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Abstract Lung cancer ranks as the most prevalent malignant neoplasm worldwide, contributing significantly to cancer-related mortality. Stemness is a well-recognized factor underlying radiotherapy resistance, recurrence and metastasis in non-small-cell lung cancer (NSCLC) patients. Our prior investigations have established the role of IQ motif containing GTPase-activating protein 3 (IQGAP3) in mediating radiotherapy resistance in lung cancer, but its impact on lung cancer stemness remains unexplored. Our bioinformatics analysis results revealed a significant correlation between IQGAP3 and lung cancer stemness. Moreover, we found that IQGAP3 depletion in lung cancer cells resulted in reduced migration, invasion and sphere-forming capabilities. Through RNA sequencing, we identified GLI1 as a pivotal downstream effector of IQGAP3. The knockdown of IQGAP3 led to the downregulation of GLI1 mRNA and protein levels, which impeded the activation of the Hedgehog-GLI1 signaling pathway. Further, our results also indicated that GLI1 is the primary effector mediating IQGAP3’s biological functions in lung cancer. These findings elucidate the role of IQGAP3 in promoting lung cancer stemness and metastasis through the Hedgehog pathway, facilitated by GLI1, highlighting the potential of IQGAP3 as a promising therapeutic target for lung cancer treatment.

Abstract In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1+/UCHL1+ EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer’s disease (AD), and Parkinson’s disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1+/UCHL1+ EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1+/UCHL1+, NMDAR2A+, and NFL+ EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1+/UCHL1+ EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A+ and NFL+ EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration.

Abstract Background The incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer. Methods In vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK. Results Genes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79–87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients. Conclusions Our findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.

Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.

With the advancement of technology, the field of deep hole processing faces dual challenges of increased precision and increased production. Although traditional honing and grinding processes dominate, they are inefficient and do not adapt to large-scale production. Rolling processing technology has become an alternative solution with its advantages of high precision and high efficiency. This study aims to apply rolling processing to deep hole processing to improve efficiency. An elastic-plastic model was constructed to clarify the relationship between stress, strain, and displacement, and it was transformed into a simulated flow plastic stress equation. A finite element model was established, and its accuracy was verified through experiments, revealing the effects of various parameters on stress and strain. In the experimental stage, the amount of interference, feed speed, and rotation speed were identified as the main influencing factors, and a multi-objective optimization model was established accordingly. Comparative analysis showed that the grinding accuracy was the highest (0.13 μm), while the multi-objective optimization combination and variance combination reached 0.22 and 0.31 μm, respectively. In terms of processing efficiency, rolling is ten times that of grinding. Rolling processing can replace some grinding processes under specific conditions, significantly improving efficiency, which is of great significance for the development of deep hole processing technology.

To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.

Abstract In situ exploration of the dynamic structure evolution of catalysts plays a key role in revealing reaction mechanisms and designing efficient catalysts. In this work, PtCu/MgO catalysts, synthesized via the co-impregnation method, outperforms monometallic Pt/MgO and Cu/MgO. Utilizing quasi/in-situ characterization techniques, it is discovered that there is an obvious structural evolution over PtCu/MgO from Pt x Cu y O z oxide cluster to PtCu alloy with surface CuO x species under different redox and CO oxidation reaction conditions. The synergistic effect between PtCu alloy and CuO x species enables good CO oxidation activity through the regulation of CO adsorption and O2 dissociation. At low temperatures, CO oxidation is predominantly catalyzed by surface CuO x species via the Mars-van Krevelen mechanism, in which CuO x can provide abundant active oxygen species. As the reaction temperature increases, both surface CuO x species and PtCu alloy collaborate to activate gaseous oxygen, facilitating CO oxidation mainly through the Langmuir-Hinshelwood mechanism.

In recent years, the Permian Maokou Formation of the Sichuan Basin shifted focus. Previously, targeting high points and exploring along the long axis were common. Now, the strategy emphasizes finding shoal grainstone reservoirs with pores, leading to significant breakthroughs and making the Maokou Formation a hotspot for exploration. This change requires strong support from sedimentary evolution studies. The eastern and northern Sichuan regions are notable for distinct tectonic and sedimentary features within the Maokou Formation, suggesting promising exploration potential. Analysis of the logging data from 386 wells was conducted and sedimentary facies analysis was carried out using field profiles and drilling cores. Combining the logging curves with sedimentary facies, the sedimentary evolution of the Maokou Formation in the study area was analyzed. Findings reveal a gentle carbonate slope from the first member to the lower submember of the second member. The stratigraphic thickness and sedimentary facies are generally influenced by the ancient Central Sichuan Palaeouplift, with low-energy shoals developing locally. A transition to a rimmed carbonate platform occurs from the upper submember of the second member to the third member, with stratigraphic thickness and sedimentary facies showing a northwest to southeast orientation. The platform develops sequentially from platform facies to platform margin, slope, and shelf facies from west to east, with high-energy shoals developing in the platform margin. Sedimentation history indicates two distinct rise to fall processes of the relative sea level during the Maokou Formation sedimentary period, corresponding to the first member to the lower submember of the second member, and the upper submember of the second member to the third member. The formation of shoal grainstone reservoirs with karst and dolomitization in the gentle slope during the first period was controlled by regional sea level changes, tectonic activities, and the type of carbonate platform. Potential hydrocarbon source rocks developed in submarine troughs during the second period. The region holds promise for unconventional oil and gas exploration, particularly on the west side of the trough with high-energy shoals on platform margins.

