Branched-Chain Amino Acid Degradation Pathway was Inactivated in Colorectal Cancer: Results from a Proteomics Study.

Background: Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. Methods: In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. Results: In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name Aldh2) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name Hadh) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. Conclusion: This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.

Icariin upregulates methyltransferase-like 14-mediated prolyl 4-hydroxylase beta subunit m6A modification to promote osteogenic differentiation of bone marrow stem cells.

Prolyl 4-hydroxylase beta subunit (P4HB) plays a vital role in bone formation. This study intends to clarify the role of P4HB in the therapeutic effect of Icariin (ICA) on osteoporosis. Herein, in vivo and in vitro models were constructed by performing ovariectomy (OVX) in rats and inducing osteogenic differentiation in bone marrow stem cells (BMSCs), respectively. Hematoxylin and eosin staining and micro-computed tomography analysis were performed to evaluate osteoporosis in OVX rats. Alizarin Red staining, alkaline phosphatase staining, and the ALP activity test were employed to assess osteogenesis. m6A dot blotting and methylated RNA immunoprecipitation were used to determine m6A modification. We found that P4HB was downregulated in bone tissues of patients with osteoporosis and OVX rats. P4HB facilitated osteogenic differentiation of BMSCs. What's more, ICA upregulated P4HB expression, promoted osteogenic differentiation of BMSCs, and alleviated osteoporosis in OVX rats, which were reversed by knocking down P4HB. ICA enhanced the stability and m6A modification of P4HB. METTL14 mediated m6A modification of P4HB mRNA. In addition, METTL14 knockdown overturned the promotive effects of ICA on P4HB m6A level and BMSC osteogenic differentiation. To sum up, ICA elevated the METTL14-mediated m6A modification of P4HB to facilitate BMSC osteogenic differentiation.

Strong Intervalley Scattering-Induced Renormalization of Electronic and Thermal Transport Properties and Selection Rule Analysis in 2D Tellurium.

The electron-phonon interaction (EPI) and phonon-phonon interactions are ubiquitous in promising two-dimensional (2D) semiconductors, determining both electronic and thermal transport properties. In this work, based on ab initio calculations, the effects of intervalley scattering on EPI and higher-order four-phonon interactions of α-Te and ß-Te are investigated. Through the proposed selection rules for scattering channels and calculations of full electron-phonon scattering rates, we demonstrate that multiple nearly degenerate local valleys/peaks produce more scattering channels, resulting in stronger intervalley scattering over intravalley scattering. The lattice thermal conductivities of α-Te and ß-Te are decreased by as much as 10.9% and 30.8% by considering EPI under the carrier concentration of 2 × 1013 cm-2 (n-type) at 300 K compared to those limited by three-phonon scattering, respectively. However, when further considering four-phonon scattering, EPI reduces the lattice thermal conductivities by 2.6% and 19.4% for α-Te and ß-Te, respectively. Furthermore, it is revealed that the four-phonon interaction is more dominant in phonon transport for α-Te than that for ß-Te due to the presence of an acoustic-optical phonon gap in α-Te. Finally, we demonstrate strong intervalley scattering induces significant renormalization effects from EPI on all the constituent parameters of thermoelectric performance. Our results show the contributions of intervalley scattering to the electronic properties as well as thermal transport properties in band-convergent thermoelectric materials are essential and highlight the potential of monolayer tellurium as a promising candidate for advanced thermoelectric applications.

Characteristics and evaluation of heavy metal pollution in a soil-wheat system of an arid oasis city in northwest China.

In this paper, the Cu and Ni accumulation and contamination levels in agricultural soils and wheat around a smelter in Jinchang City in northwest China were investigated with a combination of field investigations and indoor analytical tests, using a soil-wheat system as the study area. The average Cu and Ni contents in the soil were 119.50 mg kg-1 and 123.40 mg kg-1, respectively, both of which exceeded the local soil background values. The Cu and Ni contents in 46.15% o and 26.92% of sampling sites, respectively, exceeded the screening values for soil contamination risk in agricultural land in China. The average Cu content in different parts of wheat was in the order of roots (24.22 mg kg-1) > leaves (20.11 mg kg-1) > husks (5.51 mg kg-1) > grains (4.05 mg kg-1) > stalks (3.74 mg kg-1). Furthermore, the average Ni content ranked as leaves (24.64 mg kg-1) > roots (21.12 mg kg-1) > husks (6.95 mg kg-1) > stalks (1.75 mg kg-1) > grains (0.38 mg kg-1). The health risk evaluation showed that with average hazard index values of 0.88 for adults and 1.04 for children for Cu and Ni in wheat grain, wheat in this region is unlikely to pose a health risk to adults but may pose a lesser health risk to children. The Ni bio-concentration and translocation factors in the husk and leaves of wheat were greater than those of Cu and smaller than those of Cu in the other parts of wheat. The results of this study provide basic data for the remediation of heavy metal contamination in local agricultural soils.

