Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK/NF-κB signaling pathway.

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.

From sub-Saharan Africa to China: Evolutionary history and adaptation of Drosophila melanogaster revealed by population genomics.

Drosophila melanogaster is a widely used model organism for studying environmental adaptation. However, the genetic diversity of populations in Asia is poorly understood, leaving a notable gap in our knowledge of the global evolution and adaptation of this species. We sequenced genomes of 292 D. melanogaster strains from various ecological settings in China and analyzed them along with previously published genome sequences. We have identified six global genetic ancestry groups, despite the presence of widespread genetic admixture. The strains from China represent a unique ancestry group, although detectable differentiation exists among populations within China. We deciphered the global migration and demography of D. melanogaster, and identified widespread signals of adaptation, including genetic changes in response to insecticides. We validated the effects of insecticide resistance variants using population cage trials and deep sequencing. This work highlights the importance of population genomics in understanding the genetic underpinnings of adaptation, an effort that is particularly relevant given the deterioration of ecosystems.

Structural and Compositional Changes in Two Marine Shell Traditional Chinese Medicines: A Comparative Analysis Pre- and Post-Calcination.

BACKGROUND: Arcae concha and Meretricis concha cyclinae concha are two marine shellfish herbs with similar composition and efficacy, which are usually calcined and used clinically. OBJECTIVE: This study investigated variations in the inorganic and organic components of Arcae concha and Meretricis concha cyclinae concha from different production regions, both Arcae concha and Meretricis concha cyclinae concha. The aim was to enhance the understanding of these two types of marine shell traditional Chinese medicine (msTCM) and provide a foundation for their future development and application. METHOD: Spectroscopic techniques, including infrared spectroscopy, X-ray spectroscopy, and X-ray fluorescence spectroscopy, were used to analyze the calcium carbonate (CaCO3) crystal and trace elements. Thermogravimetric analysis was used to investigate the decomposition process during heating. The proteins were quantified using the BCA protein assay kit. Principal component analysis (PCA) was used to classify inorganic elements in the two marine shellfish traditional Chinese medicines. RESULTS: No significant differences among the various production regions. The crystal structure of CaCO3 in the raw products was aragonite, but it transformed into calcite after calcination. The contents of Ca, Na, Sr, and other inorganic elements were highest. The protein content was significantly reduced after calcination. Therefore, these factors cannot accurately reflect the internal quality of TCM, rendering qualitative identification challenging. CaCO3 dissolution in the decoction of Arcae concha and Meretricis concha cyclinae concha increased after calcination, aligning with the clinical application of calcined shell TCM. PCA revealed the inorganic elements in them, indicating that the variation in trace element composition among different drugs leads to differences in their therapeutic focus, which should be considered during usage. CONCLUSION: This study clarified the composition and structure changes of corrugated and clam shell before and after calcining, and laid the foundation for the comprehensive utilization of Marine traditional Chinese medicine. HIGHLIGHTS: These technical representations reveal the differences between raw materials and processed products, which will provide support for the quality control of other shellfish TCMS.

Magnetic-acoustic actuated spinous microrobot for enhanced degradation of organic pollutants.

A growing interest in the development of efficient strategies for the removal of organic pollutants from polluted water is emerging. As such, artificial micro/nano machines performing excellent water purification tasks have recently attracted more research attention of scientists. Hereby a spinous Fe3O4@PPy microrobot is presented that towards an efficient organic pollutant removal by enhancing Fenton-like reaction. The microrobot is fabricated by wrapping polypyrrole (PPy) on a spiny magnetic template prepared from sunflowers pollen. Modulating the sound pressure and frequency of the ultrasonic field enables the Fe3O4@PPy microrobot to present multimode motion, such as violent eruption-like motion caused by local cavitation (ELM), march-like unific motion (MLM), and typhoon-like rotation toward the center gathered motion (TLM). This multimode motion achieves the sufficient locomotion of microrobots in three-dimensional space and effective contact with organic pollutants in polluted water. Furthermore, a 5.2-fold increase in the degradation rate of methylene blue has been realized using Fe3O4@PPy microrobots under low-concentration hydrogen peroxide conditions. Also, the magnetically controlled recovery of microrobots from water after the completion of the degradation task has been demonstrated. The magnetic-acoustic actuated spinous microrobot can be extrapolated to other catalytic microrobot, developing a new strategy for an easier implementation and recovery of microrobot in real applications of water purification.

Multimode microdimer robot for crossing tissue morphological barrier.

