Mitigation and mechanism of low dose linoleic acid on depression caused by disorder of gut microbiome.

OBJECTIVES: Depression is a widely prevalent mental disorder, and nutritional interventions play an increasingly important role in its treatment. In this paper, effects of linoleic acid (LA) on depressive behavior in mice induced by gut microbiome disorders were investigated. METHODS: Fifty C57BL/6J male mice were randomly separated into five groups, control group (CK), ceftriaxone sodium group (CRO), low-dose linoleic acid group (LLA, 1 g/kg), medium-dose linoleic acid group (MLA, 2 g/kg), and high-dose linoleic acid group (HLA, 5 g/kg). In the LLA, MLA, and HLA groups, mice were treated with ceftriaxone sodium (CRO) to induce depressive behaviors, followed by LA administration. Behavioral tests were used to evaluate depressive behavior. High-throughput sequencing and Hematoxylin-eosin (H&E) staining in gut microenvironment were carried out. ELISA kits were used to measure brain inflammatory factors, and 5-hydroxy-tryptamine (5-HT). Gas chromatography and western blot were used to determine fatty acids compositions and the enzymes expression involved in lipid metabolism in brain respectively. RESULTS: The results showed that 10 weeks CRO treatment contribute to depressive behavior, gut microbiome disturbance, and serotonin system disturbance. LLA and MLA improved the depressive-like behavior, and significantly increased the levels of 5-HT1A, 5-HTT and 5-HT in the hippocampus. LLA was found to improve the diversity of gut microbiome and alleviate colon tissue damage. Meantime, LLA increased the content of linoleic acid, improved the expression of FADS2 and COX-2, increased IL-10 levels, and decreased IL-6 levels in the brain. DISCUSSION: LA alleviated depressive behavior in mice by improving the gut microenvironment, regulate fatty acid metabolism, and modulate inflammation.

Evolution of the Selection Methods of DNA-Encoded Chemical Libraries.

In the past two decades, a DNA-encoded chemical library (DEL or DECL) has emerged and has become a major technology platform for ligand discovery in drug discovery as well as in chemical biology research. Although based on a simple concept, i.e., encoding each compound with a unique DNA tag in a combinatorial chemical library, DEL has been proven to be a powerful tool for interrogating biological targets by accessing vast chemical space at a fraction of the cost of traditional high-throughput screening (HTS). Moreover, the recent technological advances and rapid developments of DEL-compatible reactions have greatly enhanced the chemical diversity of DELs. Today, DELs have been adopted by nearly all major pharmaceutical companies and are also gaining momentum in academia. However, this field is heavily biased toward library encoding and synthesis, and an underexplored aspect of DEL research is the selection methods. Generally, DEL selection is considered to be a massive binding assay conducted over an immobilized protein to identify the physical binders using the typical bind-wash-elute procedure. In recent years, we and other research groups have developed new approaches that can perform DEL selections in the solution phase, which has enabled the selection against complex biological targets beyond purified proteins. On the one hand, these methods have significantly widened the target scope of DELs; on the other hand, they have enabled the functional and potentially phenotypic assays of DELs beyond simple binding. An overview of these methods is provided in this Account.Our laboratory has been using DNA-programmed affinity labeling (DPAL) as the main strategy to develop new DEL selection methods. DPAL is based on DNA-templated synthesis; by using a known ligand to guide the target binding, DPAL is able to specifically establish a stable linkage between the target protein and the ligand. The DNA tag of the target-ligand conjugates serves as a programmable handle for protein characterization or hit compound decoding in the case of DEL selections. DPAL also takes advantage of the fast reaction kinetics of photo-cross-linking to achieve high labeling specificity and fidelity, especially in the selection of DNA-encoded dynamic libraries (DEDLs). DPAL has enabled DEL selections not only in buffer and cell lysates but also with complex biological systems, such as large protein complexes and live cells. Moreover, this strategy has also been employed in other biological applications, such as site-specific protein labeling, protein detection, protein profiling, and target identification. In the Account, we describe these methods, highlight their underlying principles, and conclude with perspectives of the development of the DEL technology.

