Association between GLIM-diagnosed malnutrition and quality of life in older patients with cancer.

BACKGROUND: Older patients with cancer have a higher risk for malnutrition and impaired quality of life (QoL). The present study aimed to investigate the relationship between malnutrition diagnosed according to the Global Leadership Initiative Malnutrition (GLIM) criteria and QoL across various tumor types, and to evaluate the combined prognostic value of malnutrition and QoL in predicting survival among older patients with cancer. METHODS: This multicenter, observational cohort study included 5310 older patients with cancer and 2184 with malnutrition (moderate stage, n = 1023; severe stage, n = 1161). An empirical cumulative distribution curve was performed to illustrate the correlation between malnutrition and QoL. The primary objective was to investigate the association between malnutrition and QoL using logistic regression analysis. Survival analyses were performed to assess the combined prognostic value of malnutrition and QoL. RESULTS: The median age of the patients (66.9% male, 33.1% female) was 70 years (interquartile range [IQR] 67-74 years) years. The median QoL score was highest in patients without malnutrition (91.88 [IQR 84.44-97.44]), followed by those with moderate (86.15 [IQR 76.18-93.85) and severe (82.31 [IQR 69.87-91.11]) malnutrition. Logistics regression revealed that the risk for developing impaired QoL increased 1.98 (95% confidence interval [CI] 1.64-2.38; P < 0.001) and 2.33 (95% CI 1.93-2.81; P < 0.001) times in patients with moderate and severe malnutrition, respectively. Kaplan-Meier curves showed that QoL in combination with GLIM criteria demonstrated a significant discriminative performance for survival and served as an independent prognostic factor among older patients with cancer, especially for lung and gastric cancers. CONCLUSIONS: Malnutrition diagnosed according to the GLIM criteria was a predictor of impaired QoL. Additionally, the combination of QoL and malnutrition demonstrated utility for predicting survival outcomes in older patients with cancer.

From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma.

Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat's oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with "Rosetta stone"-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite's capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease.

Clinical features, genomic profiling, and outcomes of adult patients with unifocal Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. RESULTS: We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18-69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAFV600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7-211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. CONCLUSIONS: In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.

Daphnetin ameliorates PM2.5-induced airway inflammation by inhibiting NLRP3 inflammasome-mediated pyroptosis in CS-exposed mice.

Epidemiologic studies have shown that fine particulate matter 2.5 (PM2.5) exaggerates airway inflammation associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Daphnetin (Daph) is a natural compound with a variety of biological activities. At present, there are limited data on whether Daph can protect against cigarette smoke (CS)-induced chronic obstructive pulmonary disease (COPD) and PM2.5-CS-induced AECOPD. Therefore, this study systematically evaluated the effects of Daph on CS-induced COPD and PM2.5-CS-induced AECOPD and determined its mechanism of action. First, in vitro studies showed that PM2.5 exacerbated cytotoxicity and NLRP3 inflammasome-mediated pyroptosis induced by low-dose cigarette smoke extracts (CSE). However, the effect was reversed by si-NLRP3 and MCC950. Similar results were obtained in PM2.5-CS-induced AECOPD mice. The results of the mechanistic studies suggested that blocking NLRP3 abolished PM2.5 combined with cigarette induced cytotoxicity, lung damage, NLRP3 inflammasome activation and pyroptosis in vitro and in vivo. Second, Daph suppressed the expression of NLRP3 inflammasome and pyroptosis in BEAS-2B cells. Third, Daph significantly protected against CS-induced COPD and PM2.5-CS-induced AECOPD by inhibiting the NLRP3 inflammasome and pyroptosis in mice. Our findings identified the NLRP3 inflammasome as a critical contributor to PM2.5-CS-induced airway inflammation, and Daph as a negative regulator of NLRP3-mediated pyroptosis, which has implications for the pathophysiology of AECOPD.

Primary Malignant Brain Tumors following Systemic Malignancies: A Population-Based Analysis.

