Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

[Ozone Sensitivity Analysis in Urban Beijing Based on Random Forest].

The basis and key step to developing ozone (O3) prevention and control measures is determining the non-linear relationship between O3 and its precursors. Based on online observations of O3, volatile organic compounds (VOCs), nitrogen oxides (NOx), and meteorological elements from April to September 2020 at an urban site in Beijing, we analyzed the pollution characteristics of O3 and its precursors, explored key factors affecting O3 using the random forest (RF) model combined with SHAP values, and explored the O3-VOCs-NOx sensitivity through a multi-scenarios analysis. The results of correlation analysis showed that the hourly concentration of O3 was significantly positively correlated with temperature (T) and negatively correlated with TVOCs and NOx. However, in terms of the daily values, O3 was significantly positively correlated with T, TVOCs, and NOx. The simulated O3 values by the RF model agreed with the measured values. The SHAP values of each characteristic variable were further calculated. The results suggested that T and NOx showed the two highest effects on O3, with positive and negative values, respectively. Based on the average NOx and VOCs on O3 pollution days during the observation period (the base scenario), multi-scenarios with different NOx and VOCs were set up. The RF model was used to calculate O3 under different scenarios and obtain the O3 isopleth (EKMA curve). The results showed that the O3-VOCs-NOx sensitivity in urban areas of Beijing was in the VOCs-limited regime, which was consistent with the results obtained from the observation-based box model(OBM). This indicated that the RF model could be used as a complementary method for O3-VOCs-NOx sensitivity analysis.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine.

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

Microcomputed-Tomographic Analysis of the Root Canal Morphology of the Mandibular First Molars in a Malaysian Subpopulation Using Two Classification Systems / Análisis por Tomografía Microcomputada de la Morfología del Conducto Radicular de los Primeros Molares Mandibulares en una Subpoblación de Malasia Utilizando dos Sistemas de Clasificación

SUMMARY: This work investigated the morphology of the root canal system of the mandibular first molar in a Malaysian subpopulation. Using micro-computed tomography with an isotropic resolution of 22 µm, 140 mandibular first molars were scanned. MIMICS software was used for segmentation, 3-D reconstruction and analysis of the acquired images. The canal configuration was described using Vertucci [supported by the supplementary configurations proposed by Sert & Bayirli (2004)] and Ahmed et al. (2027), coding systems. The chi-square test was used to assess the association between qualitative variables. By non-considering intercanal communications, Vertucci types IV (17.1%) and I (76.4%) were the most frequently reported configurations in the mesial and distal roots, respectively. Of the reported configurations, 24.3% and 4.3% were non-classifiable by Vertucci system in the mesial and distal roots, respectively. Up to 63.6% and 9.3% of the reported configurations were non- classifiable, and type I was the most frequent when considering intercanal communications (7.1% and 76.4% in the mesial and distal roots, respectively). According to Ahmed et al., system, almost half of the sample had more than four digits (47.9%), followed by the 3-digits category (20.71%). In both systems, a significant association was found between the canal configuration and the root type (p<0.001). The mandibular first molar of this Malaysian subpopulation demonstrated a wide range of root canal morphology. When compared to the Vertucci system, the system developed by Ahmed et al., successfully classified all molars configurations despite their level of complexity. The complex canal anatomy of mandibular first molars in this subpopulation warrants special attention during root canal treatment procedures.

