Low-Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells.

Intervention of the gut microbiome is a promising adjuvant strategy in cancer immunotherapy. Chemotherapeutic agents are recognized for their substantial impacts on the gut microbiome, yet their therapeutic potential as microbiome modulators remains uncertain, due to the complexity of microbiome-host-drug interactions. Here, it is showed that low-dose chemotherapy preferentially shapes the ileal microbiome to augment the extraintestinal immune response to anti-programmed death-1 (anti-PD-1) therapy without causing intestinal toxicity. Mechanistically, low-dose chemotherapy causes DNA damage restricted to highly-proliferative ileal epithelial cells, resulting in the accumulation of cytosolic dsDNA and the activation of the absent in melanoma 2 (AIM2) inflammasome. AIM2-dependent IL-18 secretion triggers the interplay between proximal Th1 cells and Paneth cells in ileal crypts, impairing the local antimicrobial host defense and resulting in ileal microbiome change. Intestinal epithelium-specific knockout of AIM2 in mice significantly attenuates CPT-11-caused IL-18 secretion, Paneth cell dysfunction, and ileal microbiome alteration. Moreover, AIM2 deficiency in mice or antibiotic microbial depletion attenuates chemotherapy-augmented antitumor responses to anti-PD1 therapy. Collectively, these findings provide mechanistic insights into how chemotherapy-induced genomic stress is transduced to gut microbiome change and support the rationale of applying low-dose chemotherapy as a promising adjuvant strategy in cancer immunotherapy with minimal toxicity.

Microplastics as emerging contaminants in textile dyeing sludge: Their impacts on co-combustion/pyrolysis products, residual metals, and temperature dependency of emissions.

As emerging contaminants in textile dyeing sludge (TDS), the presence and types of microplastics (MPs) inevitably influence the combustion and pyrolysis of TDS. Their effects on the co-combustion/pyrolysis emissions and residual metals of TDS remain poorly understood. This study aimed to quantify the impacts of polyethylene (PE) and polypropylene (PP) on the transports and transformations of gaseous emissions and residual metals generated during the TDS combustion and pyrolysis in the air, oxy-fuel, and nitrogen atmospheres. Thermal degradation of the MPs in TDS occurred between 242-600 °C. MPs decomposed and interacted with the organic components of TDS to the extent that they increased the release of VOCs, dominated by oxygenated VOCs and hydrocarbons under the incineration and pyrolysis conditions, respectively. The presence of PE exerted a limited impact on the concentration and chemical form of metals, while PP reduced the residual amount of most metals due to the decomposition of mineral additives. Also, PP (with CaCO3 filler) reduced the acid-extractable content of cadmium, copper, and manganese in the bottom slag or coke but increased that of chromium. This study provides actionable insights into optimizing gas emissions, energy recovery, and ash reuse, thus reinforcing the pollution control strategies for both the MPs and TDS.

A new strategy for enhanced electrochemically activation of persulfate on B and Co co-modified carbon felt in flow-through system for efficient organic pollutants degradation.

Electrochemical activation of persulfate (EA-PS) is gradually attracting attention as an emerging method for wastewater treatment. In this study, a novelty flow-through EA-PS system was first attempted for pollutants degradation using boron and cobalt co-doping carbon felt (B, Co-CF) as the cathode. SEM images, XPS and XRD spectra of B, Co-CF were investigated. The optimal doping ration between B and Co was 1:2. Increasing current density, PS concentration and flow rate, decreasing initial pH accelerated the removal of AO7. The mechanism involved in EA-PS were the comprehensive effect of DET, •OH and SO4•-. B, Co-CF cathode for flow-through system was stable with five cycles efficient AO7 decay performance. EA-PS in flow-through system was an efficient method with low cost and efficient pollutants degradation. This work provides a feasible strategy for synergistically enhancing PS activation and promoting the degradation of organic pollutants.

