Metabolomics analysis of advancing humification mechanism in secondary fermentation of composting by fungal bioaugmentation.

The aim of this study was to investigate the differential metabolites and core metabolic pathways caused by fungal bioaugmentation (pH regulation and Phanerochaete chrysosporium inoculation) in secondary fermentation of composting, as well as their roles in advancing humification mechanism. Metabolomics analyses showed that inoculation strengthened the expression of carbohydrate, amino acid, and aromatic metabolites, and pH regulation resulted in the up-regulation of the phosphotransferase system and its downstream carbohydrate metabolic pathways, inhibiting Toluene degradation and driving biosynthesis of aromatic amino acids via the Shikimate pathway. Partial least squares path model suggested that lignocellulose degradation, precursors especially amino acids and their metabolism process enhanced by the regulation of pH and Phanerochaete were the main direct factors for humic acid formation in composting. This finding helps to understand the regulating mechanism of fungal bioaugmentation to improve the maturity of agricultural waste composting.

MiR-134-5p inhibits the malignant phenotypes of osteosarcoma via ITGB1/MMP2/PI3K/Akt pathway.

Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Quantifying chemical correlations between fruits and processed fruit products: A non-targeted analysis approach.

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.

Immune cells: potential carriers or agents for drug delivery to the central nervous system.

Drug delivery systems (DDS) have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery. However, the access of nanoparticles/drugs to the central nervous system (CNS) remains a challenge mainly due to the obstruction from brain barriers. Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery. Herein, we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood-brain barrier. We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS, as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases. Finally, we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.

Design advanced lithium metal anode materials in high energy density lithium batteries.

Nowadays, the ongoing electrical vehicles and energy storage devices give a great demand of high-energy-density lithium battery. The commercial graphite anode has been reached the limit of the theoretical capacity. Herein, we introduce lithium metal anode to demonstrate the promising anode which can replace graphite. Lithium metal has a high theoretical capacity and the lowest electrochemical potential. Hence, using lithium metal as the anode material of lithium batteries can reach the limit of energy and power density of lithium batteries. However, lithium metal has huge flaw such as unstable SEI layer, volume change and dendrites formation. Therefore, we give a review of the lithium metal anode on its issues and introduce the existing research to overcome these. Besides, we give the perspective that the engineering problems also restrict the commercial use of lithium metal. This review provides the reasonable method to enhance the lithium metal performance and give the development direction for the subsequent research.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

PSME2 offers value as a biomarker of M1 macrophage infiltration in pan-cancer and inhibits osteosarcoma malignant phenotypes.

A growing number of studies have revealed an association between proteasome activator complex subunit 2 (PSME2) and the progression of various forms of cancer. However, the effect of PSME2 on osteosarcoma progression is unknown. Pan-cancer analyses focused on the immunological activity and prognostic relevance of PSME2 have yet to be conducted. The Cancer Genome Atlas and Genome-Tissue Expression databases were leveraged to evaluate PSME2 expression and activity across 33 cancer types. Significant PSME2 dysregulation was noted in a wide range of cancer types and this gene was found to offer significant diagnostic and prognostic utility in most analyzed cancers. From a mechanistic perspective, PSME2 expression levels were correlated with DNA methylation, DNA repair, genomic instability, and TME scores in multiple cancer types. PSME2 was subsequently established as a pan-cancer biomarker of M1 macrophage infiltration based on a combination of bulk, single-cell, and spatial transcriptomic data and confirmatory fluorescent staining results. In osteosarcoma cells, overexpressing PSME2 significantly suppressed tumor proliferative, migratory, and invasive activity. Screening efforts also successfully identified the PSME2-activating drug irinotecan, which can synergistically promote the death of osteosarcoma cells when combined with the chemotherapeutic drug paclitaxel. As a biomarker of M1 macrophage infiltration, PSME2 expression levels may offer insight into tumor development and progression for a wide range of cancers including osteosarcoma, emphasizing its potential utility as a prognostic and therapeutic target worthy of further study.

Various interventions for cancer-related fatigue in patients with breast cancer: a systematic review and network meta-analysis.

