Search

Abstract Background Diabetic kidney disease (DKD) is the major complication of diabetes concomitant with gut dysbiosis and glycometabolic disorder, which are strongly associated with bile acid (BA) metabolism. Yet studies investigating the BA metabolism involving in DKD pathogenesis are limited. This study aimed to explore the metabolomic profiling of BAs in DKD and analyze its association with DKD progression. Methods An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify BAs in the plasma, fecal and urine samples of patients with DKD or T2DM and healthy individuals (n = 30 for each group). The key BAs associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) and receiver-operating characteristic (ROC) curve. Polynomial regression and Pearson’s correlation analyses were performed to assess the correlation between the key BAs and the clinical indicators reflecting DKD progression. Results Metabolomic profiling of 50 kinds of BAs presented the markedly step-wise alterations of BAs in plasma and feces as well as the little in urine of patients with DKD. Eight kinds of BAs in the plasma, eight kinds in the feces and three kinds in the urine were abnormally expressed, accompanying with the increased conjugated/unconjugated ratios of cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid and hyocholic acid in the plasma, and of cholic acid, chenodeoxycholic acid and lithocholic acid in the feces. Moreover, the increased plasma level of glycochenodeoxycholic acid, and the increased fecal levels of glycolithocholic acid, 7-ketodeoxycholic acid and chenodeoxycholic acid-3-β-D-glucuronide are strongly correlated with the clinical indicators reflecting DKD progression, including eGFR, 24 h urinary protein and 24 h urinary microalbumin. Conclusions Our study for the first time disclosed the specific alterations of BA metabolism reflecting the step-wise progression of DKD, providing the basis for early identification and therapeutical strategies for DKD.

Abstract Background Health-related quality of life (HRQOL) in cancer patients has attracted increasing attention, which may be associated with self-rated health (SRH), anxiety, and depression. However, limited studies have focused on the mediating role of anxiety and depression in the relationship between SRH and HRQOL among cancer patients. Therefore, this study aims to explore the serial multiple mediating effects of anxiety and depression between SRH and HRQOL in cancer patients. Methods This cross-sectional study investigated a total of 565 hospitalized cancer patients in Anhui province in China from November 2020 to October 2021. SRH was assessed using a single-item measure, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D, three-level version). Socio-demographic and clinical characteristics were analyzed using descriptive statistics. The relationships between SRH, anxiety, depression, and HRQOL were evaluated by Pearson correlation analysis. The serial multiple mediation of anxiety and depression was assessed by SPSS PROCESS macro. Results SRH, anxiety, depression and HRQOL were significantly correlated(P

ZCL-278 is a selective small molecule specifically inhibiting the Cdc42-intersectin interaction, yet its in-vivo pharmacokinetic and pharmacodynamic properties against renal diseases had not been determined. Thus, our study explored the absorption, distribution and excretion of ZCL-278 as well as its pharmacological efficacy against chronic kidney disease (CKD). With the optimized detection method, absolute oral bioavailability of ZCL-278 was determined as 10.99 % in male and 17.34 % in female rats. ZCL-278 was rapidly and abundantly distributed in various tissues, especially the kidney and heart, while few excreted through urine and feces. In the adenine-induced CKD mice, the increased plasma creatinine and urea, the decreased body weight as well as the renal pathological alterations, including vacuolization of renal tubular epithelial cells, granular degeneration, cell flattening, luminal dilation, and cylindruria, were significantly ameliorated after ZCL-278 administration. Moreover, ZCL-278 could also reverse the increased intensities of renal inflammation and fibrosis in the CKD mice. These results clarified the pharmacokinetics of ZCL-278 in rats and preliminarily indicated that ZCL-278 has favorable pharmacodynamic properties for CKD primed for lead development and optimization, warranting further drug development.

