Geochemical behavior of rare earth elements in agricultural soils along the Syr Darya River within the Aral Sea Basin.

The widespread use of rare earth elements (REEs) across various industries makes them a new type of pollutant. Additionally, REEs are powerful indicators of geochemical processes. As one of the two main rivers in the Aral Sea, identifying the geochemical behavior of REEs in agricultural soils of the Syr Darya River is of great significance for subsequent indicative studies. In this study, the geochemical characteristics, influencing factors, and potential application significance of REEs in agricultural soils from three sampling areas along the Syr Darya River were analyzed using soil geography and elemental geochemical analyses. The results showed that the highest total concentration of REEs in the agricultural soil was in Area I, with a mean value of 142.49 µg/g, followed by Area III with a mean value of 124.56 µg/g, and the lowest concentration was in Area II with a mean value of 122.48 µg/g. The agricultural soils in the three regions were enriched in light rare earth elements (LREEs), with mean L/H values of 10.54, 10.13, and 10.24, respectively. The differentiation between light and heavy rare earth elements (HREEs) was also high. The concentration of REEs in agricultural soil along the Syr Darya River was primarily influenced by minerals such as monazite and zircon, rather than human activities (the pollution index of all REEs was less than 1.5). The relationship between Sm and Gd can differentiate soils impacted by agricultural activities from natural background soils. The results of this study can serve as a basis for indicative studies of REEs in Central Asia.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Single-cell systems pharmacology identifies development-driven drug response and combination therapy in B cell acute lymphoblastic leukemia.

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.

Effects of general and spinal anesthesia on postoperative rehabilitation in older adults after lower limb surgery: a retrospective cohort study.

Objective: To investigate the effects of perioperative general anesthesia (GA) and spinal anesthesia (SA) on postoperative rehabilitation in elderly patients with lower limb surgery. Methods: This retrospective propensity score-matched cohort study included patients aged 65 years or older who underwent lower limb surgery between January 1, 2020, and May 31, 2023. The GA and SA were selected at the request of the orthopedic surgeon, patient, and their family members. The main outcomes included the incidence of the patient's inability to self-care at discharge, postoperative complications including pulmonary infection, thrombus of lower extremity veins, infection of incisional wound and delirium, length of hospital stay, and incidence of severe pain in the first 2 days postoperatively. Results: In total, 697 patients met the inclusion criteria, and 456 were included in the final analysis after propensity score matching. In the GA and SA groups, 27 (11.84%) and 26 (11.40%) patients, respectively, could not care for themselves at discharge. The incidence rates did not differ between the groups (p = 0.884). In contrast, the incidence of postoperative complications (GA: 10.53% and SA: 4.39%; p = 0.013) and the length of hospital stay (GA: 16.92 ± 10.65 days and SA: 12.75 ± 9.15 days; p < 0.001) significantly differed between the groups. Conclusion: The choice of anesthesia is independent of the loss of postoperative self-care ability in older patients (>65 years) and is not a key factor affecting postoperative rehabilitation after lower limb surgery. However, compared with GA, SA reduces the incidence of postoperative complications and a prolonged hospital stay. Thus, SA as the primary anesthetic method is a protective factor against a prolonged hospital stay.

Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

An Automated Heart Shunt Recognition Pipeline Using Deep Neural Networks.