Mechanisms of Heat-Treatment-Induced Cracking in Additively Manufactured IN738 Alloy.

The present study conducts a comprehensive study on heat-treatment-induced cracking of Inconel 738 (IN738) alloy fabricated by laser powder bed fusion (LPBF) using scanning electron microscopy (SEM), energy dispersion spectrum (EDS), and electron backscatter diffraction (EBSD). The results indicate that the macroscopic crack is dominantly triggered by the strain-age cracking mechanism and propagates along grain boundaries. The initiation of cracking is facilitated by the superimposition of residual stress induced by the LPBF process and contraction stress induced by precipitation, while the reopening of compress pores at grain boundaries weakens the grain boundaries and provides fast channels for cracking. These results revealed the coupling effects in triggering heat-treatment-induced cracking, offering a fundamental guideline for crack control during heat treatment of additively manufactured IN738 alloy.

Association of Hepatic Steatosis with Adipose and Muscle Mass and Distribution in Children.

Background: Pediatric studies have shown associations between hepatic steatosis and total body fat, visceral fat, and lean mass. However, these associations have not been assessed simultaneously, leaving their relative importance unknown. Objective: To evaluate associations between hepatic steatosis and total-body adiposity, visceral adiposity, and lean mass in children. Method: In children at risk for fatty liver, hepatic steatosis, adipose, and lean mass were estimated with magnetic resonance imaging and dual-energy X-ray absorptiometry. Results: Two hundred twenty-seven children with mean age 12.1 years had mean percent body fat of 38.9% and mean liver fat of 8.4%. Liver fat was positively associated with total-body adiposity, visceral adiposity, and lean mass (P < 0.001), and negatively associated with lean mass percentage (P < 0.001). After weight adjustment, liver fat was only positively associated with measures of central adiposity (P < 0.001). Visceral adiposity also had the strongest association with liver fat (P < 0.001). Conclusions: In children, hepatic steatosis is more strongly associated with visceral adiposity than total adiposity, and the association of lean mass is not independent of weight or fat mass. These relationships may help guide the choice of future interventions to target hepatic steatosis.

Causal Inference of Central Nervous System-Regulated Hormones in COVID-19: A Bidirectional Two-Sample Mendelian Randomization Study.

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies of the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. DHEA was associated with increased risks of very severe respiratory syndrome (odds ratio [OR] = 4.21, 95% confidence interval [CI]: 1.41-12.59), consistent with multivariate MR results (OR = 3.72, 95% CI: 1.20-11.51), and hospitalization (OR = 2.31, 95% CI: 1.13-4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR = 0.83; 95% CI: 0.71-0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR = 0.09, 95% CI: 0.02-0.51), hospitalization (OR = 0.25, 95% CI: 0.08-0.78), and susceptibility (OR = 0.50, 95% CI: 0.28-0.89) in multivariate MR. We found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes.

Conceptual Design of the "Private Car" Self-Isolation Ecosystem for the 2019-nCoV Infection.

Since the beginning of the COVID-19 outbreak, confirmed and suspected cases of the disease have been increasing rapidly. The isolation of cases is one of the most effective methods for the control and containment of COVID-19 and has been rapidly popularized. Problems with isolation have gradually emerged, such as the inadequate allocation of isolation resources and the failure to properly resettle many of the suspected cases of the 2019-nCoV infection. In this paper, a self-isolation ecosystem of a rapid-deploying negative-pressurized "private car" is proposed for housing patients with 2019-nCoV infection, which could be lightweight, moderately sized and transparent to enable group supervision and communication. This "private car" isolation method aims to achieve self-isolation of patients and essentially solves the problem of where and how to isolate suspected cases while saving isolation resources and preventing the large-scale transmission of COVID-19.

Homocysteine-specific fluorescence detection and quantification for evaluating S-adenosylhomocysteine hydrolase activity.