BackgroundDisheveled, EGL-10, and pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a component of GTPase-activating protein (GAP) activity toward the RAG complex 1 (GATOR1) protein, which is an inhibitor of the amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). With the wide application of whole exome sequencing (WES), more and more variations in DEPDC5 were uncovered in FFEVF families.MethodsA family with a proband diagnosed with familial focal epilepsy with variable foci (FFEVF) was involved in this study. Whole exome sequencing (WES) was performed in the proband, and Sanger sequencing was used to confirm the variation carrying status of the family members. Mini-gene splicing assay was performed to validate the effect on the alternative splicing of the variation.ResultsA novel variant, c.1217 + 2T>A, in DEPDC5 was identified by WES in the proband. This splicing variant that occurred at the 5′ end of intron 17 was confirmed by mini-gene splicing assays, which impacted alternative splicing and led to the inclusion of an intron fragment. The analysis of the transcribed mRNA sequence indicates that the translation of the protein is terminated prematurely, which is very likely to result in the loss of function of the protein and lead to the occurrence of FFEVF.ConclusionThe results suggest that c.1217 + 2T>A variations in DEPDC5 might be the genetic etiology for FFEVF in this pedigree. This finding expands the genotype spectrum of FFEVF and provides new etiological information for FFEVF.

Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH2) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future.

Extractives have an impact on the processing and commercial value of wood. Ultrasound is an environmentally friendly technology commonly employed to reduce the extractive content and thus enhance the permeability of wood. This study aimed to understand the migration mechanism of extractives inside wood during ultrasonic treatment, which may help to obtain the desired wood properties. The extractive distribution of Ailanthus altissima was observed by using stereo microscopy, optical microscopy, and scanning electron microscopy, the extractive content was determined, and the relationship between the concentration of water-soluble extractives and absorbance was measured using a UV/Vis spectrophotometer, and the migration model of extractives was studied using layered extraction by innovatively combining the weight and the absorbance methods. The results revealed that the extractives were predominantly distributed in the vessels and diminished after ultrasonic treatment. The extractive content gradually decreased over time (0 ∼ 5 h), with a rapid decline observed within the first 2 h. The concentration of the water-soluble extractives exhibited a proportional relationship with the absorbance. Through the comparison of the layered-extractive concentration, accumulating evidence suggested that the migration of the extractives was a dynamic process, which included the extractives migrating towards easy-extracted area, moving along the direction of ultrasound propagation inside the wood, and leaching out of wood during ultrasonic treatment.

Magnetization reduction roasting is an important method for the utilization of oolitic magnetite. In this study, the magnetization reduction behavior and kinetics of oolitic hematite in gas-based roasting were systematically investigated by X-ray photoelectron spectroscopy (XPS). The results revealed that under optimal roasting conditions of 650 °C, a roasting time of 60 min, and a CO concentration of 30%, the magnetization reduction rate of the roasted product reached 44.34%. Furthermore, the weak magnetic separation concentrate presented a TFe of 58.09% and a concentrate iron recovery of 94.3%. The results of the XPS spectrum indicated that the peak area ratio (Fe2+/Fe3+) gradually increased with an increase in roasting temperature, roasting time, and CO concentration, while over-reduction occurred when the roasting temperature exceeded 750 °C. The investigation of magnetization roasting kinetics for varying particle sizes demonstrated that the magnetization reduction process is controlled by chemical reaction, with a corresponding activation energy range of 42.96 kJ/mol to 63.29 kJ/mol, indicating the particle size has little effect on the magnetization reduction of oolitic hematite.

The retrospective study aimed to describe the epidemiological characteristics and trends of cancer in Anhui Province, China between 2010 and 2018. Cancer registry data were analyzed using the Joinpoint regression model to calculate trends in cancer incidence and mortality. Age-standardized incidence rate, calculated based on the world Segi’s population (ASIRW) was higher in males (239.34 per 100 000) than in females (157.13 per 100 000), and higher in rural areas (203.98 per 100 000) compared to urban areas (189.93 per 100 000). The ASIRW for males decreased with an AAPC of −3.0%, while that of females showed an upward trend with an AAPC of 2.1%. At the same time, the ASIRW in urban areas decreased with an AAPC of −2.4%, whereas it remained relatively stable in rural areas. Among males, lung cancer was the most prevalent type of cancer, while breast cancer was the most frequent cancer among women. The age-standardized mortality rate according to the world Segi’s population (ASMRW) was 115.32 per 100 000. The ASMRW was higher in males (156.70 per 100 000) than in females (75.51 per 100 000), and higher in rural areas (122.18 per 100 000) than urban areas (109.21 per 100 000). Lung cancer accounted for the majority of cancer-associated mortalities in the province. Attention needs to be focused on women and rural areas due to rapidly increasing incidence and mortality rates for cancer. Furthermore, an effective public health response is imperative, encompassing early screening, diagnosis, and treatment of prevalent cancers in high-risk populations and regions. It’s crucial to promote healthy lifestyles among the public through health education.