En este trabajo se investigó la morfología del sistema de conductos radiculares del primer molar mandibular en una subpoblación de Malasia. Utilizando tomografía microcomputada con una resolución isotrópica de 22 µm, se escanearon 140 primeros molares mandibulares. Se utilizó el software MIMICS para segmentar (enmascarar), reconstruir en 3D, visualizar y analizar las imágenes adquiridas. La configuración del canal se describió utilizando Vertucci respaldado por las configuraciones complementarias propuestas por Sert & Bayirli (2004)] y Ahmed et al. (2017, 2020), sistemas de codificación. Se utilizó la prueba de chi-cuadrado para evaluar la asociación entre variables cualitativas. Sin considerar las comunicaciones intercanales, los tipos Vertucci IV (17,1%) y I (76,4%) fueron las configuraciones reportadas con mayor frecuencia en las raíces mesiales y distales, respectivamente. De las configuraciones reportadas, el 24,3 % y el 4,3 % fueron no clasificables por el sistema de Vertucci en las raíces mesial y distal, respectivamente. Hasta el 63,6 % y el 9,3 % de las configuraciones reportadas fueron no clasificables, siendo la tipo I la más frecuente al considerar las comunicaciones intercanales (7,1 % y 76,4 % en las raíces mesiales y distales, respectivamente). Según Ahmed et al. (2017, 2020) en el sistema, casi la mitad de la muestra tenía más de cuatro dígitos (47,9 %), seguido por la categoría de 3 dígitos (20,71 %). En ambos sistemas se encontró una asociación significativa entre la configuración del canal y el tipo de raíz (p<0,001). El primer molar mandibular de esta subpoblación de Malasia demostró una amplia gama morfológica del conducto radicular. En comparación con el sistema Vertucci, el sistema desarrollado por Ahmed et al. (2017, 2020) clasificaron con éxito todas las configuraciones de los molares a pesar de su nivel de complejidad. La compleja anatomía del canal de los primeros molares mandibulares en esta subpoblación merece una atención especial durante los procedimientos de tratamiento de conducto.

GMean-a semi-supervised GRU and K-mean model for predicting the TF binding site.

The transcription factor binding site is a deoxyribonucleic acid sequence that binds to transcription factors. Transcription factors are proteins that regulate the transcription gene. Abnormal turnover of transcription factors can lead to uncontrolled cell growth. Therefore, discovering the relationships between transcription factors and deoxyribonucleic acid sequences is an important component of bioinformatics research. Numerous deep learning and machine learning language models have been developed to accomplish these tasks. Our goal in this work is to propose a GMean model for predicting unlabelled deoxyribonucleic acid sequences. The GMean model is a hybrid model with a combination of gated recurrent unit and K-mean clustering. The GMean model is developed in three phases. The labelled and unlabelled data are processed based on k-mers and tokenization. The labelled data is used for training. The unlabelled data are used for testing and prediction. The experimental data consists of deoxyribonucleic acid experimental of GM12878, K562 and HepG2. The experimental results show that GMean is feasible and effective in predicting deoxyribonucleic acid sequences, as the highest accuracy is 91.85% in predicting K562 and HepG2. This is followed by the prediction of the sequence between GM12878 and K562 with an accuracy of 89.13%. The lowest accuracy is the prediction of the sequence between HepG2 and GM12828, which is 88.80%.

Circular RNA SLC8A1 triggers hippocampal neuronal ferroptosis by regulating FUS-mediated ATF3 mRNA stability in epilepsy.

BACKGROUND: Epilepsy is a neurological disorder characterized by recurrent seizures and is often unresponsive to current treatment options. Ferroptosis, a recently defined iron-dependent regulated cell death, has been suggested as a potential therapeutic target for epilepsy due to its association with oxidative stress. Additionally, circRNA SLC8A1 (circSLC8A1) has been implicated in various neurological disorders and oxidative stress-related diseases but its involvement in epilepsy progression, particularly in relation to ferroptosis and oxidative stress, remains unclear. METHODS: qRT-PCR, Western blot, IHC and ELISA assays were employed to validate the relative expression of targeted genes and proteins. The levels of ROS, iron, LOP and GSH were detected by commercial kits. RNA pull-down and RIP assays were employed to detect the interactions among circSLC8A1, FUS and ATF3. A rat epilepsy model was established for further in vivo confirmation. RESULTS AND CONCLUSION: In this study, we investigated the potential involvement of circSLC8A1 in epilepsy progression and its connection to ferroptosis and oxidative stress. Our findings demonstrate that circSLC8A1 triggers neuronal ferroptosis by stabilizing ATF3 mRNA expression through recruitment with FUS. The induced neuronal ferroptosis contributes to epilepsy progression. These results enhance our understanding of epilepsy pathogenesis and may provide insights for the development of novel therapeutic strategies.

