A dopant-assisted iodide-adduct chemical ionization time-of-flight mass spectrometer based on VUV lamp photoionization for atmospheric low-molecular-weight organic acids analysis.

Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry. In iodine-adduct chemical ionization mass spectrometry (CIMS), the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet (VUV) lamp initiated CIMS for on-line gaseous formic and acetic acids analysis. In this work, we present a new CIMS based on VUV lamp, and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode. Acetone was added to the photoionization zone, and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I-, and the addition of acetone reduced the amount of methyl iodide by 2/3. In the chemical ionization zone, a headspace vial containing ultrapure water was added for humidity calibration, and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation (R2 > 0.95). With humidity calibration, the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88% RH. In this mode, limits of detection of 10 and 50 pptv are obtained for formic and acetic acids, respectively. And the relative standard deviation (RSD) of quantitation stability for 6 days were less than 10.5%. This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus (Qingdao, China). In addition, we developed a simple model based formic acid concentration to assess vehicular emissions.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Dual concentric echo sign of ultrasound in primary hyperparathyroidism: The clinical and histopathologic features and differentiation from lymph nodes.

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p < 0.05). Additionally, the proportion of asymptomatic patients was significantly higher in Group 1 compared to Group 2 (p < 0.05). Pathological examination revealed that all lesions with dual concentric echo signs were parathyroid adenomas. The isoechoic central region predominantly corresponded to areas of loose edema, while the hypoechoic peripheral layer was primarily associated with chief and/or oncocytic cells. By comparing the ultrasonography of Groups 1 and 3, the parathyroid lesions with dual concentric echo signs exhibited significant distinctions from lymph nodes in size, blood flow classification, vascular distribution, and anatomical location (p < 0.05). Conclusion: The parathyroid lesions with dual concentric echo signs in US corresponded to specific histopathological manifestations and relatively mild clinical features in the patients, this finding may increase the likelihood of incidental detection of parathyroid lesions by US. Attention to the details of size, location, and blood flow, especially, may aid US physicians in differentiating parathyroid adenomas from cervical lymph nodes.

[Evaluation of the reporting quality of randomized controlled trials of acupuncture for depression based on CONSORT statement, STRICTA criteria and SHARE checklist].

OBJECTIVE: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for depression. METHODS: Systematic searches were performed in PubMed, the Cochrane Library, EMbase, CNKI, Wanfang, SinoMed and VIP Database for RCTs of acupuncture in treatment of depression. The search time was from the establishment of database to December 1, 2023, and the language restriction was Chinese and English. The reporting quality of RCTs of acupuncture for depression was evaluated using the CONSORT statement, the international standardization for trial reporting, STRICTA, the international standard for clinical trial interventions of acupuncture, and SHARE, the guideline and checklist for reporting sham acupuncture controls. RESULTS: According to the CONSORT statement items, the items with the reporting rate less than 50% was accounted for 54.05% of all of the items for Chinese articles, and there were 8 and 1 items with a reporting rate of 0% and 100%, respectively. For the English articles, the items with the reporting rate less than 50% was accounted for 35.14% of all of the items, and there were 3 and 7 items with a reporting rate of 0% and 100%, respectively. The reporting rate of 15 items in Chinese and English articles was greater than 50%, e.g. structured abstract, background and purpose. Based on STRICTA criteria, the reporting rate of either Chinese or English articles was relatively high. The items for Chinese articles with the reporting rate less than 50% was accounted for 23.53% of all of the items, and there were 1 and 4 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 11.76% of all of the items, and there was 1 item with a reporting rate of either 0% or 100%. In compliance with SHARE checklist, the reporting rate was low for either Chinese or English articles. The items with the reporting rate less than 50% was accounted for 57.89% of all of the items for Chinese articles, and there were 2 and 0 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 52.63% of all of the items, and there was 1 item with a reporting rate of 0% and 100%, respectively. CONCLUSION: The overall reporting quality of RCTs of acupuncture for depression is low currently. It is urgent to enhance the reporting of the details on sham acupuncture control especially. It is suggested that RCTs should be reported strictly in compliance with the CONSORT statement, STRICTA criteria, and SHARE checklist in the future.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability.