Although multiple vaccines have been developed and widely administered, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported to evade immune responses and spread diffusely. Here, 108 RNA-seq files from coronavirus disease 2019 (COVID-19) patients and healthy donors (HD) were downloaded to extract their TCR immune repertoire by MiXCR. Those extracted TCR repertoire were compared and it was found that disease progression was related negatively with diversity and positively with clonality. Specifically, greater proportions of high-abundance clonotypes were observed in active and severe COVID-19 samples, probably resulting from strong stimulation of SARS-CoV-2 epitopes and a continued immune response in host. To investigate the specific recognition between TCR CDR3 and SARS-CoV-2 epitopes, we constructed an accurate classifier CoV2-TCR with an AUC of 0.967 in an independent dataset, which outperformed several similar tools. Based on this model, we observed a huge range in the number of those TCR CDR3 recognizing those different peptides, including 28 MHC-I epitopes from SARS-CoV-2 and 22 immunogenic peptides from SARS-CoV-2 variants. Interestingly, their proportions of high-abundance, low-abundance and rare clonotypes were close for each peptide. To expand the potential application of this model, we established the webserver, CoV2-TCR, in which users can obtain those recognizing CDR3 sequences from the TCR repertoire of COVID-19 patients based on the 9-mer peptides containing mutation site(s) on the four main proteins of SARS-CoV-2 variants. Overall, this study provides preliminary screening for candidate antigen epitopes and the TCR CDR3 that recognizes them, and should be helpful for vaccine design on SARS-CoV-2 variants.

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p

Abstract FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.

Histone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear. Here, starting with an affinity purification-mass spectrometry approach, we have found that Isl1, a highly tissue-specific expressed LIM/homeodomain transcription factor, is physically associated with Set1/Mll complexes. We then show that Wdr5 directly binds to Isl1. And this binding is likely mediated by the homeodomain of Isl1. Functionally, using mouse β-cell and human neuroblastoma tumor cell lines, we show that both Wdr5 binding and H3K4 methylation level at promoters of some Isl1 target genes are significantly reduced upon depletion of Isl1, suggesting Isl1 is required for efficient locus-specific H3K4 methylation. Taken together, our results establish a critical role of Set1/Mll complexes in regulating the target gene expression of Isl1.

A large number of studies have shown that oolitic hematite is an iron ore that is extremely difficult to utilize because of its fine disseminated particle size, high harmful impurity content and oolitic structure. To recover iron from oolitic hematite, we developed a novel multistage dynamic magnetizing roasting technology. Compared with traditional magnetizing roasting technologies, this novel technology has the following advantages: firstly, the oolitic hematite is dynamically reduced in a multi-stage roasting furnace, which shortens the reduction time and avoids ringing and over-reduction; secondly, the novel dynamic magnetizing roasting technology has strong raw material adaptability, and the size range of raw materials can be as wide as 0–15 mm; thirdly, the roasting furnace adopts a preheating-heating process, and the low-calorific value blast furnace gas can be used as the fuel and reductant, which greatly reduces the cost. The actual industrial production data showed that the energy consumption in the roasting process can be less than 35 kg of standard coal per ton of raw ore. The iron grade of the concentrate and iron recovery reached 65% and 90%, respectively.