Purpose: To investigate the effects of various intervention approaches on cancer-related fatigue (CRF) in patients with breast cancer. Method: Computer searches were conducted on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases from their establishment to June 2023. Selection was made using inclusion and exclusion criteria, and 77 articles were included to compare the effects of 12 interventions on patients with breast cancer. Results: Seventy-seven studies with 12 various interventions were examined. The network findings indicated that cognitive behavioral therapy (CBT) (SMD, -1.56; 95%CI, -3.08~-0.04), Chinese traditional exercises (CTE) (SMD, -0.85; 95%CI, -1.34~-0.36), aerobic exercise (AE) (SMD, -0.77; 95%CI, -1.09~-0.45), multimodal exercise (ME) (SMD, -0.75; 95%CI, -1.26~-0.25), music interventions (MI) (SMD, -0.74; 95%CI, -1.45~-0.03), and yoga (YG) (SMD, -0.44; 95%CI, -0.83 to -0.06) can reduce CRF more than the control group (CG). For relaxation exercises (RE) (MD, -6.69; 95%CI, -9.81~-3.57), MI (MD, -5.45; 95%CI, -7.98~-2.92), AE (MD, -4.34; 95%CI, -5.90~-2.78), ME (MD, -3.47; 95%CI, -4.95~-1.99), YG (MD, -2.07; 95%CI, -3.56~-0.57), and mindfulness training (MD, -1.68; 95%CI, -2.91~-0.46), PSQI improvement was superior to CG. In addition, for CTE (MD, 11.39; 95%CI, 4.11-18.66), YG (MD, 11.28; 95%CI, 1.63-20.93), and AE (MD, 9.34; 95%CI, 0.26~18.42), Functional Assessment of Cancer Therapy-Breast improvement was superior to CG. Conclusion: Cognitive behavioral therapy (CBT) is the most effective measure for alleviating CRF in patients with breast cancer and Relaxation exercises (RE) is the most effective measure for improving sleep quality. In addition, Chinese traditional exercises (CTE) is the best measure for enhancing quality of life. Additional randomized controlled trials (RCTs) are expected to further investigate the efficacy and mechanisms of these interventions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023471574.

Deciphering the carbon and nitrogen component conversion in humification process mediated by distinct microbial mechanisms in composting from different domestic organic wastes.

This study aimed to compare the process of maturity and humus fraction evolution as well as bacterial community dynamics in composting from different domestic organic wastes (food waste (FW), and vegetable waste (VW)) and decipher the key biotic influencing factors of humic acid formation through correlation analysis and ecological network. The results showed that organic carbon components in FW with high ratio of soluble organic carbon and hemicellulose were more easily to be degraded in composting compared to VW. After 30 days of composting, the content of HA-C generated by VW was 35.41%, higher than 29.01% of FW, and the growth rate of HA-C generated was 38.42% and 28.34%, respectively. PARAFAC analysis showed that the structure of HA generated in VW was more complex, and the proportion of humic acid-like components (C3 + C4) was 60.32%, while FW only accounted for 43.86%. However, the evolution growth rate of aromatic components in HA in FW was 26.88% in 30 days of compost, which was higher than 15.17% in VW. High-throughput sequencing indicated that Lactobacillus was the initial dominated genera in composting from different domestic wastes. Thermobifida, Thermovum, and Pusillimas as well as Aeribacillus were core bacterial genera that promoted the humification process in FW and VW, respectively. Network analysis showed that there was higher bacterial interacted connection degree and complexity in FW compared to VW. This study was of great significance for optimizing organics conversion and humification efficiency of household waste composting.

The economy-employment-environmental health transfer and embedded inequities of China's capital metropolitan area: a mixed-methods study.