Person Re-Identification Method Based on Dual Descriptor Feature Enhancement.

Person re-identification is a technology used to identify individuals across different cameras. Existing methods involve extracting features from an input image and using a single feature for matching. However, these features often provide a biased description of the person. To address this limitation, this paper introduces a new method called the Dual Descriptor Feature Enhancement (DDFE) network, which aims to emulate the multi-perspective observation abilities of humans. The DDFE network uses two independent sub-networks to extract descriptors from the same person image. These descriptors are subsequently combined to create a comprehensive multi-view representation, resulting in a significant improvement in recognition performance. To further enhance the discriminative capability of the DDFE network, a carefully designed training strategy is employed. Firstly, the CurricularFace loss is introduced to enhance the recognition accuracy of each sub-network. Secondly, the DropPath operation is incorporated to introduce randomness during sub-network training, promoting difference between the descriptors. Additionally, an Integration Training Module (ITM) is devised to enhance the discriminability of the integrated features. Extensive experiments are conducted on the Market1501 and MSMT17 datasets. On the Market1501 dataset, the DDFE network achieves an mAP of 91.6% and a Rank1 of 96.1%; on the MSMT17 dataset, the network achieves an mAP of 69.9% and a Rank1 of 87.5%. These outcomes outperform most SOTA methods, highlighting the significant advancement and effectiveness of the DDFE network.

Joint Modal Alignment and Feature Enhancement for Visible-Infrared Person Re-Identification.

Visible-infrared person re-identification aims to solve the matching problem between cross-camera and cross-modal person images. Existing methods strive to perform better cross-modal alignment, but often neglect the critical importance of feature enhancement for achieving better performance. Therefore, we proposed an effective method that combines both modal alignment and feature enhancement. Specifically, we introduced Visible-Infrared Modal Data Augmentation (VIMDA) for visible images to improve modal alignment. Margin MMD-ID Loss was also used to further enhance modal alignment and optimize model convergence. Then, we proposed Multi-Grain Feature Extraction (MGFE) Structure for feature enhancement to further improve recognition performance. Extensive experiments have been carried out on SYSY-MM01 and RegDB. The result indicates that our method outperforms the current state-of-the-art method for visible-infrared person re-identification. Ablation experiments verified the effectiveness of the proposed method.

Spin-Orbit-Coupling-Induced Topological Transition and Anomalously Strong Intervalley Scattering in Two-Dimensional Bismuth Allotropes with Enhanced Thermoelectric Performances.

The convergence of multivalley bands is originally believed to be beneficial for thermoelectric performance by enhancing the charge conductivity while preserving the Seebeck coefficients, based on the assumption that electron interband or intervalley scattering effects are totally negligible. In this work, we demonstrate that ß-Bi with a buckled honeycomb structure experiences a topological transition from a normal insulator to a Z2 topological insulator induced by spin-orbit coupling, which subsequently increases the band degeneracy and is probably beneficial for enhancement of the thermoelectric power factor for holes. Therefore, strong intervalley scattering can be observed in both band-convergent ß- and aw-Bi monolayers. Compared to ß-Bi, aw-Bi with a puckered black-phosphorus-like structure possesses high carrier mobilities with 318 cm2/(V s) for electrons and 568 cm2/(V s) for holes at room temperature. We also unveil extraordinarily strong fourth phonon-phonon interactions in these bismuth monolayers, significantly reducing their lattice thermal conductivities at room temperature, which is generally anomalous in conventional semiconductors. Finally, a high thermoelectric figure of merit (zT) can be achieved in both bismuth monolayers, especially for aw-Bi with an n-type zT value of 2.2 at room temperature. Our results suggest that strong fourth phonon-phonon interactions are crucial to a high thermoelectric performance in these materials, and two-dimensional bismuth is probably a promising thermoelectric material due to its enhanced band convergence induced by the topological transition.

