Tumor-derived extracellular vesicle proteins as new biomarkers and targets in precision oncology.

Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

Sub-high amylose maize starch: an ideal substrate to generate starch with lower digestibility by fermentation of Qu.

BACKGROUND: The fermentation of Qu (FQ) is a novel method to modify the properties of starch to expand its application and especially to increase the resistant starch (RS) content. Using waxy maize starch (WMS) as a fermentation substrate can increase the RS content significantly but it may be time consuming and not cost effective due to the almost negligible RS content of WMS. To solve this problem, we hypothesized that sub-high amylose starch (s-HAMS), with an amylose content close to 50% could be an ideal substrate for FQ. RESULTS: The results showed that FQ did not change the shape and the particle size of starch granules, the gelatinization peak (Tp), or the conclusion temperature (Tc), but the slowly digested starch content declined. Rapidly digested starch content fluctuated during FQ and the amylose content decreased within 36 h and then increased. Within 24h, FQ significanlty increased these values: the RS content, relative crystallinity (RC), the ratio of FTIR absorbances at 1047/1022cm-1, the diffraction peak at 19.8° in X-ray diffraction (XRD), and the gelatinization onset temperature (To) increased significantly, within 24 h of FQ. However, after 24 h of fermentation, the RS content, RC, the ratio of FTIR absorbances at 1047/1022 cm-1, and gelatinization enthalpy (ΔH) decreased significantly. CONCLUSION: Sub-high amylose starch is more suitable for FQ to produce low digestibility starch, and the increase in RS may be due to the formation of 'amylose-lipid' complexes (RS5). © 2024 Society of Chemical Industry.

Evaluation of the key ingredient from the main production areas of Phellodendri Amurensis Cortex using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry.

Phellodendri Amurensis Cortex (PAC) is a medicinal herb that has been generally used to treat diarrhea and jaundice. In order to comprehensively evaluate the PAC in the main production areas quality, a qualitative and quantitative method with highly effective, sensitive, and reliable was developed. The chemical compositions of PAC were analyzed, and fingerprints were established by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). Then, the determination of berberine, canthin-6-one, dictamnine, γ-fagarine, and magnoflorine from PAC samples was simultaneously performed using UPLC-QQQ-MS. Furthermore, the chemical components of PAC from different regions were compared and analyzed by combining hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. A total of 58 compounds were identified, including 36 alkaloids, four phenylpropanoids, seven terpenoids, four flavonoids and their glycosides, an organic acid compound, and six other components. The fingerprint results show that samples have good similarity. Meanwhile, the content of the five ingredients in different habitats is quite different. By multivariate statistical analysis, 18 batches of PAC could be divided into three categories, and 20 components were identified as differential markers of various origins. A comprehensive method of PAC quality evaluation and chemical composition difference analysis was established, which provided the scientific basis for quality evaluation and further pharmacological mechanism research.

[Identification of banana ADA1 gene family members and their expression profiles under biotic and abiotic stresses].

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.

Emotion Recognition From Multimodal Physiological Signals via Discriminative Correlation Fusion With a Temporal Alignment Mechanism.

Modeling correlations between multimodal physiological signals [e.g., canonical correlation analysis (CCA)] for emotion recognition has attracted much attention. However, existing studies rarely consider the neural nature of emotional responses within physiological signals. Furthermore, during fusion space construction, the CCA method maximizes only the correlations between different modalities and neglects the discriminative information of different emotional states. Most importantly, temporal mismatches between different neural activities are often ignored; therefore, the theoretical assumptions that multimodal data should be aligned in time and space before fusion are not fulfilled. To address these issues, we propose a discriminative correlation fusion method coupled with a temporal alignment mechanism for multimodal physiological signals. We first use neural signal analysis techniques to construct neural representations of the central nervous system (CNS) and autonomic nervous system (ANS). respectively. Then, emotion class labels are introduced in CCA to obtain more discriminative fusion representations from multimodal neural responses, and the temporal alignment between the CNS and ANS is jointly optimized with a fusion procedure that applies the Bayesian algorithm. The experimental results demonstrate that our method significantly improves the emotion recognition performance. Additionally, we show that this fusion method can model the underlying mechanisms in human nervous systems during emotional responses, and our results are consistent with prior findings. This study may guide a new approach for exploring human cognitive function based on physiological signals at different time scales and promote the development of computational intelligence and harmonious human-computer interactions.

Correction to: Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.

[This corrects the article DOI: 10.1093/nsr/nwab232.].

The diagnostic or prognostic values of FADD in cancers based on pan­cancer analysis.

