Role of Trade in India’s Rising Atmospheric Mercury Emissions

India is among the largest emitters of atmospheric mercury (Hg) in the world. India’s production activities have associated Hg emissions which can be attributed to final demands (e.g., purchases by households, governments, and private investments) of nations driving upstream production from the demand perspective, or primary inputs (e.g., labor and capital supply) of nations enabling downstream production from the supply perspective. This study identifies key nations and sectors that directly and indirectly drove India’s Hg emissions from both the demand and supply perspectives during 2004–2014. While domestic final demand was the dominant driver from the demand perspective (driving about 80–85% of the total), USA, China, and UAE are important foreign drivers. Similarly, from the supply perspective, domestic primary inputs were the dominant drivers. However, the share of foreign inputs enabling Hg emissions increased from 16 to 23% during the decade. Saudi Arabia, Indonesia, Australia, and China are the top foreign supply-side drivers. The Construction sector is an important demand-side driver, whereas fossil fuel sectors are important supply-side drivers. These findings can guide global and national policies for demand- and supply-side management of Hg emissions in India and assist in the successful implementation of the Minamata Convention on Mercury

Paeoniflorin loaded liposomes modified with glycyrrhetinic acid for liver-targeting: preparation, characterization, and pharmacokinetic study

To enhance the retention times and therapeutic efficacy of paeoniflorin (PF), a liver-targeted drug delivery system has been developed using glycyrrhetinic acid (GA) as a ligand. The development and optimization of GA-modified PF liposomes (GPLs) have shown promising potential for targeted delivery to the liver, opening up new possibilities for liver disease treatment. This study aimed to identify the best prescriptions using single-factor experiments and response surface methodology. The formulation morphology was determined using transmission electron microscopy. Tissue distribution was observed through in vivo imaging, and pharmacokinetic studies were conducted. The results indicated that GPLs, prepared using the thin film dispersion method and response surface optimization, exhibited well-dispersed and uniformly sized particles. The in vitro release rate of GPLs was slower compared to PF monomers, suggesting a sustained release effect. The liver-targeting ability of GA resulted in stronger fluorescence signals in the liver for targeted liposomes compared to non-targeted liposomes. Furthermore, pharmacokinetic studies demonstrated that GPLs significantly prolonged the residence time of PF in the bloodstream, thereby contributing to prolonged efficacy. These findings suggest that GPLs are more effective than PF monomers in terms of controlling drug release and delivering drugs to specific targets, highlighting the potential of PF as a liver-protective drug.</p

Image_1_Clinicopathological characteristics, evolution, treatment pattern and outcomes of hormone-receptor-positive/HER2-low metastatic breast cancer.pdf

ObjectiveDespite the promising efficacy of the novel antibody-drug conjugate trastuzumab deruxtecan in treating Hormone Receptor (HoR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-low metastatic breast cancer (MBC), its categorization as a distinct entity remains disputed, as does the divergence in its endocrine and chemotherapy outcomes. This study aimed to elucidate the clinical characteristics, primary/metastatic lesion HER2 expression, and treatment outcomes of HoR-positive/HER2-low patients.MethodsWe included HoR-positive/HER2-negative MBC patients who underwent 1st and 2nd line endocrine treatment from July 2010 to October 2022 at the Fudan University Shanghai Cancer Center, comparing the clinical pathological characteristics, HER2 expression in primary/metastatic lesions, treatment, and therapeutic effects of the HER2-low and HER2-zero groups.ResultsAmong the 458 HoR-positive/HER2-negative MBC patients, 54.37% (249/458) were HER2-low. The HER2-low group and the HER2-zero group had similar clinical pathological characteristics and similar progression-free survival (PFS) of 1st and 2nd line endocrine treatment (median PFS: 8.05 months vs 10.12 months, p=0.114, HR 1.257, 95% CI 0.771 to 1.028). The PFS of the HER2-low and HER2-zero groups was also similar, treated with different endocrine drugs (including aromatase inhibitors, tamoxifen/toremifene, fulvestrant, palbociclib, and everolimus). However, the HER2-low group had significantly shorter PFS during 1st and 2nd line chemotherapy compared to the HER2-zero group (median PFS: 8.64 vs 9.03 months, p=0.027, HR 0.841, 95% CI 0.721-0.980). Additionally, 41.18% (63/153) of patients exhibited a change in HER2 expression between primary and metastatic lesions. Notably, patients whose HER2 status changed from zero to low expression had significantly prolonged PFS during chemotherapy compared to those who maintained low HER2 expression (median PFS: 14.29 vs 11.27 months, p=0.048, HR 0.597, 95% CI 0.358-0.996).ConclusionIn HoR-positive MBC, patients with low and zero HER2 expression have similar clinical characteristics and respond similarly to endocrine treatment, but the chemotherapy effect is worse in the HER2-low patients. Moreover, the transformation of HER2 status from primary to metastatic lesions may have potential influence on chemotherapy outcomes. Therefore, the expression and heterogeneity of HER2 should be considered in clinical decisions.</p