Integrated Life Cycle Assessment for Sustainable Remediation of Contaminated Agricultural Soil in China.

Agricultural land degradation is posing a serious threat to global food security. Restoration of the degraded land has traditionally been viewed as an inherently sustainable practice; however, restoration processes render consequential environmental impacts which could potentially exceed the benefit of restoration itself. In the present study, an integrated life cycle assessment analysis was conducted to evaluate life cycle primary, secondary, and tertiary impacts associated with the restoration of the contaminated agricultural land. The results demonstrated the importance of including spatially differentiated impacts associated with managing the land and growing crops. Comparing four risk management scenarios at a contaminated field in Southern China, it was found that the primary and secondary impacts followed the order of no action > chemical stabilization > phytoextraction > alternative planting. However, when tertiary impacts were taken into account, alternative planting rendered much higher footprint in comparison with phytoextraction and chemical stabilization, which provides evidence against an emerging notion held by some policy makers. Furthermore, assuming that the loss of the rice paddy field in Southern China is compensated by the deforested land in the Amazon rainforest, the total global environmental impact would far exceed that of no action, resulting in 687 ton CO2-e ha-1 of climate change impact. Overall, the present study provides new research findings to support more holistic policy making and also sheds lights on the future development of various restoration technologies.

Selection of DNA-Encoded Dynamic Chemical Libraries for Direct Inhibitor Discovery.

Dynamic combinatorial libraries (DCLs) is a powerful tool for ligand discovery in biomedical research; however, the application of DCLs has been hampered by their low diversity. Recently, the concept of DNA encoding has been employed in DCLs to create DNA-encoded dynamic libraries (DEDLs); however, all current DEDLs are limited to fragment identification, and a challenging process of fragment linking is required after selection. We report an anchor-directed DEDL approach that can identify full ligand structures from large-scale DEDLs. This method is also able to convert unbiased libraries into focused ones targeting specific protein classes. We demonstrated this method by selecting DEDLs against five proteins, and novel inhibitors were identified for all targets. Notably, several selective BD1/BD2 inhibitors were identified from the selections against bromodomain 4 (BRD4), an important anti-cancer drug target. This work may provide a broadly applicable method for inhibitor discovery.

Validation of chronic kidney disease risk categorization system in Chinese patients with kidney disease: A cohort study.

AIM: To validate the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines risk stratification system based on the combination of estimated glomerular filtration rate (eGFR) and proteinuria. METHODS: This was a cohort study. A total of 1219 study population were recruited. Estimated GFR and proteinuria measured by using 24 h urine protein excretion rate (PER) were predictors. Adverse outcomes included all-cause mortality (ACM) and end-stage renal disease (ESRD). Follow-up was done by regular visit, telephone interview and electronic medical records. RESULTS: Over a median follow-up of 4.6 years, 153 (12.6%) and 43 (3.5%) patients experienced ESRD and ACM, respectively. On multivariable analysis, the adjusted hazard ratio for ESRD and ACM (compared with patients with eGFR > 60 mL/min per 1.7 m²) was of 29.8 and 3.6 for those with eGFR of 15-29 mL/min per 1.73 m², respectively. The adjusted hazard ratio for ESRD and ACM (compared with patients with PER < 150 mg/24h) was of 15.9 and 3.9 for those with PER > 500 mg/24h. Higher KDIGO guidelines risk categories (indicating lower eGFR or higher proteinuria) were associated with a graded increase in the risk for the ESRD (P < 0.001) and ACM (P < 0.001). Reclassification of KDIGO guidelines risk categories yielded net reclassification improvements for those with ESRD or ACM event (NRIevents ) of 33.3% or 30.2%. CONCLUSION: Lower eGFR and higher proteinuria are risk factors for ESRD and ACM in Chinese patients. The KDIGO guidelines risk categorization system assigned patients who went on to have the event to more appropriate CKD risk categories.

[Clinical evaluation of cell population data parameters in predicting engraftment after hematopoietic stem cell transplantation].