Previous studies have determined that aberrant expression of the fas-associated death domain (FADD) contributes to the development of cancer. However, no pan-cancer analysis has been reported to explore the relationship between FADD and various cancers. Multiple databases were screened to identify cancer datasets for the present study and to validate the expression of FADD in various tumors. The association of FADD alteration with cancer prognosis, clinical features and tumor immunity was also evaluated. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to confirm the expression of FADD in breast, colon, liver and gastric cancer cells. Analysis of Gene Expression Omnibus database and The Cancer Genome Atlas database indicated that FADD was highly expressed in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD) and prostate adenocarcinoma, whereas RT-qPCR results revealed that FADD was highly expressed in breast cancer and colon cancer. Further analyses demonstrated that FADD expression was significantly altered in ESCA, head and neck squamous cell carcinoma (HNSC), lung squamous cell carcinoma and BRCA. FADD expression was observed to be a risk factor of the overall survival in patients with HNSC, LIHC and LUAD as demonstrated by Kaplan-Meier and Cox regression analyses. The results of the present study demonstrated that FADD is highly expressed in numerous malignancies and can be utilized as a biomarker for the diagnosis of BRCA, COAD, LIHC and stomach adenocarcinoma. Moreover, FADD expression is a predictive risk factor for the development of HNSC, LIHC and LUAD and can potentially be used as a prognostic marker for these cancers.

The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.

Gastric cancer is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can participate in various mechanisms of tumor malignancy. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelialmesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.

STSNet: a novel spatio-temporal-spectral network for subject-independent EEG-based emotion recognition.

How to use the characteristics of EEG signals to obtain more complementary and discriminative data representation is an issue in EEG-based emotion recognition. Many studies have tried spatio-temporal or spatio-spectral feature fusion to obtain higher-level representations of EEG data. However, these studies ignored the complementarity between spatial, temporal and spectral domains of EEG signals, thus limiting the classification ability of models. This study proposed an end-to-end network based on ManifoldNet and BiLSTM networks, named STSNet. The STSNet first constructed a 4-D spatio-temporal-spectral data representation and a spatio-temporal data representation based on EEG signals in manifold space. After that, they were fed into the ManifoldNet network and the BiLSTM network respectively to calculate higher-level features and achieve spatio-temporal-spectral feature fusion. Finally, extensive comparative experiments were performed on two public datasets, DEAP and DREAMER, using the subject-independent leave-one-subject-out cross-validation strategy. On the DEAP dataset, the average accuracy of the valence and arousal are 69.38% and 71.88%, respectively; on the DREAMER dataset, the average accuracy of the valence and arousal are 78.26% and 82.37%, respectively. Experimental results show that the STSNet model has good emotion recognition performance.

Transcriptome and Metabolomics Integrated Analysis Reveals MdMYB94 Associated with Esters Biosynthesis in Apple (Malus × domestica).

Volatile esters are major aromas contributing to the organoleptic quality of apple fruit. However, the molecular mechanisms underlying the regulation of volatile ester biosynthesis in apple remain elusive. This study investigated the volatile profiles and transcriptomes of 'Qinguan' (QG) apple fruit during development and/or postharvest storage. Although the constitution of volatiles varied widely between the peel and flesh, the volatile profiles of the peel and flesh of ripening QG fruit were dominated by volatile esters. WGCNA results suggested that 19 genes belonging to ester biosynthesis pathways and 11 hub transcription factor genes potentially participated in the biosynthesis and regulation of esters. To figure out key regulators of ester biosynthesis, correlation network analysis, dual-luciferase assays, and yeast one-hybrid assay were conducted and suggested that MdMYB94 trans-activated the MdAAT2 promoter and participated in the regulation of ester biosynthesis. This study provides a framework for understanding ester biosynthesis and regulation in apple.

Comparison of Efficacy and Safety of Laparoscopic Holmium laser Lithotripsy and Laparoscopic Bile Duct Exploration for Bile Duct Stones: A Systematic Review and Meta-Analysis.