ObjectiveNumerous studies emphasize the pivotal role of inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD) development. Some link specific systemic immune biomarkers (e.g., systemic immuno-inflammatory index [SII], neutrophil-to-albumin ratio [NPAR] and neutrophil-to-lymphocyte ratio [NLR]) to hepatic steatosis risk. However, the relevance of other markers like systemic immune-inflammation index [SIRI], platelet-to-lymphocyte ratio [PLR] and lymphocyte/monocyte ratio [LMR] in MASLD remains unclear. Limited literature covers all six markers together. This study aims to investigate the association between SII, SIRI, LMR, NLR, PLR, and NPAR and MASLD, assessing their predictive value.MethodsIn this cross-sectional analysis of adults from NHANES (2007–2018), we investigated the relationship between six systemic immune biomarkers, stratified by quartiles: quartile1 (Q1), quartile2 (Q2), quartile3 (Q3) and quartile4 (Q4), and the outcome of MASLD assessed by Fatty Liver Index (FLI) and United States Fatty Liver Index (USFLI). Logistic regression and restricted cubic splines (RCS) were employed to assess the association between systemic immune biomarkers and MASLD risks. Propensity score matching controlled for potential confounders, and receiver operating characteristic (ROC) curve analysis evaluated the biomarkers’ predictive performances for MASLD. Subgroup and interaction analysis were conducted to explore the effects of systemic immune biomarkers on MASLD risks. Multicollinearity was quantified using the variance inflation factor.ResultsIn total, 14,413 participants were included and 6,518 had MASLD. Compared with non-MASLD, participants with MASLD had higher SII, SIRI, NLR, PLR, and NPAR (p 0.05). The prevalence of MASLD increased with the Q4 of SII [OR = 1.47, 95%CI (1.24, 1.74)], SIRI [OR = 1.30, 95%CI (1.09, 1.54)], NLR [OR = 1.25, 95%CI (1.04, 1.49)], PLR [OR = 1.29, 95%CI (1.09, 1.53)] and NPAR [OR = 1.29, 95%CI (1.09, 1.54)] compared to the Q1 after adjusting for the bias caused by potential confounders. However, the propensity score matching analysis only supported an association between the highest SII, SIRI, NLR NPAR and the risk of MASLD. The results of the subgroup analysis showed considerable robustness in the relationship.ConclusionHigher SII, SIRI, NLR and NPAR were positively associated with a heightened risk of MASLD. NPAR showed the superior predictive value, followed by SII, SIRI and NLR. This needs to be validated in additional longitudinal studies and clinical trials.

Abstract The elderly frequently present impaired blood–brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Abstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.

Abstract Objective The purpose of this study was to systematically evaluate the methodological quality of massage-related clinical practice guidelines (CPGs)/consensus on massage using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument and to summarize the current status of recommendations in the CPGs. Methods The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBM), PubMed, Embase, and guideline websites (such as the Chinese Medical Ace Base, the China Association of Chinese Medicine, the World Health Organization, Guideline International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network) were searched from inception to October 31, 2022. In addition, the reference lists of relevant studies were reviewed to identify domestic and overseas massage CPGs/consensus. The search terms adopted a combination of subject words and free words, mainly including traditional Chinese medicine, complementary therapies, Tuina, massage, manipulation, chiropractic/osteopathic, spinal, acupressure, guideline, and consensus. Two researchers independently completed the eligible records and extracted the data. Before the formal research, calibrations were performed twice on AGREE II, and all reviewers completed the pilot test three times until they understood and reached an agreement on the assessment items. Three researchers appraised the methodological quality of the included guidelines using the AGREE II instrument and calculated the overall intraclass correlation coefficient (ICC) of agreement. Results The evaluation results showed that among the 49 eligible CPGs/consensus, 4 (8.2%) CPGs/consensus were considered “recommended”, 15 (30.6%) CPGs/consensus were considered “recommended with modifications”, and 30 (61.2%) CPGs/consensus were considered “not recommended”, while the consensus was considered “not recommended”. Generally, the scores in the six domains of the guidelines were all higher than the consensus. Evaluation results for the overall quality of 36 CPGs showed that 4 (11%) were “good quality”, 15 (42%) were “sufficient quality” and 17 (47%) were “lower quality”. The AGREE II quality scores of domains ranged from 0.30 to 0.75 ([ICC = 0.993, 95% CI (0.992, 0.995)]). The domain of scope and purpose (domain 1), with a median score of 0.75 (0.52~0.91), performed best in the guidelines with AGREE II, and stakeholder involvement (domain 2) [median 0.39 (0.31~0.56)] and application (domain 5) [median 0.30 (0.17~0.47] obtained lower scores. The consensus score of domain 1 was better at 26.0 (21.6~44.8), followed by rigor of development (domain 3) with a score of 18.0 (10.0~28.9). A total of 119 massage-related recommendations were extracted from 49 guidelines/consensuses, including “in favor” (102, 85.7%), “against” (9, 7.6%), and “did not make recommendations” (8, 6.7%). Conclusion The overall quality of the included guidelines was low, and most of the guidelines were not “recommended”. In future guideline updates, the existing evidence should be used, the professional composition of members of the expert group should be enriched, and patients’ values and preferences should be fully considered. It is necessary to clearly propose recognizable recommendations and strengthen the rigor and standardization of guideline formulation. Thus, clear standard guidelines can be formulated to better guide clinical practice.

