Challenging pitfalls in frozen section pathology: a case of mandible ghost cell odontogenic carcinoma and the literature review.

BACKGROUND: Ghost cell odontogenic carcinoma (GCOC) is a rare malignancy characterized by the presence of ghost cells, preferably in the maxilla. Only slightly more than 50 case reports of GCOC have been documented to date. Due to the rarity of this tumor and its nonspecific clinical criteria, there is a heightened risk of misdiagnosis in clinical examination, imaging findings, and pathology interpretation. CASE PRESENTATION: A 50-year-old male patient presented to the hospital due to experiencing pain in his lower front teeth while eating for the past 2 months. Upon examination, a red, hard, painless mass was found in his left lower jaw, measuring approximately 4.0 cm × 3.5 cm. Based on the malignant histological morphology of the tumor and the abundant red-stained keratinized material, the preoperative frozen section pathology misdiagnosed it as squamous cell carcinoma (SCC). The surgical resection specimen pathology via paraffin section revealed that the tumor was characterized by round-like epithelial islands within the fibrous interstitium, accompanied by a large number of ghost cells and some dysplastic dentin with infiltrative growth. The malignant components displayed marked heterogeneity and mitotic activity. Additionally, a calcified cystic tumor component of odontogenic origin was observed. Hemorrhage, necrosis, and calcifications were present, with a foreign body reaction around ghost cells. Immunoreactivity for ß-catenin showed strong nuclear positivity in tumor cells, while immunostaining was completely negative for p53. The Ki67 proliferation index was approximately 30-40%. The tumor cells exhibited diffuse CK5/6, p63, and p40 immunoreactivity, with varying immunopositivity for EMA. Furthermore, no BRAFV600E mutation was identified by ARMS-PCR. The final pathology confirmed that the tumor was a mandible GCOC. CONCLUSION: We have reported and summarized for the first time the specific manifestations of GCOC in frozen section pathology and possible pitfalls in misdiagnosis. We also reviewed and summarized the etiology, pathological features, molecular characteristics, differential diagnosis, imaging features, and current main treatment options for GCOC. Due to its rarity, the diagnosis and treatment of this disease still face certain challenges. A correct understanding of the pathological morphology of GCOC, distinguishing the ghost cells and the secondary stromal reaction around them, is crucial for reducing misdiagnosis rates.

Rapid detection of monkeypox virus and differentiation of West African and Congo Basin strains using endonuclease restriction-mediated real-time PCR-based testing.

The ongoing multi-country outbreak of monkeypox virus (MPXV) has continuously attracted global attention, highlighting the critical need for timely and accurate methods to detect MPXV and differentiate its clades. Herein, we devised a novel multiplex ET-PCR (endonuclease restriction-mediated real-time PCR) assay that integrates PCR amplification, restriction endonuclease cleavage and real-time fluorescence detection to diagnose MPXV infection and distinguish the Congo Basin and West African MPXV strains. In the MPXV ET-PCR system, three sets of specific primers were designed for MPXV, Congo Basin and West African strains. A short sequence, which could be recognized by restriction endonuclease enzyme BstUI, was added to the 5'end of amplification primers. Then, the modified primers were assigned different reporter dyes and corresponding quenching dyes to each of the three targets, enabling real-time fluorescence reporting of the results and multiplex detection. The designed assay enabled the detection of single or three targets in a single tube, with excellent specificity and analytical sensitivity in terms of plasmid and pseudotyped virus. Moreover, the clinical feasibility of our assay was validated using artificially simulated plasma, nasopharyngeal swab and skin swab samples. In conclusion, the multiplex ET-PCR assay devised here had the advantages of simple primer design, cost-effectiveness, low contamination risk, excellent sensitivity, high specificity and multiplex detection, making it a valuable and dependable tool for curbing the extensive spread of MPXV.

Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.

Cost effectiveness of implantable cardioverter defibrillators for 1.5 primary prevention of sudden cardiac arrest in China: an analysis from the Improve SCA study.