Swimming microrobot energized by magnetic fields exhibits remotely propulsion and modulation in complex biological experiment with high precision. However, achieving high environment adaptability and multiple tasking capability in one configuration is still challenging. Here, we present a strategy that use oriented magnetized Janus spheres to assemble the microdimer robots with two magnetic distribution configurations of head-to-side configuration (HTS-config) and head-to-head configuration (HTH-config), achieving performance of multiple tasks through multimode transformation and locomotion. Modulating the magnetic frequency enables multimode motion transformation between tumbling, rolling, and swing motion with different velocities. The dual-asynchronization mechanisms of HTS-config and HTH-config robot dependent on magnetic dipole-dipole angle are investigated by molecular dynamic simulation. In addition, the microdimer robot can transport cell crossing morphological rugae or complete drug delivery on tissues by switching motion modes. This microdimer robot can provide versatile motion modes to address environmental variations or multitasking requirements.

Construction of micro-nano robots: living cells and functionalized biological cell membranes.

Micro-nano robots have emerged as a promising research field with vast potential applications in biomedicine. The motor is the key component of micro-nano robot research, and the design of the motor is crucial. Among the most commonly used motors are those derived from living cells such as bacteria with flagella, sperm, and algal cells. Additionally, scientists have developed numerous self-adaptive biomimetic motors with biological functions, primarily cell membrane functionalized micromotors. This novel type of motor exhibits remarkable performance in complex media. This paper provides a comprehensive review of the structure and performance of micro-nano robots that utilize living cells and functionalized biological cell membranes. We also discuss potential practical applications of these mirco-nano robots as well as potential challenges that may arise in future development.

The complete and fully-phased diploid genome of a male Han Chinese.

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.

A gain-of-function variation in PLCG1 causes a new immune dysregulation disease.

BACKGROUND: Phospholipase C (PLC) γ1 is a critical enzyme regulating nuclear factor-κB (NF-κB), extracellular signal-related kinase, mitogen-activated protein kinase, and nuclear factor of activated T cells signaling pathways, yet germline PLCG1 mutation in human disease has not been reported. OBJECTIVE: We aimed to investigate the molecular pathogenesis of a PLCG1 activating variant in a patient with immune dysregulation. METHODS: Whole exome sequencing was used to identify the patient's pathogenic variants. Bulk RNA sequencing, single-cell RNA sequencing, quantitative PCR, cytometry by time of flight, immunoblotting, flow cytometry, luciferase assay, IP-One ELISA, calcium flux assay, and cytokine measurements in patient PBMCs and T cells and COS-7 and Jurkat cell lines were used to define inflammatory signatures and assess the impact of the PLCG1 variant on protein function and immune signaling. RESULTS: We identified a novel and de novo heterozygous PLCG1 variant, p.S1021F, in a patient presenting with early-onset immune dysregulation disease. We demonstrated that the S1021F variant is a gain-of-function variant, leading to increased inositol-1,4,5-trisphosphate production, intracellular Ca2+ release, and increased phosphorylation of extracellular signal-related kinase, p65, and p38. The transcriptome and protein expression at the single-cell level revealed exacerbated inflammatory responses in the patient's T cells and monocytes. The PLCG1 activating variant resulted in enhanced NF-κB and type II interferon pathways in T cells, and hyperactivated NF-κB and type I interferon pathways in monocytes. Treatment with either PLCγ1 inhibitor or Janus kinase inhibitor reversed the upregulated gene expression profile in vitro. CONCLUSIONS: Our study highlights the critical role of PLCγ1 in maintaining immune homeostasis. We illustrate immune dysregulation as a consequence of PLCγ1 activation and provide insight into therapeutic targeting of PLCγ1.

Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design.

The interleukin 1 (IL-1) pathway signals through IL-1 receptor type 1 (IL-1R1) and emerges as a central mediator for systemic inflammation. Aberrant IL-1 signaling leads to a range of autoinflammatory diseases. Here, we identified a de novo missense variant in IL-1R1 (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis (CRMO). Patient PBMCs showed strong inflammatory signatures, particularly in monocytes and neutrophils. The p.Lys131Glu substitution affected a critical positively charged amino acid, which disrupted the binding of the antagonist ligand, IL-1Ra, but not IL-1α or IL-1ß. This resulted in unopposed IL-1 signaling. Mice with a homologous mutation exhibited similar hyperinflammation and greater susceptibility to collagen antibody-induced arthritis, accompanied with pathological osteoclastogenesis. Leveraging the biology of the mutation, we designed an IL-1 therapeutic, which traps IL-1ß and IL-1α, but not IL-1Ra. Collectively, this work provides molecular insights and a potential drug for improved potency and specificity in treating IL-1-driven diseases.