BACKGROUND: Several reports have described glioma following different cancers. We assessed the prevalence of primary malignant brain tumors afterward systemic malignancies in patients in the USA based on Surveillance, Epidemiology, and End Results (SEER) program data. METHODS: The detailed data of patients with primary malignant brain tumors following an initial malignant tumor outside the central nervous system were extracted from SEER. Descriptive statistics were used to analyze patient demographic and clinical characteristics. We also extracted standardized incidence ratios (SIRs) stratified by age, race, sex, history of radiation or chemotherapy, histology findings, and primary cancer site. RESULTS: We identified 5,212 patients diagnosed with primary malignant brain tumors following systemic malignancies. Most patients had prostate cancer, breast cancer, and skin melanoma as the primary cancer. The median duration between the first diagnosis of cancer and that of the subsequent malignant brain tumor was 53 months. Glioblastoma was the most common subsequent malignant brain tumor type. The prognosis after subsequent malignant brain tumor diagnosis was poor. The SIRs differed most by race, cancer site, and cancer type. Patients with acute lymphocytic leukemia had the highest risk of developing primary malignant brain tumors. CONCLUSION: Our study provides a comprehensive analysis of clinical data and the SIRs of patients with primary malignant brain tumors afterward other systemic malignancies. Genetic relationships might play a key role in subsequent malignant brain tumor origin. Our data provide directions for future studies exploring the hidden associations between systemic malignancies and primary malignant brain tumors.

Adult Langerhans cell histiocytosis with thyroid gland involvement: clinical presentation, genomic analysis, and outcome.

The present study aims to evaluate the characteristics and treatment outcomes of adult Langerhans cell histiocytosis (LCH) patients with thyroid involvement. We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our center between January 2001 and December 2021. At the time of diagnosis, only one patient was classified as having single-system LCH, and 35 patients were classified as having multisystem (MS) LCH. Three patients had coexisting papillary thyroid carcinoma. Patients with thyroid gland involvement had higher frequencies of pituitary (88.6% vs. 53.4%, P < 0.001), liver (45.7% vs. 20.7%, P = 0.003), and lymph node (54.3% vs. 31.6%, P = 0.012) involvement and a lower frequency of bone (45.7% vs. 72.0%, P = 0.003) involvement than patients without thyroid gland involvement. Sixteen patients had abnormal thyroid function, including nine patients with primary hypothyroidism, one patient with central hypothyroidism, and six patients with subclinical hypothyroidism. BRAFV600E, BRAF N486_P490, and MAP2K1 mutations were detected in 14.3%, 57.1%, and 7.1% of patients, respectively. After a 43-month median follow-up, none of the patients died, and 15 patients experienced reactivation. The median event-free survival was 37.5 months. Two of 6 patients with subclinical hypothyroidism had normal thyroid function, and 12 patients still had hypothyroidism after treatment. As the largest adult LCH cohort with thyroid gland involvement to date, we found that patients with thyroid gland involvement had different clinical characteristics, genetic profiles, and outcomes than patients without thyroid gland involvement.

Langerhans cell histiocytosis in adolescent patients: a single-centre retrospective study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid dendritic cell disorder frequently affecting children more than adults. The presentation of LCH varies with age, however, the clinical characteristics and genetic profiles of adolescent LCH remain elusive. To address the knowledge gap, we performed a single-centre retrospective study of 36 adolescent LCH patients aged between 14 and 17 years at Peking Union Medical College Hospital. RESULTS: At the time of diagnosis, 10 patients were classified as unifocal single system LCH (27.8%), 2 patients had pulmonary single system LCH (5.6%), 5 patients had multifocal single system LCH with bone involvement (13.9%), and 19 patients had multisystem LCH (52.8%). The most prevalent involvement in multisystem patients was the pituitary gland (78.9%), followed by the bone (42.1%), lung (42.1%), and lymph nodes (42.1%). Eight (42.1%) patients had risk organ involvement. BRAFN486_P490 was detected in 50% of patients who underwent next generation sequencing, and BRAFV600E was detected in one patient. Chemotherapies were the first line treatment in 24 patients. One patient died and thirteen patients relapsed during the follow-up. The estimated 5-year OS rate and EFS rate were 94.7% and 59.0%, respectively. CONCLUSIONS: In this study, we report a large series of adolescent LCH patients. The clinical characteristics of adolescent LCH patients may be close to adult LCH. Compared with pediatric cases, adolescent LCH tends to have more pituitary lesions and pulmonary involvement, fewer skin and hematopoietic involvement, a higher frequency of BRAF deletion mutation, and a lower frequency of BRAFV600E mutation.