BACKGROUND: Metropolitan areas have complex trade linkages internally and externally. This complexity stimulates the unequal spatial transfer of environmental health consequences, economy, and employment embodied in internal trade or trade with the outside regions, resulting in unequal exchange. Existing research has rarely discussed this issue at a refined scale, hindering targeted inequity alleviation policies. METHODS: We conducted a mixed-methods study, focusing on the most polluted metropolitan area in the world, the Beijing-Tianjin-Hebei region of China, and developed an integrated modelling framework to downscale the analysis of the trade-driven unequal transfer of PM2·5- related premature deaths, value added, and job opportunities to the city scale within Beijing-Tianjin-Hebei. The study couples a nested Multi-Regional Input-Output model table containing data from 13 Beijing-Tianjin-Hebei cities and 28 outer provinces in 2017 with a bottom-up emission inventory, value added and employment statistical data, the Weather Research and Forecasting-Comprehensive Air Quality Model with Extensions, the Global Exposure Mortality Model, and human capital methods. We also constructed two indices measuring unequal exchanges between PM2·5-related deaths and economic and employment gains embodied in trades between cities in Beijing-Tianjin-Hebei and trades with outside regions. FINDINGS: The Beijing-Tianjin-Hebei region as a single entity shifted 14 985 (95% CI 12 800-16 948) net deaths to regions outside the Beijing-Tianjin-Hebei through trade, most of which occurred in the central region of China. The industrial-based peripheral Beijing-Tianjin-Hebei cities suffered the most serious inequities when trading with other Beijing-Tianjin-Hebei cities and outside regions. While gaining equivalent local jobs, these industrial-based peripheral cities had 250% higher PM2·5-related deaths (10·2 PM2·5-related deaths for obtaining 1000 local jobs) than core cities (2·9 PM2·5-related deaths for obtaining 1000 local jobs) and 57·7% higher PM2·5-related deaths than agricultural-based peripheral cities (6·5 PM2·5-related deaths for obtaining 1000 local jobs). While gaining equivalent value added, industrial-based peripheral cities had 50·6% higher PM2·5-related deaths (¥13·9 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) than core cities (¥9·2 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added) and 67·4% higher PM2·5-related deaths than agricultural-based peripheral cities (¥8·3 of reduced human capital due to PM2·5-related premature deaths to obtain ¥1000 local value added). INTERPRETATION: Treating metropolitan areas as a single entity obscured internal heterogeneity, potentially misleading policy makers into imposing strict regulations on the whole metropolitan area to alleviate the inequities it posed on outside regions. However, several peripheral Beijing-Tianjin-Hebei cities were disadvantaged in their trade with core Beijing-Tianjin-Hebei cities and outside regions. Therefore, policies should be tailored for particular cities within metropolitan areas. Future targeted policies should include, but not be limited to, making ecological compensations and incorporating the environment and health costs into the price of pollution-intensive goods and services. FUNDING: National Key Research and Devlopment Program of China, National Natural Science Foundation of China, and Jiangsu Natural Science Foundation.

Comparing bacterial dynamics for the conversion of organics and humus components during manure composting from different sources.

The study aimed to compare the differences in organic fractions transformation, humus components and bacterial community dynamics during manure composting from different sources, and to identify the key biotic and abiotic factors driving the humification process. Five types of manure [pig manure (PM), cow dung (CD), sheep manure (SM), chicken manure (CM), and duck manure (DM)] were used as raw materials for 30 days composting. The results showed the obvious difference of organic fractions decomposition with more cellulose degradation in CD and SM composting and more hemicellulose degradation in PM and CM composting. Composting of PM and CD contained significantly higher humus fractions than the other composts. Fluorescence spectra indicated that SM composting tended to form structurally stable humic acid fractions, while CM and DM tended to form structurally complex fulvic acid fractions. Pearson correlation analysis showed that humification process of composts in category A (PM, CD) with higher humification degree than category B (SM, CM, and DM) was positively correlated with lignin and hemicellulose degradation. Bioinformatics analysis found that Lysinibacillus promoted the degradation of hemicellulose and the conversion of fulvic to humic acid in the composts of category A, and in category B, Thermobifida, Lactobacillus, and Ureibacillus were key genera for humic acid formation. Network analysis indicated that bacterial interaction patterns had obvious differences in composting with different humus and humification levels.

Bacillus licheniformis inoculation promoted humification process for kitchen waste composting: Organic components transformation and bacterial metabolic mechanism.

