ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.

Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

A clinical-radiomics nomogram based on dual-layer spectral detector CT to predict cancer stage in pancreatic ductal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the efficacy of radiomics signatures derived from polyenergetic images (PEIs) and virtual monoenergetic images (VMIs) obtained through dual-layer spectral detector CT (DLCT). Moreover, it sought to develop a clinical-radiomics nomogram based on DLCT for predicting cancer stage (early stage: stage I-II, advanced stage: stage III-IV) in pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 173 patients histopathologically diagnosed with PDAC and who underwent contrast-enhanced DLCT were enrolled in this study. Among them, 49 were in the early stage, and 124 were in the advanced stage. Patients were randomly categorized into training (n = 122) and test (n = 51) cohorts at a 7:3 ratio. Radiomics features were extracted from PEIs and 40-keV VMIs were reconstructed at both arterial and portal venous phases. Radiomics signatures were constructed based on both PEIs and 40-keV VMIs. A radiomics nomogram was developed by integrating the 40-keV VMI-based radiomics signature with selected clinical predictors. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). RESULTS: The PEI-based radiomics signature demonstrated satisfactory diagnostic efficacy, with the areas under the ROC curves (AUCs) of 0.92 in both the training and test cohorts. The optimal radiomics signature was based on 40-keV VMIs, with AUCs of 0.96 and 0.94 in the training and test cohorts. The nomogram, which integrated a 40-keV VMI-based radiomics signature with two clinical parameters (tumour diameter and normalized iodine density at the portal venous phase), demonstrated promising calibration and discrimination in both the training and test cohorts (0.97 and 0.91, respectively). DCA indicated that the clinical-radiomics nomogram provided the most significant clinical benefit. CONCLUSIONS: The radiomics signature derived from 40-keV VMI and the clinical-radiomics nomogram based on DLCT both exhibited exceptional performance in distinguishing early from advanced stages in PDAC, aiding clinical decision-making for patients with this condition.

Development of a Nomogram Model to Predict the Risk of Stricture Recurrence after Urethroplasty: A Retrospective Study.

OBJECTIVE: A retrospective study was performed to analyse the influencing factors of stricture recurrence after urethroplasty and to establish a predictive nomogram model. METHODS: The clinical data of patients who underwent urethroplasty in our hospital from January 2021 to June 2023 were retrospectively analysed. Depending on whether stenosis occurs six months after surgery, the patients were divided into recurrence and nonrecurrence groups. Logistic regression analysis was performed on the indicators with statistically significant differences between the two groups in single factor analysis to analyse the influencing factors of postoperative recurrence risk of stricture. X64.4.1.3 version R language and external source packages were used to build the nomogram model. The nomogram was internally validated through 10-fold cross-validation, and C-index was calculated. The area under the curve (AUC) of the receiver operating characteristic curve was employed to evaluate the results of the internal validation. RESULTS: Amongst 105 patients who underwent urethroplasty in our hospital, 15 patients with recurrence were included in the recurrence group, and 90 patients without recurrence were included in the nonrecurrence group. The length of stricture segment, history of urethroplasty and smoking history within 3 months before surgery were risk factors for stricture recurrence, with odds ratio (OR) values of 1.874 (95% CI: 1.103-5.725), 1.670 (95% CI: 1.105-2.904) and 1.740 (95% CI: 1.456-5.785), respectively. The constructed nomogram obtained an average AUC of 0.842 and an average C-index of 0.794, calculated after 200 times of 10-fold cross-validation. CONCLUSIONS: From the data of this study, it can be deduced that the influencing factors of stricture recurrence after urethroplasty include the length of stricture segment, history of urethroplasty and smoking history of 3 months before surgery. Using the above factors as a basis to construct a predictive nomogram model is helpful to screen high-risk patients with recurrence of stricture after urethroplasty.

Identification of Key Molecular Pathways and Associated Genes as Targets to Overcome Radiotherapy Resistance Using a Combination of Radiotherapy and Immunotherapy in Glioma Patients.