OBJECTIVE: To explore the cell population data (CPD) parameters of DxH800 hematology analyzer in predicting engraftment after hematopoietic stem cell transplantation. METHODS: Data from 109 patients who underwent hematopoietic stem cell transplantation at Peking University First Hospital between July 2013 and September 2014 were selected, all CBC data including CPD parameters from the beginning to engraftment (absolute neutrophil count > 500/µl) were gathered and analyzed to find the early markers of myeloid engraftment and establish the cut-off value. RESULTS: The makers which could predict myeloid engraftment were mean neutrophil volume (MNV) and mean monocyte volume (MMV), the cut-off value was ≥ 180 fl and ≥ 190 fl, respectively, and engraftment was predicted earlier (2.2 ± 1.3) days and (2.3 ± 1.7) days than absolute neutrophil count. CONCLUSION: By analyzing the CPD data of DxH800 hematology analyzer, engraftment can be predicted approximately 2 days earlier than absolute neutrophil count.

[Clinical application of low hemoglobin density in screening for iron deficiency and the differential diagnosis of anemia].

OBJECTIVE: To investigate the clinical usefulness of the low hemoglobin density (LHD) and other red blood cell parameters in screening for iron deficiency (ID) and distinguishing iron deficiency anemia (IDA) from other kinds of anemia. METHOD: Whole blood count (CBC) and parameters of iron metabolism of the patients with ID (n = 251), IDA(n = 155), anemia of chronic disease(n = 90), renal anemia(n = 184), acute hemorrhagic anemia(n = 27) and non-anemia subjects(n = 82) were analysed by Advia 2120 hematology analyzer, Hitachi 7180 automatic biochemical analyzer, Beckman-Coulter DxI 800 immunoassay analyzer. SPSS 13.0 software was applied to anylyze data. RESULTS: The sensitivity of LHD in screening for ID was 67.2%, which was significantly higher than MCHC (38.8%) . There was a sensitivity of 91.2% for ID screening by combination of LHD and RDW. LHD only increased greatly in IDA (14.9%) group, while had no increase in other anemia. CONCLUSION: LHD is a reliable new marker with certain clinical usefulness. Combination of LHD and RDW is more suitable for screening ID. LHD is also a useful marker to distinguish IDA from other kinds of anemia.

Comparative life-cycle sustainability assessment of centralized and decentralized remediation strategies at the city level.

Remediation of contaminated soil at industrial sites has become a challenge and an opportunity for sustainable urban land use, considering the substantial secondary impacts resulting from remediation activities. The design of soil remediation strategies for multi-site remediation from a regional perspective is of great significance for cities with a large number of brownfields. Centralized and decentralized facilities have been studied in different environmental fields, yet limited research has focused on centralized soil remediation, specifically the treatment of contaminated soil from different sites through the construction of shared soil treatment facilities. This study proposes a framework for comparing centralized and decentralized strategies for contaminated soil remediation based on the integration of life-cycle sustainability assessment and multi-objective optimization. With Zhuzhou, an industrial city in China, serving as an example, results show that after optimization, the centralized scenario can reduce total environmental impacts by 25 %-41 %. In addition, the centralized scenario can reduce economic costs by 27 %-39 %, saving up to 176 million USD. The advantages of the centralized soil remediation strategy include: (1) increased use of soil washing, (2) reduced use of off-site disposal, and (3) reduced construction and efficient utilization of soil treatment facilities. In conclusion, the centralized strategy is relatively suitable for cities or areas with a large number of medium or small-sized contaminated sites. The built framework can quantitatively evaluate multiple sites soil remediation at both the city and individual site level, allowing for a straightforward and objective comparison with the optimal remediation design.

Sustainability assessment and carbon budget of chemical stabilization based multi-objective remediation of Cd contaminated paddy field.

The feasibility of chemical stabilization-based strategy for extensive field application is under debate due to lacking a proper framework for its sustainability assessment during its life cycle. Herein, a comprehensive framework consisting of crop production, soil quality, and carbon footprint was constructed for assessing agricultural land remediation based on a two-year paddy field trial. Results show that between the two representative agents, biochar scenario substantially benefits for environmental, social, and agricultural sustainability, because of its more positive impacts on human health and ecosystem, public acceptance, soil reproductive, and rice yield. A notably higher sustainability score of 80.7 for biochar scenario than that of 47.0 for lime is found, in spite of the economical sustainability of lime. The net ecosystem carbon budget of the biochar scenario exhibits an unprecedentedly positive value of 17.8 t CO2-eq ha-1, which can finely contribute to a positive carbon budget during remediation. Our finding demonstrates that biochar strategy enables a multi-objective achievement of soil quality - crop production - carbon budget during agricultural land remediation. This study provides new insights into sustainability assessment for restoring agricultural land for safe crop production and synergizing with carbon neutral plan.

