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Abstract Background Somatic copy number alterations (SCNAs) are pivotal in cancer progression and patient prognosis. Dysregulated long non-coding RNAs (lncRNAs), modulated by SCNAs, significantly impact tumorigenesis, including colorectal cancer (CRC). Nonetheless, the functional significance of lncRNAs induced by SCNAs in CRC remains largely unexplored. Methods The dysregulated lncRNA LOC101927668, induced by copy number amplification, was identified through comprehensive bioinformatic analyses utilizing multidimensional data. Subsequent in situ hybridization was employed to ascertain the subcellular localization of LOC101927668, and gain- and loss-of-function experiments were conducted to elucidate its role in CRC progression. The downstream targets and signaling pathway influenced by LOC101927668 were identified and validated through a comprehensive approach, encompassing RNA sequencing, RT-qPCR, Western blot analysis, dual-luciferase reporter assay, evaluation of mRNA and protein degradation, and rescue experiments. Analysis of AU-rich elements (AREs) within the mRNA 3’ untranslated region (UTR) of the downstream target, along with exploration of putative ARE-binding proteins, was conducted. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and dual-luciferase reporter assays were employed to elucidate potential interacting proteins of LOC101927668 and further delineate the regulatory mechanism between LOC101927668 and its downstream target. Moreover, subcutaneous xenograft and orthotopic liver xenograft tumor models were utilized to evaluate the in vivo impact of LOC101927668 on CRC cells and investigate its correlation with downstream targets. Results Significantly overexpressed LOC101927668, driven by chr7p22.3-p14.3 amplification, was markedly correlated with unfavorable clinical outcomes in our CRC patient cohort, as well as in TCGA and GEO datasets. Moreover, we demonstrated that enforced expression of LOC101927668 significantly enhanced cell proliferation, migration, and invasion, while its depletion impeded these processes in a p53-dependent manner. Mechanistically, nucleus-localized LOC101927668 recruited hnRNPD and translocated to the cytoplasm, accelerating the destabilization of RBM47 mRNA, a transcription factor of p53. As a nucleocytoplasmic shuttling protein, hnRNPD mediated RBM47 destabilization by binding to the ARE motif within RBM47 3'UTR, thereby suppressing the p53 signaling pathway and facilitating CRC progression. Conclusions The overexpression of LOC101927668, driven by SCNAs, facilitates CRC proliferation and metastasis by recruiting hnRNPD, thus perturbing the RBM47/p53/p21 signaling pathway. These findings underscore the pivotal roles of LOC101927668 and highlight its therapeutic potential in anti-CRC interventions.

Abstract Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2’s role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/β-catenin phosphorylation. AKT/β-catenin phosphorylation facilitates β-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and β-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/β-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.

Abstract Background Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC. Methods DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR. Results DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway. Conclusions We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

Summary: The gene encoding the NUAK family kinase 1 (NUAK1) is frequently amplified and its expression is upregulated, activating oncogenic signaling in various cancers. However, little is known about its role in gastric cancer (GC). We investigate the mechanistic links among NUAK1, Hedgehog signaling, and tumorigenesis in GC. NUAK1 overexpression is validated in local and public GC cohorts. Patient-derived xenograft and transgenic mouse models demonstrate that NUAK1 depletion or inhibition dramatically ameliorates gastric tumorigenesis. NUAK1 upregulates GLI1 expression by activating STAT5-mediated transcription and stabilizing GLI1 protein. NUAK1 depletion or inhibition impairs cancer cell expansion, tumor formation, and chemotherapy resistance in in vitro and in vivo models. Clinicopathological analysis confirms that upregulated NUAK1 expression correlates with poor prognosis and chemotherapy resistance in human GC. Our findings demonstrate that the signaling axis NUAK1/STAT5/GLI1 promotes cancer cell expansion and tumorigenesis and indicate that NUAK1 is an attractive therapeutic target and prognostic factor in GC.

