Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age-period-cohort analysis for the Global Burden of Disease 2019 study.

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.

CSF Parameters Predicting Contralateral Isolated Lateral Ventricle in Adult Tuberculous Meningitis with Hydrocephalus Post-Ventriculoperitoneal Shunt.

OBJECTIVE: Hydrocephalus, a major complication in tuberculous meningitis (TBM) patients, often necessitates treatment via ventriculoperitoneal shunt (VPS). However, post-VPS, some patients develop a complication called contralateral isolated lateral ventricle (CILV), leading to persistent hydrocephalus symptoms. This study aims to evaluate cerebrospinal fluid (CSF) parameters in predicting CILV occurrence post-VPS in adult TBM patients. METHODS: A retrospective analysis was conducted, focusing on the relationship between preoperative CSF parameters and the development of CILV in 40 adult TBM patients who underwent VPS. The study compared CSF parameters from lumbar puncture after admission with those from ventricular CSF post-external ventricular drainage tube insertion. RESULTS: CILV was observed in 6 of the 40 patients following VPS. Statistical analysis showed no significant difference between the CSF parameters obtained via lumbar and ventricular punctures. Notably, the mean CSF glucose level in patients with CILV was significantly lower (1.92 mmol/L) compared to the non-CILV group (3.03 mmol/L). Conversely, the median adenosine deaminase (ADA) level in the CILV group was higher (5.69 U/L) compared to the non-CILV group (3.18 U/L). The optimal cutoff values for CSF glucose and ADA levels were 1.90 mmol/L and 4.80 U/L, respectively, with a sensitivity of 66.67% and 83.33% and a specificity of 88.24% and 79.41%. CONCLUSIONS: The study identified elevated ADA levels and decreased glucose levels in CSF as potential risk factors for CILV development in adult TBM patients post-VPS. These findings suggest the necessity for more tailored surgical approaches, in patients with altered CSF parameters to mitigate the risk of CILV.

Machine-learning developed an iron, copper, and sulfur-metabolism associated signature predicts lung adenocarcinoma prognosis and therapy response.

BACKGROUND: Previous studies have largely neglected the role of sulfur metabolism in LUAD, and no study has combine iron, copper, and sulfur-metabolism associated genes together to create prognostic signatures. METHODS: This study encompasses 1564 LUAD patients, 1249 NSCLC patients, and over 10,000 patients with various cancer types from diverse cohorts. We employed the R package ConsensusClusterPlus to separate patients into different ICSM (Iron, Copper, and Sulfur-Metabolism) subtypes. Various machine-learning methods were utilized to develop the ICSMI. Enrichment analyses were conducted using ClusterProfiler and GSVA, while IOBR quantified immune cell infiltration. GISTIC2.0 and maftools were utilized for CNV and SNV data analysis. The Oncopredict package predicted drug information based on GDSC1. TIDE algorithm and cohorts GSE91061 and IMvigor210 evaluated patient response to immunotherapy. Single-cell data was processed using the Seurat package, AUCell package calculated cells geneset activity scores, and the Scissor algorithm identified ICSMI-associated cells. In vitro experiments was conducted to explore the role of ICSMRGs in LUAD. RESULTS: Unsupervised clustering identified two distinct ICSM subtypes of LUAD, each with unique clinical characteristics. The ICSMI, comprising 10 genes, was constructed using integrated machine-learning methods. Its prognostic power was validated in 10 independent datasets, revealing that LUAD patients with higher ICSMI levels had poorer prognoses. Furthermore, ICSMI demonstrated superior predictive abilities compared to 102 previously published signatures. A nomogram incorporating ICSMI and clinical features exhibited high predictive performance. ICSMI positively correlated with patients gene mutations, and integrated analysis of bulk and single-cell transcriptome data revealed its association with TME modulators. Cells representing the high-ICSMI phenotype exhibited more malignant features. LUAD patients with high ICSMI levels exhibited sensitivity to chemotherapy and targeted therapy but displayed resistance to immunotherapy. In a comprehensive analysis across various cancers, ICSMI retained significant prognostic value and emerged as a risk factor for the majority of cancer patients. CONCLUSIONS: ICSMI provides critical prognostic insights for LUAD patients, offering valuable insights into the tumor microenvironment and predicting treatment responsiveness.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4:15%Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Evaluation of an E6/E7 PCR-capillary electrophoresis fragment analysis in the genotyping of human papillomavirus in archival FFPE samples of oropharyngeal cancer.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

BACKGROUND: This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. METHODS: Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. RESULTS: The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). CONCLUSIONS: High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Therapeutic potential of targeting Nrf2 by panobinostat in pituitary neuroendocrine tumors.