Introducing aldehyde functionality to proteins using ligand-directed affinity labeling.

Aldehyde is a versatile chemical handle for protein modification. Although many methods have been developed to label proteins with aldehyde, target-specific methods amenable to endogenous proteins are limited. Here, we report a simple affinity probe strategy to introduce aldehydes to native proteins. Notably, the probe contains a latent aldehyde functionality that is only exposed upon target binding, thereby enabling a one-pot labeling procedure.

Synthesis of ortho-Phenolic Sulfilimines via an Intermolecular Sulfur Atom Transfer Cascade Reaction.

To expand the toolbox for the synthesis of ortho-phenolic sulfilimines, sigmatropic rearrangements were introduced to the field of sulfilimine chemistry. Herein we report a N-H sulfenylation/[2,3]-sigmatropic rearrangement cascade reaction. This mild reaction enables commercially available thiols to serve as the sulfenylation reagent and generates water as the sole byproduct. Moreover, the reaction has a wide substrate scope and can be conducted on a gram scale with excellent reaction efficiency.

Microplastics undergo accelerated vertical migration in sand soil due to small size and wet-dry cycles.

Microplastics (MPs) are an emerging concern and potential risk to marine and terrestrial environments. Surface soils are reported to act as a sink. However, MP vertical mobility in the subsurface remains uncertain due to a lack of scientific data. This study focused on MP penetration in sand soil column experiments. Here we report the mobility of five different MPs, which consisted of polyethylene (PE) and polypropylene (PP) particles of various sizes and densities. We observed that the smallest sized PE MPs (21 µm) had the greatest movement potential. Moreover, it was found that when these MPs were subjected to greater numbers of wet-dry cycles, the penetration depth significantly increased, with an apparent linear relationship between depth and wet-dry cycle number (r2 = 0.817). In comparison, increasing the volume of infiltration liquid or the surface MP concentration had only negligible or weak effects on migration depth (r2 = 0.169 and 0.312, respectively). Based on the observed wet-dry cycle trend, we forecast 100-year penetration depths using weather data for 347 cities across China. The average penetration depth was calculated as 5.24 m (95% CI = 2.78-7.70 m), with Beijing Municipality and Hebei, Henan and Hubei provinces being the most vulnerable to MP vertical dispersion. Our results suggest that soils may not only represent a sink for MPs, but also a feasible entryway to subsurface receptors, such as subterranean fauna or aquifers. Finally, research gaps are identified and suggested research directions are put forward to garner a better understanding MP vertical migration in soil.

Nature based solutions for contaminated land remediation and brownfield redevelopment in cities: A review.

Urban industrialization has caused severe land contamination at hundreds of thousands of sites in cities all around the world, posing a serious health risk to millions of people. Many contaminated brownfield sites are being left abandoned due to the high cost of remediation. Traditional physical and chemical remediation technologies also require high energy and resource input, and can result in loss of land functionality and cause secondary pollution. Nature-based solutions (NBS) including phytoremediation and conversion of brownfield sites to public greenspaces, holds much promise in maximizing a sustainable urban renaissance. NBS is an umbrella concept that can be used to capture nature based, cost effective and eco-friendly treatment technologies, as well as redevelopment strategies that are socially inclusive, economically viable, and with good public acceptance. The NBS concept is novel and in urgent need of new research to better understand the pros and cons, and to enhance its practicality. This review article summarizes NBS's main features, key technology choices, case studies, limitations, and future trends for urban contaminated land remediation and brownfield redevelopment.

Environmental and socio-economic sustainability appraisal of contaminated land remediation strategies: A case study at a mega-site in China.