Hyperspectral images contain abundant spectral and spatial information of the surface of the earth, but there are more difficulties in processing, analyzing, and sample-labeling these hyperspectral images. In this paper, local binary pattern (LBP), sparse representation and mixed logistic regression model are introduced to propose a sample labeling method based on neighborhood information and priority classifier discrimination. A new hyperspectral remote sensing image classification method based on texture features and semi-supervised learning is implemented. The LBP is employed to extract features of spatial texture information from remote sensing images and enrich the feature information of samples. The multivariate logistic regression model is used to select the unlabeled samples with the largest amount of information, and the unlabeled samples with neighborhood information and priority classifier discrimination are selected to obtain the pseudo-labeled samples after learning. By making full use of the advantages of sparse representation and mixed logistic regression model, a new classification method based on semi-supervised learning is proposed to effectively achieve accurate classification of hyperspectral images. The data of Indian Pines, Salinas scene and Pavia University are selected to verify the validity of the proposed method. The experiment results have demonstrated that the proposed classification method is able to gain a higher classification accuracy, a stronger timeliness, and the generalization ability.

The Chinese Altai is characterized by abundant granitoids, which not only are indicators of the interaction between crust and mantle but also provide critical constraints on the tectonic evolution of the orogen. This study presents zircon U‒Pb‒O isotopes, whole-rock major and trace element and Nd‒Hf‒Pb isotopes data for granite porphyries from the Keziergayin region in the Kelan Basin. The granite porphyries intrude in the Kangbutiebao Formation with zircon U‒Pb dating of 394 ± 3 Ma. They have the characteristics of subalkaline and metaluminous to weakly peraluminous and show geochemical affinity with I-type granite. The granite porphyry samples display negative εNd(t) (−1.9 to −1.4), positive εHf(t) (+4.3 to +11.4) values, with Nd–Hf decoupling; low Pb isotope compositions; δ18OV-SMOW (6.38‰–8.45‰) is less than 10‰, within the range of O isotopes of medium-basic igneous rocks. These geochemical signatures indicate that the granite porphyries originated from lower crust medium−basic igneous rocks extracted from the lithospheric mantle metasomatized by subducted melt. They are characterized by high SiO2 contents and Rb/Sr ratios; low CaO contents and K/Rb ratios, hinting that they were formed by highly evolved magmas, with fractionation crystallization of feldspar, apatite, garnet, allanite and/or monazite. The granite porphyries possess positive Rb, Th, U, Nd, Zr, Pb and light rare Earth elements (LREEs) anomalies with strong negative Ba, Nb, Ta, Sr, P, Ti and Eu anomalies, implying that their formation were related to an island arc. Combined with previous studies, it is suggested that the existence of the Early Devonian arc-basin system associated with subducting slab rollback in the Chinese Altai, which belongs to the Siberian active continental margin system.

ObjectivesNeoadjuvant immunochemotherapy (nICT) has been confirmed with promising pathological complete response (pCR) among locally advanced esophageal squamous cell carcinoma (ESCC). However, there were still no reliable and accurate predictors to predict the treatment response. This study aimed to explore the predictive value of inflammatory and nutritional parameters.MethodsPatients with ESCC who underwent radical surgery after nICT between January 2020 and April 2022 were included in the study. First, the least absolute shrinkage and selection operator regression (LASSO) logistic regression analysis was used to screen independent inflammatory and nutritional parameters. Secondly, univariate and multivariate logistic regression were used to screen and predict independent risk factors for pCR. Thirdly, a nomogram was constructed based on the independent predictive factors, and 30% of the included population was randomly selected as the validation cohort. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model.ResultsA total of 97 ESCC patients were screened for analysis, with 20 patients with pCR (20.32%). Only the systemic immune-inflammation index (SII) was screened after LASSO-logistic regression when λ was 0.06. The cut-off value of SII was 921.80 with an area under curve (AUC) value of 0.62. We defined SII > 921.80 as high SII and SII ≦ 921.80 as low SII. Further, the univariate and multivariate analysis further determined SII(OR = 3.94, 95%CI:1.26–12.42, P = 0.02) and clinical stage(OR = 0.35, 95%CI:0.12–0.98, P = 0.05) were independent predictive factors of pCR. One novel nomogram was established with an AUC value of 0.72 in the training cohort and 0.82 in the validation cohort. The Brier score of the calibration curve was 0.13. The calibration curve showed good agreement between the predicted results and the actual results in both the training cohort and the validation cohort. Compared with the clinical stage, the DCA confirmed a better clinical value of the nomogram model in both the training cohort and the validation cohort.ConclusionsHigh pretreatment SII and early clinical stage were independently associated with pCR among ESCC receiving nICT. We further established and validated one novel nomogram model to effectively predict pCR among ESCC after nICT.