Intermediate-dose cytarabine is an effective therapy for adults with non-Langerhans cell histiocytosis.

BACKGROUND: Non-Langerhans cell histiocytosis, including Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), indeterminate cell histiocytosis (ICH), and unclassified histiocytosis, is a rare disorder lacking a standard treatment strategy. We report our experience using intermediate-dose cytarabine as the first or subsequent therapy in non-Langerhans cell histiocytosis. RESULTS: Nine ECD patients, 5 RDD patients, 1 ICH patient and 1 unclassified histiocytosis patient were enrolled. Intermediate-dose cytarabine therapy was administered as 0.5-1.0 g/m2 of intravenous cytarabine every 12 h for 3 days every 5 weeks. The median age at cytarabine initiation was 47.5 years (range 18-70 years). The median number of cycles of cytarabine administered was 5.5 (range 2-6). The overall response rate (ORR) was 87.5% in the overall cohort, including 12.5% with complete response and 75.0% with partial response. One patient experienced disease recurrence 19 months after cytarabine therapy. The median follow-up duration for the entire cohort was 15.5 months (range 6-68 months). The estimated 2-year progression-free survival and overall survival rates were 85.6% and 92.3%, respectively. The most common toxicity was haematological adverse events, including grade 4 neutropenia and grade 3-4 thrombocytopenia. No treatment-related deaths occurred. CONCLUSIONS: Intermediate-dose cytarabine is an efficient treatment option for non-Langerhans cell histiocytosis patients, especially for those with CNS involvement.

Benefit of high-dose idarubicin as induction therapy in acute myeloid leukemia: a prospective phase 2 study.

Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.

Treatment outcomes and prognostic factors of patients with adult Langerhans cell histiocytosis.

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.

BNIP3 contributes to silibinin-induced DNA double strand breaks in glioma cells via inhibition of mTOR.

BNIP3 is found to eliminate cancer cells via causing mitochondrial damage and endoplasmic reticulum stress, but it remains elusive of its role in regulating DNA double strand breaks (DSBs). In this study, we find that silibinin triggers DNA DSBs, ROS accumulation and expressional upregulation of BNIP3 in glioma cells. Mitigation of ROS with antioxidant GSH significantly inhibits silibinin-induced DNA DSBs and glioma cell death. Then, we find knockdown of BNIP3 with SiRNA obviously prevents silibinin-induced DNA DSBs and ROS accumulation. Mechanistically, BNIP3 knockdown not only reverses silibinin-triggered depletion of cysteine and GSH via maintaining xCT level, but also abrogates catalase decrease. Notably, silibinin-induced dephosphorylation of mTOR is also prevented when BNIP3 is knocked down. Given that activated mTOR could promote xCT expression and inhibit autophagic degradation of catalase, our data suggest that BNIP3 contributes to silibinin-induced DNA DSBs via improving intracellular ROS by inhibition of mTOR.

External application of nitrogen alleviates toxicity of cadmium on poplars via starch and sucrose metabolism.

Phytoremediation technology can help achieve moderate cost and considerable effect with respect to the remediation of heavy metal (HM) pollution in soil and water. Many previous studies have suggested the role of nitrogen (N) in the alleviation of effects of HM on plants. Herein, we sought to determine the molecular mechanisms by which additional N supplementation mitigates cadmium (Cd) toxicity in poplars using a combination of physiological, transcriptomic and phosphoproteomic analyses. The application of N can alleviate the toxicity of Cd to Populus by reducing chlorophyll degradation, maintaining the stability of ions inside and outside the cell membrane and increasing the soluble sugar content. Plant samples from the control, Cd stress and Cd_N treatments were used for an integrated analysis of the transcriptome, as well as for phosphoproteomics analysis. Moreover, 1314 differentially expressed genes and 119 differentially expressed kinase genes were discovered. Application of additional N under Cd stress promoted the phosphorylation process. Furthermore, 51 significantly enriched phosphorylated protein sites and 23 differentially expressed kinases were identified using phosphoproteomic and proteomic analyses. Importantly, transcriptomic and phosphoproteomic analyses jointly determined that the application of N could activate corresponding gene expression [UDP-glucose-dehydrogenase (UGD), GAUT, PME, pectin lyase, UDP-glucose-pyrophosphorylase 2 (UGP2), sucrose phosphate synthase (SPS), SUS and SPP2] and protein phosphorylation (UGP2 and SPS) in the sugar and starch synthesis pathways, which promoted the synthesis of sucrose and soluble sugar and subsequently alleviated the damage caused by Cd.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Enhanced Anticancer Efficacy of Chemotherapy by Amphiphilic Y-Shaped Polypeptide Micelles.