Yin Yang 1 suppresses apoptosis and oxidative stress injury in SH-SY5Y cells by facilitating NR4A1 expression.

Oxidative stress plays a significant role in the development of Parkinson's disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the NR4A1 promoter. MPP+ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP+-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP+-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with NR4A1 promoter. In addition, in MPP+-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP+-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with NR4A1 promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.HIGHLIGHTSNR4A1 and YY1 are decreased in MPP+-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP+-treated SH-SY5Y cells.YY1 binds with NR4A1 promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.

Molecular Regulatory Network of Anthocyanin Accumulation in Black Radish Skin as Revealed by Transcriptome and Metabonome Analysis.

To understand the coloring mechanism in black radish, the integrated metabolome and transcriptome analyses of root skin from a black recombinant inbred line (RIL 1901) and a white RIL (RIL 1911) were carried out. A total of 172 flavonoids were detected, and the analysis results revealed that there were 12 flavonoid metabolites in radish root skin, including flavonols, flavones, and anthocyanins. The relative concentrations of most flavonoids in RIL 1901 were higher than those in RIL 1911. Meanwhile, the radish root skin also contained 16 types of anthocyanins, 12 of which were cyanidin and its derivatives, and the concentration of cyanidin 3-o-glucoside was very high at different development stages of black radish. Therefore, the accumulation of cyanidin and its derivatives resulted in the black root skin of radish. In addition, a module positively related to anthocyanin accumulation and candidate genes that regulate anthocyanin synthesis was identified by the weighted gene co-expression network analysis (WGCNA). Among them, structural genes (RsCHS, RsCHI, RsDFR, and RsUGT75C1) and transcription factors (TFs) (RsTT8, RsWRKY44L, RsMYB114, and RsMYB308L) may be crucial for the anthocyanin synthesis in the root skin of black radish. The anthocyanin biosynthesis pathway in the root skin of black radish was constructed based on the expression of genes related to flavonoid and anthocyanin biosynthesis pathways (Ko00941 and Ko00942) and the relative expressions of metabolites. In conclusion, this study not only casts new light on the synthesis and accumulation of anthocyanins in the root skin of black radish but also provides a molecular basis for accelerating the cultivation of new black radish varieties.

Contour Analysis of Three-Dimensional Peri-Implant Mucosal Model as an Endpoint Analysis of Photofunctionalization Effects on Implant Abutment Materials.

INTRODUCTION: The objective of this study was to examine the effect of photofunctionalization on the soft-tissue contour formed at the interface of various abutment materials using end-point analyses obtained from the three-dimensional oral mucosal model (3D-OMMs). METHODS: Commercially pure titanium (CPTi), alumina-toughened zirconia (ATZ), and yttria-stabilized zirconia (YSZ) made into discs shapes were classified into two groups: UV-treated (PTx) and non-treated (NTx). The materials in PTx groups were exposed to UV light for 12 min. Human gingival fibroblasts and TR146 epithelial cell lines co-cultured on the acellular dermal membrane were used to construct the 3D-OMM. After 4 days of culture, the discs were inserted into the holes prepared within the membrane of 3D-OMMs. The contour formed by the tissue was evaluated after 14 days of culture. RESULTS: The UV treatment of abutment materials resulted in the formation of more non-pocket-tissue types among the PTx group (p = 0.002). Of all materials tested, soft tissue contour around YSZ showed higher scores for the non-pocket type in both non- and UV-treated groups. CONCLUSIONS: The non-pocket type of tissue attachment was frequently found in all surfaces modified by photofunctionalization, particularly zirconia. The 3D-OMM can be used to evaluate the biological endpoints of implant surface modifications.