Steel metallurgical dust, characterized by a substantial output, minute particle size, and intricate composition, poses a considerable risk of environmental contamination while simultaneously embodying an exceptionally high potential for recycling. To achieve its resource utilization, chemical analysis, particle size analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM), Mössbauer spectroscopy, and water leaching methods were employed to investigate the chemical compositions, particle size distributions, phase compositions, and microscopic morphologies of blast furnace bag dust, sintering dust, converter fine dust, and electric arc furnace dust from steel plants. The results indicate that the four types of dust have extremely fine particle sizes, with the main distribution range of particle size being less than 100 μm. The main constituent element is Fe (19–56%), and it also contains Zn (1.4–33.5%), Pb, K, C, and other valuable elements. Alkali metals in blast furnace bag dust and sintering machine head dust existed mainly in the form of chloride. The zinc phases in sintering machine head dust and converter fine dust were ZnFe2O4, and the zinc phases in blast furnace bag dust were ZnCl2 and ZnFe2O4. Zinc in electric furnace dust was composed of ZnO and ZnFe2O4, accounting for 70.31% and 23.12%, respectively. There are significant differences in the types and contents of valuable elements among various dusts, making it difficult to achieve full-scale recovery through a single process. In view of this, a process of “in-plant recycling of harmless dusts—collaborative treatment of harmful dusts” has been proposed. Based on the characteristics of metallurgical dusts, multiple processes are used for collaborative treatment (using hydrometallurgical and pyrometallurgical methods), which can not only directly recover iron resources from dusts within the plant, but also avoid the waste of valuable elements such as Zn, Pb, K, Na, etc. It is hoped that the above work can provide a reference for steel enterprises to achieve full-scale and high value-added treatment of metallurgical dusts.

The Tumen River, which delineates the border between China, North Korea, and Russia, is a vital river in Northeast Asia. Understanding its current fish diversity holds significant scientific value for aquatic ecological protection. Therefore, traditional and eDNA sampling were conducted from 2022 to 2023. Integrating the historical literature with our field collection results reveals that the Tumen River has a total of 64 native fish species, of which 51 species have been surveyed in the wild. The fish composition is mainly dominated by cold-water species, with a high proportion of these being rare, endangered, and nationally protected. eDNA surveys are crucial complements in boundary rivers where traditional methods are not feasible. The results indicated that α diversity values were highest in the Hunchunhe River, attributed to the favorable natural geographical conditions and effective conservation efforts. Recently, the fish diversity in the Tumen River has been disrupted, primarily reflected in the absence of migratory species such as Oncorhynchus gorbuscha and Pseudaspius hakonensis. The study suggests that establishing nature reserves, preventing and controlling alien species, and strengthening international cooperation are key to protect fish diversity.

The reduction in internal ecological spaces within urban environments and the expansion of impervious surfaces have been identified as factors significantly increasing the susceptibility of cities to flood disasters. Rooftop greening, an essential component of urban stormwater management strategies, offers a versatile solution for augmenting permeable surfaces and delivering ecological services while seamlessly integrating with existing urban infrastructure. This approach has been proven effective in enhancing urban resilience against rainfall-induced flooding events. Hence, the precise identification of suitable building rooftops for green infrastructure within urbanized regions, combined with the simulation of runoff regulation effects brought about by these rooftop greening interventions, holds substantial practical significance. This study innovatively constructs a technical method for measuring the runoff control performance of urban-scale green roofs from identification, evaluation to simulation. Taking the Macao Special Administrative Region as an example, a green roof suitability evaluation index system that is consistent with urban characteristics has been constructed, integrating machine learning, comprehensive evaluation, SWMM simulation methods to evaluate the suitability of roof greening in urban areas and simulate the impact of multi-senarios green roof construction types on runoff regulation. Finally, a comprehensive strategy for rooftop greening construction in Macau is proposed, with the aim of amplifying the runoff regulation capabilities of such initiatives. The main findings of the research include the following: (1) The research area exhibits a notably high aggregate potential for rooftop greening, with suitable rooftop areas comprising approximately 34% of the total rooftop expanse. Notably, construction vintage and roof elevation are identified as the most substantive constraints on rooftop greening. (2) Discernible differences in rooftop greening construction scale exert a significant influence on runoff regulation capacity, with the magnitude of greening positively correlated with its runoff regulation efficacy. Distinct greening typologies elicit varying impacts on runoff regulation, with semi-intensive rooftop greening surpassing extensive approaches in runoff regulation performance. Disparate distribution patterns of rooftop greening engender dissimilar runoff regulation effects, with rooftop greening layouts situated distant from drainage outlets facilitating runoff mitigation, while those in close proximity to drainage outlets enhance peak flow reduction effects.

Abstract Background The accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders. Methods Primary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+ AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism. Results The number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877. Conclusions Pathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.