Kitchen waste (KW) composting always has trouble with slow humification process and low humification degree. The objective of this study was to develop potentially efficient solutions to improve the humification of KW composting, accelerate the humus synthesis and produce HS with a high polymerization degree. The impact of Bacillus licheniformis inoculation on the transformation of organic components, humus synthesis, and bacterial metabolic pathways in kitchen waste composting, was investigated. Results revealed that microbial inoculation promoted the degradation of organic constituents, especially readily degradable carbohydrates during the heating phase and lignocellulose fractions during the cooling phase. Inoculation facilitated the production and conversion of polyphenol, reducing sugar, and amino acids, leading to an increase of 20% in the content of humic acid compared to the control. High-throughput sequencing and network analysis indicated inoculation enriched the presence of Bacillus, Lactobacillus, and Streptomyces during the heating phase, while suppressing the abundance of Pseudomonas and Oceanobacillus, enhancing positive microbial interactions. PICRUSt2 analysis suggested inoculation enhanced the metabolism of carbohydrates and amino acids, promoting the polyphenol humification pathway and facilitating the formation of humus. These findings provide insights for optimizing the humification process of kitchen waste composting by microbial inoculation.

[Advances of Targeted Therapy for Acute Myeloid Leukemia--Review].

Acute myeloid leukemia (AML) has highly heterogeneous clinical manifestations and poor prognosis, and traditional chemotherapy is the main treatment. In recent years, with the in-depth development of next-generation sequencing technology, the treatment of AML is gradually exploring the precise targeted therapy in the direction of molecular biology and immunophenotype. The advent of various small-molecule inhibitors and immune-targeted drugs has brought hope to patients who cannot tolerate intensive chemotherapy or with relapsed/refractory AML. Compared with traditional chemotherapy, targeted therapy has the advantages of significant curative effect and fewer adverse effects. This article reviews the latest research progress of targeted drug therapy for AML.

Factors associated with graduation examination results from standardised residency training in Zhejiang Province, China: a cross-sectional analysis of medical examination results data from 2020.

OBJECTIVE: Standardised residency training is an important part of postgraduation medical education in China. The graduation examination tests the effect of residency training and is an important measure to guarantee the quality of residency training. This study aimed to analyse the results and associated factors of the graduation examination of standardised residency training in Zhejiang Province in 2020. DESIGN: Cross-sectional analysis of examination results data. SETTING: Medical and health institutions and universities in Zhejiang Province. PARTICIPANTS: A total of 5555 examinees took the graduation examination of standardised residency training in Zhejiang Province in 2020. PRIMARY OUTCOMES: Pass rates of the practical skill examination and written examination. RESULTS: The pass rates for the practical skill examination and written examination were 91.8% and 96.5%, respectively. Examinees aged 30 and above (adjusted OR (AOR)=0.48, 95% CI 0.26 to 0.89), those with 3 years (AOR=0.19, 95% CI 0.09 to 0.43) and 2 years (AOR=0.61, 95% CI 0.40 to 0.96) of training, those who retook the examination (AOR=0.28, 95% CI 0.20 to 0.391) and those from primary healthcare institutions (AOR=0.56, 95% CI 0.40 to 0.77) were less likely to pass the practical skill examination. Examinees with a postgraduate degree and those from colleges and universities had higher pass rates in the written examination (AOR=6.37, 95% CI 1.95 to 23.34; AOR=2.87, 95% CI 1.40 to 6.65, respectively). Examinees aged 30 and above (AOR=0.08, 95% CI 0.01 to 0.30), those aged between 25 and 30 (AOR=0.22, 95% CI 0.03 to 0.80), those who retook the examination (AOR=0.04, 95% CI 0.03 to 0.07), those from second-level hospitals (AOR=0.58, 95% CI 0.39 to 0.87) and those who failed the practical skill examination (AOR=0.17, 95% CI 0.12 to 0.25) were less likely to pass the written examination. CONCLUSIONS: The pass rate of the graduation examination of standardised residency training was associated with the individual characteristics of the examinees. The results of practical skill examination were related to the results of the written examination.

Regulating pH and Phanerochaete chrysosporium inoculation improved the humification and succession of fungal community at the cooling stage of composting.