Automated recognition of heart shunts using saline contrast transthoracic echocardiography (SC-TTE) has the potential to transform clinical practice, enabling non-experts to assess heart shunt lesions. This study aims to develop a fully automated and scalable analysis pipeline for distinguishing heart shunts, utilizing a deep neural network-based framework. The pipeline consists of three steps: (1) chamber segmentation, (2) ultrasound microbubble localization, and (3) disease classification model establishment. The study's normal control group included 91 patients with intracardiac shunts, 61 patients with extracardiac shunts, and 84 asymptomatic individuals. Participants' SC-TTE images were segmented using the U-Net model to obtain cardiac chambers. The segmentation results were combined with ultrasound microbubble localization to generate multivariate time series data on microbubble counts in each chamber. A classification model was then trained using this data to distinguish between intracardiac and extracardiac shunts. The proposed framework accurately segmented heart chambers (dice coefficient = 0.92 ± 0.1) and localized microbubbles. The disease classification model achieved high accuracy, sensitivity, specificity, F1 score, kappa value, and AUC value for both intracardiac and extracardiac shunts. For intracardiac shunts, accuracy was 0.875 ± 0.008, sensitivity was 0.891 ± 0.002, specificity was 0.865 ± 0.012, F1 score was 0.836 ± 0.011, kappa value was 0.735 ± 0.017, and AUC value was 0.942 ± 0.014. For extracardiac shunts, accuracy was 0.902 ± 0.007, sensitivity was 0.763 ± 0.014, specificity was 0.966 ± 0.008, F1 score was 0.830 ± 0.012, kappa value was 0.762 ± 0.017, and AUC value was 0.916 ± 0.006. The proposed framework utilizing deep neural networks offers a fast, convenient, and accurate method for identifying intracardiac and extracardiac shunts. It aids in shunt recognition and generates valuable quantitative indices, assisting clinicians in diagnosing these conditions.

The Prediction Effect of HbA1c on Nosocomial Infection in Diabetic Patients was Analyzed Based on Decision Curve and Dose Response.

Objective: To analyze the predictive efficacy of HbA1c on nosocomial infection in diabetic patients. Methods: 566 patients with diabetes who received treatment in our hospital from January 2021 to January 2023 were selected as the study objects. All patients received relevant treatment in the hospital. Patients with nosocomial infection during treatment were included in the occurrence group, and those without nosocomial infection were included in the non-occurrence group. The level of HbA1c and other laboratory indicators before admission were compared between the two groups of patients [gender, hypertension, age, body mass index (BMI), length of stay, primary caregiver, duration of disease, diabetes complications, antibiotic use, fasting blood glucose (FBG), invasive treatment, hemoglobin (HGB) and insulin resistance index (HO) MA-IR), to analyze the relationship between each index and the occurrence of hospital infection in diabetic patients, and to test the predictive value of HbA1c level in the occurrence of hospital infection in diabetic patients. Results: Among 566 patients with diabetes admitted to our hospital, 139 patients had nosocomial infection, accounting for 24.56%, and 427 patients did not have nosocomial infection, accounting for 75.44%. There were no differences in gender, hypertension, BMI, main caregiver, or HGB between the two groups (P > .05). Age, hospital stay, course of disease, FBG, HbA1c and HOMA-IR in the occurrence group were higher than those in the non-occurrence group, and the proportion of diabetes complications, antibiotic use and invasive treatment was significantly higher than that in the non-occurrence group, with statistical significance (P < .05). Logistics regression analysis showed that old age, long hospital stay, long course of disease, diabetes complications, antibiotic use, high level of FBG, high level of HbA1c, invasive treatment and high level of HOMA-IR were all risk factors for nosocomial infection in diabetic patients (OR > 1, P < .05). The ROC curve showed that the AUC of FBG and HbA1c in predicting the occurrence of hospital infection in diabetic patients was 0.764 and 0.875, respectively, and the predictive energy of HbA1c was higher than that of FBG. Conclusion: HbA1c level is correlated with the occurrence of hospital infection events in diabetic patients, and the correlation intensity with the occurrence of hospital infection events in diabetic patients presents a nonlinear dose-response relationship. Detection of HbA1c levels in diabetic patients is conducive to predicting the probability of hospital infection events, and strict control of HbA1c levels in diabetic patients is conducive to improving patient prognosis.

[Distribution Characteristics and Environmental Driving Factors of Cyanobacteria Community in Impounded Lakes and Reservoirs in Shandong on the East Route of South-to-North Water Diversion Project].

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Transcription factor FOXM1 specifies chromatin DNA to extracellular vesicles.