Recent mechanistic studies have indicated that combinations of radiotherapy (RT) plus immunotherapy (via CSF-1R inhibition) can serve as a strategy to overcome RT resistance and improve the survival of glioma mice. Given the high mortality rate for glioma, including low-grade glioma (LGG) patients, it is of critical importance to investigate the mechanism of the combination of RT and immunotherapy and further translate the mechanism from mouse studies to improve survival of RT-treated human glioma patients. Using the RNA-seq data from a glioma mouse study, 874 differentially expressed genes (DEGs) between the group of RT-treated mice at glioma recurrence and the group of mice with combination treatment (RT plus CSF-1R inhibition) were translated to the human genome to identify significant molecular pathways using the KEGG enrichment analysis. The enrichment analysis yields statistically significant signaling pathways, including the phosphoinositide 3-kinase (PI3K)/AKT pathway, Hippo pathway, and Notch pathway. Within each pathway, a candidate gene set was selected by Cox regression models as genetic biomarkers for resistance to RT and response to the combination of RT plus immunotherapies. Each Cox model is trained using a cohort of 295 RT-treated LGG patients from The Cancer Genome Atlas (TCGA) database and validated using a cohort of 127 RT-treated LGG patients from the Chinese Glioma Genome Atlas (CGGA) database. A four-DEG signature (ITGB8, COL9A3, TGFB2, JAG1) was identified from the significant genes within the three pathways and yielded the area under time-dependent ROC curve AUC = 0.86 for 5-year survival in the validation set, which indicates that the selected DEGs have strong prognostic value and are potential intervention targets for combination therapies. These findings may facilitate future trial designs for developing combination therapies for glioma patients.

Recent Progress in Enzymatic Preparation of Chitooligosaccharides with a Single Degree of Polymerization and Their Potential Applications in the Food Sector.

Chitosan oligosaccharides (COS), derived from chitin, have garnered considerable attention owing to their diverse biological activities and potential applications. Previous investigations into the bioactivity of COS often encountered challenges, primarily stemming from the use of COS mixtures, making it difficult to discern specific effects linked to distinct degrees of polymerization (DP). Recent progress underscores the significant variation in the biological activities of COS corresponding to different DPs, prompting dedicated research towards synthesizing COS with well-defined polymerization. Among the available methods, enzymatic preparation stands out as a viable and environmentally friendly approach for COS synthesis. This article provides a comprehensive overview of emerging strategies for the enzymatic preparation of single COS, encompassing protein engineering, enzymatic membrane bioreactors, and transglycosylation reactions. Furthermore, the bioactivities of single COS, including anti-tumor, antioxidant, antibacterial, anti-inflammatory, and plant defense inducer properties, exhibit close associations with DP values. The potential applications of single COS, such as in functional food, food preservation, and crop planting, are also elucidated.

Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer.

Background: Transmembrane E3 ubiquitin ligase (RNF43) mutations are present in approximately 6-18% of colorectal cancers (CRC) and could enhance Wnt/ß-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of RNF43-mutant CRC. Methods: A total of 78 patients with RNF43-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, clinical characteristics, treatment regimens used, and survival outcomes were collected and analyzed. Results: Our study uncovered that patients with RNF43 mutations in the N-terminal domain (NTD; n = 50) exhibited shorter overall survival (OS; median months, 50.80 versus not reached; p = 0.043) compared to those in the C-terminal domain (CTD; n = 17). Most RNF43 mutations in NTD had positive primary lymph node status, low tumor mutation burden (TMB-L), and correlated with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status. By contrast, RNF43 mutations in CTD were significantly enriched in deficient MMR (dMMR)/microsatellite instability (MSI-H) tumors with high TMB (TMB-H). N-terminal RNF43-mutated tumors harbored a hotspot variant (RNF43 R117fs), which independently predicted a significantly worse outcome in pMMR/MSS CRC with a median OS of 18.9 months. Patients with RNF43 mutations and the BRAF V600E alterations demonstrated sensitivity to BRAF/EGFR inhibitors. Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy. Conclusion: Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.

Kelp as a biomonitor of persistent organic pollutants in coastal areas of China: Contamination levels and human health risk.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321-4.24 ng/g dry weight (dw), 0.255-25.5 ng/g dw and 3.00 × 10-3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.

Self-constructed water-in-oil Pickering emulsions as a tool for increasing bioaccessibility of betulin.

Self-constructed water-in-oil emulsions can be stabilized by a natural pentacyclic triterpenoid, betulin. A higher betulin concentration (3%) results in smaller emulsion droplet sizes. Microscopy, confocal laser scanning microscopy and rheology indicate that the stabilizing mechanism is attributed to betulin crystals on the emulsion interface and within the continuous phase, thereby enabling excellent freeze/thaw and thermal stability. The betulin Pickering emulsion (1%) significantly increased betulin bioaccessibility (22.4%) compared to betulin alone (0.2%) and betulin-oil physical mixture (7.9%). A higher level of betulin at 3% leads to smaller emulsion particle size, potentially resulting in a greater surface area. This, in return, promotes a higher release of free fatty acids (FFA), contributing to the release and solubilization of betulin from emulsions. Additionally, it leads to the formation of micelles, further increasing betulin bioaccessibility (29.3%). This study demonstrates Pickering emulsions solely stabilized by phytochemical betulin provides an innovative way to improve its bioaccessibility.