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study.

OBJECTIVES: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. METHODS: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. RESULTS: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DISCUSSION: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

[Analysis of Influencing Factors of Complications for CT-guided 
Percutaneous Lung Biopsy].

BACKGROUND: Computed tomography guided percutaneous lung biopsy (CT-PLB) is a widely used method for the diagnosis of lung lesions. However, it is invasive, and the most common complications are pneumothorax and pulmonary hemorrhage, which can be life-threatening in severe cases. Therefore, the aim of this study is to analyze the independent risk factors affecting the occurrence of different complications of CT-PLB, so as to reduce the incidence of complications. METHODS: The 605 patients with complete clinical data who underwent CT-PLB in our hospital from May 2018 to December 2019 were retrospectively analyzed. According to the location of the lesions, they were divided into subpleural group and non-subpleural group. The patients were divided into pneumothorax group, pulmonary hemorrhage group, pneumothorax with pulmonary hemorrhage group and non-pneumothorax/pulmonary hemorrhage group according to the complications. The risk factors affecting the incidence of different complications and the independent risk factors of each complication were analyzed. RESULTS: The incidence of pneumothorax was 34.1%, the incidence of pulmonary hemorrhage was 28.1%, and the incidence of pneumothorax complicated with pulmonary hemorrhage was 10.8% (63 cases). The independent risk factor affecting the incidence of subpleural pneumothorax was lesion size (P=0.002). The independent risk factors affecting the occurrence of pneumothorax in the non-subpleural group were plain scan CT value (P=0.035), length of needle through lung tissue (P=0.003), and thickness of needle through chest wall (P=0.020). Independent risk factors affecting the occurrence of pulmonary hemorrhage in the non-subpleural group were length of needle through lung tissue (P<0.001), △CT value of needle travel area (P=0.001), lesion size (P=0.034) and body position (P=0.014). The independent risk factors affecting the co-occurrence of pneumothorax and pulmonary hemorrhage were the length of needle through lung tissue (P<0.001) and the △CT value of needle travel area (P<0.001). CONCLUSIONS: CT-PLB is a safe and effective diagnostic method, which of high diagnostic value for lung lesions. Selecting the appropriate puncture program can reduce complications such as pneumothorax and pulmonary hemorrhage, and improve diagnosis and treatment efficiency.

Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Prediction Model of Lean Coal Adsorption of Power Plant Flue Gas.

To minimize errors in calculating coal flue gas adsorption capacity due to gas compressibility and to preclude prediction inaccuracies in abandoned mine flue gas storage capacity for power plants, it is imperative to account for the influence of compression factor calculation accuracy while selecting the optimal theoretical adsorption model. In this paper, the flue gas adsorption experiment of a power plant with coal samples gradually pressurized to close to 5 MPa at two different temperatures is carried out, and the temperature and pressure data obtained from the experiment are substituted into five different compression factor calculation methods to calculate different absolute adsorption amounts. The calculated adsorption capacities were fitted into six theoretical adsorption models to establish a predictive model suitable for estimating the coal adsorption capacity in power plant flue gas. Results reveal significant disparities in the absolute adsorption capacity determined by different compression factors, with an error range of 0.001278-7.8262 (cm3/kg). The Redlich-Kwong equation of state emerged as the most suitable for the flue gas of the selected experimental coal sample and the chosen composition ratio among the five compression factors. Among the six theoretical adsorption models, the Brunauer-Emmett-Teller model with three parameters demonstrated the highest suitability for predicting the adsorption capacity of coal samples in power plant smoke, achieving a fitting accuracy as high as 0.9922 at 49.7 °C.

Identification of a novel ADCC-related gene signature for predicting the prognosis and therapy response in lung adenocarcinoma.