Abstract Tibetan pigs (TPs) can adapt to the extreme environments in the Tibetan plateau implicated by their self-genome signals, but little is known about roles of the gut microbiota in the host adaption. Here, we reconstructed 8210 metagenome-assembled genomes from TPs (n = 65) living in high-altitude and low-altitude captive pigs (87 from China—CPs and 200 from Europe—EPs) that were clustered into 1050 species-level genome bins (SGBs) at the threshold of 95% average nucleotide identity. 73.47% of SGBs represented new species. The gut microbial community structure analysis based on 1,048 SGBs showed that TPs was significantly different from low-altitude captive pigs. TP-associated SGBs enabled to digest multiple complex polysaccharides, including cellulose, hemicellulose, chitin and pectin. Especially, we found TPs showed the most common enrichment of phyla Fibrobacterota and Elusimicrobia, which were involved in the productions of short- and medium-chain fatty acids (acetic acid, butanoate and propanoate; octanomic, decanoic and dodecanoic acids), as well as in the biosynthesis of lactate, 20 essential amino acids, multiple B vitamins (B1, B2, B3, B5, B7 and B9) and cofactors. Unexpectedly, Fibrobacterota solely showed powerful metabolic capacity, including the synthesis of acetic acid, alanine, histidine, arginine, tryptophan, serine, threonine, valine, B2, B5, B9, heme and tetrahydrofolate. These metabolites might contribute to host adaptation to high-altitude, such as energy harvesting and resistance against hypoxia and ultraviolet radiation. This study provides insights into understanding the role of gut microbiome played in mammalian high-altitude adaptation and discovers some potential microbes as probiotics for improving animal health.

Indices for predicting HBsAg or HBeAg seroconversion in patients with chronic hepatitis B virus (HBV) infection during antiviral therapy remain elusive. We aimed to investigate if the presence of HBsAb-specific B cells at baseline can predict HBsAg or HBeAg seroconversion. In this study, 134 treatment-naive patients with chronic HBV were enrolled. A baseline HBsAb-specific B cell ELISpot assay was performed for all the patients that enrolled. Serum samples were collected at 12, 24, and 48 weeks for patients treated with Peg-IFN-α, or at 1 year, 3 years, and 5 years for patients treated with NAs. Laboratory testing of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA, ALT, and AST was done. We observed a significantly lower frequency of HBsAb-specific B cells in patients with chronic HBV than in healthy individuals . In the Peg-IFN-α-treated group, 41.2% of patients with baseline HBsAb-specific B cells achieved HBsAg seroconversion, while only 13.6% of patients without baseline HBsAb-specific B cells achieved HBsAg seroconversion (p = 0.006). By logistic regression analysis, patients with baseline HBsAb-specific B cells and HBsAg ≤ 1500 had higher HBsAg clearance at the end of treatment (p < 0.05). In the NA-treated group, 58.3% of patients with baseline HBsAb-specific B cells achieved HBeAg seroconversion, whereas only 30.0% of patients without baseline HBsAb-specific B cells achieved HBeAg seroconversion (p = 0.114). Our result revealed that baseline HBsAb-specific B cells by ELISpot assay might be a valuable predictive biomarker of HBsAg or HBeAg seroconversion in patients with chronic HBV on treatment.

Abstract Background and Objective Considering that physicians and patients widely use acupuncture, it is necessary to explore its adverse effects during treatment. Herein, an evidence map was generated based on published studies to identify acupuncture-induced adverse effects and assess their severity, with the overarching goal of providing references for safe and effective implementation. Methods A comprehensive literature search was performed in four public databases (PubMed, Embase, Web of science, and the Cochrane Library) to identify relevant studies published up to 15th June 2022. In addition, relevant studies were explored in the Epistemonikos database and reference lists were retrieved as a supplement. A MeaSurement Tool to Assess systematic Reviews, Version 2 (AMSTAR-2) quality assessment tool was applied to determine the methodological quality of included systematic reviews (SRs) and/or meta-analysis (MAs), whereas Microsoft Excel 2019 tool was used for data extraction and coding. Heatmaps were generated to display disease type, countries of origin for the first authors, and the sample sizes of original studies. Moreover, bubble charts comprehensively presented intervention categories, adverse reaction types, and evidence levels. Results A total of 535 SRs involving 33 adverse reactions were included. Among them, 22 studies were rated as high quality, 28 as moderate, 106 as low, and the rest were of critically-low quality. Numerous adverse effects were described in the studies, including syncope (86 SRs), organ or tissue injury (233 SRs), systemic reactions (113 SRs), infection (19 SRs), and other adverse events (373 SRs). Importantly, these adverse reactions were mainly associated with 19 acupuncture techniques, including electroacupuncture (n = 67), manual acupuncture (n = 47) and acupoint catgut embedding (n = 41). Furthermore, the 535 SRs described 23 diseases, among which symptoms, signs or clinical findings (83 SRs), mental, behavioral or neurodevelopmental disorders (67 SRs), and diseases of the nervous system (66 SRs) had the highest incidence. Conclusion This evidence mapping explores the adverse effects of acupuncture, showing that there are multiple types of adverse reactions to acupuncture, with milder symptoms. The methodological assessment revealed that most of the included studies were of low- or critically low-quality. Therefore, there is a need for future randomized controlled trials and SRs to comprehensively analyze acupuncture-related adverse events in order to provide reliable and credible evidence.

Although complete remission could be achieved in about 60%–70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates improved prognosis and reduced toxicities, which may offer novel therapeutic rationales. However, one of the major difficulties in developing immune therapies against AML is that the target antigens are also significantly expressed on healthy hematopoietic stem cells; B-cell malignancies are different because CD20/CD19/healthy B-cells are readily replaceable. Only the anti-CD33 antibody-drug conjugate gemtuzumab-ozogamicin is approved by the FDA for AML. Thus, drug development remains extremely active, although it is still in its infancy. This review summarizes the clinical results of immune therapeutic agents for AML, such as antibody-based drugs, chimeric antigen receptor therapy, checkpoint inhibitors, and vaccines.