This study aimed to explore the effect of regulating pH and Phanerochaete chrysosporium inoculation at the cooling stage of composting on the lignocellulose degradation, humification process and related precursors as well as fungal community for secondary fermentation. Results showed that composting with P. chrysosporium inoculation and pH regulation (T4) had 58% cellulose decomposition, 73% lignin degradation and improved enzyme activities for lignin decomposition. There was 81.98% increase of humic substance content and more transformation of polyphenols and amino acids in T4 compared to control. Inoculating P. chrysosporium affected the fungal community diversity, and regulating pH helped to increase the colonization of P. chrysosporium. Network analysis showed that the network complexity and synergy between microorganisms was improved in T4. Correlation and Random Forest analysis suggested that enriched Phanerochaete and Thermomyces in the mature stage of T4 were key taxa for lignocellulose degradation, and humic acid formation by accumulating precursors.

[Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ï¼»66 cases of them were screened by propensity score matching (PSM), as control groupï¼½. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION: Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Development of a novel vasculogenic mimicry-associated gene signature for the prognostic assessment of osteosarcoma patients.

BACKGROUND: Osteosarcoma (OS) is a form of primary bone malignancy associated with poor prognostic outcomes. Recent work has highlighted vasculogenic mimicry (VM) as a key mechanism that supports aggressive tumor growth. The patterns of VM-associated gene expression in OS and the relationship between these genes and patient outcomes, however, have yet to be defined. METHODS: Here, 48 VM-related genes were systematically assessed to examine correlations between the expression of these genes and OS patient prognosis in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohort. Patients were classified into three OS subtypes. Differentially expressed genes for these three OS subtypes were then compared with hub genes detected in a weighted gene co-expression network analysis, leading to the identification of 163 overlapping genes that were subject to further biological activity analyses. A three-gene signature (CGREF1, CORT, and GALNT14) was ultimately constructed through a least absolute shrinkage and selection operator Cox regression analysis, and this signature was used to separate patients into low- and high-risk groups. The K-M survival analysis, receiver operating characteristic analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. Furthermore, the expression patterns of three genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: VM-associated gene expression patterns were successfully established, and three VM subtypes of OS that were associated with patient prognosis and copy number variants were defined. The developed three-gene signature was constructed, which served as independent prognostic markers and prediction factors for the clinicopathological features of OS. Finally, lastly, the signature may also have a guiding effect on the sensitivity of different chemotherapeutic drugs. CONCLUSION: Overall, these analyses facilitated the development of a prognostic VM-associated gene signature capable of predicting OS patient outcomes. This signature may be of value for both studies of the mechanistic basis for VM and clinical decision-making in the context of OS patient management.

Large Virtual Transboundary Hazardous Waste Flows: The Case of China.

The Basel Convention and prior studies mainly focused on the physical transboundary movements of hazardous waste (transporting waste from one region to another for cheaper disposal). Here, we take China, the world's largest waste producer, as an example and reveal the virtual hazardous waste flows in trade (outsourcing waste by importing waste-intensive products) by developing a multiregional input-output model. Our model characterizes the impact of international trade between China and 140 economies and China's interprovincial trade on hazardous waste generated by 161,599 Chinese enterprises. We find that, in 2015, virtual hazardous waste flows in China's trade reached 26.6 million tons (67% of the national total), of which 31% were generated during the production of goods that were ultimately consumed abroad. Trade-related production is much dirtier than locally consumed production, generating 26% more hazardous waste per unit of GDP. Under the impact of virtual flows, 40% of the waste-intensive production and relevant disposal duty is unequally concentrated in three Chinese provinces (including two least-developed ones, Qinghai and Xinjiang). Our findings imply the importance of expanding the scope of transboundary waste regulations and provide a quantitative basis for introducing consumer responsibilities. This may help relieve waste management burdens in less-developed "waste havens".

Multiple metal exposure and metabolic syndrome in elderly individuals: A case-control study in an active mining district, Northwest China.