Role of Trade in India’s Rising Atmospheric Mercury Emissions

India is among the largest emitters of atmospheric mercury (Hg) in the world. India’s production activities have associated Hg emissions which can be attributed to final demands (e.g., purchases by households, governments, and private investments) of nations driving upstream production from the demand perspective, or primary inputs (e.g., labor and capital supply) of nations enabling downstream production from the supply perspective. This study identifies key nations and sectors that directly and indirectly drove India’s Hg emissions from both the demand and supply perspectives during 2004–2014. While domestic final demand was the dominant driver from the demand perspective (driving about 80–85% of the total), USA, China, and UAE are important foreign drivers. Similarly, from the supply perspective, domestic primary inputs were the dominant drivers. However, the share of foreign inputs enabling Hg emissions increased from 16 to 23% during the decade. Saudi Arabia, Indonesia, Australia, and China are the top foreign supply-side drivers. The Construction sector is an important demand-side driver, whereas fossil fuel sectors are important supply-side drivers. These findings can guide global and national policies for demand- and supply-side management of Hg emissions in India and assist in the successful implementation of the Minamata Convention on Mercury

Gymnemic Acid Alleviates Type 2 Diabetes Mellitus and Suppresses Endoplasmic Reticulum Stress <i>in Vivo</i> and <i>in Vitro</i>

Gymnemic acid (GA) is an herbal ingredient that can improve glucose metabolism in patients with diabetes mellitus. In this study, we evaluated the ameliorative effects of GA on insulin resistance (IR) and identified the mechanisms in type 2 diabetes mellitus (T2DM) rats and IR HepG2 cells. GA effectively enhanced glucose uptake in IR HepG2 cells from 11.9 ± 1.09 to 14.7 ± 1.38 mmol/L and lowered fasting blood glucose (blood glucose levels in groups treated with GA at 40 and 80 mg/kg/day were reduced by 15.2% and 26.7%, respectively) and oral glucose tolerance. Both in vivo and in vitro, GA downregulated the expression of endoplasmic reticulum (ER) stress indicator proteins such as ORP150, p-c-Jun, p-PERK, and p-eIF2α. In addition, the improvement of ER stress regulated the insulin signal transduction proteins, reducing p-IRS-1­(ser) levels and increasing p-IRS-1­(tyr) in GA-treated T2DM rats and IR HepG2 cells. In summary, the mechanism underlying the hypoglycemic effects of GA may be associated with alleviation of ER stress and facilitation of insulin signal transduction in T2DM rats and IR HepG2 cells

Efficient Fresh Lamp Light-Harvesting Films with the Self-Activating Continuous and Recyclable Bactericidal Ability for Ultrapersistent Freshness of Perishable Muscle Food

A large quantity of perishable muscle food is being wasted due to harmful bacteria infestation during the sales and circulation each year and facing challenges. In this study, a self-activated bactericidal active film (PLA/g-C3N4@PCN-224) responsive to fresh lamp light was prepared, which showed excellent hydrophobicity, water vapor resistance, and thermal stability. Due to the synergistic effect between light-induced reactive oxygen species and the high specific surface area of g-C3N4@PCN-224, this film still maintains 99.99% bactericidal efficacy against Escherichia coli and Staphylococcus aureus after 10 days of continuous bactericidal activity test. The results of cell and hemolysis experiments indicated that the film was safe and nontoxic and can effectively preserve fresh pork for 7 days. Moreover, the film also exhibited a recyclable and efficient killing activity. A strategy for achieving ultrapersistent freshness of perishable muscle food was provided