The Chinese section of the Irtysh River Basin and the Ulungur River Basin, two major river basins of the Altay region, are located at the northwest of Xinjiang Uygur Autonomous Region of China. As an international river, the Chinese section has seven state-level protected fish and seven local-level protected species as well. Many more commercial species have been introduced from eastern China and other countries, accompanied by some low-value and small-sized fish in recent decades. The non-native fish species have already threatened these protected fish. This study investigated the distribution of non-native fish species in the Chinese section of the Irtysh River Basin and the Ulungur River Basin. The basic data for the biodiversity conservation and the information of the non-native fish in these two river basins were gathered.There are a lot of studies on native fish in the Chinese section of the Irtysh River Basin and Urungur River Basin in China, but there is a lack of studies on non-native fish. Thirteen non-native fish belonging to four orders, nine families and 12 genera were collected in this study. The study includes one dataset. The dataset presents taxonomy, distribution, water body and location for each of the non-native fish collected from the Chinese section of the Irtysh River Basin and the Ulungur River Basin. Our study has found that the proportion of native species has declined, while the number of non-native species has increased from 2013 to 2022. The information we provided could help to develop an international strategy for the protection of aquatic biodiversity.

A cost-effective method for cloud removal and reconstruction of remote sensing images has been a long-standing research challenge in remote sensing data processing. In this article, we address this challenge by presenting a fast and simple method for cloud detection and cloud-free image reconstruction using Landsat-8 OLI and Sentinel-2 MSI series data. The proposed method utilizes the spectral difference between cloud pixels and transparent pixels to develop a fast and simple cloud detection algorithm for multispectral remote sensing sensors. Subsequently, the cloud-free data of the complementary image and the target image undergo histogram matching, and the cloud-free pixels of the complementary image are seamlessly integrated into the original image, leading to the generation of a cloud-free image reconstruction algorithm. Comparative analysis between the results obtained from our proposed method and the corresponding artificial results reveals an accuracy rate exceeding 90% and a high consistency in the reconstructed spatial spectrum. By addressing the need for cost-effective cloud removal and image reconstruction, our method contributes to the advancement of remote sensing data processing and applications.

To improve the ride comfort of a light commercial vehicle, the dynamic performance of the hybrid air suspension was analyzed and optimizaed by multi-body dynamics. Through the quasi-static compression test, the dynamic model of the air spring under different air pressures was established, and then the dynamic performance of the vehicle under random and pulse input were studied through the multi-body dynamics simulation. A combined model for ride comfort simulation was established ob basis of Isight, Matlab and Adams/Car. Through performing the sensitivity analysis, the parameters that have a great impact on the ride comfort performance were determined. Finally, the ride comfort of the whole vehicle under random and impulse input is optimized through the Co-simulation platform and NSGA-Ⅱ optimization algorithm. The simulation results of ride comfort after optimization show that: under random input, the root mean square value of weighted acceleration at the driver is reduced by 13.6%, and that at the passenger is reduced by 25.6%; under pulse input, the maximum vertical acceleration at the driver is reduced by 15.9%, and that at the passenger is reduced by 29.4%, and the ride comfort of the whole vehicle is significantly improved.

Abstract The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to find MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukaemic niche formation. RNA sequence results revealed that T-ALL derived MSCs secreted fibroblast growth factor 2 (FGF2), which combined with fibroblast growth factor receptor 2 (FGFR2) on leukaemia cells, resulting in activation of PI3K/AKT/mTOR signalling pathway in leukaemia cells. In vitro blocking the interaction between FGF2 and FGFR2 with BGJ398 (infigratinib), a FGFR1-3 kinase inhibitor, or knockdown FGF2 in MSCs by interference caused deactivation of PI3K/AKT/mTOR pathway and dysregulations of genes associated with cell cycle and apoptosis in ALL cells, leading to decrease of leukaemia cells. In mouse model received BGJ398, overall survival was extended and dissemination of leukaemia cells in BM, spleen, liver and peripheral blood was decreased. After subcutaneous injection of primary human T-ALL cells with MSCs, tumour growth was suppressed when FGF2/FGFR2 was interrupted. Thus, inhibition of FGF2/FGFR2 interaction appears to be a valid strategy to overcome BM-MSCs mediated progression of T-ALL, and BGJ398 could indeed improve outcomes in T-ALL, which provide theoretical basis of BGJ398 as a BM microenvironment based therapeutic strategy to control disease progression.

Summary: KRAS is the most commonly mutated oncogene in human cancer, and mutant KRAS is responsible for over 90% of pancreatic ductal adenocarcinoma (PDAC), the most lethal cancer. Here, we show that RNA polymerase II-associated factor 1 complex (PAF1C) is specifically required for survival of PDAC but not normal adult pancreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining overaccumulation of enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) driven by mutant Kras. Loss of PAF1C leads to cancer-specific lengthening and accumulation of pervasive transcripts on chromatin and concomitant aberrant R-loop formation and DNA damage, which, in turn, trigger cell death. We go on to demonstrate that the global transcriptional hyperactivation driven by Kras signaling during tumorigenesis underlies the specific demand for PAF1C by cancer cells. Our work provides insights into how enhancer transcription hyperactivation causes general transcription factor addiction during tumorigenesis.

Flexible control of atomization pressure and bar material feeding speed was achieved during preparation of TC11 alloy 3D-printing spherical powder on basis of a vacuum-induced multistage atomization process. Collision at the metal drop atomization stage was effectively avoided and spherical powder quality was significantly enhanced while ensuring the high fine-powder yield. Under the optimized atomization process conditions, the powder with D90 of 59.2 μm, highest sphericity, O and N element increment below 0.04%, and 15–53 μm powder yield of 30% was obtained. These comprehensive mechanical properties meet the requirement for 3D printing.