Disruption of redox balance in glutaminolytic triple negative breast cancer by inhibition of glutamate export and glutaminase.

In triple-negative breast cancer (TNBC) that relies on catabolism of amino acid glutamine, glutaminase (GLS) converts glutamine to glutamate, which facilitates glutathione synthesis by mediating the enrichment of intracellular cystine via xCT antiporter activity. To overcome chemo resistant TNBC, we have tested a strategy of disrupting cellular redox balance by inhibition of GLS and xCT by CB839 and Erastin, respectively. Key findings of our study include: 1. Dual metabolic inhibition (CB839+Erastin) led to significant increases of cellular superoxide level in both parent and chemo resistant TNBC cells, but superoxide level was distinctly lower in resistant cells. 2. Dual metabolic inhibition combined with doxorubicin or cisplatin induced significant apoptosis in TNBC cells and is associated with high degrees of GSH depletion. In vivo , dual metabolic inhibition plus cisplatin led to significant growth delay of chemo resistant human TNBC xenografts. 3. Ferroptosis is induced by doxorubicin (DOX) but not by cisplatin or paclitaxel. Addition of dual metabolic inhibition to DOX chemotherapy significantly enhanced ferroptotic cell death. 4. Significant changes in cellular metabolites concentration preceded transcriptome changes revealed by single cell RNA sequencing, underscoring the potential of capturing early changes in metabolites as pharmacodynamic markers of metabolic inhibitors. Here we demonstrated that 4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) PET detected xCT blockade by Erastin or its analog in mice bearing human TNBC xenografts. In summary, our study provides compelling evidence for the therapeutic benefit and feasibility of non-invasive monitoring of dual metabolic blockade as a translational strategy to sensitize chemo resistant TNBC to cytotoxic chemotherapy.

Characteristics of premanufacture CD8+T cells determine CAR-T efficacy in patients with diffuse large B-cell lymphoma.

Although chimeric antigen receptor (CAR) T cells have become an important treatment option for patients with relapsed/refractory B-cell malignancies, more than 60% of patients with diffuse large B-cell lymphoma (DLBCL) treated with CAR-T cell therapies fail to achieve a durable response. To reveal changes in CAR-T cell therapy and identify response biomarkers, we conducted a retrospective analysis of pre-manufacture source T cells and CAR-T cell products and their association with outcome in 58 patients with r/rDLBCL who received tandem CD19/CD20 CAR-T cell therapy. We performed bulk RNA-Seq, single-cell RNA-Seq, and paired T cell receptor sequencing on CAR-T cell products and pre-manufacture T cells from DLBCL patients. We note that a CD8+ stem cell-like memory T cell population with a higher proportion and enhanced activating capacity of the CAR-T cell products was key to achieving durable clinical response. By analysing autologously-derived, pre-manufacture T cells, our data suggest that heterogeneity in the cellular and molecular features of pre-manufacture T cells contribute to the variation in efficacy after CAR-T cell therapy in DLBCL. The differences in anti-tumour efficacy of CAR-T cells among patients with different clinical outcomes appear to be due to the loss of CCR7 gene expression, coupled with increased expression of activation- and inhibitor-related genes in the CD8+ naïve-T cell populations among the apheresis T cells from patients with a poor molecular response. These findings significantly advance our understanding of the underlying molecular determinants of pre-manufacture T cell function.

UPLC-Q-TOF-MS, network analysis, and molecular docking to investigate the effect and active ingredients of tea-seed oil against bacterial pathogens.

