Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) holds a prominent position among global cancer types. Classically, HCC manifests in individuals with a genetic predisposition when they encounter risk elements, particularly in the context of liver cirrhosis. Peroxisome proliferator-activated receptors (PPARs), which are transcription factors activated by fatty acids, belong to the nuclear hormone receptor superfamily and play a pivotal role in the regulation of energy homeostasis. At present, three distinct subtypes of PPARs have been recognized: PPARα, PPARγ, and PPARß/δ. They regulate the transcription of genes responsible for cellular development, energy metabolism, inflammation, and differentiation. In recent years, with the rising incidence of HCC, there has been an increasing focus on the mechanisms and roles of PPARs in HCC. PPARα primarily mediates the occurrence and development of HCC by regulating glucose and lipid metabolism, inflammatory responses, and oxidative stress. PPARß/δ is closely related to the self-renewal ability of liver cancer stem cells (LCSCs) and the formation of the tumor microenvironment. PPARγ not only influences tumor growth by regulating the glucose and lipid metabolism of HCC, but its agonists also have significant clinical significance for the treatment of HCC. Therefore, this review offers an exhaustive examination of the role of the three PPAR subtypes in HCC progression, focusing on their mediation of critical cellular processes such as glucose and lipid metabolism, inflammation, oxidative stress, and other pivotal signaling pathways. At the end of the review, we discuss the merits and drawbacks of existing PPAR-targeted therapeutic strategies and suggest a few alternative combinatorial therapeutic approaches that diverge from conventional methods.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk.

BACKGROUND: Soy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. METHODS: A two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. RESULTS: A nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57-0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). CONCLUSIONS: We identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.

BACKGROUND: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells. METHODS: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation. RESULTS: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions. CONCLUSIONS: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.

Uncovering the differentiated impacts of carbon neutrality and clean air policies in multi-provinces of China.

Ambitious action plans have been launched to address climate change and air pollution. Through coupling the IMED|CGE, GAINS, and IMED|HEL models, this study investigate the impacts of implementing carbon neutrality and clean air policies on the energy-environment-health-economy chain in the Beijing-Tianjin-Hebei-Henan-Shandong-Shanxi region of China. Results show that Shandong holds the largest reduction in energy consumption and carbon emissions toward the 1.5°C target. Shandong, Henan, and Hebei are of particularly prominent pollutant reduction potential. Synergistic effects of carbon reduction on decreasing PM2.5 concentration will increase in the future, specifically in energy-intensive regions. Co-deployment of carbon reduction and end-of-pipe technologies are beneficial to decrease PM2.5-related mortalities and economic loss by 4.7-12.9% in 2050. Provincial carbon reduction cost will be higher than monetary health benefits after 2030, indicating that more zero-carbon technologies should be developed. Our findings provide scientific enlightenment on policymaking toward achieving carbon reduction and pollution mitigation from multiple perspectives.

Understanding the mechanism of high viscosity food delaying gastric emptying.

Controlling the structure and viscosity of food can influence the development of diet-related diseases. Food viscosity has been linked with health through its impact on human digestion and gastrointestinal transit, however, there is limited understanding of how the viscosity of food regulates gastric emptying. Here, we used model food preparations with different viscosities using guar gum, to explore the mechanism underlying the influence of viscosity on gastric motility, gastric emptying and postprandial blood glucose. Based on experiments in human volunteers and animals, we demonstrated that high viscosity meals increased gastric antrum area and gastric retention rate. Viscosity also affected gut hormone secretion, reduced the gene expression level of interstitial cells of Cajal, resulting in a delay of gastric emptying and limiting the increase in postprandial glucose. This improved mechanistic understanding of food viscosity during gastric digestion is important for designing new foods to benefit human health.

Thermal stability and in vitro biological fate of lactoferrin-polysaccharide complexes.