OBJECTIVES: Implantable cardioverter defibrillator (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) is underutilized in developing countries. The Improve SCA study has identified a subset of 1.5 primary prevention (1.5PP) patients with a higher risk of SCA and a significant mortality benefit from ICD therapy. From the perspective of China's healthcare system, we evaluated the cost-effectiveness of ICD therapy vs. no ICD therapy among 1.5PP patients with a view to informing clinical and policy decisions. METHODS: A published Markov model was adjusted and verified to simulate the course of the disease and describe different health states of 1.5PP patients. The patient characteristics, mortality, utility and complication estimates were obtained from the Improve SCA study and other literature. Cost inputs were sourced from government tender prices, medical service prices and clinical experts' surveys in 9 Chinese public hospitals. For both ICD and no ICD therapy, the total medical costs and quality-adjusted life-years (QALYs) were modelled over a lifetime horizon and the incremental cost-effectiveness ratio (ICER) was calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. We used the willingness-to-pay (WTP) threshold recommended by China Guidelines for Pharmacoeconomic Evaluations, one to three times China's GDP per capita (CNY85,698-CNY257,094) in 2022 Chinese Yuan. RESULTS: The incremental cost effectiveness ratio (ICER) of ICD therapy compared to no ICD therapy is 139,652 CNY/QALY, which is about 1-2 times China's GDP per capita. The probability that ICD therapy is cost effective was 92.1%. Results from sensitivity analysis supported the findings of the base case. CONCLUSIONS: ICD therapy compared to no ICD therapy is cost-effective for the 1.5PP patients in China.

Microbial response and recovery strategy of the anammox process under ciprofloxacin stress from pure strain and consortia perspectives.

Ciprofloxacin (CIP) poses a high risk of resistance development in water environments. Therefore, comprehensive effects and recovery strategies of CIP in anaerobic ammonia oxidation (anammox) process were systematically elucidated from consortia and pure strains perspectives. The anammox consortia was not significantly affected by the stress of 10 mg L-1 CIP, while the higher concentration (20 mg L-1) of CIP caused a dramatic reduction in the nitrogen removal performance of anammox system. Simultaneously, the abundances of dominant functional bacteria and corresponding genes also significantly decreased. Such inhibition could not be mitigated by the recovery strategy of adding hydrazine and hydroxylamine. Reducing nitrogen load rate from 5.1 to 1.4 kg N m-3 d-1 promoted the restoration of three reactors. In addition, the robustness and recovery of anammox systems was evaluated using starvation and shock strategies. Simultaneously, antibiotic resistance genes and key metabolic pathways of anammox consortia were upregulated, such as carbohydrate and energy metabolisms. In addition, 11 pure stains were isolated from the anammox system and identified through phylogenetic analysis, 40 % of which showed multidrug resistance, especially Pseudomonas. These findings provide deep insights into the responding mechanism of anammox consortia to CIP stress and promote the application of anammox process for treating wastewater containing antibiotics.

Comprehensive analysis of histone acetylation-related genes in glioblastoma and lower-grade gliomas: Insights into drug sensitivity, molecular subtypes, immune infiltration, and prognosis.

OBJECTIVES: The purpose of this research was to study the impact of histone acetylation on glioblastoma multiforme (GBM) and lower-grade gliomas (LGG) and its potential implications for patient prognosis. We aimed to assess the histone acetylation score (HAs) and its relationship with key genes involved in histone acetylation regulation. METHOD: The TCGA-GBMLGG dataset, which provides comprehensive genomic and clinical information, was utilized for this study. We calculated the HAs by analyzing the expression levels of histone acetylation-related genes, including histone acetyltransferases and histone deacetylases, in GBM and LGG patients. Kaplan-Meier survival analysis was performed to evaluate the prognostic value of the HAs. Furthermore, correlation analysis and differential expression analysis were conducted to assess the relationship between the HAs and key genes involved in histone acetylation regulation, as well as the expression differences of immune checkpoint genes. RESULTS: Our analysis revealed a significant association between the HAs and patient prognosis, with higher HAs correlating to poorer outcomes in GBM and LGG patients. We observed a positive correlation between the HAs and key genes involved in histone acetylation regulation, indicating their potential role in modulating histone acetylation levels. Moreover, we found significant expression differences for immune checkpoint genes between high and low HAs groups, suggesting a potential impact of histone acetylation on the immune response in GBM and LGG. CONCLUSION: This study highlights the significance of histone acetylation in GBM and LGG. The HAs demonstrated prognostic value, indicating its potential as a clinically relevant biomarker. The correlation between the HAs and key genes involved in histone acetylation regulation provides insights into the underlying mechanisms driving histone acetylation dysregulation in GBM and LGG. Furthermore, the observed expression differences of immune checkpoint genes suggest a potential link between histone acetylation and the immune response. These findings contribute to our understanding of the molecular basis of GBM and LGG and have implications for personalized treatment approaches targeting histone acetylation and the immune microenvironment. Further validation and functional studies are needed to confirm these findings and explore potential therapeutic strategies.