Neoantigens recognized by cytotoxic T cells are effective targets for tumor-specific immune responses for personalized cancer immunotherapy. Quite a few neoantigen identification pipelines and computational strategies have been developed to improve the accuracy of the peptide selection process. However, these methods mainly consider the neoantigen end and ignore the interaction between peptide-TCR and the preference of each residue in TCRs, resulting in the filtered peptides often fail to truly elicit an immune response. Here, we propose a novel encoding approach for peptide-TCR representation. Subsequently, a deep learning framework, namely iTCep, was developed to predict the interactions between peptides and TCRs using fusion features derived from a feature-level fusion strategy. The iTCep achieved high predictive performance with AUC up to 0.96 on the testing dataset and above 0.86 on independent datasets, presenting better prediction performance compared with other predictors. Our results provided strong evidence that model iTCep can be a reliable and robust method for predicting TCR binding specificities of given antigen peptides. One can access the iTCep through a user-friendly web server at http://biostatistics.online/iTCep/, which supports prediction modes of peptide-TCR pairs and peptide-only. A stand-alone software program for T cell epitope prediction is also available for convenient installing at https://github.com/kbvstmd/iTCep/.

Type 2C protein phosphatases (PP2Cs) represent a major group of protein phosphatases in plants, some of which have already been confirmed to play important roles in diverse plant processes. In this study, analyses of the phylogenetics, gene structure, protein domain, chromosome localization, and collinearity, as well as an identification of the expression profile, protein–protein interaction, and subcellular location, were carried out on the PP2C family in wild sugarcane (Saccharum spontaneum). The results showed that 145 PP2C proteins were classified into 13 clades. Phylogenetic analysis suggested that SsPP2Cs are evolutionarily closer to those of sorghum, and the number of SsPP2Cs is the highest. There were 124 pairs of SsPP2C genes expanding via segmental duplications. Half of the SsPP2C proteins were predicted to be localized in the chloroplast (73), with the next most common predicted localizations being in the cytoplasm (37) and nucleus (17). Analysis of the promoter revealed that SsPP2Cs might be photosensitive, responsive to abiotic stresses, and hormone-stimulated. A total of 27 SsPP2Cs showed cold-stress-induced expressions, and SsPP2C27 (Sspon.01G0007840-2D) and SsPP2C64 (Sspon.03G0002800-3D) were the potential hubs involved in ABA signal transduction. Our study presents a comprehensive analysis of the SsPP2C gene family, which can play a vital role in the further study of phosphatases in wild sugarcane. The results suggest that the PP2C family is evolutionarily conserved, and that it functions in various developmental processes in wild sugarcane.

A central aim of neuroethological research is to discover the mechanisms of natural behaviors in controlled laboratory studies. This goal, however, comes with challenges, namely the selection of experimental paradigms that allow full expression of natural behaviors. Here, we explore this problem in echolocating bats that evolved Doppler shift compensation (DSC) of sonar vocalizations to yield close matching between echo frequency and hearing sensitivity. We ask if behavioral tasks influence the precision of DSC in Pratt’s roundleaf bat, Hipposideros pratti, in three classic laboratory paradigms evoking audio-vocal adjustments: Stationary bats listening to echo playbacks, bats transported on a moving pendulum, and bats flying freely. We found that experimental conditions had a strong influence on the expression of the audiovocal frequency adjustments in bats. H. pratti exhibited robust DSC in both free-flying and moving-pendulum experiments but did not exhibit consistent audiovocal adjustments in echo playback experiments. H. pratti featured a maximum compensation magnitude of 87% and a compensation precision of 0.27% in the free flight experiment. Interestingly, in the moving pendulum experiment H. pratti displayed surprisingly high-precision DSC, with an 84% maximum compensation magnitude and a 0.27% compensation precision. Such DSC performance places H. pratti among the bat species exhibiting the most precise audio-vocal control of echo frequency. These data support the emerging view that Hipposiderid bats have a high-precision DSC system and highlight the importance of selecting experimental paradigms that yield the expression of robust natural behaviors.