Lactoferrin (LF) is a thermally sensitive iron-binding globular glycoprotein. Heat treatment can induce its denaturation and aggregation and thus affect its functional activity. In this study, carrageenan (CG), xanthan gum (XG) and locust bean gum (LBG), allowed to apply in infant food, were used to form protein-polysaccharide complexes to improve the thermal stability of LF. Meanwhile, in vitro simulated infant digestion and absorption properties of LF were also estimated. The results showed that the complexes formed by CG and XG with LF (LF-CG and LF-XG) could significantly inhibit the loss of α-helix structure of LF against heating. LF-CG and LF-LBG could protect LF from digestion in simulated infant gastric fluid and slow down the degradation of LF under the simulated intestinal conditions. Besides, LF, LF-CG and LF-XG showed no adverse effects on the growth of Caco-2 cells in the LF concentration range of 10-300 µg/mL, and LF-XG exhibited better beneficial to improve the cell uptake of the digestive product than the other protein-polysaccharides at the LF concentration of 100 µg/mL. This study may provide a reference for the enhancement of thermal processing stability of LF and development infant food ingredient with high nutrients absorption efficiency in the gastrointestinal environment in the future.

Clinical nomogram prediction model to assess the risk of prolonged ICU length of stay in patients with diabetic ketoacidosis: a retrospective analysis based on the MIMIC-IV database.

BACKGROUND: The duration of hospitalization, especially in the intensive care unit (ICU), for patients with diabetic ketoacidosis (DKA) is influenced by patient prognosis and treatment costs. Reducing ICU length of stay (LOS) in patients with DKA is crucial for optimising healthcare resources utilization. This study aimed to establish a nomogram prediction model to identify the risk factors influencing prolonged LOS in ICU-managed patients with DKA, which will serve as a basis for clinical treatment, healthcare safety, and quality management research. METHODS: In this single-centre retrospective cohort study, we performed a retrospective analysis using relevant data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Clinical data from 669 patients with DKA requiring ICU treatment were included. Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) binary logistic regression model. Subsequently, the selected variables were subjected to a multifactorial logistic regression analysis to determine independent risk factors for prolonged ICU LOS in patients with DKA. A nomogram prediction model was constructed based on the identified predictors. The multivariate variables included in this nomogram prediction model were the Oxford acute severity of illness score (OASIS), Glasgow coma scale (GCS), acute kidney injury (AKI) stage, vasoactive agents, and myocardial infarction. RESULTS: The prediction model had a high predictive efficacy, with an area under the curve value of 0.870 (95% confidence interval [CI], 0.831-0.908) in the training cohort and 0.858 (95% CI, 0.799-0.916) in the validation cohort. A highly accurate predictive model was depicted in both cohorts using the Hosmer-Lemeshow (H-L) test and calibration plots. CONCLUSION: The nomogram prediction model proposed in this study has a high clinical application value for predicting prolonged ICU LOS in patients with DKA. This model can help clinicians identify patients with DKA at risk of prolonged ICU LOS, thereby enhancing prompt intervention and improving prognosis.

Effects of Multicomponent Exercise on Community-Dwelling Older Adults With Mild Cognitive Impairment.

PURPOSE: To explore the effects of a group-based multicomponent exercise program on general cognitive functioning, depression, and social functioning in community-dwelling older adults with mild cognitive impairment (MCI) and whether the effects can be maintained. METHOD: Fifty older adults with MCI were conveniently recruited from two communities in the study area and randomly assigned to the intervention group or control group. The intervention group received three sessions of 60-minute, multicomponent exercise per week for 3 months, plus MCI-related health education. The control group only received MCI-related health education. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Beijing Version (MoCA-BJ) were used to assess general cognitive function. The Functional Activities Questionnaire (FAQ) and Geriatric Depression Scale (GDS-30) were used to evaluate participants' social function and depression, respectively. Participants' exercise intensity was assessed using the Category Ratio Scale. RESULTS: After the 3-month intervention, there were significant improvements in general cognitive function (p = 0.046), attention (p = 0.009), delayed recall (p = 0.015), and social function (p = 0.011) in the intervention group compared with the control group. However, after 3-month postintervention follow up, no significant differences in MMSE, MoCA-BJ, GDS-30, and FAQ scores were noted between groups. CONCLUSION: The 3-month multicomponent exercise program improved general cognitive function and social functioning in community-dwelling older adults with MCI. However, there was no evidence that these benefits lasted for another 3 months after stopping the exercise program. [Research in Gerontological Nursing, 17(2), 65-79.].

