circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Chitiniphilus purpureus sp. nov., a novel chitin-degrading bacterium isolated from crawfish pond sediment.

A novel Gram-stain-negative, curved rod-shaped, motile and chitin-degrading strain, designated CD1T, was isolated from crawfish pond sediment in Caidian District (30° 58' N 114° 03' E), Wuhan City, Hubei Province, PR China. Growth of this strain was observed at 15-40°C (optimum between 28 and 30 °C), at pH 7.0-9.0 (optimum between pH 7.0 and 8.0) and with 0-1 % (w/v) NaCl (optimum at 0 %). With respect to the 16S rRNA gene sequences, strain CD1T had the highest similarity (96.91-97.25 %) to four type strains of the genera 'Chitinolyticbacter' and Chitiniphilus within the family Chitinibacteraceae. The phylogenetic trees based on genome sequences and 16S rRNA gene sequences indicated that strain CD1T was close to members of these two genera, in particular to the genus Chitiniphilus. The genomic DNA G+C content of strain CD1T was 64.8 mol%. The average nucleotide identity and the Genome-to-Genome Distance Calculator results showed low relatedness (below 95 and 70 %, respectively) between strain CD1T and the closely related type strains. Ubiquinone-8 was the predominant quinone. The major cellular fatty acids were C10 : 0, C16 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile was composed of a mixture of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified lipids, two unidentified phospholipids, two unidentified aminolipids and an unidentified aminoglycolipid. On the basis of the evidences presented in this study, strain CD1T represents a novel species of the genus Chitiniphilus, for which the name Chitiniphilus purpureus sp. nov. is proposed, with strain CD1T (=CCTCC AB 2022395T=KCTC 92850T) as the type strain.

Transcriptional determinants of lipid mobilization in human adipocytes.

Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins. On the basis of its strong relationship with multiple readouts of lipolysis in patient samples, we performed mechanistic studies on one hit, ZNF189, which encodes the zinc finger protein 189. Using mass spectrometry and chromatin profiling techniques, we show that ZNF189 interacts with the tripartite motif family member TRIM28 and represses the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). The regulation of lipid mobilization by ZNF189 requires PDE1B2, and the overexpression of PDE1B2 is sufficient to attenuate hormone-stimulated lipolysis. Thus, our work identifies the ZNF189-PDE1B2 axis as a determinant of human adipocyte lipolysis and highlights a link between chromatin architecture and lipid mobilization.

Degradable PDA@PNIPAM-TA Nanocomposites for Temperature- and NIR light-Controlled Pesticide Release.

Controlled pesticide delivery systems offer many distinctive advantages over conventional pesticide formulations. In this work, degradable poly(N-isopropylacrylamide) (PNIPAM)-tannic acid (TA) microgels and multifunctional PDA@PNIPAM-TA nanocomposites were prepared in a high-gravity rotating packed bed reactor (RPB) for smart pesticide delivery and release. The as-prepared microgels and nanocomposites showed reversible temperature-dependent swelling/deswelling behavior and irreversible pH-induced degradation. A dynamic contact angle test suggested that the introduction of TA and PDA into the PNIPAM matrix could enhance foliar adhesion and deposition efficiency. The nanocomposites were further used for the encapsulation and delivery of imidacloprid (IMI) to protect it from rapid photolysis and improve its pest-control efficiency. Their thermoresponsive behavior as well as pesticide loading capacity could be tuned by tailoring the PNIPAM-TA shell thickness, which could be varied by the NIPAM amount. The release rate of IMI from the core/shell nanocomposites was positively correlated with environmental temperature and near-infrared (NIR) light, which was adaptive to the positive temperature-dependent toxicity correlation of IMI and the increasing trend of pests under high temperature. The cumulative release of IMI was 23.5% at 25 °C, while it was 81.2% at 40 °C after 24 h of incubation, and the release rate was greatly enhanced under NIR irradiation. The results indicated that the facile control of pesticide release could be realized by regulating environmental conditions. This work also provides an idea for using high-gravity technology to conveniently construct a smart, effective, and environmentally friendly pesticide delivery system for sustainable crop protection.