Studies have shown that homocysteine (Hcy) levels are closely related to cardiovascular and cerebrovascular diseases. In this work, we have developed and synthesized three copper complexes, F542-Cu2+, F508-Cu2+, and F465-Cu2+ for Hcy detection. The different binding constants (Ks) of the copper complexes endow them with dramatic reactivity toward biothiols. The pyridine-containing tetraazacycle was employed in the construction of F542-Cu2+, which renders the medium Ks value for the copper complex compared with cyclen and TACN and effectively prevented the disintegration of the complexes. Pyridine-containing tetraazacycle provided the basis and possibility for the hypothesis for the reduction of Cu2+ by biothiols to shape into a stable six-membered ring structure. The obtained results verified that F542-Cu2+ could be utilized to specifically probe Hcy in a switched-on fluorescence mode. F542-Cu2+ exhibited excellent environmental stability, superior sensitivity, and outstanding selectivity toward Hcy under physiological conditions. The mechanism of Hcy specificity was confirmed to be related to the generation of Hcy-induced six-membered ring by fluorescence imaging, time-dependent fluorescence spectra, ESI-MS, and electron paramagnetic resonance (EPR) analyses. Furthermore, we exploited the application of F542-Cu2+ and developed a strategy for evaluating the activity of S-adenosylhomocysteine hydrolase (AHCY) in vitro by fluorescence analysis. More importantly, real-time in vivo evaluation of the enzymatic activity of AHCY was realized and assisted by our probe, providing the possibility of opening up a new avenue for enzymatic reaction assessment.

Revealing the Key MSCs Niches and Pathogenic Genes in Influencing CEP Homeostasis: A Conjoint Analysis of Single-Cell and WGCNA.

Degenerative disc disease (DDD), a major contributor to discogenic pain, which is mainly resulted from the dysfunction of nucleus pulposus (NP), annulus fibrosis (AF) and cartilage endplate (CEP) cells. Genetic and cellular components alterations in CEP may influence disc homeostasis, while few single-cell RNA sequencing (scRNA-seq) report in CEP makes it a challenge to evaluate cellular heterogeneity in CEP. Here, this study conducted a first conjoint analysis of weighted gene co-expression network analysis (WGCNA) and scRNA-seq in CEP, systematically analyzed the interested module, immune infiltration situation, and cell niches in CEP. WGCNA and protein-protein interaction (PPI) network determined a group of gene signatures responsible for degenerative CEP, including BRD4, RAF1, ANGPT1, CHD7 and NOP56; differentially immune analysis elucidated that CD4+ T cells, NK cells and dendritic cells were highly activated in degenerative CEP; then single-cell resolution transcriptomic landscape further identified several mesenchymal stem cells and other cellular components focused on human CEP, which illuminated niche atlas of different cell subpopulations: 8 populations were identified by distinct molecular signatures. Among which, NP progenitor/mesenchymal stem cells (NPMSC), also served as multipotent stem cells in CEP, exhibited regenerative and therapeutic potentials in promoting bone repair and maintaining bone homeostasis through SPP1, NRP1-related cascade reactions; regulatory and effector mesenchymal chondrocytes could be further classified into 2 different subtypes, and each subtype behaved potential opposite effects in maintaining cartilage homeostasis; next, the potential functional differences of each mesenchymal stem cell populations and the possible interactions with different cell types analysis revealed that JAG1, SPP1, MIF and PDGF etc. generated by different cells could regulate the CEP homeostasis by bone formation or angiogenesis, which could be served as novel therapeutic targets for degenerative CEP. In brief, this study mainly revealed the mesenchymal stem cells populations complexity and phenotypic characteristics in CEP. In brief, this study filled the gap in the knowledge of CEP components, further enhanced researchers' understanding of CEP and their cell niches constitution.

Dynamic pyrolytic reaction mechanisms, pathways, and products of medical masks and infusion tubes.