Extracellular vesicle DNAs (evDNAs) hold significant diagnostic value for various diseases and facilitate transcellular transfer of genetic material. Our study identifies transcription factor FOXM1 as a mediator for directing chromatin genes or DNA fragments (termed FOXM1-chDNAs) to extracellular vesicles (EVs). FOXM1 binds to MAP1LC3/LC3 in the nucleus, and FOXM1-chDNAs, such as the DUX4 gene and telomere DNA, are designated by FOXM1 binding and translocated to the cytoplasm before being released to EVs through the secretory autophagy during lysosome inhibition (SALI) process involving LC3. Disrupting FOXM1 expression or the SALI process impairs FOXM1-chDNAs incorporation into EVs. FOXM1-chDNAs can be transmitted to recipient cells via EVs and expressed in recipient cells when they carry functional genes. This finding provides an example of how chromatin DNA fragments are specified to EVs by transcription factor FOXM1, revealing its contribution to the formation of evDNAs from nuclear chromatin. It provides a basis for further exploration of the roles of evDNAs in biological processes, such as horizontal gene transfer.

Clerodendranthus spicatus inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-κB/Snail signalling pathway in hyperuricaemia nephropathy.

CONTEXT: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). OBJECTIVE: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. RESULTS: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 µg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. DISCUSSION AND CONCLUSIONS: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.

68Ga-PSMA-11 PET/CT versus 68Ga-PSMA-11 PET/MRI for the detection of biochemically recurrent prostate cancer: a systematic review and meta-analysis.

Purpose: Our aim was to conduct a meta-analysis and systematic review in order to compare the diagnostic efficacy of 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI in patients with biochemically recurrent after radical prostatectomy and biochemically recurrent prostate cancers (BCR) after hybrid RT and RP. Methods: Up until February 2023, we searched PubMed, Embase, and Web of Science for pertinent papers. Studies examining the utility of 68Ga-PSMA-11 PET/CT or PET/MRI as a screening tool for biochemically recurrent prostate cancer were included. To measure heterogeneity, we employed the I2 statistic. In cases of substantial heterogeneity (I2 > 50%), we used the random effect model to produce a forest plot. In other cases, we utilized the fixed model. Furthermore, we assessed the quality of the studies included using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) method. Results: In total, 37 studies involving 8409 patients were examined. For 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI, the combined total detection rate was 0.70 (95% CI: 0.65-0.75) and 0.71 (95% CI:0.67-0.75), respectively. 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI did not substantially differ in terms of the overall detection rate for BCR (P = 0.58). The detection rate was unaffected by the PSA values (all P > 0.05). Conclusion: The diagnostic efficacy of 68Ga-PSMA-11 PET/CT appears to be equivalent to that of 68Ga-PSMA-11 PET/MRI in detecting biochemically recurrent prostate cancer. Nonetheless, it should be noted that not all studies have used pathological biopsies as the gold standard. Therefore, additional larger prospective studies are needed to address this issue. Systematic review registration: identifier CRD42023410039.

Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. We systematically examined the frequency of germline NBN variants in pediatric B-ALL and identified 25 putatively damaging NBN coding variants in 50 of 4,183 B-ALL patients. Compared with the frequency of NBN variants in 118,479 gnomAD non-cancer controls we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.77). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as pathogenic or likely pathogenic. Finally, we found that heterozygous germline NBN variant carriers showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

Electrospun chitosan-based nanofibers loading tea tree oil for fresh salmon fillet shelf-life extension.

Bioactive packaging can improve the shelf-life of food products and enhance consumer health. It can also alleviate environmental stress on the planet by reducing food waste. Here, the electrospinning of tea tree oil-loaded 2-hydroxypropyltrimethyl ammonium chloride chitosan nanofibers was investigated. The fabricated nanofiber films were characterized by scanning electron microscopy, thermal gravimetric analysis, Fourier transform infrared spectroscopy, and contact angle meter analysis. The prepared nanofibers have a well-defined diameter of about 200 nm and a smooth shape. They have good antibacterial properties against Staphylococcus aureus and Escherichia coli in vitro. Tea tree oil-loaded chitosan-based nanofibers were found to be effective in delaying spoilage and extending the shelf life of salmon by sensory evaluation, texture analysis, color, total viable counts, thiobarbituric acid, and total volatile basic nitrogen during storage in the freshness experiments, thus indicating their health benefits in bioactive packaging.