Diesel exhaust particles exposure induces liver dysfunction: Exploring predictive potential of human circulating microRNAs signature relevant to liver injury risk.

Diesel exhaust particles (DEP) pollution should be taken seriously because it is an extensive environmental and occupational health concern. Exploring early effect biomarkers is crucial for monitoring and managing DEP-associated health risk assessment. Here, we found that serum levels of 67 miRNAs were dysregulated in DEP exposure group. Notably, 20 miRNAs were identified as each having a significant dose-response relationship with the internal exposure level of DEP. Further, we revealed that the DEP exposure could affect the liver function of subjects and that 7 miRNAs (including the well-known liver injury indicator, miR-122-5p) could serve as the novel epigenetic-biomarkers (epi-biomarkers) to reflect the liver-specific response to the DEP exposure. Importantly, an unprecedented prediction model using these 7 miRNAs was established for the assessment of DEP-induced liver injury risk. Finally, bioinformatic analysis indicated that the unique set of miRNA panel in serum might also contribute to the molecular mechanism of DEP exposure-induced liver damage. These results broaden our understanding of the adverse health outcomes of DEP exposure. Noteworthy, we believe this study could shed light on roles and functions of epigenetic biomarkers from environmental exposure to health outcomes by revealing the full chain of exposure-miRNAs-molecular pathways-disease evidence.

Unmet supportive care needs of breast cancer survivors: a systematic scoping review.

BACKGROUND: Breast cancer is the most common type of cancer in women worldwide. Though improved treatments and prolonged overall survival, breast cancer survivors (BCSs) persistently suffer from various unmet supportive care needs (USCNs) throughout the disease. This scoping review aims to synthesize current literature regarding USCNs among BCSs. METHODS: This study followed a scoping review framework. Articles were retrieved from Cochrane Library, PubMed, Embase, Web of Science, and Medline from inception through June 2023, as well as reference lists of relevant literature. Peer-reviewed journal articles were included if USCNs among BCSs were reported. Inclusion/exclusion criteria were adopted to screen articles' titles and abstracts as well as to entirely assess any potentially pertinent records by two independent researchers. Methodological quality was independently appraised following Joanna Briggs Institute (JBI) critical appraisal tools. Content analytic approach and meta-analysis were performed for qualitative and quantitative studies respectively. Results were reported according to the PRISMA extension for scoping reviews. RESULTS: A total of 10,574 records were retrieved and 77 studies were included finally. The overall risk of bias was low to moderate. The self-made questionnaire was the most used instrument, followed by The Short-form Supportive Care Needs Survey questionnaire (SCNS-SF34). A total of 16 domains of USCNs were finally identified. Social support (74%), daily activity (54%), sexual/intimacy (52%), fear of cancer recurrence/ spreading (50%), and information support (45%) were the top unmet supportive care needs. Information needs and psychological/emotional needs appeared most frequently. The USCNs was found to be significantly associated with demographic factors, disease factors, and psychological factors. CONCLUSION: BCSs are experiencing a large number of USCNs in fearing of cancer recurrence, daily activity, sexual/intimacy, psychology and information, with proportions ranging from 45% to 74%. Substantial heterogeneity in study populations and assessment tools was observed. There is a need for further research to identify a standard evaluation tool targeted to USCNs on BCSs. Effective interventions based on guidelines should be formulated and conducted to decrease USCNs among BCSs in the future.

Development of a prognostic nomogram based on objective blood test data for patients with advanced cancer undergoing palliative care.