Green and sustainable remediation (GSR) has become a global trend in the contaminated land remediation field. Growing numbers of countries have adopted GSR procedures published in regulatory and/or technical guidance. China is fast becoming one of the largest remediation markets in the world, and is beginning to engage with GSR. Among other efforts, a taskforce is currently developing the first Chinese technical standard on GSR. This paper presents the context positioning and development of a sustainable remediation assessment indicator set for China. This sustainability indicator set was formed based on existing sustainable remediation guidelines and literature. LCA was used to evaluate environmental impacts, and the results combined with social and economic appraisal via MCA. The indicator set was applied to a remediation 'mega-site' in China. The results showed that compared to excavation and landfill, an alternative treatment strategy of soil washing, thermal desorption and S/S brought about relatively less waste generation, better worker safety, and preferable local impacts, leading to higher scores in the environmental and social-economic domains. However, the social-economic scores were limited by a lack of public engagement. The results of the case study have shown that the indicator set is valid, with lessons learnt and suggestions for improvement discussed.

Sustainable in situ remediation of recalcitrant organic pollutants in groundwater with controlled release materials: A review.

The removal of recalcitrant organic pollutants in groundwater is a challenge being faced around the world. Achieving effective long-term remediation of contaminated aquifers faces a variety of significant issues such as back diffusion, tailing, and rebound. In recent years, some researchers have proposed the use of controlled release materials (CRMs) as a new approach to counteracting such issues. The novelty of CRMs lies in that they release their active products slowly, over prolonged periods of time, in order to sustain in situ treatments and long-term effectiveness. Here we review the main constituents of CRMs, analyze their production, characterization, and applications, with a focus on reaction mechanisms, effectiveness, and secondary effects. This review shows that the reactive components of CRMs most commonly involve either: (i) chemical oxidants to treat contaminants such as TCE, PCE, BTEX, and 1,4-Dioxane; (ii) sources of dissolved oxygen to stimulate aerobic biodegradation of contaminants such as BTEX and 1,4-Dioxane; or, (iii) substrates that stimulate reductive dechlorination of contaminants such as TCE and 1,2-DCA. It was found that in some studies, CRMs provided sustained delivery of CRM treatment reagents over several years, and achieved complete contaminant removal. However, lower removal rates were apparent in other cases, which may be ascribed to insufficient dispersion in the subsurface. There are a relatively limited number of field-scale applications of CRMs in contaminated land remediation. Those conducted to date suggest that CRMs could prove to be an effective future remediation strategy. Lessons learned from field applications, suggestions for future research directions, and conclusions are put forward in this review.

Lead-based paint remains a major public health concern: A critical review of global production, trade, use, exposure, health risk, and implications.

Human exposure to lead (Pb) is a growing global public health concern. Elevated blood lead is thought to cause the mental retardation of >0.6 million children globally each year, and has recently been attributed to ~18% of all-cause mortality in the US. Due to the severe health risk, the international community, led by the United Nations Environment Programme (UNEP) and the World Health Organization (WHO), is actively supporting the global phase-out of lead-based paint by 2020. However, there are many significant hurdles on the way to achieving this goal. In light of the importance of the lead-based paint issue, and the urgency of achieving the 2020 phase-out goal, this review provides critical insights from the existing scientific literature on lead-based paint, and offers a comprehensive perspective on the overall issue. The global production and international trade of lead-based paints across Asia, Africa, Latin America, and Europe are critically discussed - revealing that lead-based paints are still widely used in many low and middle-income developing countries, and that the production and trade of lead-based paint is still wide-spread globally. In India, as well as many south-east Asian, African, Latin American and European countries, lead concentrations in paints often exceed 10,000 mg/kg. This will certainly pose a serious global threat to public health from surfaces painted with these products for many decades to come. The sources and pathways of exposure are further described to shed light on the associated health risk and socioeconomic costs. Finally, the review offers an overview of the potential intervention and abatement strategies for lead-based paints. In particular, it was found that there is a general lack of consensus on the definition of lead based paint; and, strengthening regulatory oversight, public awareness, and industry acceptance are vital in combating the global issue of lead based paint.

Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1ß (IL-1ß2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1ß mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.