The novel lactoferrin and DHA-codelivered liposomes with different membrane structures: Fabrication, in vitro infant digestion, and suckling pig intestinal organoid absorption.

Inspired by membrane structure of breast milk and infant formula fat globules, four liposomes with different particle size (large and small) and compositions (Single phospholipids contained phosphatidylcholine, complex phospholipids contained phosphatidylcholine, phosphatidylethanolamine and sphingomyelin) were fabricated to deliver lactoferrin and DHA. In vitro infant semi-dynamic digestive behavior and absorption in intestinal organoids of liposomes were investigated. Liposomal structures were negligible changed during semi-dynamic gastric digestion while damaged in intestine. Liposomal degradation rate was primarily influenced by particle size, and complex phospholipids accelerated DHA hydrolysis. The release rate of DHA (91.7 ± 1.3 %) in small-sized liposomes (0.181 ± 0.001 µm) was higher than free DHA (unencapsulated, 64.6 ± 3.4 %). Complex phospholipids liposomal digesta exhibited higher transport efficiency (3.4-fold for fatty acids and 2.0-fold for amino acids) and better organoid growth than digesta of bare nutrients. This study provided new insights into membrane structure-functionality relationship of liposomes and may aid in the development of novel infant nutrient carriers.

Incorporating environmental capacity considerations to prioritize control factors for the management of heavy metals in soil.

Heavy metals (HMs) pollution threatens food security and human health. While previous studies have evaluated source-oriented health risk assessments, a comprehensive integration of environmental capacity risk assessments with pollution source analysis to prioritize control factors for soil contamination is still lacking. Herein, we collected 837 surface soil samples from agricultural land in the Nansha District of China in 2019. We developed an improved integrated assessment model to analyze the pollution sources, health risks, and environmental capacities of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn. The model graded pollution source impact on environmental capacity risk to prioritize control measures for soil HMs. All HMs except Pb exceeded background values and were sourced primarily from natural, transportation, and industrial activities (31.26%). Approximately 98.92% (children), 97.87% (adult females), and 97.41% (adult males) of carcinogenic values exceeded the acceptable threshold of 1E-6. HM pollution was classified as medium capacity (3.41 kg/hm2) with mild risk (PI = 0.52). Mixed sources of natural backgrounds, transportation, and industrial sources were identified as priority sources, and As a priority element. These findings will help prioritize control factors for soil HMs and direct resources to the most critical pollutants and sources of contamination, particularly when resources are limited.

Peroxisome proliferator-activated receptors: A key link between lipid metabolism and cancer progression.

Lipids represent the essential components of membranes, serve as fuels for high-energy processes, and play crucial roles in signaling and cellular function. One of the key hallmarks of cancer is the reprogramming of metabolic pathways, especially abnormal lipid metabolism. Alterations in lipid uptake, lipid desaturation, de novo lipogenesis, lipid droplets, and fatty acid oxidation in cancer cells all contribute to cell survival in a changing microenvironment by regulating feedforward oncogenic signals, key oncogenic functions, oxidative and other stresses, immune responses, or intercellular communication. Peroxisome proliferator-activated receptors (PPARs) are transcription factors activated by fatty acids and act as core lipid sensors involved in the regulation of lipid homeostasis and cell fate. In addition to regulating whole-body energy homeostasis in physiological states, PPARs play a key role in lipid metabolism in cancer, which is receiving increasing research attention, especially the fundamental molecular mechanisms and cancer therapies targeting PPARs. In this review, we discuss how cancer cells alter metabolic patterns and regulate lipid metabolism to promote their own survival and progression through PPARs. Finally, we discuss potential therapeutic strategies for targeting PPARs in cancer based on recent studies from the last five years.