Estimates of bladder cancer burden attributable to high fasting plasma glucose: Findings of the Global Burden of Disease Study 2019.

BACKGROUND: High fasting plasma glucose (FPG) has been listed as one of the risk factors for bladder cancer. We here estimated the global, regional, and national levels of bladder cancer burden attributable to high FPG from 1990 to 2019. METHODS: Bladder cancer data attributable to high FPG were extracted from the Global Burden of Disease Study 2019, and analyzed by age, sex, year, and location. Age-standardized rates were utilized to evaluate the burden between different populations. The temporal trend of the burden was estimated through the Joinpoint analysis. RESULTS: In 2019, high FPG contributed to 22,823.33 (95% uncertainty interval [UI], 4694.88-48,962.26) deaths and 399,654.91 (95% UI, 81,609.35-865,890.95) disability-adjusted life years (DALYs) of bladder cancer globally. Since 1990, the global age-standardized death and DALY rates of bladder cancer attributable to high FPG increased apparently by 39.18% and 41.48%, respectively. During the last 30 years, high FPG-related age-standardized death and DALY rates of bladder cancer have increased in all countries. In 2019, Central Europe showed the greatest high FPG-related age-standardized death and DALY rates of bladder cancer, but Andean Latin America had the lowest rates. Nationally, Lebanon showed the greatest high FPG-related age-standardized death and DALY rates of bladder cancer in 2019. High FPG-attributable deaths and DALYs of bladder cancer were more considerable among males and older people. Countries with high SDI showed higher levels of age-standardized death and DALY rates of bladder cancer due to high FPG and presented remarkable upward trends in rates in the last 30 years. CONCLUSIONS: Globally, the high FPG-associated bladder cancer burden has remarkably increased in all countries, and showed a higher level among countries with higher SDI. Monitoring FPG levels among patients with bladder cancer is critical to lower the corresponding burden.

The diagnostic value of circulating abnormal cells in early lung cancer.

Lung cancer is the leading cause of cancer-related deaths globally. Early detection of lung cancer can lead to more effective treatment and improved survival. Circulatory abnormal cells (CACs) with specific chromosomal variation may be used to diagnose lung cancer and to differentiate benign from malignant nodules. The value of CAC in precancer diagnosis, however, remains controversial. In this study, a systematic review and meta-analysis are conducted to clarify the diagnostic value of CAC in early-stage lung cancer. A systematic literature search was conducted using the following medical topic title terms and text-free words: "circulating genetically abnormal cells", "CACs", "liquid biopsy", "early lung cancer", "non-small cell lung cancer", "diagnostic accuracy", "sensitivity" and "specificity" in Science Direct, CNKI and Wanfang databases, respectively. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were analyzed by STATA15.0 (MP) software. Deek funnel plots were used to assess potential publication bias. Heterogeneity was tested using the I2 statistic and the Cochrane Q test. 7 major studies were included in this meta-analysis, and a total of 53728 participants were analyzed. In the diagnosis of early lung cancer, CAC had pooled sensitivity, specificity, and receiver operating characteristics of 0.80 (95% CI: 0.73-0.86), 0.85 (95% CI: 0.69-0.94), and 0.87 (95% CI: 0.84-0.90). The combined positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and diagnostic score were 23.36 (95% CI: 7.33-74.46), 5.42 (95% CI: 2.37-12.43), 0.23 (95% CI: 0.16-0.35) and 3.15 (95% CI: 1.99-4.31) respectively. Publication bias was not detected. The CAC is effective at detecting lung cancer in its early stages.

Transcriptome sequencing identifies novel EVX fusions involved in transcriptional activation of HOX family genes in pediatric immature T-cell acute lymphoblastic leukemia: two cases reports and a literature review.

Driver genomic alterations in pediatric immature T-cell acute lymphoblastic leukemia are not fully known. We report two cases of novel EVX fusions involved in the transcriptional activation of HOX family genes, ETV6::EVX2 and MSI2::EVX1/HOXA13, which activate HOXD and HOXA cluster genes transcription through enhancer hijacking. HOXA and HOXD were the only key transcription factors activated in these cases, which indicates their important roles in leukemogenesis. Our findings elucidate potential drivers for development of T-cell lymphoblastic leukemia, and are valuable for diagnosis and risk stratification of pediatric T-ALL in the era of precision medicine.