Neoantigens are widely reported to induce T-cell response and lead to tumor regression, indicating a promising potential to immunotherapy. Previously, we constructed an open-access database, i.e., dbPepNeo, providing a systematic resource for human tumor neoantigens to storage and query. In order to expand data volume and application scope, we updated dbPepNeo to version 2.0 (http://www.biostatistics.online/dbPepNeo2). Here, we provide about 801 high-confidence (HC) neoantigens (increased by 170%) and 842,289 low-confidence (LC) HLA immunopeptidomes (increased by 107%). Notably, 55 class II HC neoantigens and 630 neoantigen-reactive T-cell receptor-β (TCRβ) sequences were firstly included. Besides, two new analytical tools are developed, DeepCNN-Ineo and BLASTdb. DeepCNN-Ineo predicts the immunogenicity of class I neoantigens, and BLASTdb performs local alignments to look for sequence similarities in dbPepNeo2.0. Meanwhile, the web features and interface have been greatly improved and enhanced.

Abstract Background We need to monitor patterns of antibiotic prescribing in order to develop and evaluate antibiotic stewardship interventions in rural China. As part of a multidisciplinary study of antibiotic use in Anhui Province we assessed the validity of electronic records (e-records) as a source of surveillance data. Methods One township healthcare centre and one village clinic were selected in each of three different counties. Patients with symptoms of Upper Respiratory Tract Infection (URTI), exacerbation of Chronic Obstructive Pulmonary Disease (COPD) or Urinary Tract Infection (UTI) were recruited consecutively. Researchers observed and documented clinic consultations and interviewed each of the study participants. E-records were compared to clinic observations and patient interviews. Results A total of 1030 patients were observed in clinic. Antibiotics were prescribed in 917 (89%) of consultations. E-records were created only for individuals with health insurance, with considerable between-site variation in completeness (0 to 98.7% of clinic consultations) and in the timing of documentation (within-consultation up to weeks afterwards). E-record accuracy was better in relation to antibiotics (82.8% of e-records accurately recorded what was prescribed in clinic) than for diagnosis and symptoms (45.0 and 1.1% accuracy). Only 31 participants (3.0%) presented with UTI symptoms. Conclusions We have confirmed very high rates of outpatient antibiotic prescribing in rural Anhui province. E-records could provide useful information to inform stewardship interventions, however they may be inaccurate and/or biased. Public Health authorities should focus on improving technical infrastructure and record-keeping culture in outpatient settings. Further research is needed into community treatment of UTIs.

The Chinese economy is in a critical period of continuous transformation of new and old kinetic energy and economic transformation and upgrading. Copper, the second largest strategic raw material, is still central to China’s economic development. As the major producer and consumer of electrical and electronic equipment (EEE), China’s production and consumption of refined copper is the largest in the world. Thus, it is necessary to forecast the supply and demand of China’s future copper. There is a huge gap between copper production and consumption in China, the current identified copper resources cannot meet copper consumption in the next five years, thus the import of copper will be more crucial for China’s future copper industry. Due to trade frictions, restriction on imports and other reasons, the import of copper from other countries will exist a lot of uncertainties. Hence, the domestic copper waste and scraps could be the suitable secondary resource for recycling copper in China. According to the grade and value of copper scraps, establishing quality standards and optimizing the disassembly process of the domestic Cu-bearing waste & scraps, and using the suitable method are the key to recycling the domestic copper scraps.