BACKGROUND: Laparoscopic holmium laser lithotripsy (LHLL) has been used to treat bile duct stones with unclear outcomes. A meta-analysis was conducted to investigate the LHLL and laparoscopic bile duct exploration (LBDE) efficacy and safety in treating bile duct stones. METHODS: The correlational studies were searched databases, such as PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP, to identify eligible studies from inception to July 2022. The dichotomous and continuous outcomes were evaluated using odds ratio (OR), risk difference (RD) and weighted mean difference (WMD) with 95% confidence intervals (CIs). Stata 15.0 and Review Manager 5.3 software helped in data analyses. RESULTS: A total of 23 studies with 1,890 patients, primarily from China, were included. The results indicated that operation time (WMD = - 26.94; 95% CI:(- 34.30, - 19.58); P < 0.00001), estimated blood loss (WMD = - 17.97; 95% CI: (- 22.94, - 13.00); P = 0.002), rate of residual stone (OR = 0.15, 95%CI: (0.10, 0.23); P < 0.00001), length of hospital stay (WMD = - 2.88; 95% CI:(- 3.80, - 1.96); P < 0.00001) and time to bowel function recovery (WMD = - 0.59; 95% CI: (- 0.76, - 0.41); P < 0.00001) had statistically significant differences between the two groups. In postoperative complications, biliary leakage (RD = -0.03; 95% CI: (- 0.05, -0.00); P = 0.02), infection (RD = - 0.06; 95% CI: (- 0.09,- 0.03); P < 0.00001) and Hepatic injury (RD = - 0.06; 95% CI: (- 0.11, - 0.01); P = 0.02) revealed statistically significant differences. However, no significant differences were observed in biliary damage (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.06) and hemobilia (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.08). CONCLUSION: The current meta-analysis indicated that LHLL could be more effective and safer than LBDC. However, these results should be confirmed with a larger sample size and rigorously designed randomized controlled trials.

Quality marker discovery of Danggui Jianzhong decoction for treating primary dysmenorrhoea based on chinmedomics strategy.

BACKGROUND: Danggui Jianzhong Decoction (DGJZD) has been proven as an effective classical prescription for clinically treating primary dysmenorrhoea (PD). However, the industrialisation development and drug innovation of DGJZD remain limited due to its undefined effective constituents and quality markers (Q-markers). PURPOSE: Elucidating the Q-markers of DGJZD, which is related to clinical efficacy. METHODS: In accordance with chinmedomics strategy, we evaluated the therapeutic efficacy of DGJZD on the basis of the metabolomic profile and biomarker of a PD rat model to further identify the constituents of DGJZD in vivo that originated from the formula under the acting condition of DGJZD. The potential effective constituents and Q-markers were identified by mining the dynamic relation between the constituents in vivo and the biomarkers. RESULTS: Subsequently, 29 serum metabolites were characterized as biomarkers for PD, and DGJZD adjusted the levels of the primary biomarkers involved in arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism as well as the synthesis of steroid hormones. Under the active condition of DGJZD, 20 prototype ingredients and 4 metabolites of DGJZD were found in vivo, five of which were mostly related with the efficacy of PD, namely, ferulic acid, zizyphusin, cinnamic acid, protocatechuic acid-3-glucoside, and azelaic acid. They were the potential pharmacodynamic constituents for treating PD, and they could be regarded as the Q-markers of DGJZD. CONCLUSION: Taken together, the Q-markers of DGJZD identified in this research are credible and assist in solving problems related to quality control and drug innovation, accelerating industrialisation development. Besides, the efficacy, mechanism and active ingredients of DGJZD for the treatment of PD were innovatively elucidated for the first time on the basis of the chinmedomics strategy for uncovering the Q-markers of drugs from the system perspective.

A nomogram for predicting survival in patients with skin non-keratinizing large cell squamous cell carcinoma: A study based on the Surveillance, Epidemiology, and End Results database.

Introduction: This study aimed to develop and validate a nomogram for predicting cancer-specific survival (CSS) in patients with non-keratinized large cell squamous cell carcinoma (NKLCSCC) at 3, 5, and 8 years after diagnosis. Methods: Data on SCC patients were collected from the Surveillance, Epidemiology, and End Results database. Training (70%) and validation (30%) cohorts were generated using random selection of patients. Independent prognostic factors were selected using the backward stepwise Cox regression model. To predict the CSS rates in patients with NKLCSCC at 3, 5, and 8 years after diagnosis, all of the factors were incorporated into the nomogram. Indicators such as the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration curve, and decision-curve analysis (DCA) were then used to validate the performance of the nomogram. Results: This study included 9,811 patients with NKLCSCC. Twelve prognostic factors were identified by Cox regression analysis in the training cohort, which were age, number of regional nodes examined, number of positive regional nodes, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, surgery status, chemotherapy status, radiotherapy status, summary stage, and income. The constructed nomogram was validated both internally and externally. The nomogram had good discrimination ability, as indicated by the comparatively high C-indices and AUC values. The nomogram was properly calibrated, as indicated by the calibration curves. Our nomogram was superior to the AJCC model, as illustrated by its superior NRI and IDI values. DCA curves indicated the clinical usability of the nomogram. Conclusion: The first nomogram for prognosis predictions of patients with NKLCSCC has been developed and verified. Its performance and usability demonstrated that the nomogram could be utilized in clinical settings. However, additional external verification is still required.