Discovering genetic linkage between periodontitis and type 1 diabetes: A bioinformatics study.

Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases. Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis. Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets. Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.

Neural network-based optimization of sub-diffuse reflectance spectroscopy for improved parameter prediction and efficient data collection.

In this study, a general and systematical investigation of sub-diffuse reflectance spectroscopy is implemented. A Gegenbauer-kernel phase function-based Monte Carlo is adopted to describe photon transport more efficiently. To improve the computational efficiency and accuracy, two neural network algorithms, namely, back propagation neural network and radial basis function neural network are utilized to predict the absorption coefficient µ a , reduced scattering coefficient µ s ' and sub-diffusive quantifier γ , simultaneously, at multiple source-detector separations (SDS). The predicted results show that the three parameters can be predicated accurately by selecting five SDSs or above. Based on the simulation results, a four wavelength (520, 650, 785 and 830 nm) measurement system using five SDSs is designed by adopting phase-lock-in technique. Furtherly, the trained neural-network models are utilized to extract optical properties from the phantom and in vivo experimental data. The results verify the feasibility and effectiveness of our proposed system and methods in mucosal disease diagnosis.

Hybrid Visual-Ranging Servoing for Positioning Based on Image and Measurement Features.

In this article, a hybrid visual-ranging servoing method is proposed to realize high-precision positioning tasks with a 6-degree of freedom (DOF) manipulator. This method utilizes the image and measurement features directly in the control loop. Without the need of complex image feature design and attitude estimation, this method realizes the 6-DOF control of a robot. A vital challenge in traditional vision-based systems is avoiding local minima and singularity problems. To tackle this issue, a full-rank interaction matrix hybrid visual servo (FRHVS) design criterion is proposed, which guarantees that the hybrid interaction matrix and its pseudoinverse matrix are both full rank. Moreover, the interaction matrix for these hybrid strategies, which combines image features with other sensors features, is derived in an analytical form. Experiments on a 6-DOF manipulator show that the proposed method is effective and has global asymptotic stability and high precision.

Effect of Secondary-Phase Precipitation on Mechanical Properties and Corrosion Resistance of 00Cr27Ni7Mo5N Hyper-Duplex Stainless Steel during Solution Treatment.

In this work, the effect of secondary-phase precipitation on the microstructure, mechanical properties, and corrosion resistance of 00Cr27Ni7Mo5N hyper-duplex stainless steel (HDSS) during solution treatment was investigated. The results reveal that σ-phase precipitates at the interface between the α and γ phase when the solution treatment temperature is lower than 1070 °C. It is not only brittle, but also prone to create a Cr-depleted zone, which significantly deteriorates the mechanical properties and corrosion resistance. With the increase in the solution treatment temperature, the volume fraction of ferrite gradually increases. The yield strength and tensile strength increase slightly, but the elongation decreases. At the same time, the impact toughness shows a trend of first increasing and then decreasing. When the solution treatment temperature is higher than 1130 °C, Cr2N precipitates in the ferrite. The precipitation of Cr2N causes a decrease in the plastic toughness, but it does not deteriorate the mechanical properties as significantly as the σ phase. However, it can also cause the formation of a Cr-depleted zone that significantly decreases the corrosion resistance. There is no secondary-phase precipitation in the sample after solution treatment at 1100 °C, which shows the best mechanical properties and corrosion resistance.

Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4 T1 murine breast cancer model.

Fibroblast activation protein (FAPα) is a tumor stromal antigen expressed by cancer-associated fibroblasts (CAFs) in more than 90 % of malignant epithelial carcinomas. FAPα-based immunotherapy has been reported and showed that FAPα-specific immune response can remold immune microenvironment and contribute to tumor regression. Many FAPα-based vaccines have been investigated in preclinical trials, which can elicit strong and durable cytolytic T lymphocytes (CTL) with good safety. However, epitope-based FAPα vaccines are rarely reported. To break tolerance against self-antigens, analogue epitopes with modified peptides at the anchor residues are typically used to improve epitope immunogenicity. To investigate the feasibility of a FAPα epitope-based vaccine for cancer immunotherapy in vivo, we conducted a preclinical study to identify a homologous CTL epitope of human and mouse FAPα and obtained its analogue epitope in BALB/c mice, and explored the anti-tumor activity of their minigene vaccines in 4 T1 tumor-bearing mice. By using in silico epitope prediction tools and immunogenicity assays, immunodominant epitope FAP.291 (YYFSWLTWV) and its analogue epitope FAP.291I9 (YYFSWLTWI) were identified. The FAP.291-based epitope minigene vaccine successfully stimulated CTLs targeting CAFs and exhibited anti-tumor activity in a 4 T1 murine breast cancer model. Furthermore, although the analogue epitope FAP.291I9 enhanced FAP.291-specific immune responses, improvement of anti-tumor immunity effects was not observed. Check of immunosuppressive factors revealed that the high levels of IL-10, IL-13, myeloid-derived suppressor cells and iNOS induced by FAP.291I9 increased, which considered the main cause of the failure of the analogue epitope-based vaccine. Thus, we demonstrated for the first time that the FAP.291 minigene vaccine could induce mouse CTLs and also function as a tumor regression antigen, providing the basis for future studies of FAPα epitope-based vaccines. This study may also be valuable for further improvement of the immunogenicity of analogue epitope vaccines.