The value of lactate dehydrogenase to albumin ratio and immune inflammation biomarkers in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal cancers. Evidence for the importance of inflammation and immunology in the development and progression of CRC is growing steadily. The purpose of this study was to determine the clinical importance of Lactic Dehydrogenase (LDH) to Albumin (ALB) Ratio (LAR) and immune-inflammation biomarkers (IIBs) in patients with CRC. Methods: This study enrolled 382 CRC patients. The LAR was determined as the serum LDH(U/l) to ALB(g/l) ratio. We compared the levels of LAR and IIBs in different TNM stages and tumor differentiation. The relationship between LAR and IIBs and overall survival (OS) of CRC was determined by Cox regression models. A prognostic nomogram was created using the results of the multivariate analysis and the effectiveness of the nomogram was assessed using the ROC, calibration, and decision curves. We evaluated the relationship between LAR and IIBs and clinical features of CRC. Results: The levels of LAR, SII, NLR and PLR in TNM IV stage group (LAR:5.92 (5.23-8.24); SII: 1040.02 (499.51-1683.54); NLR: 2.87 (2.07-5.3); PLR:187.08 (125.31-276.63)) were significantly higher than those in other groups. LAR and NLR showed no significant difference in different tumor differentiation groups, while SII and PLR in undifferentiated groups (SII:543.72 (372.63-1110.20); PLR: 147.06 (106.04-203.92)) were significantly higher than those in well and moderate groups (SII: 474.29 (323.75-716.01); PLR: 126.28 (104.31-167.88)). LAR (HR = 1.317, 95% CI = 1.019-1.454), TNM stage (HR = 2.895, 95% CI = 1.838-4.559), age (HR = 1.766, 95% CI = 1.069-2.922) and lymphocytes (HR = 0.663, 95% CI = 0.456-0.963) were predictors of OS. IIBs, including SII, NLR, and PLR are independent of OS. The LAR-based nomogram AUCs of 1-year, 3-year and 5-year survival probabilities in the training cohort were 0.86, 0.72, and 0.71, respectively, and the AUCs of the validation cohort were 0.85, 0.71, and 0.69 respectively. The LAR-based nomogram's ROC curves and calibration curves demonstrated higher OS discriminative performance. The decision curves demonstrated greater net benefit in the survival prediction. Conclusion: Preoperative LAR is a potential prognostic marker in CRC patients, while SII, NLR, and PLR are independent of OS. LAR was associated with tumor stage in CRC patients, but not with tumor differentiation.

Progress of proteomics in research of colon cancer / 中国生物制品学杂志

@#The diagnosis and treatment of colon cancer has always been a difficult problem in the medical field.In recent years,there have been more and more researches on differential proteins in colon cancer.It has become a new trend to find differential proteins in cancer tissues by proteomic technology and study their functions and roles in cancer,which was so as to used in cancer diagnosis and treatment.We have found two differential proteins ATP-binding cassette sub-family G member 2(ABCG2)and protein disulfide-isomerase A2(PDIA2)in colon cancer by proteomic technology before,and this article reviews the expression and function of these two proteins in colon cancer.

PDIA2 Bridges Endoplasmic Reticulum Stress and Metabolic Reprogramming During Malignant Transformation of Chronic Colitis.

