establishment-rat-peri-implantitis-model-via-maxillary-titanium

Establishment of a Rat Peri-Implantitis Model <em>via</em> Maxillary Titanium Implant Placement and Porphyromonas gingivalis-Ligature Induction

Peri-implantitis (PI) is a leading cause of dental implant failure, characterized by inflammatory soft tissue lesions and progressive bone loss, ...

Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term = ADI-PEG20&rank = 12 ). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to ≤10 μM. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.

A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients.

Glioblastoma (GBM) is the most lethal primary brain tumor and is highly resistant to current treatments. GBM harbors glioma stem cells (GSCs) that not only initiate and maintain malignant growth but also promote therapeutic resistance including radioresistance. Thus, targeting GSCs is critical for overcoming the resistance to improve GBM treatment. Because the bone marrow and X-linked (BMX) nonreceptor tyrosine kinase is preferentially up-regulated in GSCs relative to nonstem tumor cells and the BMX-mediated activation of the signal transducer and activator of transcription 3 (STAT3) is required for maintaining GSC self-renewal and tumorigenic potential, pharmacological inhibition of BMX may suppress GBM growth and reduce therapeutic resistance. We demonstrate that BMX inhibition by ibrutinib potently disrupts GSCs, suppresses GBM malignant growth, and effectively combines with radiotherapy. Ibrutinib markedly disrupts the BMX-mediated STAT3 activation in GSCs but shows minimal effect on neural progenitor cells (NPCs) lacking BMX expression. Mechanistically, BMX bypasses the suppressor of cytokine signaling 3 (SOCS3)-mediated inhibition of Janus kinase 2 (JAK2), whereas NPCs dampen the JAK2-mediated STAT3 activation via the negative regulation by SOCS3, providing a molecular basis for targeting BMX by ibrutinib to specifically eliminate GSCs while preserving NPCs. Our preclinical data suggest that repurposing ibrutinib for targeting GSCs could effectively control GBM tumor growth both as monotherapy and as adjuvant with conventional therapies.

Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance.

Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and its association with tumor cell phenotypes remain largely unknown. Here we found that GSCs were more glycolytic than NSTCs, and voltage-dependent anion channel 2 (VDAC2), a mitochondrial membrane protein, was critical for metabolic switching between GSCs and NSTCs to affect their phenotypes. VDAC2 was highly expressed in NSTCs relative to GSCs and coupled a glycolytic rate-limiting enzyme platelet-type of phosphofructokinase (PFKP) on mitochondrion to inhibit PFKP-mediated glycolysis required for GSC maintenance. Disruption of VDAC2 induced dedifferentiation of NSTCs to acquire GSC features, including the enhanced self-renewal, preferential expression of GSC markers, and increased tumorigenicity. Inversely, enforced expression ofVDAC2 impaired the self-renewal and highly tumorigenic properties of GSCs. PFK inhibitor clotrimazole compromised the effect of VDAC2 disruption on glycolytic reprogramming and GSC phenotypic transition. Clinically, VDAC2 expression inversely correlated with glioma grades (Immunohistochemical staining scores of VDAC2 were 4.7 ± 2.8, 3.2 ± 1.9, and 1.9 ± 1.9 for grade II, grade III, and IV, respectively, p < 0.05 for all) and the patients with high expression of VDAC2 had longer overall survival than those with low expression of VDAC2 (p = 0.0008). In conclusion, we demonstrate that VDAC2 is a new glycolytic regulator controlling the phenotype transition between glioma stem cells and non-stem cells and may serves as a new prognostic indicator and a potential therapeutic target for glioma patients.

VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells.

Prone positioning in intubated and mechanically ventilated patients with SARS-CoV-2.

It has been widely reported that the prognostic nutritional index (PNI) played a pivotal role in nutritional assessment of surgical patients and tumor prognosis. In order to improve the accuracy of evaluation in Western China, we established reference intervals (RIs) of PNI in healthy controls.

Normal reference intervals of prognostic nutritional index in healthy adults: A large multi-center observational study from Western China.

 Few reports concerning inactivated vaccine efficacy in elderly patients with Omicron infection. We aimed at demonstrating the clinical characteristics of elderly patients with mild disease and assessing the protective effect of the vaccine preliminarily.  13,120 mild patients who aged beyond 60 years old were included in this study totally, medical records were collected and analyzed.  Patients beyond 60 years had more chronic comorbidities, significantly lower ORF1ab and N gene CT values, and longer time of nucleic acid conversion than other age groups. Higher CT value of ORF1ab and N gene were found in older patients who received a booster dose of vaccine than in those who received two doses. The time of nucleic acid conversion was longest in unvaccinated old patients, with a decreasing trend from those who received two doses to those who received a booster doses. We also used random forest and logistic regression to screen for factors strongly associated with nucleic acid conversion and to predict the time of nucleic acid conversion.  For mild patients with Omicron infection, patients aged>60 years had mild clinical symptoms, higher viral loads, and longer time of nucleic acid conversion, when compared with younger patients. The inactivated SARS-CoV-2 vaccine provided effective protection among adults with omicron variant infection, and the effectiveness of three doses of the vaccine was greater than that of two doses of the vaccine. Special attention should be given to elderly patients.