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression.

N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

Extraction Optimization and Anti-Tumor Activity of Polysaccharides from Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii polysaccharides (CRPs) are bioactive compounds derived from C. reinhardtii, yet their potential in cancer therapy remains largely unexplored. This study optimized the ultrasound-assisted extraction conditions using response surface methodology and proceeded with the isolation and purification of these polysaccharides. The optimal extraction conditions were identified as a sodium hydroxide concentration of 1.5%, ultrasonic power of 200 W, a solid-to-liquid ratio of 1:25 g/mL, an ultrasonic treatment time of 10 min, and a water bath duration of 2.5 h, yielding an actual extraction rate of 5.71 ± 0.001%, which closely aligns with the predicted value of 5.639%. Infrared analysis revealed that CRP-1 and CRP-2 are α-pyranose structures containing furoic acid, while CRP-3 and CRP-4 are ß-pyranose structures containing furoic acid. Experimental results demonstrated that all four purified polysaccharides inhibited the proliferation of cervical (HeLa) hepatoma (HepG-2) and colon (HCT-116) cancer cells, with CRP-4 showing the most significant inhibitory effect on colon cancer and cervical cancer, achieving inhibition rates of 60.58 ± 0.88% and 40.44 ± 1.44%, respectively, and significantly reducing the migration of HeLa cells. DAPI staining confirmed that the four purified polysaccharides inhibit cell proliferation and migration by inducing apoptosis in HeLa cells. CRP-1 has the most significant inhibitory effect on the proliferation of liver cancer cells. This study not only elucidates the potential application of C. reinhardtii polysaccharides in cancer therapy but also provides a scientific basis for their further development and utilization.

Changes in immunophenotypes after neoadjuvant endocrine therapy for prostate cancer and their clinical significance.

Background: To investigate changes in the immunophenotypes of androgen receptor (AR), prostate-specific antigen (PSA), synaptophysin (Syn), chromogranin A (CgA), p53 and Ki-67 after neoadjuvant endocrine therapy (NET) for prostate cancer (PCa) and to analyze their clinical significance. Methods: Paired paraffin samples were collected from 40 PCa patients before and after NET, and immunohistochemistry were used to detect AR, PSA, Syn, CgA, p53 and Ki-67 expression. Based on The Cancer Genome Atlas (TCGA), Kaplan‒Meier survival curves were plotted for analysis of PSA and Ki-67 expression in relation to progression-free survival (PFS). Results: After NET, the mean scores for PSA and Ki-67 expression in PCa patients were lower than those before NET (P < 0.05), while the mean scores for Syn and CgA expression were higher than those before NET (P < 0.05). The mean Gleason score and WHO/ISUP (World Health Organization/International Society of Urological Pathology) grade after NET were lower than those before NET (P < 0.05). In PCa patients who had not yet received NET, PSA expression correlated positively with Gleason score and WHO/ISUP grade and negatively with Ki-67 expression (P < 0.05); p53 expression correlated negatively with Gleason score and WHO/ISUP grade (P < 0.05). TCGA showed that PFS was lower in PCa patients with high PSA and Ki-67 expression (P < 0.05). Conclusions: PSA and Ki-67 protein expressions decreased significantly in PCa patients after NET and can be used as biological markers for prognostic assessment of PCa patients. NETs may induce a neuroendocrine (NE) phenotype in PCa. Monitoring the immunophenotypes of PCa patients after NET may inform assessment of efficacy and prognosis.

Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood. AIM: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment. METHODS: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases. RESULTS: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo. Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients. CONCLUSION: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.

Small Intestinal Submucosa Hydrogel Loaded With Gastrodin for the Repair of Achilles Tendinopathy.