The prevalence of metabolic syndrome (MetS) is increasing at an alarming rate worldwide, particularly among elderly individuals. Exposure to various metals has been linked to the development of MetS. However, limited studies have focused attention on the elderly population living in active mining districts. Participants with MetS (N = 292) were matched for age (±2 years old) and sex with a healthy subject (N = 292). We measured the serum levels of 14 metals in older people aged 65-85 years. Conditional logistic regression, restricted cubic spline model, multiple linear regression, and Bayesian Kernel Machine Regression (BKMR) were applied to estimate potential associations between multiple metals and the risk of MetS. Serum levels of Sb and Fe were significantly higher than the controls (0.58 µg/L vs 0.46 µg/L, 2167 µg/L vs 2042 µg/L, p < 0.05), while Mg was significantly lower (20035 µg/L vs 20,394 µg/L, p < 0.05). An increased risk of MetS was associated with higher serum Sb levels (adjusted odds ratio (OR) = 1.61 for the highest tertile vs. the lowest tertile, 95% CI = 1.08-2.40, p-trend = 0.018) and serum Fe levels (adjusted OR = 1.55 for the highest tertile, 95% CI = 1.04-2.33, p-trend = 0.032). Higher Mg levels in serum may have potential protective effects on the development of MetS (adjusted OR = 0.61 for the highest tertile, 95% CI = 0.41-0.91, p-trend = 0.013). A joint exposure analysis by the BKMR model revealed that the mixture of 12 metals (except Tl and Cd) was associated with increased risk of MetS. Our results indicated that exposure to Sb and Fe might increase the risk of MetS in an elderly population living in mining-intensive areas. Further work is needed to confirm the protective effect of Mg on MetS.

Gomisin N attenuated cerebral ischemia-reperfusion injury through inhibition of autophagy by activating the PI3K/AKT/mTOR pathway.

BACKGROUND: Ischemic stroke is a major global cause of mortality and permanent disability.  Studies have shown that autophagy is essential to maintain cell homeostasis and inevitably lead to neuronal damage after cerebral ischemia. Gomisin N (GN), lignin isolated from Schisandra chinensis, possesses multiple pharmacological activities. However, there is no research on the potential of GN for neuroprotection in ischemic stroke. PURPOSE: The current work aimed to explore the potential therapeutic possibilities of GN on ischemic stroke and investigate the underlying molecular mechanisms. STUDY DESIGN: The neuroprotective effects of GN on PC12 cells induced by oxygen glucose deprivation/reoxygenation (OGD/R) and mice with middle cerebral artery occlusion/reperfusion (MCAO/R) injury were investigated. METHODS: On day 3 after ischemia, the infarct volume and neurological function were assessed. The level of autophagy was measured in vivo and in vitro using Transmission electron microscopy (TEM) and Monodansylcadaverine (MDC) staining. The interaction between GN and PI3K/AKT/mTOR pathway was investigated by molecular docking. Additionally, the expressions of critical proteins in the PI3K/AKT/mTOR signaling pathway and autophagy markers were determined by western blotting. RESULTS: In compared to the Model group, GN might considerably improve the neurological and locomotor function following a stroke, as well as lower the volume of the cerebral infarct volume and the number of autophagosomes. GN therapy may suppress autophagy by activating the PI3K/Akt/mTOR signaling pathway in the penumbra. In vitro, MDC and TEM results showed that GN treatment obviously suppressed autophagy. Meanwhile, GN downregulated LC3II/LC3I expression ratio while upregulated the p62 expression level. In further studies, GN dramatically boosted the expression ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR proteins in PC12 cells following OGD/R damage. However, the PI3K inhibitor (LY294002) reversed the increase of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR expression ratio induced by GN administration. Also, LY294002 significantly partially attenuated GN induced reduction of autophagy and increase of cell viability compared with GN treatment alone. CONCLUSIONS: Here, we first demonstrate the neuroprotective effects of GN on MCAO mice and OGD/R induced PC12 cells injury. A possible mechanism by which GN prevents ischemic stroke is proposed: GN could restrain autophagy by stimulating the PI3K/AKT/mTOR signaling pathways. More effects and mechanisms of GN on the rehabilitation of ischemic stroke are worthy to be explored in the future.