Given the COVID-19 epidemic, the quantity of hazardous medical wastes has risen unprecedentedly. This study characterized and verified the pyrolysis mechanisms and volatiles products of medical mask belts (MB), mask faces (MF), and infusion tubes (IT) via thermogravimetric, infrared spectroscopy, thermogravimetric-Fourier transform infrared spectroscopy, and pyrolysis-gas chromatography/mass spectrometry analyses. Iso-conversional methods were employed to estimate activation energy, while the best-fit artificial neural network was adopted for the multi-objective optimization. MB and MF started their thermal weight losses at 375.8 °C and 414.7 °C, respectively, while IT started to degrade at 227.3 °C. The average activation energies were estimated at 171.77, 232.79, 105.14, and 205.76 kJ/mol for MB, MF, and the first and second IT stages, respectively. Nucleation growth for MF and MB and geometrical contraction for IT best described the pyrolysis behaviors. Their main gaseous products were classified, with a further proposal of their initial cracking mechanisms and secondary reaction pathways.

High-Throughput Sequencing Reveals CXCR4 and IGF1 Behave Different Roles in Weightlessness Osteoporosis.

Objective: This study is aimed at screening the differential expression profiles of mRNA under weightlessness osteoporosis through high-throughput sequencing technology, as well as investigating the pathogenesis of weightlessness osteoporosis at the molecular level especially in bone marrow mesenchymal stem cells (BMSCs). Methods: The mouse bone marrow mesenchymal stem cell line was divided into ground group and simulated microgravity (SMG) group. BMP-2 was used to induce osteogenic differentiation, and SMG group was placed into 2D-gyroscope to simulate weightless condition. Transcriptome sequencing was performed by Illumina technology, DEGs between ground and SMG group was conducted using the DEseq2 algorithm. Molecular functions and signaling pathways enriched by DEGs were then comprehensively analyzed via multiple bioinformatic approaches including but not limited to GO, KEGG, GSEA, and PPI analysis. Results: A total of 263 DEGs were identified by comparing these 2 groups, including 186 upregulated genes and 77 downregulated genes. GO analysis showed that DEGs were enriched in osteoblasts, osteoclasts cell proliferation, differentiation, and apoptosis; KEGG analysis revealed that DEGs were significantly enriched in the TNF signaling pathway and FoxO signaling pathway; the enrichment results from Reactome database displayed that DEGs were mainly involved in the transcription of Hoxb3 gene, RUNX1 recruitment KMT2A gene, and activation of Hoxa2 chromatin signaling pathway. The four genes, IL6, CXCR4, IGF1, and PLOD2, were identified as hub genes for subsequent analysis. Conclusions: This study elucidated the significance of 10 hub genes in the development of weightlessness osteoporosis. In addition, the results of this study provide a theoretical basis and novel ideas for the subsequent research of the pathogenesis and clinical treatment of weightlessness osteoporosis.

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD.

Objectives: Intervertebral disc degeneration is a progressive and chronic disease, usually manifesting as low back pain. This study aimed to screen effective biomarkers for medical practice as well as figuring out immune infiltration situations between circulation and intervertebral discs. Methods: Gene expression profiles of GSE124272 was included for differentially analysis, WGCNA and immune infiltration analysis from GEO database, and other GSE series were used as validation datasets. A series of validation methods were conducted to verify the robustness of hub genes, such as principal component analysis, machine learning models, and expression verification. Lastly, nomogram was established for medical practice. Results: 10 genes were commonly screened via combination of DEGs, WGCNA analysis and lipid metabolism related genes. Furthermore, 3 hub gens CYP27A1, FAR2, CYP1B1 were chosen for subsequent analysis based on validation of different methods. GSEA analysis discovered that neutrophil extracellular traps formation and NOD-like receptor signaling pathway was activated during IDD. Immune infiltration analysis demonstrated that the imbalance of neutrophils and γδT cells were significantly correlated with IDD progression. Nomogram was established based on CYP27A1, FAR2, CYP1B1 and age, the calibration plot confirmed the stability of our model. Conclusion: CYP27A1, FAR2, CYP1B1 were considered as hub lipid metabolism related genes (LMRGs) in the development of IDD, which were regarded as candidate diagnostic biomarkers especially in circulation. The effects are worth expected in the early diagnosis of IDD through detecting these genes in blood.