BACKGROUND: Previous studies have largely neglected the role of ADCC in LUAD, and no study has systematically compiled ADCC-associated genes to create prognostic signatures. METHODS: In this study, 1564 LUAD patients, 2057 NSCLC patients, and more than 5000 patients with various cancer types from diverse cohorts were included. R package ConsensusClusterPlus was utilized to classify patients into different subtypes. A number of machine-learning algorithms were used to construct the ADCCRS. GSVA and ClusterProfiler were used for enrichment analyses, and IOBR was used to quantify immune cell infiltration level. GISTIC2.0 and maftools were used to analyze the CNV and SNV data. The Oncopredict package was used to predict drug information based on the GDSC1. Three immunotherapy cohorts were used to evaluate patient response to immunotherapy. The Seurat package was used to process single-cell data, the AUCell package was used to calculate cells' geneset activity scores, and the Scissor algorithm was used to identify ADCCRS-associated cells. RESULTS: Through unsupervised clustering, two distinct subtypes of LUAD were identified, each exhibiting distinct clinical characteristics. The ADCCRS, consisted of 16 genes, was constructed by integrated machine-learning methods. The prognostic power of ADCCRS was validated in 28 independent datasets. Further, ADCCRS shows better predictive abilities than 102 previously published signatures in predicting LUAD patients' survival. A nomogram incorporating ADCCRS and clinical features was constructed, demonstrating high predictive performance. ADCCRS positively correlates with patients' gene mutation, and integrated analysis of bulk and single-cell transcriptome data revealed the association of ADCCRS with TME modulators. Cells representing high-ADCCRS phenotype exhibited more malignant features. LUAD patients with high ADCCRS levels exhibited sensitivity to chemotherapy and targeted therapy, while displaying resistance to immunotherapy. In pan-cancer analysis, ADCCRS still exhibited significant prognostic value and was found to be a risk factor for most cancer patients. CONCLUSIONS: ADCCRS offers a critical prognostic insight for patients with LUAD, shedding light on the tumor microenvironment and forecasting treatment responsiveness.

Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Alternations of Blood Pressure Following Surgical or Drug Therapy for Prolactinomas.

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

Risk model based on genes regulating the response of tumor cells to T-cell-mediated killing in esophageal squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) represent a promising therapeutic approach for esophageal squamous cell carcinoma (ESCC). However, the subpopulations of ESCC patients expected to benefit from ICIs have not been clearly defined. The anti-tumor cytotoxic activity of T cells is an important pharmacological mechanism of ICIs. In this study, the prognostic value of the genes regulating tumor cells to T cell-mediated killing (referred to as GRTTKs) in ESCC was explored by using a comprehensive bioinformatics approach. Training and validation datasets were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. A prognostic risk scoring model was developed by integrating prognostic GRTTKs from TCGA and GEO datasets using a ridge regression algorithm. Patients with ESCC were divided into high- and low-risk groups based on eight GRTTKs (EIF4H, CDK2, TCEA1, SPTLC2, TMEM209, RGP1, EIF3D, and CAPZA3) to predict overall survival in the TCGA cohort. Using Kaplan-Meier curves, receiver operating characteristic curves, and C-index analysis, the high reliability of the prognostic risk-scoring model was certified. The model scores served as independent prognostic factors, and combining clinical staging with risk scoring improved the predictive value. Patients in the high-risk group exhibited abundant immune cell infiltration, including immune checkpoint expression, antigen presentation capability, immune cycle gene expression, and high tumor inflammation signature scores. The high-risk group exhibited a greater response to immunotherapy and neoadjuvant chemotherapy than the low-risk group. Drug sensitivity analysis demonstrated lower IC50 for AZD6244 and PD.0332991 in high-risk groups and lower IC50 for cisplatin, ATRA, QS11, and vinorelbine in the low-risk group. Furthermore, the differential expression of GRTTK-related signatures including CDK2, TCEA1, and TMEM209 were verified in ESCC tissues and paracancerous tissues. Overall, the novel GRTTK-based prognostic model can serve as indicators to predict the survival status and immunotherapy response of patients with ESCC, thereby providing guidance for the development of personalized treatment strategies.