Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.

Megacity pathways in China under the dual carbon goal:The case of Shanghai

The pathways to achieving carbon neutrality at the city level are diverse due to varying energy supply and demand conditions.Shanghai faces obstacles such as limited land resources,high costs of renewable energy technologies,and instability of renewable energy.These challenges hinder the city’s efforts to achieve carbon peak and carbon neutrality(dual carbon).Therefore,Shanghai must identify and optimize its development path for renewable energy under the dual carbon goal.We employed the Low Emissions Analysis Platform Shanghai(LEAP-SH)model to simulate the impact of policies,such as industrial upgrading,energy efficiency improvement,energy structure optimization,increased technical innovation on energy,and ecological restoration,on the carbon emission pathways from 2022 to 2060 using five different scenarios.Our results indicate that Shanghai has the potential to achieve carbon neutrality in 2059 by promoting carbon reduction,pollution control,and green expansion.Moreover,we determined that the manufacturing industry;power generation industry;and transportation,storage,and mail services are the three major sectors for emission reduction under the dual carbon goal.Furthermore,the capacity and output of coal-fired power plants will be gradually replaced by offshore wind power in the dual carbon pathway.Finally,this study proposes countermeasures and suggestions for Shanghai to attain the dual carbon goal and high-quality development.