ObjectivesNeoadjuvant immunochemotherapy (nICT) is a novel pattern for locally advanced esophageal squamous cell carcinoma (ESCC), and the time to surgery (TTS) is recommended as 4-6 weeks. However, there were some patients with prolonged TTS(> 6 weeks). This study aimed to explore whether prolonged TTS (> 6 weeks) would affect the outcomes.MethodsPatients diagnosed with locally advanced ESCC between January 2020 and March 2022 and undergoing esophagectomy following nICT were identified based on a prospectively collected database. Primary outcome measures were pathological complete response (pCR) and disease-free survival (DFS), and the secondary outcomes were 30-day postoperative mortality and morbidity, surgical time, postoperative hospital stay, and hospital expense.ResultsTotal of 95 patients were included for analysis, with 52 patients in the standard TTS group and 43 patients in the prolonged TTS group. The clinical and demographic characteristics of the two groups were comparable. The prolonged group had a median 18 days longer TTS(P

BackgroundThis study aimed to investigate whether the difference between “lung age” and real age (L–R) could be useful for the prediction of postoperative complications and long-term survival in patients with esophageal cancer followed by minimally invasive esophagectomy (MIE).MethodsThis retrospective cohort study included 625 consecutive patients who had undergone MIE. “Lung age” was determined by the calculation method proposed by the Japanese Respiratory Society. According to L–R, patients were classified into three groups: group A: L–R ≦ 0 (n = 104), group B: 15 > L–R > 0 (n = 199), group C: L–R ≥ 15 (n = 322). Clinicopathological factors, postoperative complications evaluated by comprehensive complications index (CCI), and overall survival were compared between the groups. A CCI value >30 indicated a severe postoperative complication.ResultsMale, smoking status, smoking index, chronic obstructive pulmonary disease, American Society of Anesthesiologists status, lung age, and forced expiratory volume in 1 s were associated with group classification. CCI values, postoperative hospital stays, and hospital costs were significantly different among groups. Multivariate analysis indicated that L–R, coronary heart disease, and 3-field lymphadenectomy were significant factors for predicting CCI value >30. Regarding the prediction of CCI value >30, area under the curve value was 0.61(95%: 0.56–0.67), 0.46 (95% CI, 0.40–0.54), and 0.46 (95% CI, 0.40–0.54) for L–R, Fev1, and Fev1%, respectively. Regarding overall survival, there was a significant difference between group A and group B + C (log-rank test: p = 0.03).ConclusionsEsophageal cancer patients with impaired pulmonary function had a higher risk of severe postoperative complications and poorer prognosis than those with normal pulmonary function. The difference between “lung age” and “real age” seems to be a novel and potential predictor of severe postoperative complications and long-term survival.

ObjectivesThe combination of neoadjuvant chemotherapy and immunotherapy (nICT) is a novel treatment for locally advanced esophageal cancer. There is concern that nICT may increase operation difficulty, postoperative morbidity, and mortality. This study aimed to compare short-term outcomes among esophagectomy after neoadjuvant chemoradiotherapy (nCRT) and nICT and for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsA retrospective analysis of a prospectively maintained database was performed to identify patients (from January 2017 through July 2021) who underwent surgery for ESCC following neoadjuvant therapy. A 1:1 propensity score matching (PSM) with a caliper 0.05 was conducted to balance potential bias.ResultsA 1:1 PSM was conducted based on clinical stage, age, body mass index (BMI), and tumor location, and then 32 comparable pairs were matched. After PSM, age, gender, BMI, American Society of Anesthesiologists (ASA) status, smoking history, clinical stage, tumor location, lymphadenectomy field, pathological stage, anastomotic position, route of gastric conduit, procedure type, and operative approach were comparable between groups. Compared with the nICT group (median, 300 min), the operation time was significantly longer in the nCRT group (median, 376 min). However, both groups were comparable in intraoperative blood loss, thoracic drainage volume, intensive care unit (ICU) stay, postoperative hospital stays, and hospital cost. Further, 30-day mortality, 30-day readmission, ICU readmission, and major complications were similar in both groups. The nCRT group had an advantage in pathological response. The pathological complete response (pCR) was 18.8% (6/32) in the nICT group and 43.8% (14/32) in the nCRT group (p = 0.03). The major pathological response (MPR) was 71.9% (23/32) in the nCRT group and 34.4% (11/32) in the nICT group (p = 0.03).ConclusionsBased on our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy with chemotherapy for locally advanced esophageal cancer.