Co-combustion, life-cycle circularity, and artificial intelligence-based multi-objective optimization of two plastics and textile dyeing sludge.

Given the globally abundant availability of waste plastics and the negative environmental impacts of textile dyeing sludge (TDS), their co-combustion can effectively enhance the circular economies, energy recovery, and environmental pollution control. The (co-)combustion performances, gas emissions, and ashes of TDS and two plastics of polypropylene (PP) and polyethylene (PE) were quantified and characterized. The increased blend ratio of PP and PE improved the ignition, burnout, and comprehensive combustion indices. The two plastics interacted with TDS significantly in the range of 200-600 â„ƒ. TDS pre-ignited the combustion of the plastics which in turn promoted the combustion of TDS. The co-combustions released more CO2 but less CH4, C-H, and CO as CO2 was less persistent than the others in the atmosphere. The Ca-based minerals in the plastics enhanced S-fixation and reduced SO2 emission. The activation energy of the co-combustion fell from 126.78 to 111.85 kJ/mol and 133.71-79.91 kJ/mol when the PE and PP additions rose from 10% to 50%, respectively. The co-combustion reaction mechanism was best described by the model of f(α) = (1-α)n. The reaction order was reduced with the additions of the plastics. The co-combustion operation interactions were optimized via an artificial neural network so as to jointly meet the multiple objectives of maximum energy production and minimum emissions.

Novel Natural Inhibitors Targeting Enhancer of Zeste Homolog 2: A Comprehensive Structural Biology Research.

The enhancer of zeste homolog 2 (EZH2) is a methylated modification enzyme of Histone H3-Lys 27. The high expression of EZH2 in cells is closely related to the progression, invasion, and metastasis of neoplasm. Therefore, this target is gradually becoming one of the research hot spots of tumor pathogenesis, and the inhibitors of the EZH2 enzyme are expected to become new antitumor drugs. This study used a series of virtual screening technologies to calculate the affinity between the compounds obtained from the ZINC15 database and the target protein EZH2, the stability of the ligand-receptor complex. This experiment also predicted the toxicity and absorption, distribution, metabolism, and excretion (ADME) properties of the candidate drugs in order to obtain compounds with excellent pharmacological properties. Finally, the ligand-receptor complex under in vivo situation was estimated by molecular dynamics simulation to observe whether the complex could exist steadily in the body. The experimental results showed that the two natural compounds ZINC000004217536 and ZINC000003938642 could bind tightly to EZH2, and the ligand-receptor complex could exist stably in vivo. Moreover, these two compounds were calculated to be nontoxic. They also had a high degree of intestinal absorption and high bioavailability. In vitro experiments confirmed that drug ZINC000003938642 could inhibit the proliferation and migration of osteosarcoma, which could serve as potential lead compounds. Therefore, the discovery of these two natural products had broad prospects in the development of EZH2 inhibitors, providing new clues for the treatment or adjuvant treatment of tumors.

Transcriptome research identifies four hub genes related to primary myelofibrosis: a holistic research by weighted gene co-expression network analysis.