Prioritization of control factors for heavy metals in groundwater based on a source-oriented health risk assessment model.

Heavy metals (HMs) in groundwater seriously threaten ecological safety and human health. To facilitate the effective management of groundwater contamination, priority control factors of HMs in groundwater need to be categorized. A total of 86 groundwater samples were collected from the Huangpi district of Wuhan city, China, during the dry and wet seasons. To determine priority control factors, a source-oriented health risk assessment model was applied to compare the pollution sources and health risks of seven HMs (Cu, Pb, Zn, Cr, Ni, As, and Fe). The results showed that the groundwater had higher As and Fe contents. The sources of HM pollution during the wet period were mainly industrial and agricultural activities and natural sources. During the dry period, origins were more complex due to the addition of domestic discharges, such as sewage wastewater. Industrial activities (74.10% during the wet period), agricultural activities (53.84% during the dry period), and As were identified as the priority control factors for groundwater HMs. The results provide valuable insights for policymakers to coordinate targeted management of HM pollution in groundwater and reduce the cost of HM pollution mitigation.

The role of EPAS1 polymorphisms on COPD susceptibility in southern Chinese.

Objective: COPD is the most common chronic respiratory disease with complex environmental and genetic etiologies. It was reported that EPAS1 might participate in the occurrence and development of respiratory diseases. However, the association between EPAS1 and COPD was unclear. Methods: First, a case-control study enrolling 1130 COPD patients and 1115 healthy controls in Guangzhou was conducted to clarify the association between EPAS1 polymorphisms and COPD susceptibility. Secondly, a prevalence study recruited 882 participants in Gansu to verify the effect of positive polymorphisms on lung function. Finally, the 10-year absolute risk considering environmental factors and genetic variations was calculated by the method of Gail and Bruzzi. Results: EPAS1 rs13419896 AA genotype reduced COPD risk in southern Chinese (AA vs. GG: adjusted OR = 0.689, 95% CI = 0.498-0.955; AA vs. GG/GA: adjusted OR = 0.701, 95% CI = 0.511-0.962). Further, the rs13419896 A allele was significantly associated with higher pre-FEV1/pre-FVC in both the Guangzhou and Gansu populations (P < 0.05). Smoking status, coal as fuels, education level, and rs13419896 G > A were finally retained to develop a relative risk model for males. Smoking status, biomass as fuels, and rs13419896 G > A were retained in the female model. The population-attributable risk of the male or female model was 0.457 (0.283-0.632) and 0.421 (0.227-0.616), respectively. Conclusions: This study first revealed that EPAS1 rs13419896 G > A decreased COPD susceptibility and could be a genetic marker to predict the 10-year absolute risk for COPD.

Effect of chewing ability on in vivo oral digestive characteristics and in vitro gastrointestinal starch hydrolysis of three different types of cooked rice.

Chewing ability has a strong effect on food digestion. However, little is known about the relationship between the food mastication degree and the subsequent gastric emptying. This study was to explore the effects of individual chewing ability (strong and weak) on the in vivo oral processing characteristics and in vitro dynamic gastrointestinal starch hydrolysis of three types of rice (japonica rice, indica rice and waxy rice). Results showed that the swallowable bolus in the weak chewing group had larger holes and a looser microstructure with more small rice particles, while the strong chewing ones obtained a bolus with higher saliva content (up to 28%) and starch hydrolysis degree (up to 13.55%). Moreover, the gastric retention and starch hydrolysis of the strong chewing ability group were higher in the artificial gastric dynamic system (AGDS). The indica rice particles with the higher degree of fragmentation contacted enzymes easier and hydrolyzed quicker, thus emptying through the stomach faster (81.76%). However, the oral chewing properties of rice mainly influenced the starch digestion in the stomach and the initial stage of the small intestine (∼5 min). This study suggested that the chewing ability and rice variety can influence the bolus properties, which in turn affected the gastric emptying and the degree of starch hydrolysis during digestion.