Ag-modified CuO cavity arrays as a SERS-electrochemical dual signal platform for thiram detection.

Rapid and sensitive determination of pesticide residues in fruits and vegetables is critical for human health and ecosystems. This paper used an Ag-modified CuO sphere-cavity array (CuO@Ag) electrode as a thiram SERS/electrochemical dual readout detection platform. Numerous Raman "hotspots" generated by uniformly distributed silver nanoparticles, charge transfer at the CuO@Ag interface, and the formation of Ag-thiram complexes contribute to the significant enhancement of this SERS substrate, which results in excellent SERS performance with an enhancement factor up to 1.42 × 106. When using SERS as the readout technique, the linear range of the substrate for thiram detection was 0.05-20 nM with a detection limit (LOD) of up to 0.0067 nM. Meanwhile, a correlation between the value of change in current density and thiram concentration was established due to the formation of stable complexes of thiram with Cu2+ generated at specific potentials. The linear range of electrochemical detection was 0.05-20.0 µM, and the detection limit was 0.0167 µM. The newly devised dual-readout sensor offers notable sensitivity and stability. The two signal readout methods complement each other in terms of linear range and detection limit, making it a convenient tool for assessing thiram residue levels in agro-food. At the same time, the combination of commercially available portable equipment makes on-site monitoring possible.

Synthesis and Mechanism of 1D ZnO Based on Alkaline Dissolution-Conversion Strategy of High Stable and Soluble ɛ-Zn(OH)2.

A high soluble and stable ɛ-Zn(OH)2 precursor is synthesized at below room temperature to efficiently prepare ZnO whiskers. The experimental results indicate that the formation of ZnO whiskers is carried out mainly via two steps: the formation of ZnO seeds from ɛ-Zn(OH)2 via the in situ solid conversion, and the following growth of whiskers via dissolution-precipitation route. The decrease of temperature from 25 to 5 °C promotes the formation of ɛ-Zn(OH)2 with higher solubility and stability, which balances the conversion and dissolution rates of precursor. The Rietveld refinement, DFT calculations and MD simulations reveal that the primary reason for these characteristics is the expansion of ɛ-Zn(OH)2 lattice due to temperature, causing difficulties in the dehydration of adjacent ─OH. Simultaneously, the larger specific surface area favors the dissolution of ɛ-Zn(OH)2 . Based on this precursor, well-dispersed ZnO whiskers with 9.82 µm in length, 242.38 nm in diameter, and an average aspect ratio of 41 are successfully synthesized through a SDSN-assisted hydrothermal process at 80 °C. The process has an extremely high solid content of 2.5% (mass ratio of ZnO to solution) and an overall yield of 92%, which offers a new approach for the scaled synthesis of high aspect ratio ZnO whiskers by liquid-phase method.

Fine-tuning of thermally induced SCO behaviors of trinuclear cyanido-bridged complexes by regulating the electron donating ability of CCN-terminal fragments.

To achieve fine regulation of FeII SCO behavior, a series of trinuclear cyanido-bridged complexes trans-[CpMen(dppe)MII(CN)]2[Fe1II(abpt)2](OTf)2 (1-4) (1, M = Fe2 and n = 1; 2, M = Fe2 and n = 4; 3, M = Fe2 and n = 5; 4, M = Ru and n = 5; CpMen = alkyl cyclopentadienyl with n = 1, 4, 5; dppe = 1,2-bis-(diphenylphosphino)ethane; abpt = 4-amino-3,5-bis-(pyridin-2-yl)-1,2,4-triazole and OTf = CF3SO3-) were synthesized and fully characterized by using elemental analysis, X-ray crystallography, magnetic measurements, variable-temperature IR spectroscopy and Mössbauer spectroscopy. It is worth mentioning that different from many mononuclear Fe(abpt)2X2 (X = NCS, NCSe, N(CN)2, C(CN)3, (NC)2CC(OCH3)C(CN)2, (NC)2CC(OC2H5)C(CN)2, C16SO3 and Cl) complexes with more than one polymorph, only one polycrystalline form was found in complexes 1-4. Moreover, the thermally induced SCO behaviors of these four complexes are independent of intermolecular π-π interactions. The electron-donating ability of the CCN-terminal fragment of CpMen(dppe)MIICN can be flexibly regulated by changing the methyl number (n) of the cyclopentadiene ligand or metal ion type (MII). These investigations indicate that the electron-donating ability of the CCN-terminal fragment has an influence on the SCO behavior of Fe1II. The spin transition temperature (T1/2) of the complexes decreases with the increase of the electron-donating ability of the fragment CpMen(dppe)MII. This study provides a new strategy to predict and precisely regulate the behaviors of SCO complexes.