In this study, the manganese (Mn) was doped in the MnFe2O4 crystal by the solid-phase synthesis method. Under the optimum conditions (pH = 3), the max removal rate and adsorption quantity of Cr(VI) on MnFe2O4 adsorbent obtain under pH = 3 were 92.54% and 5.813 mg/g, respectively. The DFT calculation results indicated that the adsorption energy (Eads) between HCrO4− and MnFe2O4 is −215.2 KJ/mol. The Cr(VI) is mainly adsorbed on the Mn atoms via chemical bonds in the form of HCrO4−. The adsorption of Mn on the MnFe2O4 surface belonged to chemisorption and conformed to the Pseudo-second-order equation. The mechanism investigation indicated that the Mn in MnFe2O4 has an excellent enhancement effect on the Cr(VI) removal process. The roles of Mn in the Cr(VI) removal process included two parts, providing adsorbing sites and being reductant. Firstly, the Cr(VI) is adsorbed onto the MnFe2O4 via chemisorption. The Mn in MnFe2O4 can form ionic bonds with the O atoms of HCrO4−/CrO42−, thus providing the firm adsorbing sites for the Cr(VI). Subsequently, the dissolved Mn(II) can reduce Cr(VI) to Cr(III). The disproportionation of oxidized Mn(III) produced Mn(II), causing Mn(II) to continue to participate in the Cr(VI) reduction. Finally, the reduced Cr(III) is deposited on the MnFe2O4 surface in the form of Cr(OH)3 colloids, which can be separated by magnetic separation.

Dietary methionine restriction (MR) has been shown to decrease plasma trimethylamine-N-oxide (TMAO) levels in high-fat diet mice; however, the specific mechanism used is unknown. We speculated that the underlying mechanism is related with the gut microbiota, and this study aimed to confirm the hypothesis. In this study, we initially carried out an in vitro fermentation experiment and found that MR could reduce the ability of gut microbiota found in the contents of healthy mice and the feces of healthy humans to produce trimethylamine (TMA). Subsequently, mice were fed a normal diet (CON, 0.20% choline + 0.86% methionine), high-choline diet (H-CHO, 1.20% choline + 0.86% methionine), or high-choline + methionine-restricted diet (H-CHO+MR, 1.20% choline + 0.17% methionine) for 3 months. Our results revealed that MR decreased plasma TMA and TMAO levels in H-CHO-diet-fed mice without changing hepatic FMO3 gene expression and enzyme activity, significantly decreased TMA levels and expression of choline TMA-lyase (CutC) and its activator CutD, and decreased CutC activity in the intestine. Moreover, MR significantly decreased the abundance of TMA-producing bacteria, including Escherichia-Shigella (Proteobacteria phylum) and Anaerococcus (Firmicutes phylum), and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels. Furthermore, both MR and sodium butyrate supplementation significantly inhibited bacterial growth, down-regulated CutC gene expression levels in TMA-producing bacteria, including Escherichia fergusonii ATCC 35469 and Anaerococcus hydrogenalis DSM 7454 and decreased TMA production from bacterial growth under in vitro anaerobic fermentation conditions. In conclusion, dietary MR alleviates choline-induced TMAO elevation by manipulating gut microbiota in mice and may be a promising approach to reducing circulating TMAO levels and TMAO-induced atherosclerosis.

Sugarcane is an important crop across the globe, and the rapid multiplication of excellent cultivars is an important object of the sugarcane industry. As one of the plant growth regulators, paclobutrazol (PBZ) has been frequently used in the tissue culture of sugarcane seedlings. However, little is known about the molecular mechanisms of response to PBZ in this crop. Here, we performed a comparative transcriptome analysis between sensitive (LC05−136) and non−sensitive (GGZ001) sugarcane cultivars treated by PBZ at three time points (0 d, 10 d, and 30 d) using RNA sequencing (RNA−Seq). The results showed that approximately 70.36 Mb of clean data for each sample were generated and assembled into 239,212 unigenes. A total of 6108 and 4404 differentially expressed genes (DEGs) were identified within the sensitive and non−sensitive sugarcane cultivars, respectively. Among them, DEGs in LC05−136 were most significantly enriched in the photosynthesis and valine, leucine and isoleucine degradation pathways, while in GGZ001, DEGs associated with ion channels and plant–pathogen interaction were mainly observed. Notably, many interesting genes, including those encoding putative regulators, key components of photosynthesis, amino acids degradation and glutamatergic synapse, were identified, revealing their importance in the response of sugarcane to PBZ. Furthermore, the expressions of sixteen selected DEGs were tested by quantitative reverse transcription PCR (RT−qPCR), confirming the reliability of the RNA−seq data used in this study. These results provide valuable information regarding the transcriptome changes in sugarcane treated by PBZ and provide an insight into understanding the molecular mechanisms underlying the resistance to PBZ in sugarcane.