Object: This research intended to probe the antibacterial effect and pharmacodynamic substances of Tea-Seed Oil (TSO) through the use of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) analysis, network analysis, and molecular docking. Methods: The major chemical components in the methanol-extracted fractions of TSO were subjected to UPLC-Q-TOF-MS. Network pharmacology and molecular docking techniques were integrated to investigate the core components, targets, and potential mechanisms of action through which the TSO exert their antibacterial properties. To evaluate the inhibitory effects, the minimum inhibitory concentration and diameter of the bacteriostatic circle were calculated for the potential active ingredients and their equal ratios of combinatorial components (ERCC) against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Moreover, the quantification of the active constituents within TSO was achieved through the utilization of high-performance liquid chromatography (HPLC). Results: The methanol-extracted fractions contained a total of 47 chemical components, predominantly consisting of unsaturated fatty acids and phenolic compounds. The network pharmacology analysis and molecular docking analysis revealed that various components, including gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phlorizin, have the ability to interact with critical core targets such as serine/threonine protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), a monoclonal antibody to mitogen-activated protein kinase 14 (MAPK14), HSP90AA1, and estrogen receptor 1 (ESR1). Furthermore, these components can modulate the phosphatidylinositol-3-kinase protein kinase B (PI3K-AKT), estrogen, MAPK and interleukin 17 (IL-17) signaling pathways, hereby exerting antibacterial effects. In vitro validation trials have found that seven components, namely gallocatechin, gallic acid, epigallocatechin, theophylline, chlorogenic acid, puerarin, and phloretin, displayed substantial inhibitory effects on E. coli, S. aureus, P. aeruginosa, and C. albicans, and are typically present in tea oil, with a total content ranging from 15.87∼24.91 µg·g-1. Conclusion: The outcomes of this investigation possess the possibility to expand our knowledge base concerning the utilization of TSO, furnish a theoretical framework for the exploration of antibacterial drugs and cosmetics derived from inherently occurring TSO, and establish a robust groundwork for the advancement and implementations of TOS products within clinical settings.

Clinical-radiomics-based treatment decision support for KIT Exon 11 deletion in gastrointestinal stromal tumors: a multi-institutional retrospective study.

Objective: gastrointestinal stromal tumors (GISTs) with KIT exon 11 deletions have more malignant clinical outcomes. A radiomics model was constructed for the preoperative prediction of KIT exon 11 deletion in GISTs. Methods: Overall, 126 patients with GISTs who underwent preoperative enhanced CT were included. GISTs were manually segmented using ITK-SNAP in the arterial phase (AP) and portal venous phase (PVP) images of enhanced CT. Features were extracted using Anaconda (version 4.2.0) with PyRadiomics. Radiomics models were constructed by LASSO. The clinical-radiomics model (combined model) was constructed by combining the clinical model with the best diagnostic effective radiomics model. ROC curves were used to compare the diagnostic effectiveness of radiomics model, clinical model, and combined model. Diagnostic effectiveness among radiomics model, clinical model and combine model were analyzed in external cohort (n=57). Statistics were carried out using R 3.6.1. Results: The Radscore showed favorable diagnostic efficacy. Among all radiomics models, the AP-PVP radiomics model exhibited excellent performance in the training cohort, with an AUC of 0.787 (95% CI: 0.687-0.866), which was verified in the test cohort (AUC=0.775, 95% CI: 0.608-0.895). Clinical features were also analyzed. Among the radiomics, clinical and combined models, the combined model showed favorable diagnostic efficacy in the training (AUC=0.863) and test cohorts (AUC=0.851). The combined model yielded the largest AUC of 0.829 (95% CI, 0.621-0.950) for the external validation of the combined model. GIST patients could be divided into high or low risk subgroups of recurrence and mortality by the Radscore. Conclusion: The radiomics models based on enhanced CT for predicting KIT exon 11 deletion mutations have good diagnostic performance.

Can dexamethasone improve postoperative sleep and postoperative delirium in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy? Protocol for a prospective, randomized, double-blind, controlled study.

BACKGROUND: Perioperative sleep disorders (PSD) are an independent risk factor for postoperative delirium (POD), which is a common complication after surgery. Elderly patients who undergo robot-assisted radical prostatectomy (RARP) often experience perioperative sleep disorders (PSD). Dexamethasone, a medication that works by inhibiting the hypothalamic-pituitary-suprarenal cortical axis, can reduce the negative effects of surgical stress. The objective of this study was to determine whether intravenous administration of dexamethasone at the time of anesthesia induction could improve postoperative sleep quality in elderly patients, thereby indirectly reducing the risk of postoperative cognitive impairment and accelerating postoperative rehabilitation. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled trial that was conducted at a single center. A sample size of 116 patients was determined through calculation, and these patients were randomly assigned to either the dexamethasone group (group D, n = 58) or the blank control group (group C, n = 58). On the day of surgery, the anesthesia nurse prepared either diluted dexamethasone or saline in advance, according to the patient's assigned group. The blinded anesthesiologist administered the medication during induction, and a dedicated person followed up with the patient for three consecutive postoperative days. All other aspects of care were managed equally between the two groups. The primary outcome measure was sleep quality, while secondary outcome measures included postoperative sleep time, postoperative delirium (POD), pain scores, and other complications. Relevant test measures were recorded for analysis. DISCUSSION: This study aims to investigate the impact of intravenous dexamethasone on sleep quality and duration of patients undergoing robot-assisted radical prostatectomy (RARP). If the findings of this study protocol are affirmative, it could enhance the sleep quality of elderly patients after surgery, thereby minimizing the risk of postoperative delirium (POD), and providing substantial evidence for the perioperative enhanced recovery management of elderly patients. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200063488, Registered on 5 October 2022.