Modeling denitrification nitrogen losses in China's rice fields based on multiscale field-experiment constraints.

Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.

Azo-Cyanamide bridged dinuclear iron complexes exhibiting no electronic coupling but moderate magnetic coupling between the two iron centers.

To investigate the effect of long-distance organic ligand on electronic coupling between metallic atoms, the mononuclear and dinuclear complexes [Cp(dppe)Fe(apc)] (1), [{Cp(dppe)Fe}2 (µ-adpc)] (2), [{CpMe5 (dppe)Fe}2 (µ-adpc) (3) and their oxidized complexes [Cp(dppe)Fe(apc)][PF6 ] (1[PF6 ]), [{Cp(dppe)Fe}2 (µ-adpc)][PF6 ] (2[PF6 ]2 ), [{CpMe5 (dppe)Fe}2 (µ-adpc)][PF6 ]2 (3[PF6 ]2 ) (Cp=1,3-cyclopentadiene, CpMe5 =1,2,3,4,5-pentamethylcyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane), apc- =4-azo(phenylcyanamido)benzene and adpc2- =4,4'-azodi(phenylcyanamido)) were synthesized and characterized by cyclic voltammetry, UV-vis, single-crystal X-ray diffraction and Mössbauer spectra. Electrochemical measurements showed no electronic coupling between the two terminal Fe units, However, the investigation results of the magnetic properties of the two-electron oxidized complexes indicate the presence of moderate antiferromagnetic coupling across 18 Šdistance.

High-density lipoprotein cholesterol is associated with lowered cognitive recovery among acute ischemic stroke patients with mild cognitive impairment.

High-density lipoprotein (HDL) has been documented to be related to mild cognitive impairment (MCI) and dementia occurrence; however, the underlying basis behind this association remains unclear. We aimed to elucidate this basis by examining the association between HDL levels and cognitive improvements after 6 months, among acute ischemic stroke (AIS) patients with MCI. Five hundred fifty-eight AIS and MCI patients from the NICE study were enrolled, and divided into four groups, according to their baseline HDL quartiles; median HDL was 1.12 mmol/L (interquartile range 0.96-1.34 mmol/L). The primary outcome examined was the extent of cognitive improvement, defined as ΔMoCA (Montreal Cognitive Assessment) ≥ 2, while the secondary outcome was cognitive deterioration, defined as ΔADAS-cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) ≥ 4 or ΔMMSE (Mini-Mental State Examination) ≤ - 3, at 6-months post-AIS. We found that 314 (56.27%), 49 (8.78%), and 31 (5.56%) patients had ΔMoCA ≥ 2, ΔADAS-cog ≥ 4, and ΔMMSE ≤ - 3, respectively. Furthermore, cognitive improvement negatively correlated to HDL levels, with the lowest being present among patients in quartiles 4 (Q4; adjusted OR = 0.44, 95% CI 0.25-0.78, P = 0.0050) and Q3 (OR = 0.38, CI 0.23-0.65, P = 0.0004), compared to Q2 (OR = 0.57, CI 0.34-0.96, P = 0.0331). Q2 patients also had positive correlations with ΔADAS-cog ≥ 4 (OR = 5.18, CI 1.55-17.29, P = 0.0074). However, no association between HDL and ΔMMSE ≤ - 3 was observed, nor with LDL and any cognitive changes. Additionally, restricted cubic spline analysis found a nonlinear relationship between HDL and cognitive improvements. All these findings suggested that low plasma HDL was positively associated with improved cognitive functioning among AIS patients with MCI after 6 months.

Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment.

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2 O2 ), which reacts with copper ions (Cu2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy.

Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

Loop-mediated isothermal amplification coupled with nanoparticle-based lateral flow biosensor for monkeypox virus detection.