Achilles tendinopathy (AT) is an injury caused by overuse of the Achilles tendon or sudden force on the Achilles tendon, with a considerable inflammatory infiltrate. As Achilles tendinopathy progresses, inflammation and inflammatory factors affect the remodeling of the extracellular matrix (ECM) of the tendon. Gastrodin(Gas), the main active ingredient of Astrodia has anti-inflammatory, antioxidant, and anti-apoptotic properties. The small intestinal submucosa (SIS) is a naturally decellularized extracellular matrix(dECM)material and has a high content of growth factors as well as good biocompatibility. However, the reparative effects of SIS and Gas on Achilles tendinopathy and their underlying mechanisms remain unknown. Here, it is found that SIS hydrogel loaded with gastrodin restored the mechanical strength of the Achilles tendon, facilitated ECM remodeling, and restored ordered collagen arrangement by promoting the translocation of protein synthesis. It also decreases the expression of inflammatory factors and reduces the infiltration of inflammatory cells by inhibiting the NF-κB signaling pathway. It is believed that through further research, Gas + SIS may be used in the future for the treatment of Achilles tendinopathy and other Achilles tendon injury disorders.

Unraveling the relationship between anoikis-related genes and cancer-associated fibroblasts in liver hepatocellular carcinoma.

This study intended to determine the molecular subtypes of liver hepatocellular carcinoma (LIHC) on the strength of anoikis-related genes (ARGs) and to assess their prognostic value and prospective relationship with immune cell infiltration and cancer-associated fibroblasts (CAFs). Univariate Cox regression analysis yielded 66 prognosis-related ARGs and classified LIHC into two distinct subtypes, with subtype A demonstrating overexpression of most prognosis-related ARGs and a significant survival disadvantage. Furthermore, a reliable prediction model was developed using ARGs to evaluate the risk of LIHC patients. This model served as an independent prognostic indicator and a quantitative tool for clinical prognostic prediction. Additionally, subtype-specific differences in immune cell infiltration were observed, and the risk score was potentially linked to immune-related characteristics. Moreover, the study identified a significant association between CAF score and LIHC prognosis, with a low CAF score indicating a favorable patient prognosis. In conclusion, this study reveals the molecular mechanisms underlying the development and progression of LIHC and identifies potential therapeutic targets for the disease.

Biotransformation, Bioaccumulation, and Bioelimination of Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate In Vivo.

Aryl phosphorus flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), are widely used worldwide. Understanding the fates of aryl-PFRs in vivo is crucial to assessing their toxicity and the risks they pose. Seven TPHP metabolites, including Phase I hydrolysis and hydroxylation and Phase II glucuronidation products, were identified in C57BL/6J male mice following subacute dietary exposure to aryl-PFRs (70 µg/kg body weight (bw)/day) for 7 days. TPHP was almost completely metabolized by mice (∼97%), with DPHP the major metabolite formed (34%-58%). In addition, mice were exposed to aryl-PFRs (7 µg/kg bw/day) for 12 weeks. Both TPHP and DPHP occurred at higher concentrations in the digestive tract (intestine and stomach), liver and heart. The total concentration of DPHP in all organs was 3.55-fold greater than that of TPHP. Recovery analysis showed that the rate of TPHP elimination from mouse organs reached 38%, while only 3%-5% of DPHP was removed, suggesting that the rates of degradation and elimination of DPHP were slower than TPHP and its bioaccumulation potential was higher. These results highlight the critical role of DPHP in the biotransformation, bioaccumulation, and bioelimination of TPHP, providing valuable insights into the fate of aryl-PFRs in vivo.

BNIP3-mediated mitophagy attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62-KEAP1-NRF2 pathway activation to maintain iron and redox homeostasis.

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE.

Variations, effectiveness and its associated factors of a nationwide web-based hypertension management training project in China: insights from a government-led campaign for 1.2 million lay health workers.