Magnetite-type tin-bearing tailing is a typically complex secondary resource in China, of which iron and tin are with greater value. The utilization of this resource has long been a challenge due to the complex mineralogy of tin and iron minerals. In this study, the mineralogical characteristics of the tailings were studied. It was found that tin mainly existed as fine-grained cassiterite and lattice Sn4+ (Fe3-xSnxO4) in magnetite particles, which was almost impossible to recover by physical mineral processing. Fe2.6Sn0.4O4 samples were synthesized to study the mineral phase reconstructions of Fe3-xSnxO4 under CO−CO2 atmosphere, as well as in the presence of Na2CO3 or CaO. Then, three proposed processes of selective reduction roasting, sodium roasting and calcium roasting processes were demonstrated and applied in the separation of tin and iron. Finally, some suggestions were recommended for the separation of tin from magnetite-type tin-bearing tailings. Keywords: Fe3-xSnxO4, Cassiterite, Separation, Selective reduction roasting, Sodium roasting, Calcium roasting

Cancer immunotherapy works by stimulating and strengthening the body’s anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy has shown remarkable efficacy in the treatment of cancer, particularly the success of immune checkpoint blockade targeting CTLA-4, PD-1 and PDL1, which has led to a breakthrough in tumor immunotherapy. Tumor neoantigens, a new approach to tumor immunotherapy, include antigens produced by tumor viruses integrated into the genome and antigens produced by mutant proteins, which are abundantly expressed only in tumor cells and have strong immunogenicity and tumor heterogeneity. A growing number of studies have highlighted the relationship between neoantigens and T cells’ recognition of cancer cells. Vaccines developed against neoantigens are now being used in clinical trials in various solid tumors. In this review, we summarized the latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy. Finally, the application prospects and existing problems of neoantigens were discussed.

In this study, high pure humic acid (HA) extracted from lignite was fractionated into four fractions according to their molecular weights by the ultrafiltration method. The structural characteristics of various HA fractions were investigated by UV–Vis,FTIR, and 3D fluorescence spectra and 13C/1H-NMR tests. The experiment results showed that the HA fractions with the molecular weight ＞50 KDa are major, containing 70.89%. The active hydrogen proportion declined from 43.96% to 21.27% with the increase of HA molecular weight, meaning the decrease of the large HA molecules’ acidic group content. On the other hand, 80.93% of the aromatic nucleus content and 12.5% of the alkyl carbon (aliphatic structure) were observed in the large HA molecules that are much higher than those in the small HA molecules. The NMR and spectra studies indicated that the small HA molecules have more acidic groups such as hydroxy, carboxyl. Meanwhile, the large HA molecules have more aromatic and aliphatic structures. The above research indicated that the HA fractions with low molecular weight could provide more active sites for the interaction between HA and iron minerals. Moreover, the carbon chain and aromatic nucleus in the high molecular weight HA fractions could keep the space structure of HA stable.

Methionine restriction (MR) has been reported to have many beneficial health effects, including stress resistance enhancement and lifespan extension. However, the effects of MR on the splenic metabolic dysfunction induced by obesity in mice remain unknown. This study aimed to investigate the scientific problem and clarify its possible mechanisms. C57BL/6J mice in the control group were fed a control diet (0.86% methionine, 4.2% fat) for 34 weeks, and others were fed a high-fat diet (0.86% methionine, 24% fat) for 10 weeks to establish diet-induced obese (DIO) mouse models. Then, the obtained DIO mice were randomly divided into two groups: the DIO group (DIO diet), the DIO + MR group (0.17% methionine, 24% fat) for 24 weeks. Our results indicated that MR decreased spleen weight, and spleen and plasma lipid profiles, promoted lipid catabolism and fatty acid oxidation, glycolysis and tricarboxylic acid cycle metabolism, and improved mitochondrial function and ATP generation in the spleen. Moreover, MR normalized the splenic redox state and inflammation-related metabolite levels, and increased plasma levels of immunoglobulins. Furthermore, MR increased percent lean mass and splenic crude protein levels, activated the autophagy pathway and elevated nucleotide synthesis to maintain protein synthesis in the spleen. These findings indicate that MR can ameliorate metabolic dysfunction by reducing lipid accumulation, oxidative stress, and inflammation in the spleen, and the mechanism may be the activation of autophagy pathway.