Table_1_Risk scores of incident mild cognitive impairment in a Beijing community-based older cohort.docx

Objective: It is very important to identify individuals who are at greatest risk for mild cognitive impairment (MCI) to potentially mitigate or minimize risk factors early in its course. We created a practical MCI risk scoring system and provided individualized estimates of MCI risk.Methods: Using data from 9,000 older adults recruited for the Beijing Ageing Brain Rejuvenation Initiative, we investigated the association of the baseline demographic, medical history, lifestyle and cognitive data with MCI status based on logistic modeling and established risk score (RS) models 1 and 2 for MCI. We evaluated model performance by computing the area under the receiver operating characteristic (ROC) curve (AUC). Finally, RS model 3 was further confirmed and improved based on longitudinal outcome data from the progression of MCI in a sub-cohort who had an average 3-year follow-up.Results: A total of 1,174 subjects (19.8%) were diagnosed with MCI at baseline, and 72 (7.8%) of 849 developed MCI in the follow-up. The AUC values of RS models 1 and 2 were between 0.64 and 0.70 based on baseline age, education, cerebrovascular disease, intelligence and physical activities. Adding baseline memory and language performance, the AUC of RS model 3 more accurately predicted MCI conversion (AUC = 0.785).Conclusion: A combination of risk factors is predictive of the likelihood of MCI. Identifying the RSs may be useful to clinicians as they evaluate their patients and to researchers as they design trials to study possible early non-pharmaceutical interventions to reduce the risk of MCI and dementia.</p

Role of Trade in India’s Rising Atmospheric Mercury Emissions

India is among the largest emitters of atmospheric mercury (Hg) in the world. India’s production activities have associated Hg emissions which can be attributed to final demands (e.g., purchases by households, governments, and private investments) of nations driving upstream production from the demand perspective, or primary inputs (e.g., labor and capital supply) of nations enabling downstream production from the supply perspective. This study identifies key nations and sectors that directly and indirectly drove India’s Hg emissions from both the demand and supply perspectives during 2004–2014. While domestic final demand was the dominant driver from the demand perspective (driving about 80–85% of the total), USA, China, and UAE are important foreign drivers. Similarly, from the supply perspective, domestic primary inputs were the dominant drivers. However, the share of foreign inputs enabling Hg emissions increased from 16 to 23% during the decade. Saudi Arabia, Indonesia, Australia, and China are the top foreign supply-side drivers. The Construction sector is an important demand-side driver, whereas fossil fuel sectors are important supply-side drivers. These findings can guide global and national policies for demand- and supply-side management of Hg emissions in India and assist in the successful implementation of the Minamata Convention on Mercury

Nucleophilic Aromatic Substitution of 5‑Bromo-1,2,3-triazines with Phenols

Nucleophilic aromatic substitution (SNAr) reaction in classic textbook is a stepwise mechanism, and few examples of concerted reactions have been reported. Herein, we developed a concerted SNAr reaction of 5-bromo-1,2,3-triazines with phenols in which the nonclassic mechanism of this reaction could be revealed by calculation. Furthermore, the resulting 5-aryloxy-1,2,3-triazines could be used as convenient precursors to access biologically important 3-aryloxy-pyridines in one-pot manner

Global Supply Chain Drivers of Agricultural Antibiotic Emissions in China

Antibiotic pollution causes serious environmental and social issues. China is the largest antibiotic producer and user in the world, with a large share of antibiotics used in agriculture. This study quantified agricultural antibiotic emissions of mainland China in 2014 as well as critical drivers in global supply chains. Results show that China’s agriculture discharged 4131 tons of antibiotics. Critical domestic supply chain drivers are mainly located in Central China, North China, and East China. Foreign final demand contributes 9% of agricultural antibiotic emissions in mainland China and leads to 5–40% of emissions in each province. Foreign primary inputs (e.g., labor and capital) contribute 5% of agricultural antibiotic emissions in mainland China and lead to 2–63% of emissions in each province. Critical international drivers include the final demand of the United States and Japan for foods and textile products, as well as the primary inputs of the oil seeds sector in Brazil. The results indicate the uniqueness of supply chain drivers for antibiotic emissions compared with other emissions. Our findings reveal supply chain hotspots for multiple-perspective policy decisions to control China’s agricultural antibiotic emissions as well as for international cooperation