OBJECTIVES: This study aimed to identify specific diagnostic as well as predictive targets of primary myelofibrosis (PMF). METHODS: The gene expression profiles of GSE26049 were obtained from Gene Expression Omnibus (GEO) dataset, WGCNA was constructed to identify the most related module of PMF. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Protein-Protein interaction (PPI) network were conducted to fully understand the detailed information of the interested green module. Machine learning, Principal component analysis (PCA), and expression pattern analysis including immunohistochemistry and immunofluorescence of genes and proteins were performed to validate the reliability of these hub genes. RESULTS: Green module was strongly correlated with PMF disease after WGCNA analysis. 20 genes in green module were identified as hub genes responsible for the progression of PMF. GO, KEGG revealed that these hub genes were primarily enriched in erythrocyte differentiation, transcription factor binding, hemoglobin complex, transcription factor complex and cell cycle, etc. Among them, EPB42, CALR, SLC4A1 and MPL had the most correlations with PMF. Machine learning, Principal component analysis (PCA), and expression pattern analysis proved the results in this study. CONCLUSIONS: EPB42, CALR, SLC4A1 and MPL were significantly highly expressed in PMF samples. These four genes may be considered as candidate prognostic biomarkers and potential therapeutic targets for early stage of PMF. The effects are worth expected whether in the diagnosis at early stage or as therapeutic target.

Co-pyrolysis performances, synergistic mechanisms, and products of textile dyeing sludge and medical plastic wastes.

This study aimed to quantify the co-pyrolysis of textile dyeing sludge (TDS) and the two medical plastic wastes of syringes (SY) and medical bottles (MB) in terms of their performances, synergistic mechanisms, and products. The pyrolysis of polyolefin plastics with its high calorific value and low ash content can offset the poor mono-pyrolytic performance of TDS. The synergistic mechanisms occurred mainly in the range of 400-550 °C. The addition of 10% SY or MB achieved the best co-pyrolysis performance with the lowest activation energy. The co-pyrolysis increased the contents of CH4 and CH but reduced CO2 emission. The co-pyrolysis released more fatty hydrocarbons, alcohols, and cyclic hydrocarbon during but reduced the yields of ethers and furans, through the synergistic mechanisms. The addition of the polyolefin plastics made the micro surface particles of chars smaller and looser. Our results can benefit energy utilization, pollution control, and optimal operational conditions for the industrial thermochemical conversions of hazardous wastes.

Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9.

OBJECTIVES: This study aimed to identify novel targets in the carcinogenesis, therapy and prognosis of osteosarcoma from genomic level, together with screening ideal lead compounds with potential inhibition regarding MMP-9. METHODS: Gene expression profiles from GSE12865, GSE14359, GSE33382, GSE36001 and GSE99671 were obtained respectively from GEO database. Differentially expressed genes were identified, and functional enrichment analysis, such as GO, KEGG, GSEA, PPI were performed to make a comprehensive understanding of the hub genes. Next, a series of high-precision computational techniques were conducted to screen potential lead compounds targeting MMP9, including virtual screening, ADME, toxicity prediction, and accurate docking analysis. RESULTS: 10 genes, MMP9, CD74, SPP1, CXCL12, TYROBP, FCER1G, HCLS1, ARHGDIB, LAPTM5 and IGF1R were identified as hub genes in the initiation of osteosarcoma. Machine learning, multivariate Cox analysis, ssGSEA and survival analysis demonstrated that these genes had values in prognosis, immune-correlation and targeted treatment. Tow novel compounds, ZINC000072131515 and ZINC000004228235, were screened as potential inhibitor regarding MMP9, and they could bind to MMP9 with favorable interaction energy and high binding affinity. Meanwhile, they were precited to be efficient and safe drugs with low-ames mutagenicity, none weight evidence of carcinogenicity, as well as non-toxic with liver. CONCLUSIONS: This study revealed the significance of 10-gene signature in the development of osteosarcoma. Besides, drug candidates identified in this study provided a solid basis on MMP9 inhibitors' development.

Transcriptome profiling reveals target in primary myelofibrosis together with structural biology study on novel natural inhibitors regarding JAK2.