Knockdown of KLF5 ameliorates renal fibrosis in MRL/lpr mice via inhibition of MX1 transcription.

OBJECTIVE: This study aims to elucidate the role of Kruppel-like factor (KLF5) and myxovirus resistance 1 (MX1) in the progression of renal fibrosis in lupus nephritis (LN). METHODS: First, the expression of KLF5 and MX1 was assessed in the peripheral blood of LN patients and healthy participants. Next, the pathological changes in renal tissues were evaluated and compared in BALB/c and MRL/lpr mice, by detecting the expression of fibrosis marker proteins (transforming growth factor-ß [TGF-ß] and CTGF) and α-SMA, the content of urine protein, and the levels of serum creatinine, blood urea nitrogen, and serum double-stranded DNA antibody. In TGF-ß1-induced HK-2 cells, the messenger RNA levels of KLF5 and MX1 were tested by qRT-PCR, and the protein expression of α-SMA, type I collagen (Col I), fibronectin (FN), and matrix metalloproteinase 9 (MMP9) was measured by western blot analysis. Moreover, the relationship between KLF5 and MX1 was predicted and verified. RESULTS: In renal tissues of MRL/lpr mice and the peripheral blood of LN patients, KLF5 and MX1 were highly expressed. Pearson analysis revealed that KLF5 was positively correlated with MX1. Furthermore, KLF5 bound to MX1 promoter and promoted its transcription level. MRL/lpr mice showed substantial renal injury, accompanied by increased expression of α-SMA, TGF-ß, CTGF, Col I, FN, and MMP9. Injection of sh-KLF5 or sh-MX1 alone in MRL/lpr mice reduced renal fibrosis in LN, while simultaneous injection of sh-KLF5 and ad-MX1 exacerbated renal injury and fibrosis. Furthermore, we obtained the same results in TGF-ß1-induced HK-2 cells. CONCLUSION: Knockdown of KLF5 alleviated renal fibrosis in LN through repressing the transcription of MX1.

Comparing Magnetic Resonance Fingerprinting (MRF) and the MAGiC Sequence for Simultaneous T1 and T2 Quantitative Measurements in the Female Pelvis: A Prospective Study.

The aim of this study was to explore the potential of magnetic resonance fingerprinting (MRF), an emerging quantitative MRI technique, in measuring relaxation values of female pelvic tissues compared to the conventional magnetic resonance image compilation (MAGiC) sequence. The study included 32 female patients who underwent routine pelvic MRI exams using anterior and posterior array coils on a 3T clinical scanner. Our findings demonstrated significant correlations between MRF and MAGiC measured T1 and T2 values (p < 0.0001) for various pelvic tissues, including ilium, femoral head, gluteus, obturator, iliopsoas, erector spinae, uterus, cervix, and cutaneous fat. The tissue contrasts generated from conventional MRI and synthetic MRF also showed agreement in bone, muscle, and uterus for both T1-weighted and T2-weighted images. This study highlights the strengths of MRF in providing simultaneous T1 and T2 mapping. MRF offers distinct tissue contrast and has the potential for accurate diagnosis of female pelvic diseases, including tumors, fibroids, endometriosis, and pelvic inflammatory disease. Additionally, MRF shows promise in monitoring disease progression or treatment response. Overall, the study demonstrates the potential of MRF in the field of female pelvic organ imaging and suggests that it could be a valuable addition to the clinical practice of pelvic MRI exams. Further research is needed to establish the clinical utility of MRF and to develop standardized protocols for its implementation in clinical practice.

Mitochondrial DNA Copy Number and Risk of Diabetes Mellitus and Metabolic Syndrome.