In this study, an intelligent monitoring platform is established for continuous quantification of soil, vegetation, and atmosphere parameters (e.g. soil suction, rainfall, tree canopy, air temperature, and wind speed) to provide an efficient dataset for modeling suction response through machine learning. Two characteristic parameters representing suction response during wetting processes, i.e. response time and mean reduction rate of suction, are formulated through multi-gene genetic programming (MGGP) using eight selected influential parameters including depth, initial soil suction, vegetation- and atmosphere-related parameters. An error standard–based performance evaluation indicated that MGGP has appreciable potential for model development when working with even fewer than 100 data. Global sensitivity analysis revealed the importance of tree canopy and mean wind speed to estimation of response time and indicated that initial soil suction and rainfall amount have an important effect on the estimated suction reduction rate during a wetting process. Uncertainty assessment indicated that the two MGGP models describing suction response after rainfall are reliable and robust under uncertain conditions. In-depth analysis of spatial variations in suction response validated the robustness of two obtained MGGP models in prediction of suction variation characteristics under natural conditions.

Radiative transfer models (RTMs) provide reliable information about crop yield and traits with high resource efficiency. In this study, we have conducted a systematic literature review (SLR) to fill the gaps in the overall insight of RTM-based crop yield prediction (CYP) and crop traits retrieval. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 76 articles were found to be relevant to crop traits retrieval and 15 for CYP. China had the highest number of RTM applications (33), followed by the USA (13). Crop-wise, cereals, and traits-wise, leaf area index (LAI) and chlorophyll, had a high number of research studies. Among RTMs, the PROSAIL model had the highest number of articles (62), followed by SCOPE (6) with PROSAIL accuracy for CYP (median R2 = 0.62) and crop traits (median R2 = 0.80). The same was true for crop traits retrieval with LAI (CYP median R2 = 0.62 and traits median R2 = 0.85), followed by chlorophyll (crop traits median R2 = 0.70). Document co-citation analysis also found the relevancy of selected articles within the theme of this SLR. This SLR not only focuses on information about the accuracy and reliability of RTMs but also provides comprehensive insight towards understanding RTM applications for crop yield and traits, further exploring possibilities of new endeavors in agriculture, particularly crop yield modeling.

The effects of SAP97 mutations associated with schizophrenia on synaptic function are unclear. Here, the authors show that schizophrenia-related SAP97 mutations enhance glutamatergic synapse strength in the dentate gyrus, impairing contextual episodic memory in rats.

Abstract Background Precision medicine has increased the accuracy of cancer diagnosis and treatment, especially in the era of cancer immunotherapy. Despite recent advances in cancer immunotherapy, the overall survival rate of advanced NSCLC patients remains low. A better classification in advanced NSCLC is important for developing more effective treatments. Method The calculation of abundances of tumor-infiltrating immune cells (TIICs) was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), xCell (xCELL), Tumor IMmune Estimation Resource (TIMER), Estimate the Proportion of Immune and Cancer cells (EPIC), and Microenvironment Cell Populations-counter (MCP-counter). K-means clustering was used to classify patients, and four machine learning methods (SVM, Randomforest, Adaboost, Xgboost) were used to build the classifiers. Multi-omics datasets (including transcriptomics, DNA methylation, copy number alterations, miRNA profile) and ICI immunotherapy treatment cohorts were obtained from various databases. The drug sensitivity data were derived from PRISM and CTRP databases. Results In this study, patients with stage 3–4 NSCLC were divided into three clusters according to the abundance of TIICs, and we established classifiers to distinguish these clusters based on different machine learning algorithms (including SVM, RF, Xgboost, and Adaboost). Patients in cluster-2 were found to have a survival advantage and might have a favorable response to immunotherapy. We then constructed an immune-related Poor Prognosis Signature which could successfully predict the advanced NSCLC patient survival, and through epigenetic analysis, we found 3 key molecules (HSPA8, CREB1, RAP1A) which might serve as potential therapeutic targets in cluster-1. In the end, after screening of drug sensitivity data derived from CTRP and PRISM databases, we identified several compounds which might serve as medication for different clusters. Conclusions Our study has not only depicted the landscape of different clusters of stage 3–4 NSCLC but presented a treatment strategy for patients with advanced NSCLC.

An anal fistula is an external abnormal anatomical connection between the rectum and the outer skin of the anus. Symptoms include anorectal pain, abscesses, perianal cellulitis, smelly or bloody drainage of pus, and, in some cases, difficulty controlling bowel movements. Diagnosis and evaluation of anal fistulas is crucial for prognosis and for the choice of the treatment method. In this study, we aimed to discover potential biomarkers from serum proteins for the prediction of anal fistulas.

Major depressive disorder (MDD) is a serious mental disease characterized by depressed mood, loss of interest and suicidal ideation. Its rising prevalence has rendered MDD one of the largest contributors to the global disease burden. However, its pathophysiological mechanism is still unclear, and reliable biomarkers are lacking. Extracellular vesicles (EVs) are widely considered important mediators of intercellular communication, playing an important role in many physiological and pathological processes. Most preclinical studies focus on the related proteins and microRNAs in EVs, which can regulate energy metabolism, neurogenesis, neuro-inflammation and other pathophysiological processes in the development of MDD. The purpose of this review is to describe the current research progress of EVs in MDD and highlight their potential roles as biomarkers, therapeutic indicators and drug delivery carriers for the treatment of MDD.