Background: Chronic inflammation contributes to approximately 20% of cancers; the underlying mechanisms are still elusive. Here, using an animal model of colitis to colon-cancerous transformation, we demonstrated that endoplasmic reticulum (ER) stress couples with metabolic reprogramming to promote a malignant transformation of chronic inflammation. Methods: The animal model for chronic colitis to colon-cancerous transformation was established in C57BL/6N mice by azoxymethane (AOM) and dextran sodium sulfate (DSS) treatments. The differential proteins in control and AOM/DSS-treated colon mucosa were determined using proteomic analysis; the kinetics of metabolic modifications were monitored by mitochondrial oxygen flux, extracellular acidification, and targeted metabolomics; the molecule linker between ER stress and metabolic modifications were identified by coimmunoprecipitation, KEGG pathway analysis, and the subcutaneous tumor model using gene-specific knockdown colon cancer cells. Tissue array analysis were used to evaluate the differential protein in cancer and cancer-adjacent tissues. Results: AOM/DSS treatment induced 38 tumors in 10 mice at the 14th week with the mean tumor size 9.35 ± 3.87 mm2, which was significantly decreased to 5.85 ± 0.95 mm2 by the ER stress inhibitor 4-phenylbutyric acid (4PBA). Seven differential proteins were determined from control (1,067 ± 48) and AOM/DSS-treated mucosa (1,077 ± 59); the level of ER protein PDIA2 (protein disulfide isomerase-associated 2) was increased over 7-fold in response to AOM/DSS treatment. PDIA2 interacted with 420 proteins that were involved in 8 signaling pathways, in particular with 53 proteins in metabolic pathways. PDIA2 translocated from ER to mitochondria and interacted with the components of complexes I and II to inhibit oxophosphorylation but increase glycolysis. Knockdown PDIA2 in colon cancer cells restored the metabolic imbalance and significantly repressed tumor growth in the xenograft animal model. 4PBA therapy inhibited the AOM/DSS-mediated overexpression of PDIA2 and metabolic modifications and suppressed colon cancer growth. In clinic, PDIA2 was overexpressed in colon cancer tissues rather than cancer-adjacent tissues and was related with the late stages and lymph node metastasis of colon cancer. Conclusions: Persistent ER stress reprograms the metabolism to promote the malignant transformation of chronic colitis; PDIA2 serves as a molecule linker between ER stress and metabolic reprogramming. The inhibition of ER stress restores metabolic homeostasis and attenuates the cancerous transformation of chronic inflammation.

[Enhanced Dewaterability of Waste-Activated Sludge in Presence of Fe(â ¡)-Activated Calcium Peroxide].

Ferrous iron-activated calcium peroxide (Fe2+/CaO2) was innovatively put forward to improve the dewaterability of waste-activated sludge. The effects of initial pH, Fe2+, and CaO2dosages on sludge dewatering performance were investigated and its internal mechanism for achieving deep sludge dewatering was thoroughly explored. The results indicated that the best dewatering performance was obtained by dosing 3.31 mmol·g-1 Fe2+ and 3.68 mmol·g-1 CaO2 under neutral pH, in which specific resistance to filtration (SRF) and water content (WC) reduced from 20.99×1012 m·kg-1 and 86.61% to 3.91×1012 m·kg-1 and 76.15%, respectively. Fe2+/CaO2 oxidation caused sludge microbial cell lysis, release of intracellular organic matter, and degradation of extracellular polymeric substances (EPS). Meanwhile, the generated Fe3+ facilitated re-flocculation of sludge particles into rigid and porous structure flocs, which was beneficial to the release of EPS-bound water to achieve deep sludge dewatering. From the perspective of technology and economy, the Fe2+/CaO2 process is economical and practical, and has a promising application prospect in improving the dewatering performance of waste-activated sludge.

[Heterologous expression of Streptomyces coelicolor trehalose synthase and whole-cell biocatalyst production of trehalose in Escherichia coli].

The trehalose synthase (ScTreS) gene from Streptomyces coelicolor was successfully cloned and heterologously expressed in Escherichia coli BL21(DE3). The protein purified by Ni-NTA affinity column showed an apparent molecular weight (MW) of 62.3 kDa analyzed by SDS-PAGE. The optimum temperature of the enzyme was 35 °C and the optimum pH was 7.0; the enzyme was sensitive to acidic conditions. By homologous modeling and sequence alignment, the enzyme was modified by site-directed mutagenesis. The relative activities of the mutant enzymes K246A and A165T were 1.43 and 1.39 times that of the wild type, an increased conversion rate of 14% and 10% respectively. To optimize the synthesis conditions of trehalose, the mutant strain K246A was cultivated in a 5-L fermentor and used for whole-cell transformation. The results showed that with the substrate maltose concentration of 300 g/L at 35 °C and pH 7.0, the highest conversion rate reached 71.3%, and the yield of trehalose was 213.93 g/L. However, when maltose concentration was increased to 700 g/L, the yield of trehalose can reach 465.98 g/L with a conversion rate of 66%.

Upregulation of Breast Cancer Resistance Protein Expression was Decreased in Plasma Membrane of Colon Cancer with Metastasis of Lymphatic Node.

