, 1.0, or 2.5 mg per kilogram of body weight) or placebo. In part B, patients without recent attacks were randomly assigned to receive once-monthly injections of one of two doses of givosiran (0.35 or 1.0 mg per kilogram) or placebo (total of two injections 28 days apart). In part C, patients who had recurrent attacks were randomly assigned to receive injections of one of two doses of givosiran (2.5 or 5.0 mg per kilogram) or placebo once monthly (total of four injections) or once quarterly (total of two injections) during a 12-week period, starting on day 0. Safety, pharmacokinetic, pharmacodynamic, and exploratory efficacy outcomes were evaluated.RESULTS: A total of 23 patients in parts A and B and 17 patients in part C underwent randomization. Common adverse events included nasopharyngitis, abdominal pain, and diarrhea. Serious adverse events occurred in 6 patients who received givosiran in parts A through C combined. In part C, all 6 patients who were assigned to receive once-monthly injections of givosiran had sustained reductions in ALAS1 messenger RNA (mRNA), delta aminolevulinic acid, and porphobilinogen levels to near normal. These reductions were associated with a 79% lower mean annualized attack rate than that observed with placebo (exploratory efficacy end point).CONCLUSIONS: Once-monthly injections of givosiran in patients who had recurrent porphyria attacks resulted in mainly low-grade adverse events, reductions in induced ALAS1 mRNA levels, nearly normalized levels of the neurotoxic intermediates delta aminolevulinic acid and porphobilinogen, and a lower attack rate than that observed with placebo. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02452372 .).</p

Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication

Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2aPol levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2aPol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control