BackgroundCombination of neoadjuvant immunotherapy and chemotherapy (nICT) is a novel treatment for locally esophageal cancer squamous cell carcinoma (ESCC). This study aimed to evaluate the potential effect of nICT on surgery safety by comparing short-term outcomes between the surgery alone group and the nICT followed by surgery group.MethodsA retrospective analysis was performed to identify patients (from January 2017 to July 2021) who underwent surgery for ESCC with or without nICT. A propensity score matching (PSM) comparison (1:1) was conducted to reduce selection biases and balance the demographic and oncologic characteristics between groups.ResultsAfter PSM, the nICT group (n = 38) was comparable to the surgery alone group (n = 38) in the following characteristics: age, sex, BMI, ASA status, smoking, tumor location, lymph node resection, clinical stage, anastomotic location, surgical approach, and surgical approach. The operation time and incidence of postoperative pneumonia in the nICT group were higher than those in the control group (p < 0.05). However, other complications and major complications were comparable between the two groups. There was no significant difference between the two groups in intraoperative blood loss, ICU stay time, postoperative hospital stay, and hospitalization cost. The 30-day mortality, 30-day readmission, and ICU readmission rates were also similar in the nICT and control groups. In the nICT group, the pathological complete response rate in primary tumor was 18.4%, and the major pathological response rate in tumor was 42.1%.ConclusionsBased on our preliminary experience, nICT followed by surgery is safe and effective with acceptable increased operation risk, manageable postoperative complications, and promising pathological response. Further multicenter prospective trials are needed to validate our results.

Power saving has always been an important research direction in the field of microcontrollers. Dozens of low power technologies have been proposed to achieve the goal of reducing their power consumption. However, most of them focus mostly on lowering the consumption rate. It is well known that energy is the integral of power over time. Thus, our view is that both power and time should be carefully considered to achieve better energy efficiency. We reviewed some commonly used low power technologies and proposed our assumptions and strategy for improving energy efficiency. A series of test sets are designed to validate our hypotheses for improving energy efficiency. The experimental results suggest that time has no less impact on energy consumption than power. To support the operation of the processor, some peripheral components consume a constant amount of power regardless of the clock frequency, but the power consumption will be reduced when the processor enters low-power modes. This results in some interesting phenomena that are different from the usual thinking that energy can be saved by increasing processor clock frequency. For STM32F407 and Xtensa LX6 processors, this article also analyzes and calculates the minimum sleep time required for achieving energy saving based on our analytical models. Our energy efficiency strategy has been verified, and in some cases, it can indeed improve energy efficiency. We also proposed some suggestions on hardware design and software development for better energy efficiency.

Energy consumption is a critical evaluation index of embedded systems, and it has impacts on battery-life, thermal design, as well as device security and reliability. Since energy is the time integral of power, power consumption should be considered, along with the impact of “time”; thus, we propose two designs of automatic energy consumption measuring platforms utilizing General Purpose Input/Output (GPIO). Using these designs, we developed software and introduced auxiliary hardware for solutions with better timing and synchronization. A series of test sets were designed to verify our designs’ capabilities and accuracy levels. Both of our designs showed an accuracy similar to that of traditional measuring methods, which can satisfy the needs of different occasions. In addition, our designs provide real-time energy consumption data, as well as unattended automated measurements.

How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children.