CONTEXT: Mitochondrial DNA (mtDNA) plays a key role in diabetes mellitus and metabolic syndrome (MetS). An increasing number of studies have reported the association between mtDNA copy number (mtDNA-CN) and the risk of diabetes mellitus and MetS; however, the associations remain conflicted and a systematic review and meta-analysis on the association between mtDNA-CN and diabetes mellitus and MetS is lacking. OBJECTIVE: We aimed to investigate the association of mtDNA-CN and diabetes mellitus and MetS using a systematic review and meta-analysis of observational studies. METHODS: PubMed, EMBASE, and Web of Science were searched up to December 15, 2022. Random-effect models were used to summarize the relative risks (RRs) and 95% CIs. RESULTS: A total of 19 articles were included in the systematic review and 6 articles (12 studies) in the meta-analysis involving 21 714 patients with diabetes (318 870 participants) and 5031 MetS (15 040 participants). Compared to the highest mtDNA-CN, the summary RR (95% CIs) for the lowest mtDNA-CN were 1.06 (95% CI, 1.01-1.12; I2 = 79.4%; n = 8) for diabetes (prospective study: 1.11 (1.02-1.21); I2 = 22.6%; n = 4; case-control: 1.27 (0.66-2.43); I2 = 81.8%; n = 2; cross-sectional: 1.01 (0.99-1.03); I2 = 74.7%; n = 2), and 1.03 (0.99-1.07; I2 = 70.6%; n = 4) for MetS (prospective: 2.87 (1.51-5.48); I2 = 0; n = 2; cross-sectional: 1.02 (1.01-1.04); I2 = 0; n = 2). CONCLUSION: Decreased mtDNA-CN was associated with increased risk of diabetes mellitus and MetS when limited to prospective studies. More longitudinal studies are warranted.

CCL19+ dendritic cells potentiate clinical benefit of anti-PD-(L)1 immunotherapy in triple-negative breast cancer.

BACKGROUND: The extensive involvement of dendritic cells (DCs) in immune contexture indicates their potent value in cancer immunotherapy. Understanding DC diversity in patient cohorts may strengthen the clinical benefit of immune checkpoint inhibitors (ICIs). METHODS: Single-cell profiling of breast tumors from two clinical trials was performed to investigate DC heterogeneity. Multiomics, tissue characterization, and pre-clinical experiments were used to evaluate the role of the identified DCs in the tumor microenvironment. Four independent clinical trials were leveraged to explore biomarkers to predict ICI and chemotherapy outcomes. FINDINGS: We identified a distinct CCL19-expressing functional state of DCs associated with favorable responses to anti-programmed death (ligand)-1 (PD-(L)1), which displayed migratory and immunomodulatory phenotypes. These cells were correlated with antitumor T cell immunity and the presence of tertiary lymphoid structures and lymphoid aggregates, defining immunogenic microenvironments in triple-negative breast cancer. In vivo, CCL19+ DC deletion by Ccl19 gene ablation dampened CCR7+CD8+ T cells and tumor elimination in response to anti-PD-1. Notably, high circulating and intratumoral CCL19 levels were associated with superior response and survival in patients receiving anti-PD-1 but not chemotherapy. CONCLUSIONS: We uncovered a critical role of DC subsets in immunotherapy, which has implications for designing novel therapies and patient stratification strategies. FUNDING: This study was funded by the National Key Research and Development Project of China, the National Natural Science Foundation of China, the Program of Shanghai Academic/Technology Research Leader, the Natural Science Foundation of Shanghai, the Shanghai Key Laboratory of Breast Cancer, the Shanghai Hospital Development Center (SHDC), and the Shanghai Health Commission.

Root and canal anatomy of mandibular first molars using micro-computed tomography: a systematic review.