Omicron variant of SARS-COV-2 in Shanghai: Clinical features and inactivated vaccine efficacy in 13,120 elderly patients.

To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China.

Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China.

, with 150-170 species, is the second largest and perhaps most taxonomically challenging genus within the subfamily Lamioideae (Lamiaceae). With about 60 species, China is one of three major biodiversity centers of . Although some  species from China have been included in previous molecular phylogenetic studies, a robust and broad phylogeny of this lineage has yet to be completed. Moreover, given the myriad new additions to the genus, the existing infrageneric classification needs to be evaluated and revised. Here, we combine molecular and morphological data to investigate relationships within , with a focus on Chinese species. We observed that plastid DNA sequences can resolve relationships within  better than nuclear ribosomal internal and external transcribed spacer regions (nrITS and nrETS). Molecular phylogenetic analyses confirm the monophyly of , but most previously defined infrageneric groups are not monophyletic. In addition, morphological analysis demonstrates the significant taxonomic value of eight characters to the genus. Based on our molecular phylogenetic analyses and morphological data, we establish a novel section  within , and propose three new combinations as well as three new synonyms. This study presents the first molecular phylogenetic analyses of  in which taxa representative of the entire genus are included, and highlights the phylogenetic and taxonomic value of several morphological characters from species of  from China. Our study suggests that a taxonomic revision and reclassification for the entire genus is necessary in the future.

Molecular phylogeny and taxonomy of  (Lamiaceae subfamily Lamioideae) in China: Insights from molecular and morphological data.

In oilfield extraction activities, traditional downhole condition monitoring is typically conducted using dynamometer cards to capture the dynamic changes in the load and displacement of the sucker rod. However, this method has severe limitations in terms of real-time performance and maintenance costs, making it difficult to meet the demands of modern extraction. To overcome these shortcomings, this paper proposes a novel fault detection method based on the analysis of motor power parameters. Through the dynamic mathematical modeling of the pumping unit system, we transform the indicator diagram of beam-pumping units into electric power diagrams and conduct an in-depth analysis of the characteristics of electric power diagrams under five typical operating conditions, revealing the impact of different working conditions on electric power. Compared to traditional methods, we introduce fourteen new features of the electrical parameters, encompassing multidimensional analyses in the time domain, frequency domain, and time-frequency domain, significantly enhancing the richness and accuracy of feature extraction. Additionally, we propose a new effectiveness evaluation method for the FCM clustering algorithm, integrating fuzzy membership degrees and the geometric structure of the dataset, overcoming the limitations of traditional clustering algorithms in terms of accuracy and the determination of the number of clusters. Through simulations and experiments on 10 UCI datasets, the proposed effectiveness function accurately evaluates the clustering results and determines the optimal number of clusters, significantly improving the performance of the clustering algorithm. Experimental results show that the fault diagnosis accuracy of our method reaches 98.4%, significantly outperforming traditional SVM and ELM methods. This high-precision diagnostic result validates the effectiveness of the method, enabling the efficient real-time monitoring of the working status of beam-pumping unit wells. In summary, the proposed method has significant advantages in real-time performance, diagnostic accuracy, and cost-effectiveness, solving the bottleneck problems of traditional methods and enhancing fault diagnosis capabilities in oilfield extraction processes.

Article	Year
A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients. Scientific reports\| PubMed ID: 28900115	2017
Ibrutinib inactivates BMX-STAT3 in glioma stem cells to impair malignant growth and radioresistance. Science translational medicine\| PubMed ID: 29848664	2018
VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells. Cell death & disease\| PubMed ID: 30250190	2018
Prone positioning in intubated and mechanically ventilated patients with SARS-CoV-2. Journal of clinical anesthesia\| PubMed ID: 33812212	2021
Normal reference intervals of prognostic nutritional index in healthy adults: A large multi-center observational study from Western China. Journal of clinical laboratory analysis\| PubMed ID: 34018637	2021
Omicron variant of SARS-COV-2 in Shanghai: Clinical features and inactivated vaccine efficacy in 13,120 elderly patients. International journal of medical sciences\| PubMed ID: 37575277	2023
Identification of Novel Hb Guiyang [HBA2: c.151C > A α2 50 (CE8) His- Asn] and Phenotype- Genotype Correlation of Abnormal Hemoglobins in Guizhou, Southwest China. Journal of blood medicine\| PubMed ID: 38895162	2024
Molecular phylogeny and taxonomy of (Lamiaceae subfamily Lamioideae) in China: Insights from molecular and morphological data. Plant diversity\| PubMed ID: 39280970	2024
A Fault Diagnosis Method for Oil Well Electrical Power Diagrams Based on Multidimensional Clustering Performance Evaluation. Sensors (Basel, Switzerland)\| PubMed ID: 40292812	2025

Yaping Chen

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