OBJECTIVES: To evaluate the effectiveness of a large-scale, web-based, in-service hypertension management training project among lay health workers (LHWs) at primary care health (PHC) settings in China, and to examine the factors contributing to the variations of effectiveness. METHODS: We used data from a web-based national hypertension management training project implemented in 2018, it was designed to facilitate LHWs to learn, understand, and apply the relevant knowledge and skills in hypertension management through providing training courses by use of the web-based platform with unified standards. All LHWs were required to participate in the exams before and after training to acquire scores for the use of evaluating their performance of hypertension management knowledge. We first used descriptive analysis to present the variations of effectiveness in hypertension management knowledge among LHWs by important subgroups. Afterwards, we used multilevel logistic regression to examine the individual and regional factors contributing to the variations and quantify the magnitude of how these factors affected training effectiveness. RESULTS: There were 1,208,610 LHWs who completed training and were certificated. Nationally, the scores of LHWs increased significantly from 62.87 ± 21.14 out of 100 in the pre-test to 88.30 ± 11.31 in the post-test by 25.43 (95% confidence interval [CI]: 25.40-25.47). Training contents involved in antihypertensive medication showed the lowest score (54.36) in the pre-test and soared the most after training, up to 84.22 by 54.94%. Individual factors associated with disparities in the knowledge of hypertension management decreased substantially after training, which included sex, age, education, practice type, professional level, and hierarchy of working institutions. Geographical variations were shown at the provincial level, with the majority of them being explained by factors at the regional level. CONCLUSIONS: Accessible web-based training modality, government efforts, accompanied with experiences derived from the training, could be generalized to other low- and middle-income countries in facilitating the hypertension management capacity of LHWs. Localization and evaluation is warranted on the way to its further application.

Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

Development and validation of a glioma prognostic model based on telomere-related genes and immune infiltration analysis.

Background: Gliomas are the most prevalent primary brain tumors, and patients typically exhibit poor prognoses. Increasing evidence suggests that telomere maintenance mechanisms play a crucial role in glioma development. However, the prognostic value of telomere-related genes in glioma remains uncertain. This study aimed to construct a prognostic model of telomere-related genes and further elucidate the potential association between the two. Methods: We acquired RNA-seq data for low-grade glioma (LGG) and glioblastoma (GBM), along with corresponding clinical information from The Cancer Genome Atlas (TCGA) database, and normal brain tissue data from the Genotype-Tissue Expression (GTEX) database for differential analysis. Telomere-related genes were obtained from TelNet. Initially, we conducted a differential analysis on TCGA and GTEX data to identify differentially expressed telomere-related genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on these genes. Subsequently, univariate Cox analysis and log-rank tests were employed to obtain prognosis-related genes. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis were sequentially utilized to construct prognostic models. The model's robustness was demonstrated using receiver operating characteristic (ROC) curve analysis, and multivariate Cox regression of risk scores for clinical characteristics and prognostic models were calculated to assess independent prognostic factors. The aforementioned results were validated using the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, the CIBERSORT algorithm analyzed differences in immune cell infiltration levels between high- and low-risk groups, and candidate genes were validated in the Human Protein Atlas (HPA) database. Results: Differential analysis yielded 496 differentially expressed telomere-related genes. GO and KEGG pathway analyses indicated that these genes were primarily involved in telomere-related biological processes and pathways. Subsequently, a prognostic model comprising ten telomere-related genes was constructed through univariate Cox regression analysis, log-rank test, LASSO regression analysis, and multivariate Cox regression analysis. Patients were stratified into high-risk and low-risk groups based on risk scores. Kaplan-Meier (K-M) survival analysis revealed worse outcomes in the high-risk group compared to the low-risk group, and establishing that this prognostic model was a significant independent prognostic factor for glioma patients. Lastly, immune infiltration analysis was conducted, uncovering notable differences in the proportion of multiple immune cell infiltrations between high- and low-risk groups, and eight candidate genes were verified in the HPA database. Conclusions: This study successfully constructed a prognostic model of telomere-related genes, which can more accurately predict glioma patient prognosis, offer potential targets and a theoretical basis for glioma treatment, and serve as a reference for immunotherapy through immune infiltration analysis.

Comparison of intestinal absorption of soybean protein isolate-, glutenin- and peanut protein isolate-bound Nε-(carboxymethyl) lysine after in vitro gastrointestinal digestion.