EPO rs1617640 A>C is a Protective Factor for Chronic Obstructive Pulmonary Disease: A Case Control Study.

BACKGROUND: The occurrence and development of chronic obstructive pulmonary disease (COPD) are regulated by environmental and genetic factors. In hypoxia, Erythropoietin (EPO) satisfies the body's need for oxygen by promoting the production of red blood cells. Hypoxia was proven to be a common physiological condition in COPD progression and associated with many complications. Some studies have found that EPO is involved in the development of COPD. But the mechanism has not been fully proven. METHODS: We conducted a case-control study enrolled 1095 COPD patients and 1144 healthy controls in Guangdong Province to evaluate the association between EPO polymorphisms (rs1617640 A>C, rs507392 A>G, rs564449 G>T) and COPD susceptibility. 872 participants from southern Gansu Province were recruited to verify the effect of EPO polymorphisms on lung function. RESULTS: EPO rs1617640 C allele reduced COPD susceptibility in southern Chinese significantly (AC vs. AA: adjusted Odds ratio (OR) = 0.805, 95% CI = 0.669-0.969; AC+CC vs. AA: adjusted OR = 0.822, 95% CI = 0.689-0.980). However, there was no association between rs507392 A>G and rs564449 G>T polymorphisms and COPD susceptibility (p > 0.05). We further observed that the rs1617640 C allele was associated with higher FEV1 and FVC in Guangdong and Gansu populations significantly (both p < 0.05). In brief, the level of FEV1 and FVC increased with the C allele number. We modeled the relative risk for men and women, in which the population-attributable risks chances were 0.449 (0.258-0.641) and 0.262 (0.128-0.396) respectively. In this model, smoking status, coal as fuels, education level, and rs1617640 A>C were finally retained for males, while smoking status, biomass as fuels, and1617640 A>C were retained for females. In the end, using the method developed by Gail and Bruzzi, we fitted a 10-year absolute risk model for southern Chinese with different individual relative risks, which was presented as a table. CONCLUSIONS: In conclusion, this study found that EPO rs1617640 A>C polymorphism is associated with COPD susceptibility in southern Chinese, and the C allele was associated with better lung function. In addition, it could also be considered a genetic marker associated with environmental factors to predict the absolute 10-year risk of COPD in southern Chinese.

Application of e-health on neonatal intensive care unit discharged preterm infants and their parents: Protocol for systematic review and meta-analysis.

Background: After preterm birth, parents often conformed with difficulties such as negative emotions, lack of care knowledge and skills, and insufficient professional support. As a remote health guidance method, e-health can provide a series of support for premature infants and their parents during the transition period from neonatal intensive care unit (NICU) to home care. Objectives: To determine the efficacy of e-health interventions in discharged preterm infants as well as their parents, and to describe the process outcomes and elements of these e-health interventions to inform the effective design of future interventions. Methods: The systematic review of the randomized and non-randomized controlled trials on the follow-up effect of e-health on preterm infants and their parents discharged from NICU between the inception to May 2023 will be electronically searched in the following nine databases: Web of Science, CINAHL Complete (EBSCO), PubMed, Embase, the Cochrane Library, Ovid MEDLINE, China National Knowledge Infrastructure, WANFANG DATA, and SinoMed. Quality will be appraised, respectively, via the revised tool to assess risk of bias (RoB 2) and the tool for risk of bias in non-randomized studies of interventions (ROBINS-I). The main outcome indicators of preterm infants are breastfeeding rate, readmission rate, neurobehavioral development, and premature infant's body mass. The outcome indicators for parents of premature infants are anxiety, depression scale, and parenting competency scale. The RevMan 5.4 software provided by the Cochrane Collaboration will be used for statistical analysis of the data. Conclusion: The results of this study may provide future development opportunities for e-health follow-up prevention in preterm infants and may support evidence-based decision-making for e-health interventions of post-discharge developmental support in preterm infants. PROSPERO registration number: CRD42023410334.