Although the treatment modalities of cancers are developing rapidly, chemotherapy is still the primary treatment strategy for most solid cancers. The progress in nanotechnology provides an opportunity to upregulate the tumor suppression efficacy and decreases the systemic toxicities. As a promising nanoplatform, the polymer micelles are fascinating nanocarriers for the encapsulation and delivery of chemotherapeutic agents. The chemical and physical properties of amphiphilic co-polymers could significantly regulate the performances of the micellar self-assembly and affect the behaviors of controlled release of drugs. Herein, two amphiphilic Y-shaped polypeptides are prepared by the ring-opening polymerization of cyclic monomer l-leucine N-carboxyanhydride (l-Leu NCA) initiated by a dual-amino-ended macroinitiator poly(ethylene glycol) [mPEG-(NH2)2]. The block co-polypeptides with PLeu8 and PLeu16 segments could form spontaneously into micelles in an aqueous solution with hydrodynamic radii of 80.0 ± 6.0 and 69.1 ± 4.8 nm, respectively. The developed doxorubicin (DOX)-loaded micelles could release the payload in a sustained pattern and inhibit the growth of xenografted human HepG2 hepatocellular carcinoma with decreased systemic toxicity. The results demonstrated the great potential of polypeptide micellar formulations in cancer therapy clinically.

Discrepant antitumor efficacies of three CpG oligodeoxynucleotide classes in monotherapy and co-therapy with PD-1 blockade.

Unmethylated CpG oligodeoxynucleotides (ODNs) activate plasmacytoid dendritic cells (pDCs) and B cells to induce humoral and cellular immunity, and are under development for the treatment of multiple cancers. However, the specific differences in antitumor effects among the three CpG ODN classes when administered as a monotherapy or in co-therapy with the anti-PD-1 antibody are unclear. We compared the immunostimulatory effects in vitro and antitumor effects in a CT26 subcutaneous mouse tumor model among the three CpG ODN classes. We found that CpG-A slightly suppressed tumor growth but possessed no synergistic antitumor effects with the anti-PD-1 antibody. CpG-B at low doses significantly inhibited tumor growth and possessed synergistic antitumor effects with the anti-PD-1 antibody. A high dose of CpG-C was required to achieve antitumor effects comparable to those of CpG-B, which was consistent with the immunostimulatory effects in B-cell proliferation and TLR9-NF-κB activation. Importantly, CpG-C in combination with anti-PD-1 antibody inhibited tumor growth more quickly and effectively than CpG-B because CpG-B significantly upregulated PD-L1 expression on multiple host immune cells to promote tumor immune escape. Moreover, co-therapy increased the infiltration of effector memory T cells. In summary, CpG-B and CpG-C with different optimal concentrations possessed strong antitumor effects, while CpG-C was more rapid and effective for co-therapy with the anti-PD-1 antibody.

Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo.

Early pulmonary fibrosis after acute lung injury leads to poor prognosis and high mortality. Pterostilbene (Pts), a bioactive component in blueberries, possesses anti-inflammatory, antioxidative and antifibrotic properties. However, the effects of Pts on lipopolysaccharide (LPS)-induced pulmonary fibrosis are still unknown. In our study, the Pts group showed lower lung injury and fibrosis scores, and lower levels of hydroxyproline and protein (collagen I and transforming growth factor-ß) than the scores and levels in mice treated with LPS. MMP-1 was the degrading enzyme of collagen I and LPS caused the inhibition of MMP-1, disturbing the degradation of collagen. Additionally, Pts remarkably reversed the LPS-induced inhibition of interleukin-10 and the release of tumor necrosis factor-α, interleukin-6 and interleukin-1ß. In terms of cellular pathways, Pts treatment ameliorated LPS-activated nuclear factor kappa B (NF-κB) and NOD-like receptor NLRP3 signaling. Besides, LPS-induced low levels of A20 could be activated by Pts. In addition, Pts treatment reversed the high levels of Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl2-associated X protein (Bax) expression and the low levels of B cell lymphoma/lewkmia-2 (Bcl2) that had been induced by LPS. Moreover, oxidative stress is also involved in the pathogenesis of fibrosis. Our findings indicate that LPS injection triggered the production of myeloperoxidase (MPO) and malondialdehyde (MDA) and the depletion of superoxide dismutase (SOD) and glutathione (GSH), and that these effects were notably reversed by treatment with Pts. In addition, Pts induced the dissociation of Kelch-like epichlorohydrin-associated protein-1 (Keap-1) and NF-E2 related factor-2 (Nrf2) and the activation of downstream genes (heme oxygenase-1, NAD(P)H:quinine oxidoreductase, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier). In conclusion, oxidative stress, apoptosis and inflammation are involved in early pulmonary fibrosis and Pts exerts a protective effect by activating Keap-1/Nrf2, inhibiting caspase-dependent A20/NF-κB and NLRP3 signaling pathways.