BACKGROUND: ATP-binding cassette sub-family G member 2 (ABCG2), an ABC transport protein involved in the efflux of anticancer compounds, has been reported to have altered expression levels in several cancers including breast, colon, and gastric cancer, etc. However, its expression change (up- or down-regulated in cancer) is still contradictory. METHODS: We performed immunohistochemistry to examine ABCG2 expression in the microarray with 90 pairs of colon cancer and their adjacent normal tissues. To find the expression of ABCG2 in lymphatic node metastasis (N1) and N0, we performed immunofluorescence, analyzed by Confocal technology. RESULTS: Compared to adjacent normal tissues, the percentage and density of positive cells expressing ABCG2 in colon cancer were significantly increased. In addition, ABCG2 expression in plasma membrane was related to lymph node metastasis in colon cancer, which was further verified to be downregulated by 2.7-fold in N1 to N0 through immunofluorescent analysis. CONCLUSIONS: ABCG2 expression in colon cancer was up-regulated, and its expression was decreased in the plasma membrane of colon cancer with lymphatic node metastasis (N metastasis).

iTRAQ based investigation of plasma proteins in HIV infected and HIV/HBV coinfected patients - C9 and KLK are related to HIV/HBV coinfection.

OBJECTIVES: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) share similar routes of transmission, and rapid progression of hepatic and immunodeficiency diseases has been observed in coinfected individuals. Our main objective was to investigate the molecular mechanism of HIV/HBV coinfections. METHODS: We selected HIV infected and HIV/HBV coinfected patients with and without Highly Active Antiretroviral Therapy (HAART). Low abundance proteins enriched using a multiple affinity removal system (MARS) were labeled with isobaric tags for relative and absolute quantitation (iTRAQ) kits and analyzed using liquid chromatography-mass spectrometry (LC-MS). The differential proteins were analyzed by Gene Ontology (GO) database. RESULTS: A total of 41 differential proteins were found in HIV/HBV coinfected patients as compared to HIV mono-infected patients with or without HAART treatment, including 7 common HBV-regulated proteins. The proteins involved in complement and coagulation pathways were significantly enriched, including plasma kallikrein (KLK) and complement component C9 (C9). C9 and KLK were verified to be down-regulated in HIV/HBV coinfected patients through ELISA analysis. CONCLUSION: The present iTRAQ based proteomic analyses identified 7 proteins that are related to HIV/HBV coinfection. HBV might influence hepatic and immune functions by deregulating complement and coagulation pathways. C9 and KLK could potentially be used as targets for the treatment of HIV/HBV coinfections.

[Effect of topographical factors on podophyllotoxin content in Sinopodophyllum hexandrum and study on ecological suitability].

In order to find the optimal topographical factor for regionslization, the content of cimetidine in 116 Sinopodophyllum hexandrum sample collected from Sichuan, Qinghai, Gansu, Tibet, Yunnan and Shaanxi provinces, was determined. Using mathematical statistics and geographical spatial analysis of GIS analysis, the relationship between content of podophyllotoxin and influencing factors including altitude gradient and gradient position was analyzed. It is found that the optimal altitude was 2 800 m to 3 600 m, the aspect of slope north or northeast and northwest and the slope 12 degrees to 65 degrees with a high suitability degree. Considering the artificial planting, the suitable planting area for S. hexandrum is comfirmed. The topographical factor is important for S. hexandrum regionalization, but has hardly effect on podophyllotoxin content. The results of the study provide an important scientific basis for S. hexandrum production development. But there are many factors which affect suitability index and podophyllotoxin content of S. hexandrum, it is necessary to consider other factors like climate and soil while exploitation and protection of S. hexandrum.

[Correlation research on contents of podophyllotoxin and total lignans in Sinopodophyllum hexandrum and ecological factors].

To explore the correlation between the ecological factors and the contents of podophyllotoxin and total lignans in root and rhizome of Sinopodophyllum hexandrum, podophyllotoxin in 87 samples (from 5 provinces) was determined by HPLC and total lignans by UV. A correlation and regression analysis was made by software SPSS 16.0 in combination with ecological factors (terrain, soil and climate). The content determination results showed a great difference between podophyllotoxin and total lignans, attaining 1.001%-6.230% and 5.350%-16.34%, respective. The correlation and regression analysis by SPSS showed a positive linear correlation between their contents, strong positive correlation between their contents, latitude and annual average rainfall within the sampling area, weak negative correlation with pH value and organic material in soil, weaker and stronger positive correlations with soil potassium, weak negative correlation with slope and annual average temperature and weaker positive correlation between the podophyllotoxin content and soil potassium.