Infection of epithelioma papulosum cyprini (EPC) cells with spring viremia of carp virus (SVCV) induces autophagy and apoptosis through endoplasmic reticulum stress.

Spring viremia of carp virus (SVCV) is a lethal freshwater pathogen of cyprinid fish that has caused significant economic losses to aquaculture. To reduce the economic losses caused by SVCV, its pathogenic mechanism needs to be studied more thoroughly. Here, we report for the first time that SVCV infection of Epithelioma papulosum cyprini (EPC) cells can induce cellular autophagy and apoptosis through endoplasmic reticulum stress. The presence of autophagic vesicles in infected EPC cells was shown by transmission electron microscopy. Quantitative fluorescence PCR and Western blot results showed that p62 mRNA expression was decreased, and the expression of Beclin1 and LC3 mRNA was increased. The p62 protein was decreased, and the Beclin1 protein and LC3 were increased in the endoplasmic reticulum stress activation state. To further clarify the mode of death of SVCV-infected EPC cells, we examined caspase3, caspase9, BCL-2, and Bax mRNA, which showed that they were all increased. Apoptosis of SVCV-infected cells increased upon activation of endoplasmic reticulum stress. Our results suggest that endoplasmic reticulum stress can regulate SVCV infection-induced autophagy and apoptosis. The results of this study provide theoretical data for the pathogenesis of SVCV and lay the foundation for future drug development and vaccine construction.

Head and Neck Hemangiopericytoma: A Rare Case Report and Literature Review.

Hemangiopericytomas (HPCs) are rare vascular tumors, and head and neck hemangiopericytoma (HNHPC) accounts for 11% to 16% of all HPCs, possibly occurring at any age. However, according to a recent study, HNHPC was most frequently observed in middle-aged adults and had a slight predominance of female patients. In the present case, we report the successful treatment of HNHPC.

Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.

Data resources and computational methods for lncRNA-disease association prediction.

Increasing interest has been attracted in deciphering the potential disease pathogenesis through lncRNA-disease association (LDA) prediction, regarding to the diverse functional roles of lncRNAs in genome regulation. Whilst, computational models and algorithms benefit systematic biology research, even facilitate the classical biological experimental procedures. In this review, we introduce representative diseases associated with lncRNAs, such as cancers, cardiovascular diseases, and neurological diseases. Current publicly available resources related to lncRNAs and diseases have also been included. Furthermore, all of the 64 computational methods for LDA prediction have been divided into 5 groups, including machine learning-based methods, network propagation-based methods, matrix factorization- and completion-based methods, deep learning-based methods, and graph neural network-based methods. The common evaluation methods and metrics in LDA prediction have also been discussed. Finally, the challenges and future trends in LDA prediction have been discussed. Recent advances in LDA prediction approaches have been summarized in the GitHub repository at https://github.com/sheng-n/lncRNA-disease-methods.

The small peptide CEP1 and the NIN-like protein NLP1 regulate NRT2.1 to mediate root nodule formation across nitrate concentrations.

Legumes acquire fixed nitrogen (N) from the soil and through endosymbiotic association with diazotrophic bacteria. However, establishing and maintaining N2-fixing nodules are expensive for the host plant, relative to taking up N from the soil. Therefore, plants suppress symbiosis when N is plentiful and enhance symbiosis when N is sparse. Here, we show that the nitrate transporter MtNRT2.1 is required for optimal nodule establishment in Medicago truncatula under low-nitrate conditions and the repression of nodulation under high-nitrate conditions. The NIN-like protein (NLP) MtNLP1 is required for MtNRT2.1 expression and regulation of nitrate uptake/transport under low- and high-nitrate conditions. Under low nitrate, the gene encoding the C-terminally encoded peptide (CEP) MtCEP1 was more highly expressed, and the exogenous application of MtCEP1 systemically promoted MtNRT2.1 expression in a compact root architecture 2 (MtCRA2)-dependent manner. The enhancement of nodulation by MtCEP1 and nitrate uptake were both impaired in the Mtnrt2.1 mutant under low nitrate. Our study demonstrates that nitrate uptake by MtNRT2.1 differentially affects nodulation at low- and high-nitrate conditions through the actions of MtCEP1 and MtNLP1.