BACKGROUND: Accurate estimation of prognosis can help provide early palliative care to patients. However, few studies have developed nomograms that are totally based on objective blood test parameters. The current study constructed a simple and objective prognostic nomogram and validated the model using advanced cancer patients. METHODS: A total of 245 patients were retrospectively analyzed (training sample, n=162; validation sample, n=54), from January 2020 to December 2021. Blood test and demographic data were collated. Cox proportional hazard regression was performed to identify the independent factors, which were built into a nomogram to visualize the probability of patient survival within 30 days. Calibration and discrimination of the model was assessed. The decision curve analysis (DCA) was developed to summarize the performance of the model in supporting decision making. RESULTS: The median survival was 17.0 [8, 37] days and 21.0 [10, 46] days for the training set and the validation set, respectively. Serum calcium (>2.65 mmol/L), neutrophil count (<2 mmol/L and >7 mmol/L), urea (>7.6 nmol/L), and glutamic oxalacetic transaminase (>40 U/L) were identified and an easily obtained nomogram predicting the 30-day probability of mortality was developed. The nomogram model had adequate discrimination and calibration. The Harrell's concordance index (C-index) of the training set and validation set was 0.69 and 0.71, respectively, while the values of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were 0.76 and 0.70, respectively. CONCLUSIONS: A simple and objective prognostic nomogram model for predicting the 30-day survival of patients with advanced cancer was developed and validated, with adequate calibration and discrimination. It is expected to guide practical prognosis evaluation in the clinical setting. Further validation is still required in a prospective, multicenter, and large sample study.

Genomic Characterization Revealed PM2.5-Associated Mutational Signatures in Lung Cancer Including Activation of APOBEC3B.

Fine particulate matter (PM2.5) exposure causes DNA mutations and abnormal gene expression leading to lung cancer, but the detailed mechanisms remain unknown. Here, analysis of genomic and transcriptomic changes upon a PM2.5 exposure-induced human bronchial epithelial cell-based malignant transformed cell model in vitro showed that PM2.5 exposure led to APOBEC mutational signatures and transcriptional activation of APOBEC3B along with other potential oncogenes. Moreover, by analyzing mutational profiles of 1117 non-small cell lung cancers (NSCLCs) from patients across four different geographic regions, we observed a significantly higher prevalence of APOBEC mutational signatures in non-smoking NSCLCs than smoking in the Chinese cohorts, but this difference was not observed in TCGA or Singapore cohorts. We further validated this association by showing that the PM2.5 exposure-induced transcriptional pattern was significantly enriched in Chinese NSCLC patients compared with other geographic regions. Finally, our results showed that PM2.5 exposure activated the DNA damage repair pathway. Overall, here we report a previously uncharacterized association between PM2.5 and APOBEC activation, revealing a potential molecular mechanism of PM2.5 exposure and lung cancer.

Sphingobium nicotianae sp. nov., isolated from tobacco soil.

Bacterial strain H33T was isolated from tobacco plant soil and was characterized using a polyphasic taxonomy approach. Strain H33T was a Gram-stain-negative, rod-shaped, non-motile and strictly aerobic bacterium. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of the up-to-date bacterial core gene set (92 protein clusters) indicated that H33T belongs to the genus Sphingobium. Strain H33T showed the highest 16S rRNA gene sequence similarity to Sphingobium xanthum NL9T (97.2%) and showed 72.3-80.6 % average nucleotide identity and 19.7-29.2 % digital DNA-DNA hybridization identity with the strains of other species of the genus Sphingobium. Strain H33T grew optimally at 30°C, pH 7 and could tolerate 0.5 % (w/v) NaCl. The isoprenoid quinones were ubiquinone-9 (64.1%) and ubiquinone-10 (35.9%). Spermidine was the major polyamine. The major fatty acids of H33T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile consisted of a mixture of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid, two unidentified lipids, two unidentified glycolipids, two unidentified aminoglycolipids and an unidentified phospholipid. The genomic DNA G+C content of H33T was 64.9 mol%. Based on the phylogenetic and phenotypic data, H33T was considered a representative of a novel species in the genus Sphingobium. We propose the name Sphingobium nicotianae sp. nov., with H33T (=CCTCC AB 2022073T=LMG 32569T) as the type strain.

Near-infrared fluorescence-assisted thoracoscopic diverticulectomy of esophageal diverticulum: a case report.