The next generation of mobile communication aims to extend the capabilities of traditional communication by reshaping the environment with wireless signals. The channel state information can describe the propagation characteristics in wireless communications, which is beneficial in developing wireless communication networks towards intelligent communication and wireless sensing networks. Raspberry PI with Nexmon firmware patched can extract the channel state information from WiFi signals and realize human activity recognition. However, the phase values on some carriers are susceptible to noise, resulting in phase errors after singular value decomposition. To solve this problem, a method is proposed in this paper to find the optimal phase value by dynamic time warping algorithm utilizing the property of orthogonality between amplitude and phase. In contrast to the conventional recognition strategies, the proposed optimal phase extraction method with commercial WiFi signals can further improve the accuracy of the recognition strategy under different complicated scenarios.

With the popularization of small batch production, the main cutting method for sheet metal parts has changed. Laser cutting has become the main production method for coil material cutting. Developing an irregular part nesting method for the continuous cutting of coil material is urgent. Based on the coil material cutting process, this paper proposes an intelligent approach for the unit nesting problem of coil material. Firstly, a unit nesting model of coil material was constructed. Secondly, an intelligent approach using an improved marine predator algorithm was used to solve this model. In solving the model, the minimum nesting unit was continuously updated by changing the position, angle, and quantity of the nesting parts. Thirdly, the geometric characteristics of this minimum nesting unit were extracted. Finally, the nesting units for production were obtained using a single row or opposite row of the minimum nesting unit. The computational results and comparison prove that the presented approach is feasible and effective in improving material utilization, reducing production costs, and meeting the requirements of the production site.

Abstract. Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, is highly heterogeneous and invasive. Although the majority of DLBCL patients show a good response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment, approximately one-third of patients still have a poor prognosis. Many immune-targeted drugs, such as bispecific T-cell engagers and CAR T-cell therapy, have been proven effective for refractory and relapsed patients. This article reviews the progress of immune targeted therapy for DLBCL.

Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients.Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system.Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%); shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs); increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant.Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.

Quantifying the allocation of photosynthetic products among different carbon (C) pools is critical for understanding and predicting plant C turnover response to climate change. A field experiment with ectomycorrhizal fungi (EMF) and nitrogen (N) was established to investigate the effects on allocation of photosynthetic products in Pinus massoniana (Lamb.) seedlings given increased N deposition. Seedlings were subjected to N addition and symbiosis with EMF, and the short-term allocation of a 13C photosynthetic pulse into leaves, branches, stems, roots, and soil was traced. Photosynthetic rate and root respiration were measured. It was found that N addition changed the allocation pattern of photosynthetic products in various organs of P. massoniana. Furthermore, N addition, mycorrhizal symbiosis, and interaction of N and EMF, all increased the amount of C produced by photosynthesis. N application less than 60 kg N hm–1 a–1 could promote the transfer and allocation of photosynthetic products in P. massoniana organs, which peaks at 60 kg N hm–1 a–1, and the highest N treatment began to decrease at 90 kg N hm–1 a–1. EMF inoculation could expand the absorption area of plant roots to obtain more nutrients and synthesize more C and N compounds for promoting the growth of itself and the host plant, improving the net photosynthetic rate and the distribution of C produced by photosynthesis in various organs. This forms a benign C and N cycle, thereby reducing the effect of high N addition on plants. The optimal N addition concentration was 60 kg N hm–1 a–1, and the optimal EMF was Pt, which provides a theoretical basis for inoculating EMF during increasing N deposition in the future climate change scenario. This enables plants to distribute more photosynthetic products to their roots, thus affecting their own C distribution for promoting growth.

Abstract Lung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

With excessive consumption of sulfide ores, using low-grade Pb-Zn mixed ores to obtain Zn has attracted more attention. Acid leaching is an effective method for Zn recovery; however, a high concentration of inorganic acid brings severe environmental issues, including acidic wastewater, contaminated soil, etc. Compared with inorganic acid, organic acid showed lower acidity and toxicity. Herein, we applied an effective method for Zn recovery from carbonate-type Pb-Zn mixed ore (CMO), by combining organic acid leaching with mechanical activation. Among the organic acids applied (lactic, malonic, citric, amber, acetic, and tartaric one), lactic acid was selected for its high leaching efficiency. The optimum condition was identified via response surface methodology, with a lactic acid concentration of 1.15 mol/L, L/S ratio of 20, leaching time of 75 min, and temperature of 75 °C. The effect of mechanical activation on Zn leaching was further investigated. The leaching efficiency increased to 90.1% after mechanical activation, which was the highest leaching efficiency for organic acid leaching. Mineralogical characterization showed that the bulk minerals were milled into small particles while the proportion of amorphization increased. Such activation effects improved the acid-solubility of Zn speciation. This work provided a potential green method for metal recovery from low-grade sources.

Abstract. Bone marrow (BM) microenvironment regulates and supports the production of blood cells which are necessary to maintain homeostasis. In analogy to normal hematopoiesis, leukemogenesis is originated from leukemic stem cells (LSCs) which gives rise to more differentiated malignant cells. Leukemia cells occupy BM niches and reconstruct them to support leukemogenesis. The abnormal BM niches are the main sanctuary of LSCs where they can evade chemotherapy-induced death and acquire drug resistance. In this review, we focus on the protective effects of BM niche cells on acute lymphoblastic leukemia cells.