BACKGROUND: A thorough understanding of root and canal anatomy is crucial for successful root canal treatment outcomes. This systematic review aims to explore the published micro-CT studies investigated the anatomy of root and canal system in permanent mandibular first molars. METHOD: An electronic search was performed on Web of science, PubMed, and Scopus. Micro-CT journal studies investigated the root and canal anatomy of permanent double-rooted mandibular first molars were included. Data on study characteristics, objectives of interest, specifications of the studies, and micro-CT specifications were extracted. Risk of bias assessment (ROB) of the included studies was performed using Anatomical Quality Assessment (AQUA) tool. The extracted data were presented in tables and figures to present and synthesise the results. A meta-analysis was performed for the studies related to the prevalence of Vertucci's canal configurations, middle mesial canal (MMC) configurations, and Fan's isthmus types. RESULTS: Amongst 1358 identified studies, thirty met the inclusion criteria. In terms of the objectives, the selected studies showed high anatomical variability in mandibular first molars. Twenty-two (73%), 25 (83%), and 12 (40%) of the studies reported the population/ethnicity, micro-CT specifications, and ethical approval, respectively. 28 (93%) studies did not disclose the method of sample size estimation. In only 6 (20%) of the studies, the authors had calibrated the assessment approaches. Mostly, a potential ROB was reported in domain 1 (objective(s) and subject characteristics) and domain 3 (methodology characterization). Whilst, low risk was reported in domains 2 (study design), 4 (descriptive anatomy), and 5 (reporting of results). The overall ROB was reported to be ''moderate'' in the vast majority of the studies (27/30). Meta-analysis results showed high levels of heterogeneity among the studies related to MMCs (I2 = 86%) and Fan's isthmus (I2 = 87%). As for the root canal configuration, pooled prevalence showed that Vertucci type IV and type I were the most prevalent in mesial and distal root canals, respectively. CONCLUSION: Based on moderate risk of bias level of evidence, micro-CT studies have shown wide range of qualitative and quantitative data presentations of the roots and canals in mandibular first molars. Protocol and registration. The protocol of this systematic review was prospectively registered in the Open Science Framework database ( https://osf.io ) on 2022-06-20 with the registration number 10.17605/OSF.IO/EZP7K.

Prevalence of Relative Energy Deficiency in Sport (RED-S) among National Athletes in Malaysia.

Relative energy deficiency in sport (RED-S), which underpins the concept of low energy availability (LEA), can negatively affect athletes' health and performance. This study aims to investigate the prevalence of RED-S among national athletes in Malaysia. A total of 192 national athletes (97 males, 18-39 years old) responded to an online survey regarding the RED-S risk. Most athletes (67.2%) were classified as having a medium/high RED-S risk. Female (41.2%), weight-class (23.9%), and intermittent sports (20.3%) had the highest prevalence of medium/high RED-S risk. Overall, most athletes spent 2-5 h daily (55.2%) and 6-7 days weekly (53.6%) practicing or playing their sport, and 47.9% reported feeling tired recently. The athletes were also terrified of being overweight (61.5%), worried about what they eat (64.7%), concerned about having fat on their bodies (62.6%), and thinking about burning calories while exercising (69.3%). Only 16.7% of the athletes had a prior history of stress fractures, and 40.6% continued to participate in activities 6-7 days per week while injured. The majority of female athletes (88.3%) had regular menstrual cycles. These findings support the notion that RED-S screening should be addressed in the athletic community. Future research is needed to clinically assess these athletes and investigate the impacts of RED-S on their health and sports performance.

Structural, spectroscopic, luminescence sensing and TD-DFT theoretical studies of a CuP2N-type complex.

Luminescent cuprous complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title heteroleptic cuprous complex, [2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl-κ2P,P'](2-phenylpyridine-κN)copper(I) hexafluoridophosphate, rac-[Cu(C44H32P2)(C11H9N)]PF6, conventionally abbreviated rac-[Cu(BINAP)(2-PhPy)]PF6 (I), where BINAP and 2-PhPy represent 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl and 2-phenylpyridine, respectively, is described. In this complex, the asymmetric unit consists of a hexafluoridophosphate anion and a heteroleptic cuprous complex cation, in which the cuprous centre in a CuP2N coordination triangle is coordinated by two P atoms from the BINAP ligand and by one N atom from the 2-PhPy ligand. Time-dependent density functional theory (TD-DFT) calculations show that the UV-Vis absorption of I should be attributed to ligand-to-ligand charge transfer (LLCT) characteristic excited states. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine.