BACKGROUND: Esophageal diverticulum is a rare condition that requires treatment only when symptoms are present. Surgery has been considered to be the only curative option for symptomatic cases. The most popular procedure is diverticulectomy. Clear and intact exposure of the diverticulum's neck is the basis for safe and effective diverticulectomy. CASE PRESENTATION: We herein report a case of a 57 year-old woman with an epiphrenic diverticulum. VATS diverticulectomy was scheduled. To better identify the diverticulum neck, we injected indocyanine green (ICG) into the diverticulum through the endoscopic channel, and the diverticulum wall and neck were clearly visible under near-infrared (NIR) fluorescence. With the help of this method, diverticulectomy was successfully performed. CONCLUSION: This case shows that NIR fluorescence with ICG is safe, simple and reliable and can be used for diverticulectomy.

Croceibacterium selenioxidans sp. nov., isolated from seleniferous soil.

A Gram-negative, aerobic bacterial strain, designated LX-88T, was isolated from seleniferous soil in Enshi, Hubei Province, PR China. Strain LX-88Toxidized elemental selenium to selenite, and produced carotenoids but not bacteriochlorophyll. The isolate grew optimally at 28 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysies of the organism's 16S rRNA and bacterial core gene set sequences indicated that LX-88T belongs to the genus Croceibacterium, and has the highest degree of 16S rRNA gene sequence similarity to Croceibacterium soli MN-1T (97.4 %). The LX-88T genome was 3.4 Mbp and had a G+C content of 63.6 mol%. The average nucleotide identity and digital DNA-DNA hybridization values showed low relatedness (below 95 and 70 %, respectively) between strain LX-88T and other strains in the genus Croceibacterium. Ubiquinone-10 was the predominant quinone. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acid was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). These physiological and biochemical tests facilitated the differentiation of strain LX-88T from other members of the genus Croceibacterium. The results of this multifaceted taxonomic study indicate that strain LX-88T represents a novel species in the genus Croceibacterium, for which the name Croceibacterium selenioxidans sp. nov. is proposed. The type strain is LX-88T (=MCCC 1K08007T=LMG 32570T).

Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in nine major cities of China, 2016-2020: a retrospective observational study based on inpatient and outpatient hospital data.

OBJECTIVES: It is unclear whether the use of antineoplastic drugs for patients with lung cancer in China has changed after the implementation of the national drug price negotiation in 2016 and continual update of clinical guidelines. This study aims to evaluate the trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in major cities of China. DESIGN: We conducted a retrospective observational study using data from January 2016 to December 2020. SETTING: This study used prescription records based on inpatient and outpatient hospital data from 97 hospitals in 9 major cities of China. PARTICIPANTS: A total of 218 325 antineoplastic drug prescriptions in patients with lung cancer were retrospectively collected from the Hospital Prescription Analysis Cooperative Project during the study period. OUTCOME MEASURES: Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer. RESULTS: The yearly antineoplastic prescriptions increased by 85.6% from 28 594 in 2016 to 53 063 in 2020 (Z=1.71, p=0.086). Significant increases were seen in the prescriptions for protein kinase inhibitors (PKIs) and monoclonal antibodies (mAbs), whereas significant decreases were observed in antimetabolites, plant alkaloids and platinum compounds. The yearly cost increased progressively by 145.0% from ¥113.6 million in 2016 to ¥278.3 million in 2020 (Z=2.20, p=0.027). The top three anticancer drug classes in terms of total cost were PKIs, antimetabolites and mAbs. In prescribing patterns of antineoplastic agents for lung cancer, monotherapy, and triple or more drug combinations gradually increased, while dual combinations decreased significantly from 30.8% to 19.6%. CONCLUSIONS: Prescription practices among patients with lung cancer in China underwent major changes during the study period. The observed trends can aid in understanding the present medication use status of patients with lung cancer in China and provide information for future drug management.