The effect of an electric field with different polarities on the inner wall of a submerged entry nozzle made of rare earth steel was investigated. The results show that the electric field induces a change in the decarburization, erosion, and clogging processes of the nozzle. In the casting of rare earth steel, the negative electric field affects the decarburization, erosion, and clogging of the nozzle. Moreover, when a reverse positive electric field is applied on the wall of the submerged entry nozzle, these processes can be effectively reduced. This ensures the integrity of the submerged entry nozzle and its smooth production during the continuous casting process.

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is still a consolidation treatment choice for relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) patients and some aggressive B-cell NHL as frontline therapy. Due to the shortage of carmustine, we switched to idarubicin-substituted BEAC (IEAC) conditioning regimen. We retrospectively compared the outcomes of 72 aggressive B-cell NHL patients treated with IEAC or BEAC regimens followed by ASCT as upfront consolidative treatment. The median time to neutrophil and platelet reconstitution showed no difference between IEAC and BEAC groups. IEAC regimen was well tolerated without increase of adverse events. Transplant-related mortality didn’t occur. The overall survival (OS) and progression-free survival (PFS) of IEAC group (33 and 23 months) were a little longer than that of BEAC group (30 and 18 months). However, due to the small sample numbers, there’s no significant difference in OS and PFS between IEAC and BEAC group with DLBCL or MCL. Multivariate analysis showed that AnnArbor staging, IPI score, lactate dehydrogenase level, remission of disease, modified regimen were related with PFS and OS. In conclusion, IEAC regimen was well tolerated and replacement with idarubicin could be an alternative when carmustine was not available.

Sintered MgO was prepared by using MgO powder with different particle sizes by calcination of by crystal magnesite as the raw material and CeO2 powder as an additive. In addition, the effect of the CeO2 addition on the performance of the sintered MgO was investigated. The results showed that (i) the densification of the sintered MgO with a small amount of CeO2 addition appreciably promoted, (ii) the maximum bulk density reached 3.48 g cm−3, and (iii) the apparent porosity was 0.35%. In the sintering process, the Ca2+ could approach into CeO2 lattices, forming O2− vacancy at CeO2 grains, which resulted in promoting the growth of CeO2 grains filling the pores between the MgO grains, and enhanced the densification of sintered MgO. In addition, the solid solution reaction limited the formation of silicate phase in MgO, improving the bonding degree between the MgO grains.

Abstract Parkinson’s disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of α-synuclein (α-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic α-syn species. Recently, peripheral α-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant α-syn. In this study, we first demonstrated that erythrocyte-derived EVs isolated from Parkinson’s disease patients carried elevated levels of oligomeric α-syn, compared to those from healthy controls. Moreover, human erythrocyte-derived EVs, when injected into peripheral blood in a mouse model of Parkinson’s disease, were found to readily cross the blood-brain barrier (BBB). These EVs accumulated in astrocyte endfeet, a component of the BBB, where they impaired glutamate uptake, likely via interaction between excitatory amino acid transporter 2 (EAAT2) and oligomeric α-syn. These data suggest that erythrocyte-derived EVs and the oligomeric α-syn carried in them may play critical roles in the progression or even initiation of Parkinson’s disease. Additionally, the mechanisms involved are attributable at least in part to dysfunction of astrocytes induced by these EVs. These observations provide new insight into the understanding of the mechanisms involved in Parkinson’s disease.

The combined effects of W, Mn and Mo additions on the microstructure and properties of a hypereutectic high chromium cast iron (HCCI) were studied. The results indicated that W was distributed uniformly in the matrix and carbides. The W and Mo addition promoted the formation of M2C and M6C carbides. When 13 wt.% Mn was added to the samples, the solubility of Mn in the matrix increased the stability of the austenite phase and improved the toughness of the materials. Moreover, Mn and Cr form the M7C3 carbides in hypereutectic HCCI. A large number of (Fe, Mn)3C carbides were produced in the matrix during the later stage of solidification, which significantly improved the wear resistance of the matrix. When the amount of W, Mn and Mo added was 6 wt.%, 15 wt.% and 4.2 wt.%, respectively, the HCCI exhibited the best performance herein. The addition of 6 wt.% W led to an increase in the average hardness of the samples and the microhardness of carbides of up to 57.5 HRC and 1680 HV, respectively. Similarly, it is worth mentioning that the impact toughness of the 6% W sample reached 6.35 J/cm2, and the mass loss of the Cr16 and 0% W samples was 1.43 and 1.23 times that of the 6% W sample, respectively. The wear resistance of the 6% W sample showed no significant change before and after heat treatment. The combination of W, Mn and Mo simultaneously improved the wear resistance and impact toughness of the hypereutectic HCCI.

A novel phosphorus sensor based on the bilayer structure of ZrO2(MgO)/CaAl1.64O3.46 was fabricated and tested in high phosphorus liquid iron in this work, where the 4CaO∙P2O5 used as the auxiliary electrode was synthesized in situ by the CaAl1.64O3.46 layer during the measurement. The results indicated that phosphorus sensor showed fairly good reproducibility and sensibility to phosphorus content in high phosphorus liquid iron and the empirical equation was obtained. The application conditions of this phosphorus sensor were that the relationship between a[P] and a[O] should be satisfied to be lna[P]2a[O]5≥−29.30 at 1773 K and lna[P]2a[O]5≥−26.40 at 1823 K. After the measurement, the 4CaO∙P2O5 was detected in the CaAl1.64O3.46 layer and further confirmed that the auxiliary electrode had been formed in situ in the liquid iron. This work would be beneficial to online detecting the phosphorus content in the dephosphorization process of high phosphorus liquid iron and then improve production efficiency.