Monkeypox virus (MPXV) infection is currently an evolving public health concern, highlighting an urgent need for early and rapid detection of MPXV. Here, we present a diagnostic test called MPXV-LAMP-LFB, which combines loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor (LFB) for the simple, sensitive and specific detection of MPXV and differentiation of its two clades. The MPXV-LAMP-LFB can be conducted at a heating block and the detection results can be visually indicated with the biosensor without any specialized apparatus. Two sets of LAMP primers targeting the D14L and ATI genes were designed for the Central and West African MPXV isolates, respectively. The optimal amplification condition was 64 °C for 40 min. Thus, the MPXV-LAMP-LFB test can be completed within 1 h, incorporating rapid DNA extraction (∼15 min), LAMP reaction (∼40 min) and result indicating (∼5 min). The MPXV-LAMP-LFB assay could detect down to 5 copies of plasmid template and 12.5 copies of pseudotyped virus in simulated blood samples. Furthermore, the MPXV-LAMP-LFB assay correctly identified all the positive controls and successfully avoided cross-reactivity with the non-MPXV pathogens or clinical samples, demonstrating its high specificity. Overall, the MPXV-LAMP-LFB test developed in this study showed great promise as a rapid, sensitive and accurate molecular tool for diagnosing MPXV infection.

Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

LAFEM: A Scoring Model to Evaluate Functional Landscape of Lysine Acetylome.

Protein lysine acetylation is a critical post-translational modification involved in a wide range of biological processes. To date, about 20,000 acetylation sites of Homo sapiens were identified through mass spectrometry-based proteomic technology, but more than 95% of them have unclear functional annotations because of the lack of existing prioritization strategy to assess the functional importance of the acetylation sites on large scale. Hence, we established a lysine acetylation functional evaluating model (LAFEM) by considering eight critical features surrounding lysine acetylation site to high-throughput estimate the functional importance of given acetylation sites. This was achieved by selecting one of the random forest models with the best performance in 10-fold cross-validation on undersampled training dataset. The global analysis demonstrated that the molecular environment of acetylation sites with high acetylation functional scores (AFSs) mainly had the features of larger solvent-accessible surface area, stronger hydrogen bonding-donating abilities, near motif and domain, higher homology, and disordered degree. Importantly, LAFEM performed well in validation dataset and acetylome, showing good accuracy to screen out fitness directly relevant acetylation sites and assisting to explain the core reason for the difference between biological models from the perspective of acetylome. We further used cellular experiments to confirm that, in nuclear casein kinase and cyclin-dependent kinase substrate 1, acetyl-K35 with higher AFS was more important than acetyl-K9 with lower AFS in the proliferation of A549 cells. LAFEM provides a prioritization strategy to large scale discover the fitness directly relevant acetylation sites, which constitutes an unprecedented resource for better understanding of functional acetylome.

Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-inflammatory Activity.

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.

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OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Rapid, ultrasensitive and highly specific diagnosis of Mycoplasma pneumoniae by a CRISPR-based detection platform.

Mycoplasma pneumoniae (MP) is an important causative agent of morbidity and mortality among all age groups, especially among patients of extreme ages. Improved and readily available tests for accurate, sensitive and rapid diagnosis of MP infection is sorely needed. Here, we developed a CRISPR-Cas12b-based detection platform on the basis of recombinase polymerase amplification (RPA) for rapid, simple, and accurate diagnosis of MP infection, named MP-RPA-CRISPR. The RPA was employed for amplifying the community-acquired respiratory distress syndrome (CARDS) toxin gene of MP strains at the optimal reaction temperature 37°C. The resulting amplicons were decoded by the CRISPR-Cas12b-based detection platform, which was interpreted by real-time PCR system and by naked eye under blue light. The MP-RPA-CRISPR can detected down to 5 fg of genomic DNA templates of MP strains and accurately distinguish MP strains from non-MP strains without any cross-reactivity. A total of 96 bronchoalveolar lavage fluid (BALF)samples collected from patients suspected of respiratory infection were used to evaluate the clinical performance of the MP-RPA-CRISPR assay. As a result, our assay accurately diagnosed 45 MP-infected samples and 51 non-MP infected sample, and the results obtained from MP-RPA-CRISPR were consistent with microfluidic chip technology. In conclusion, our MP-RPA-CRISPR assay is a simple, rapid, portable and highly sensitive method to diagnose MP infection, which can be used as a promising tool in a variety of settings including clinical, field, and resource-limited aeras.