Pharmacovigilance-based drug repurposing: searching for putative drugs with hypohidrosis or anhidrosis adverse events for use against hyperhidrosis.

BACKGROUND: Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing. OBJECTIVES: We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents. METHODS: In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined. RESULTS: There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation. CONCLUSIONS: Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.

Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity.

The advantage of oncolytic viruses (OV) in cancer therapy is their dual effect of directly killing tumours while prompting anti-tumour immune response. Oncolytic parapoxvirus ovis (ORFV) and other OVs are thought to induce apoptosis, but apoptosis, being the immunogenically inert compared to other types of cell death, does not explain the highly inflamed microenvironment in OV-challenged tumors. Here we show that ORFV and its recombinant therapeutic derivatives are able to trigger tumor cell pyroptosis via Gasdermin E (GSDME). This effect is especially prominent in GSDME-low tumor cells, in which ORFV-challenge pre-stabilizes GSDME by decreasing its ubiquitination and subsequently initiates pyroptosis. Consistently, GSDME depletion reduces the proportion of intratumoral cytotoxic T lymphocytes, pyroptotic cell death and the success of tumor ORFV virotherapy. In vivo, the OV preferentially accumulates in the tumour upon systemic delivery and elicits pyroptotic tumor killing. Consequentially, ORFV sensitizes immunologically 'cold' tumors to checkpoint blockade. This study thus highlights the critical role of GSDME-mediated pyroptosis in oncolytic ORFV-based antitumor immunity and identifies combinatorial cancer therapy strategies.

Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4.

The Th2 cytokine interleukin 4 (IL4) promotes macrophage differentiation into alternative subtypes and plays important roles in physiology, in metabolic and inflammatory diseases, in cancer and in tissue regeneration. While the regulatory transcription factor networks governing IL4 signaling are already well-characterized, it is currently less understood which transcriptional coregulators are involved and how they operate mechanistically. In this study, we discover that G protein pathway suppressor 2 (GPS2), a core subunit of the HDAC3 corepressor complex assembled by SMRT and NCOR, represses IL4-dependent enhancer activation in mouse macrophages. Our genome-wide and gene-specific characterization revealed that, instead of directly repressing STAT6, chromatin-bound GPS2 cooperates with SMRT and NCOR to antagonize enhancer activation by lysine demethylase 1A (KDM1A, LSD1). Mechanistically, corepressor depletion increased KDM1A recruitment to enhancers linked to IL4-induced genes, accompanied by demethylation of the repressive histone marks H3K9me2/3 without affecting H3K4me1/2, the classic KDM1A substrates for demethylation in other cellular contexts. This in turn caused enhancer and gene activation already in the absence of IL4/STAT6 and sensitized the STAT6-dependent IL4 responsiveness of macrophages. Thus, our work identified with the antagonistic action of a GPS2-containing corepressor complex and the lysine demethylase KDM1A a hitherto unknown epigenetic corepressor-coactivator switching mechanism that governs alternative macrophage activation.

Prevalence of psychological symptoms and associated risk factors among nurses in 30 provinces during the COVID-19 pandemic in China.

Background: With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recognition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health consequences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associated factors among nurses in China. Methods: We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom. Findings: A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial proportion of nurses reported symptoms of burnout (34%), depression (55·5%), and anxiety (41·8%). In line with the disproportionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression. Interpretation: Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating countermeasures to safeguard nurses' health. Funding: The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17].

Oral microbiome characteristics in patients with pediatric solid tumor.