Prognosis of the Keratinizing Squamous Cell Carcinoma of the Tongue Based on Surveillance, Epidemiology, and End Results Database.

Background: The objective of this study is to determine the prognostic factors of keratinizing squamous cell carcinoma of the tongue (KTSCC) and to establish a prognostic nomogram of KTSCC to assist clinical diagnosis and treatment. Methods: This study identified 3874 patients with KTSCC from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were randomly divided into the training (70%, (n = 2711) and validation (30%, n = 1163) cohorts. Cox regression was then used to filter variables. Nomograms were then constructed based on meaningful variables. Finally, the concordance index (C-index), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration charts, and decision-curve analysis (DCA), were used to evaluate the discrimination, accuracy and effectiveness of the model. Results: A nomogram model was established for predicting the 3-, 5-, and 8-year overall survival (OS) probabilities of patients with KTSCC. The model indicated that age, radiotherapy sequence, SEER stage, marital status, tumor size, American Joint Committee on Cancer (AJCC) stage, radiotherapy status, race, lymph node dissection status, and sex were factors influencing the OS of patients with KTSCC. Verified by C-index, NRI, IDI, calibration curve, and DCA curve, our model has better discrimination, calibration, accuracy and net benefit compared to the AJCC system. Conclusions: This study identified the factors that affect the survival of KTSCC patients and established a prognostic nomogram that can help clinicians predict the 3-, 5-, and 8-year survival rates of KTSCC patients.

Calcium-binding protein OsANN1 regulates rice blast disease resistance by inactivating jasmonic acid signaling.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases in rice (Oryza sativa L.). Plant annexins are calcium- and lipid-binding proteins that have multiple functions; however, the biological roles of annexins in plant disease resistance remain unknown. Here, we report a rice annexin gene, OsANN1 (Rice annexin 1), that was induced by M. oryzae infection and negatively regulated blast disease resistance in rice. By yeast 2-hybrid screening, we found that OsANN1 interacted with a cytochrome P450 monooxygenase, HAN1 ("HAN" termed "chilling" in Chinese), which has been reported to catalyze the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile. Pathogen inoculation assays revealed that HAN1 was also a negative regulator in rice blast resistance. Genetic evidence showed that OsANN1 acts upstream of HAN1. OsANN1 stabilizes HAN1 in planta, resulting in the inactivation of the endogenous biologically active JA-Ile. Taken together, our study unravels a mechanism where an OsANN1-HAN1 module impairs blast disease resistance via inactivating biologically active JA-Ile and JA signaling in rice.

Challenges and developments for the blue perovskite nanocrystal light-emitting diodes.

Perovskite nanomaterials have been highly thought as next-generation light emitters after recent development owing to their benefits of simple synthesis, low-cost, large-area, and wide color gamut. Encouragingly, the external quantum efficiencies (EQEs) of green, red, and near-infrared perovskite light-emitting diodes (PeLEDs) have exceeded more than 20%. However, the performance of the blue PeLEDs is still lower than other analogs, which severely limits the applications of PeLEDs in future full-color displays. Herein, we have reviewed the advances in blue perovskite NCs and their applications in blue PeLEDs. Promising blue perovskite emitters and strategies for fabricating highly efficient blue PeLEDs based on perovskite NCs are investigated and highlighted. Moreover, we point out the main challenges in blue perovskite NC LEDs including low electroluminescence efficiency (EL), spectral instability, the difficulty of charge injection, and device optimization. The perspectives for the further development of blue PeLEDs are also presented.

Large-scale mRNA transfer between Haloxylon ammodendron (Chenopodiaceae) and herbaceous root holoparasite Cistanche deserticola (Orobanchaceae).

Exchanges of mRNA were shown between host and stem parasites but not root parasites. Cistanche deserticola (Orobanchaceae) is a holoparasitic herb which parasitizes on the roots of woody plant Haloxylon ammodendron (Chenopodiaceae). We used transcriptome sequencing and bioinformatic analyses to identify nearly ten thousand mobile mRNAs. Transcript abundance appears to be a driving force for transfer event and mRNA exchanges occur through haustorial junction. Mobility of selected mRNAs was confirmed in situ and in sunflower-Orobanche cumana heterologous parasitic system. Four C. deserticola →H. ammodendron mobile mRNAs appear to facilitate haustorium development. Of interest, two mobile mRNAs of putative resistance genes CdNLR1 and CdNLR2 cause root-specific hypersensitive response and retard parasite development, which might contribute to parasitic equilibrium. The present study provides evidence for the large-scale mRNA transfer event between a woody host and a root parasite, and demonstrates the functional relevance of six C. deserticola genes in host-parasite interactions.