Discovery of selective and potent USP22 inhibitors via structure-based virtual screening and bioassays exerting anti-tumor activity.

Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development, invasion, metastasis and immune reprogramming, which has been proposed as a potential therapeutic target for cancer. Herein, we employed a structure-based discovery and biological evaluation and discovered that Rottlerin (IC50 = 2.53 µM) and Morusin (IC50 = 8.29 µM) and as selective and potent USP22 inhibitors. Treatment of HCT116 cells and A375 cells with each of the two compounds resulted in increased monoubiquitination of histones H2A and H2B, as well as reduced protein expression levels of Sirt1 and PD-L1, all of which are known as USP22 substrates. Additionally, our study demonstrated that the administration of Rottlerin or Morusin resulted in an increase H2Bub levels, while simultaneously reducing the expression of Sirt1 and PD-L1 in a manner dependent on USP22. Furthermore, Rottlerin and Morusin were found to enhance the degradation of PD-L1 and Sirt1, as well as increase the polyubiquitination of endogenous PD-L1 and Sirt1 in HCT116 cells. Moreover, in an in vivo syngeneic tumor model, Rottlerin and Morusin exhibited potent antitumor activity, which was accompanied by an enhanced infiltration of T cells into the tumor tissues. Using in-depth molecular dynamics (MD) and binding free energy calculation, conserved residue Leu475 and non-conserved residue Arg419 were proven to be crucial for the binding affinity and inhibitory function of USP22 inhibitors. In summary, our study established a highly efficient approach for USP22-specific inhibitor discovery, which lead to identification of two selective and potent USP22 inhibitors as potential drugs in anticancer therapy.

Specific surface modification of liposomes for gut targeting of food bioactive agents.

Liposomes have become a research hotspot in recent years as food delivery systems with attractive properties, including the bilayer structure assembled like the cell membrane, reducing the side-effect and improving environmental stability of cargos, controlling release, extending duration of functional ingredients, and high biodegradable and biocompatible abilities in the body. However, the conventional liposomes lack stability during storage and are weak in targeted absorption in the gastrointestinal track. At present, surface modification has been approved to be an effective platform to shield these barricades and help liposomes deliver the agents safely and effectively to the ideal site. In this review, the gastrointestinal stability of conventional liposomes, cargo release models from liposomes, and the biological fate of the core materials after release were emphasized. Then, the strategies in both physical and chemical perspectives to improve the stability and utilization of liposomes in the gastrointestinal tract, and the emerging approaches for improving gut targeting by specifically modified liposomes and the intestinal receptors relative to liposomes/cargos absorption were highlighted. Last but not the least, the safety, challenges, and opportunities for the improvement of liposomal bioavailability were also discussed to inspire new applications of liposomes as oral carriers.

Large-scale renewable energy brings regionally disproportional air quality and health co-benefits in China.

Developing renewable energy could jointly reduce air pollution, greenhouse gas emissions, and bring air pollution-related health co-benefits. However, the temporal and sub-national distributions of investment costs and human health co-benefits from renewable energy deployment remain unclear. To investigate this gap, we linked multiple models for a more comprehensive assessment of the economic-environmental-health co-benefits of renewable energy development in China. The results show that developing renewable energy can avoid 0.6 million premature mortalities, 151 million morbidities, and 111 million work-loss days in 2050. Meanwhile, the human health and economic co-benefits vary substantially across regions in China. Renewable energy can undoubtedly bring health and economic co-benefits. Nevertheless, the economic benefits lag considerably behind the high initial investment cost, first negative in 2030 (-0.6 trillion Yuan) and then positive in 2050 (2.9 trillion Yuan). Hence, renewable energy deployment strategy must be carefully designed considering the regional disparities.