This study aimed to identify effective targets for carcinogenesis of primary myelofibrosis (PMF), as well as to screen ideal lead compounds with potential inhibition effect on Janus kinase 2 to contribute to the medication design and development. Gene expression profiles of GSE26049, GSE53482, GSE61629 were obtained from the Gene Expression Omnibus database. The differentially expressed genes were identified, and functional enrichment analyses such as Gene Ontology, protein-protein interaction network etc., were performed step by step. Subsequently, highly-precise computational techniques were conducted to identify potential inhibitors of JAK2. A series of structural biology methods including virtual screening, ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction, molecule docking, molecular dynamics simulation etc., were implemented to discover novel natural compounds. Results elucidated that PMF patients had abnormal LCN2, JAK2, MMP8, CAMP, DEFA4, LTF, MPO, HBD, STAT4, EBF1 mRNA expression compared to normal patients. Functional enrichment analysis revealed that these genes were mainly enriched in erythrocyte differentiation, neutrophil degranulation and killing cells of other organisms. Two novel natural compounds, ZINC000013513540 and ZINC000004099068 were found binding to JAK2 with favorable interaction energy together with high binding affinity. They were predicted with non-Ames mutagenicity, low-rodent carcinogenicity, less developmental toxicity potential as well as non-toxicity with liver. Molecular dynamics simulation demonstrated that these two complexes: ZINC000013513540-JAK2 and ZINC000004099068-JAK2 could exist stably under natural circumstances. In conclusion, this study revealed hub genes in the carcinogenesis of PMF. ZINC000013513540 and ZINC000004099068 were promising drugs in dealing with PMF. This study may also accelerate exploration of new drugs.

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration.

Low back pain (LBP), which is one of the most severe medical and social problems globally, has affected nearly 80% of the population worldwide, and intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that happens to be the primary trigger of LBP. The pathology of IDD is based on the impaired homeostasis of catabolism and anabolism in the extracellular matrix (ECM), uncontrolled activation of immunologic cascades, dysfunction, and loss of nucleus pulposus (NP) cells in addition to dynamic cellular and biochemical alterations in the microenvironment of intervertebral disc (IVD). Currently, the main therapeutic approach regarding IDD is surgical intervention, but it could not considerably cure IDD. Exosomes, extracellular vesicles with a diameter of 30-150 nm, are secreted by various kinds of cell types like stem cells, tumor cells, immune cells, and endothelial cells; the lipid bilayer of the exosomes protects them from ribonuclease degradation and helps improve their biological efficiency in recipient cells. Increasing lines of evidence have reported the promising applications of exosomes in immunological diseases, and regarded exosomes as a potential therapeutic source for IDD. This review focuses on clarifying novel therapies based on exosomes derived from different cell sources and the essential roles of exosomes in regulating IDD, especially the immunologic strategy.

Pyrolysis dynamics of two medical plastic wastes: Drivers, behaviors, evolved gases, reaction mechanisms, and pathways.

The public has started to increasingly scrutinize the proper disposal and treatment of rapidly growing medical wastes, in particular, given the COVID-19 pandemic, raised awareness, and the advances in the health sector. This research aimed to characterize pyrolysis drivers, behaviors, products, reaction mechanisms, and pathways via TG-FTIR and Py-GC/MS analyses as a function of the two medical plastic wastes of syringes (SY) and medical bottles (MB), conversion degree, degradation stage, and the four heating rates (5,10, 20, and 40 °C/min). SY and MB pyrolysis ranged from 394.4 to 501 and from 417.9 to 517 °C, respectively. The average activation energy was 246.5 and 268.51 kJ/mol for the SY and MB devolatilization, respectively. MB appeared to exhibit a better pyrolysis performance with a higher degradation rate and less residues. The most suitable reaction mechanisms belonged to a geometrical contraction model (R2) for the SY pyrolysis and to a nucleation growth model (A1.2) for the MB pyrolysis. The main evolved gases were C4-C24 alkenes and dienes for SY and C6-C41 alkanes and C8-C41 alkenes for MB. The pyrolysis dynamics and reaction pathways of the medical plastic wastes have important implications for waste stream reduction, pollution control, and reactor optimization.