Background: Pediatric solid tumor, the abnormal proliferation of solid tissues in children resulting in the formation of tumors, represent a prevailing malignant ailment among the younger population. Extensive literature highlights the inseparable association linking oral microbiome and adult tumors, but due to differences in age of onset, characteristics of onset, etc., there are many differences between Pediatric solid tumors and adult tumors, and therefore, studying the relationship between Pediatric solid tumor and the oral microbiota is also essential. Methods: To unravel the distinct characteristics of the oral microbiota within Pediatric solid tumor patients, 43 saliva samples, encompassing 23 Pediatric solid tumor patients and 20 healthy controls, were diligently procured. A meticulous screening process ensued, and conducted microbial MiSeq sequencing after screening. Results: We documented the oral microbiome attributes among pediatric diagnosed with solid tumors (PST), and meanwhile, we observed a significant trend of decreased oral microbiota diversity in the pediatric solid tumor group. There were notable disparities in microbial communities observed between the two groups, 18 genera including Veillonellaceae, Firmicutes unclassified, Coriobacteriia, Atopobiaceae, Negativicutes, were significantly enriched in PST patients, while 29 genera, including Gammaproteobacteria, Proteobacteria, Burkholderiales, Neisseriaceae, were dominant in the HCs group. It was found that PST group had 16 gene functions, including Amino acid metabolism, Cysteine and methionine metabolism, Photosynthesis antenna proteins, Arginine and proline metabolism, and Aminoacyl tRNA biosynthesi, were significantly dominant, while 29 gene functions that prevailed in HCs. Conclusion: This study characterized the oral microbiota of Pediatric solid tumor patients for the first time, and importantly, targeted biomarkers of oral microbiota may serve as powerful and non-invasive diagnostic tools for pediatric solid tumor patients.

CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin.

BACKGROUND: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. METHODS: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. RESULTS: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. CONCLUSIONS: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody-based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.

Development and validation of a machine learning model to predict venous thromboembolism among hospitalized cancer patients.

Objective: Hospitalized cancer patients are at high risk of venous thromboembolism (VTE). However, no predictive model has been specifically developed for this population. Machine learning (ML) is advantageous for model development. This study was aimed at developing predictive models using three different ML algorithms and logistic regression for VTE risk among hospitalized cancer patients and comparing their predictive performance. Methods: A retrospective case-control study was conducted on hospitalized cancer patients at Hunan Cancer Hospital, China, between October 1, 2021, and February 30, 2022. Patients diagnosed with vein thrombosis before or after admission were excluded. Patient, tumor, treatment, and laboratory indicator information was obtained from the hospital information system. The data were randomly split into distributions of 80% for training and 20% for testing. Logistic regression and three ML algorithms-the support vector machine, random forest, and extreme gradient boosting (XGBoost)-were used to develop the models. Model performance was compared using F1, G-mean, area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall rate, and specificity. Feature rankings were achieved based on the permutation scores of the selected features in the optimal model. Results: A total of 1100 patients (mean [SD] age, 54.75 [11.08] years; 485 [44.09%] male) were included in this study. There were 340 patients (30.9%) in the VTE group. The XGBoost model achieved the best performance with the following evaluation metrics: F1 (0.750), G-mean (0.816), AUROC (0.818), accuracy (0.845), precision (0.750), recall rate (0.750), and specificity (0.888). D-dimer level, diabetes, hypertension, pleural metastasis, and hematological malignancies were identified as the five most significant features of the XGBoost model. Conclusions: Four predictive models were developed using ML algorithms. The XGBoost model was the optimal predictive model compared with the other three models. This study indicates that ML may play an important role in VTE risk estimation among hospitalized patients with cancer and provides a reference for thromboprophylaxis.

Preparation of pyrrolidinyl diglycolamide bonded silica particles and its rare earth separation properties.

The separation of rare earth elements by solid phase containing diglycolamide-type ligands is a hot topic. In this study, 2-[2-oxo-2-(1-pyrrolidinyl)ethoxy]acetic acid (PYRDGA) was synthesized and attached to the silica. The binding strength of SiO2@PYRDGA for rare earths showed a single increasing trend with the radius of rare earth atoms. IR and XPS spectra demonstrated that carbonyl oxygen and ether bond oxygen are binding sites for rare earth ions. SiO2@PYRDGA was used for the chromatographic separation of REEs, and the primary separation of 16 REEs was achieved at pH = 2.0 using HNO3 solution as the eluent, and La, Ce, Pr, Nd, Sm, and Eu reached the baseline separation level.