Breast cancer is still the most common and leading cause of cancer-related deaths in women worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have shown key regulator roles in various cancers. Previous reports have identified miR-125b as a critical tumor suppressor in breast cancer. However, the role of lncRNAs in breast cancer is far from well-characterized. In this study, we identified a novel lncRNA LINC01787, which specifically binds pre-miR-125b, inhibits the binding between DICER and pre-miR-125b, represses the processing of pre-miR-125b by DICER, and therefore induces pre-miR-125b accumulation and represses mature miR-125b generation. Functional assays showed that LINC01787 promotes breast cancer cell proliferation and migration and breast cancer xenograft growth in vivo, which is abolished by the mutation of pre-miR-125b binding sites on LINC01787 or overexpression of miR-125b. Furthermore, LINC01787 is up-regulated in breast cancer tissues and is associated with advanced stages and poor survival. The expression of LINC01787 is inversely associated with that of miR-125b in breast cancer tissues. In conclusion, our findings identified a novel up-regulated and oncogenic lncRNA LINC01787 in breast cancer, which binds pre-miR-125b and represses mature miR-125b generation. Our data suggests LINC01787 as a potential prognostic biomarker and therapeutic target for breast cancer.

The host cell factor cyclophilin A (CypA) interacts with the HIV-1 capsid and regulates infectivity. Here the authors combine cryo-EM, solid-state NMR and all-atom MD simulations, identifying an interaction interface between CypA and the HIV capsid that stabilizes the viral capsid and regulates infectivity.

The Fe3O4 and Fe2SiO4 in copper slag were successfully reduced to metallic iron by coal-based direct reduction. Under the best reduction conditions of 1300 °C reduction temperature, 30 min reduction time, 35 wt.% coal dosage, and 20 wt.% CaO dosage (0.75 binary basicity), the Fe grade of obtained iron concentration achieved 91.55%, and the Fe recovery was 98.13%. The kinetic studies on reduction indicated that the reduction of copper slag was controlled by the interfacial reaction and carbon gasification at 1050 °C. When at a higher reduction temperature, the copper slag reduction was controlled by the diffusion of the gas. The integral kinetics model research illustrated that the reaction activation energy increased as the reduction of copper slag proceeded. The early reduction of Fe3O4 needed a low reaction activation energy. The subsequent reduction of Fe2SiO4 needed higher reaction activation energy compared with that of Fe3O4 reduction.

Sodium stannate (Na2SnO3) has been successfully prepared by a novel process of roasting cassiterite concentrates and sodium carbonate (Na2CO3) under CO−CO2 atmosphere, namely soda roasting-leaching process. However, more than 22 wt. % tin of the cassiterite was not converted into Na2SnO3 and entered the leach residues. Quartz (SiO2) is the predominant gangue in the cassiterite, and phase evolution of SnO2−SiO2−Na2CO3 system roasted under CO−CO2 atmosphere was still uncertain. In this study, the effect of SiO2 in cassiterite concentrates on preparation of Na2SnO3 was clarified. The results indicated that Na8SnSi6O18 was inevitably formed when cassiterite and Na2CO3 were roasted above 775 °C under CO−CO2 atmosphere via the reaction of SnO2 + 6SiO2 + 4Na2CO3 = Na8SnSi6O18 + 4CO2, and formation of Na8SnSi6O18 would be increased with increasing roasting temperature and Si/Sn mole fraction. In addition, it was found that Na8SnSi6O18 was insoluble in the leachate at pH value range of 1−14, which, therefore, was enriched in the leach residues. The silicon content of the cassiterite concentrates should be controlled as lower as possible to obtain a higher conversion ratio of Na2SnO3.