Advanced glycation end products (AGEs), a heterogeneous compound existed in processed foods, are related to chronic diseases when they are accumulated excessively in human organs. Protein-bound Nε-(carboxymethyl) lysine (CML) as a typical AGE, is widely determined to evaluate AGEs level in foods and in vivo. This study investigated the intestinal absorption of three protein-bound CML originated from main food raw materials (soybean, wheat and peanut). After in vitro gastrointestinal digestion, the three protein-bound CML digests were ultrafiltered and divided into four fractions: less than 1 kDa, between 1 and 3 kDa, between 3 and 5 kDa, greater than 5 kDa. Caco-2 cell monolayer model was further used to evaluate the intestinal absorption of these components. Results showed that the absorption rates of soybean protein isolate (SPI)-, glutenin (Glu)-, peanut protein isolate (PPI)-bound CML were 30.18%, 31.57% and 29.5%, respectively. The absorption rates of components with MW less than 5 kDa accounted for 19.91% (SPI-bound CML), 22.59% (Glu-bound CML), 23.64% (PPI-bound CML), respectively, and these samples were absorbed by paracellular route, transcytosis route and active route via PepT-1. Taken together, these findings demonstrated that all three protein-bound CML digests with different MW can be absorbed in diverse absorption pathways by Caco-2 cell monolayer model. This research provided a theoretical basis for scientific evaluation of digestion and absorption of AGEs in food.

Application of Hydrothermal Synthesized Titanium Dioxide-Doped Multiwalled Carbon Nanotubes on Filtration Properties-Response Surface Methodology Study.

The success of any drilling activity mainly depends on the characteristics of the drilling fluid. Therefore, a high-performance drilling fluid is substantial for any drilling operation. During overbalance drilling operations, the drilling mud invades the permeable formations and causes the loss of circulation, which is responsible for nonproductive time events. Hence, the filtration characteristics of the drilling mud are an imperative property. The purpose of this study is to evaluate the filtration characteristics of water-based mud systems in the presence of polyanionic cellulose (PAC) and multiwalled carbon nanotubes (MWCNTs)/TiO2 nanoparticles. The nanoparticles were synthesized by using the hydrothermal technique. For the first time, a composite of MWCNTs and TiO2 has been utilized as a fluid loss control additive in the petroleum sector, marking a significant development in the field. The filtration properties of water-based mud were assessed at two concentrations (0.35 g and 3.5 g). Furthermore, based on the two levels (concentrations) and two factors (particles), the novel application of the central composite response surface design of experiment (CCD) was implemented. The results showed that the predicted model from CCD was in good agreement with the filter press experimental result with R 2 = 0.8446. Furthermore, based on the ANOVA analysis, the concentration of MWCNTs/TiO2 nanoparticles was the most significant parameter with p-value < 0.05. In addition, 10 out of 13 experimental points fall under the ±10% error window, thus indicating a higher accuracy of the regression model. The 2D interactive plots further show that the concentration of PAC is insignificant and has no considerable influence on fluid loss control, which was also validated by p-value > 0.05. The performance of MWCNTs/TiO2 nanoparticles is superior to PAC because these nanodimension particles plug the pore-spacing and block the permeation channels on the filter paper. However, the PAC, because of its long molecular chain, entangles around the pore spaces and plugs the microsize pores, which eventually reduces the filtration loss volume up to some extent. By observing the synergistic interaction between MWCNTs/TiO2 nanoparticles and PAC, this study develops valuable insights that assist in improving the performance of drilling fluid and minimizes the wellbore instability issues in the oil and gas sector.

Sequential high-dose methotrexate and cytarabine administration improves outcomes in real-world patients with primary central nervous system lymphoma: A report from the Australasian Lymphoma Alliance.

Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) (n = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) (n = 19, 10%), HD-MTX/Ara-C (n = 31, 16%), HD-MTX monotherapy (n = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m2 (range: 1-64 g/m2) and 12 g/m2 (0-32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS. Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.