Piperlongumine Induces Cellular Apoptosis and Autophagy via the ROS/Akt Signaling Pathway in Human Follicular Thyroid Cancer Cells.

Thyroid cancer (TC) is the most common endocrine malignancy. Recently, the global incidence of TC has increased rapidly. Differentiated thyroid cancer includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), which are the most common types of TC. Although PTCs and FTCs exert good prognoses and high survival rates, FTCs tend to be more aggressive than PTCs. There is an urgent need to improve patient outcomes by developing effective therapeutic agents for FTCs. Piperlongumine exerts anti-cancer effects in various human carcinomas, including human anaplastic TCs and PTCs. However, the anti-cancer effects of piperlongumine in FTCs and the underlying mechanisms are yet to be elucidated. Therefore, in the present study, we evaluated the effect of piperlongumine on cell proliferation, cell cycle, apoptosis, and autophagy in FTC cells with flowcytometry and Western blot. We observed that piperlongumine caused growth inhibition, cell cycle arrest, apoptosis induction, and autophagy elevation in FTC cells. Activities of reactive oxygen species and the downstream PI3K/Akt pathway were the underlying mechanisms involved in piperlongumine mediated anti-FTC effects. Advancements in our understanding of the effects of piperlongumine in FTC hold promise for the development of novel therapeutic strategies.

18ß-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells.

The development of endocrine therapy resistance in the luminal A subtype of breast cancer is related to the appearance of protective autophagy. The bioactive component from the root of licorice, 18ß-glycyrrhetinic acid (18ß-GA), has many antitumor properties. Whether 18ß-GA can modulate autophagy to inhibit proliferation of the luminal A subtype is still unclear. The proportion of apoptosis caused by 18ß-GA in MCF-7 and T-47D cells was determined using flow cytometry. The autophagy marker, LC3-II conversion, was investigated using Western blotting, and a PremoTM Tandem Autophagy Sensor Kit. We found that the concentration (150-µM) of 18ß-GA caused caspase-dependent apoptosis and LC3-II accumulation or blocked autophagic flux. Moreover, 18ß-GA-mediated apoptosis was improved using rapamycin but reversed by 3-methyladenine (3-MA) addition. The phosphorylation level of Jun-amino-terminal kinase (JNK) was increased significantly in the 18ß-GA treatment and combined incubation using rapamycin. A JNK inhibitor (SP600125) significantly inhibited 18ß-GA-mediated apoptosis, LC3-II accumulation and rescued the numbers of MCF-7 and T-47D colony formation. Especially, 18ß-GA can inhibit xenograft tumor growth in BALB/c nude mice. These data indicate the combination of 18ß-GA with rapamycin or 3-MA can sensitize or decrease MCF-7 and T-47D cells to 18ß-GA-induced apoptosis, respectively. 18ß-GA modulated autophagy is cytotoxic to luminal A subtype breast cancer cells through apoptosis promotion and JNK activation.

Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.

Colon cancer is the fourth leading cause of cancer death worldwide, and its progression is accompanied by a complex array of genetic variations. CRISPR/Cas9 can identify new drug-resistant or sensitive mutations in colon cancer, and can use gene editing technology to develop new therapeutic targets and provide personalized treatments, thereby significantly improving the treatment of colon cancer patients. CRISPR/Cas9 systems are driving advances in biotechnology. RNA-directed Cas enzymes have accelerated the pace of basic research and led to clinical breakthroughs. This article reviews the rapid development of CRISPR/Cas in colon cancer, from gene editing to transcription regulation, gene knockout, genome-wide CRISPR tools, therapeutic targets, stem cell genomics, immunotherapy, metabolism-related genes and inflammatory bowel disease. In addition, the limitations and future development of CRISPR/Cas9 in colon cancer studies are reviewed. In conclusion, this article reviews the application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.