Near-infrared-IIb probe affords ultrahigh contrast inflammation imaging.

Deep tissue imaging in the near-infrared II (NIR-II) window with significantly reduced tissue autofluorescence and scattering provides an important modality to visualize various biological events. Current commercially used contrast agents in the near-infrared spectrum suffer from severe photobleaching, high tissue scattering, and background signals, hampering high-quality in vivo bioimaging, particularly in small animals. Here, we applied a NIR-IIb quantum dot (QD) probe with greatly suppressed photon scattering and zero autofluorescence to map inflammatory processes. Two-layer surface modification by a combination of amphiphilic polymer and mixed linear and multi-armed polyethylene glycol chains prolonged probe circulation in vivo and improved its accumulation in the inflammation sites. Compared to indocyanine green, a widely applied dye in the clinic, our QD probe showed greater photostability and capacity for deeper tissue imaging with superior contrast. The longer circulation of QDs also improved vessel imaging, which is vital for better understanding of biological mechanisms of the inflammation microenvironment. Our proposed NIR-IIb in vivo imaging modality proved effective for the visualization of inflammation in small animals, and its use may be extended in future to studies of immunity and cancer.

Chromatin-regulating genes are associated with postoperative prognosis and isocitrate dehydrogenase mutation in astrocytoma.

BACKGROUND: Abnormality in chromatin regulation is a major determinant in the progression of multiple neoplasms. Astrocytoma is a malignant histologic morphology of glioma that is commonly accompanied by chromatin dysregulation. However, the systemic interpretation of the expression characteristics of chromatin-regulating genes in astrocytoma is unclear. METHODS: In this study, we investigated the expression profile of chromatin regulation genes in 194 astrocytoma patients sourced from The Cancer Genome Atlas (TCGA) database. The relevance of gene expression and postoperative survival outcomes was assessed. RESULTS: Based on the expression patterns of chromatin regulation genes, two primary clusters and three subclusters with significantly different survival outcomes were identified. The patients in cluster_1 (or subcluster_1) had a poorer prognosis than the other groups, and this particular cohort were older, with a more advanced grade of tumor and isocitrate dehydrogenase-wildtype distribution. Detection of the differentially expressed genes revealed that the group with poor prognosis was characterized by downregulation of H2AFY2, WAC, HDAC5, ZMYND11, TET1, SATB1, and MYST4, and overexpression of EYA4. Moreover, all eight genes were significantly correlated with overall survival (OS) in astrocytoma. Age-associated genes were investigated and the expression levels of EYA4, TET1, SATB1, WAC, ZMYND11, and H2AFY2 were found to be closely correlated with advanced age. Regression analysis suggested that the expression levels of H2AFY2, HILS1, EYA1, EYA4, and KDM5B were independently associated with IDH mutation status. The differential expressions of 34 common genes were significantly associated with age, grade, and IDH mutant. CONCLUSIONS: The study revealed that the expression pattern of chromatin regulation genes was significantly associated with postoperative prognosis in astrocytoma. Moreover, the differential expression of particular genes was strongly associated with clinical characteristics such as age, grade, and IDH subtype. These results suggest that the genes involved in chromatin regulation play important roles in the biological process of astrocytoma progression, and these molecules could potentially serve as therapeutic targets in astrocytoma.