Application of biochar activated persulfate in the treatment of typical azo pigment wastewater.

With the increase of the azo pigment wastewater, it is necessary to seek an efficient and sustainable treatment method to address issues of damaging water ecosystems and human health. In this work, organic representing azo dye Acid Orange 7 (AO7), heavy metal representing hexavalent chromium (Cr(VI)), and inorganic representing ammonia nitrogen (NH4+-N) were selected to roughly simulate the azo pigment wastewater. The simultaneous decontamination of multi-target pollutants by 700 °C pyrolyzed peanut shell biochar (BC) with persulfate (PDS) was evaluated. The results showed that AO7, Cr(VI) and NH4+-N could finally reach 100%, 85% and 30% removal ratios separately in the BC/PDS/mixed pollutants system under certain basic conditions. Functional groups (hydroxyl groups (C-OH) and carboxylic ester/lactone groups (O-C=O)) were found by XPS as competing sites for adsorption and activation and were gradually consumed as the reaction proceeded. Combining a series of experiments results and EPR analysis, it was found that AO7 removal worked best and it relied on both the radical pathway (including SO4•-, •OH, O2-•, but not 1O2) and adsorption. Cr(VI) was mainly adsorbed and reduced by BC surface to form Cr(OH)3 and Cr2O3, and the remaining part could be reduced by O2-•, followed by •OH. NH4+-N was removed primarily by the radical same as AO7. Meanwhile, the three target pollutants have a co-competitive mechanism. Specifically, they competed for radicals and adsorption sites simultaneously, while the presence of AO7 and NH4+-N would consume the generated oxidizing radicals and further promote the removal of Cr(VI). The fixed-bed reactor simulated the continuous treatment of wastewater. Various anions (chloride (Cl-), nitrate (NO3-), carbonate (CO32-), and hydrogen phosphate (HPO42-)) interfered differently with the pollutant removal. These findings demonstrate a new dimension of BC potential for decontamination of azo pigment wastewater.

Exogenous GABA improves the resistance of apple seedlings to long-term drought stress by enhancing GABA shunt and secondary cell wall biosynthesis.

Drought stress is an important factor limiting apple production. γ-Aminobutyric acid (GABA) exists widely in plants and participates in the response to abiotic stress as a metabolite or signaling molecule. The role of exogenous GABA in apple plants, response to long-term drought stress remains unclear. Our study confirmed that exogenous GABA affects the drought resistance of apple plants under long-term drought stress. We found that 1 mM exogenous GABA improved the resistance of apple seedlings to long-term drought stress. The plants showed better growth, less reactive oxygen radical accumulation, less damage to cell membranes and greater active photosynthetic capacity. Under long-term drought stress, exogenous GABA facilitated GABA shunt, resulting in more accumulation of organic acids, namely citric acid, succinic acid and malic acid, in roots and stems of apple seedlings. In addition, exogenous GABA upregulated the expression of cellulose-related genes and lignin-related genes, and activated secondary cell wall-related transcription factors to synthesize more cellulose and lignin. A multiple factorial analysis confirmed that the GABA shunt and the biosynthesis of cellulose and lignin substantially contributed to the growth of apple seedlings with the application of exogenous GABA under long-term drought stress. Our results suggested that exogenous GABA improved the resistance of apple seedlings to long-term drought stress by enhancing GABA shunt and secondary cell wall biosynthesis.

Magnetic-Driven Hydrogel Microrobots Selectively Enhance Synthetic Lethality in MTAP-Deleted Osteosarcoma.

Background: Drugs based on synthetic lethality have advantages such as inhibiting tumor growth and affecting normal tissue in vivo. However, specific targets for osteosarcoma have not been acknowledged yet. In this study, a non-targeted but controllable drug delivery system has been applied to selectively enhance synthetic lethality in osteosarcoma in vitro, using the magnetic-driven hydrogel microrobots. Methods: In this study, EPZ015666, a PRMT5 inhibitor, was selected as the synthetic lethality drug. Then, the drug was carried by hydrogel microrobots containing Fe3O4. Morphological characteristics of the microrobots were detected using electron microscopy. In vitro drug effect was detected by the CCK-8 assay kit, Western blotting, etc. Swimming of microrobots was observed by a timing microscope. Selective inhibition was verified by cultured tumors in an increasing magnetic field. Results: Genomic mutation of MTAP deletion occurred commonly in pan-cancer in the TCGA database (nearly 10.00%) and in osteosarcoma in the TARGET database (23.86%). HOS and its derivatives, 143B and HOS/MNNG, were detected by MTAP deletion according to the CCLE database and RT-PCR. EPZ015666, the PRMT5 inhibitor, could reduce the SDMA modification and inhibition of tumor growth of 143B and HOS/MNNG. The hydrogel microrobot drug delivery system was synthesized, and the drug was stained by rhodamine. The microrobots were powered actively by a magnetic field. A simulation of the selected inhibition of microrobots was performed and lower cell viability of tumor cells was detected by adding a high dose of microrobots. Conclusion: Our magnetic-driven drug delivery system could carry synthetic lethality drugs. Meanwhile, the selective inhibition of this system could be easily controlled by programming the strength of the magnetic field.

Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial-mesenchymal transition.

BACKGROUND: Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored. METHODS: A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial-mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism. RESULTS: A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = - 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process. CONCLUSIONS: This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.

Resource utilization of agricultural waste: Converting peanut shell into an efficient catalyst in persulfate activation for degradation of organic pollutant.

Agricultural waste was characterized by large quantity and low degree of resource utilization. The peanut shell waste was converted into value-added biochar to alleviate the pollution of dyeing wastewater, which caters to the concept of resource recovery and sustainable utilization. In this work, peroxydisulfate (PDS) could be efficiently activated by biochar obtained by pyrolysis at 700 °C (BC) and Acid Orange 7 (AO7) was rapidly eliminated with 96% removal ratio in 10 min. Meanwhile, BC catalyst performed good stability and reusability. In addition, remarkable removal performance within 40 min (>94%) could be achieved in a wide range of pH (3.0-11.0). Through series characterizations, it was found that 700 °C was the critical pyrolysis temperature to prepare material with excellent property mainly attributing to large specific surface area (SSA), followed by high defect structure and rich C-O. It was speculated that radical pathway mainly especially surface-bounded radicals (SO4•-、•OH、O2-•) worked in the degradation of AO7. Specifically, abundant and typical oxygen-containing functional groups (OFGs) and defect structure catalytic sites of BC enhanced PDS activation. In addition, various radicals participated the whole degradation processes, such as the cleavage of azo bond (-NN-), hydroxylation, deamination and desulfurization.

Altered Homotopic Connectivity in the Cerebellum Predicts Stereopsis Dysfunction in Patients With Comitant Exotropia.

Purpose: Comitant exotropia (CE) is a common eye disorder characterized by impaired stereoscopic vision and eye deviation. Previous neuroimaging studies demonstrated that patients with CE were accompanied by specific functional and structural abnormalities of the brain. However, the effect of impaired stereoscopic vision and eye deviation on interhemispheric homotopic connectivity remains unknown. Methods: A total of thirty-six patients with CE (25 males and 11 females) and 36 well-matched healthy controls underwent magnetic resonance imaging scanning. The voxel-mirrored homotopic connectivity (VMHC) method was applied to assess the interhemispheric homotopic connectivity changes in patients with CE. Furthermore, the support vector machine method was applied to assess to differentiate patients with CE from healthy controls (HCs) with the VMHC maps as a feature. Results: Compared with HCs, patients with CE showed significantly increased VMHC values in the bilateral cerebelum_ 8 and cerebelum_4_5. Moreover, we found that the VMHC maps showed an accuracy of 81.94% and an area under the curve of 0.87 for distinguishing the patients with CE from HCs. Conclusion: Our study demonstrates that patients with CE showed interhemispheric homotopic connectivity changes in the cerebellum, which might reflect the neurological mechanisms of impaired stereoscopic vision and eye deviation in patients with CE.