Endogenous HMGB1 regulates GSDME-mediated pyroptosis via ROS/ERK1/2/caspase-3/GSDME signaling in neuroblastoma.

Pyroptosis, a newly discovered mode of programmed cell death (PCD), is important in the regulation of cancer development. High mobility group box 1 (HMGB1) is a non-histone nuclear protein that is closely related to tumor development and chemotherapy resistance. However, whether endogenous HMGB1 regulates pyroptosis in neuroblastoma remains unknown. Here, we showed that HMGB1 showed ubiquitous higher expression in SH-SY5Y cells and clinical tumors, and was positively correlated with the risk factors of patients with neuroblastoma. Knockdown of GSDME or pharmacological inhibition of caspase-3 blocked pyroptosis and cytosolic translocation of HMGB1. Moreover, knockdown of HMGB1 inhibited cisplatin (DDP) or etoposide (VP16)-induced pyroptosis by decreasing GSDME-NT and cleaved caspase-3 expression, resulting in cell blebbing and LDH release. Knockdown of HMGB1 expression increased the sensitivity of SH-SY5Y cells to chemotherapy and switched pyroptosis to apoptosis. Furthermore, the ROS/ERK1/2/caspase-3/GSDME pathway was found to be functionally connected with DDP or VP16-induced pyroptosis. Hydrogen peroxide (H2O2, a ROS agonist) and EGF (an ERK agonist) promoted the cleavage of GSDME and caspase-3 in DDP or VP16 treatment cells, both of which were inhibited by HMGB1 knockdown. Importantly, these data were further supported by the in vivo experiment. Our study suggests that HMGB1 is a novel regulator of pyroptosis via the ROS/ERK1/2/caspase-3/GSDME pathway and a potential drug target for therapeutic interventions in neuroblastoma.

5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

Expression of Interleukin-1ß and Histological Changes of the Three-Dimensional Oral Mucosal Model in Response to Yttria-Stabilized Nanozirconia.

Over the years, advancement in ceramic-based dental restorative materials has led to the development of monolithic zirconia with increased translucency. The monolithic zirconia fabricated from nano-sized zirconia powders is shown to be superior in physical properties and more translucent for anterior dental restorations. Most in vitro studies on monolithic zirconia have focused mainly on the effect of surface treatment or the wear of the material, while the nanotoxicity of this material is yet to be explored. Hence, this research aimed to assess the biocompatibility of yttria-stabilized nanozirconia (3-YZP) on the three-dimensional oral mucosal models (3D-OMM). The 3D-OMMs were constructed using human gingival fibroblast (HGF) and immortalized human oral keratinocyte cell line (OKF6/TERT-2), co-cultured on an acellular dermal matrix. On day 12, the tissue models were exposed to 3-YZP (test) and inCoris TZI (IC) (reference material). The growth media were collected at 24 and 48 h of exposure to materials and assessed for IL-1ß released. The 3D-OMMs were fixed with 10% formalin for the histopathological assessments. The concentration of the IL-1ß was not statistically different between the two materials for 24 and 48 h of exposure (p = 0.892). Histologically, stratification of epithelial cells was formed without evidence of cytotoxic damage and the epithelial thickness measured was the same for all model tissues. The excellent biocompatibility of nanozirconia, as evidenced by the multiple endpoint analyses of the 3D-OMM, may indicate the potential of its clinical application as a restorative material.

Stress and depressive symptoms in university students in Hong Kong under the pandemic: Moderating effect of positive psychological attributes.

Introduction: There are very few studies examining the psychological well-being of university students in Hong Kong under the COVID-19 pandemic. Besides COVID-19-related stress, the "social event" in 2019-2020 has caused significant stress in young people. As such, we attempted to answer several research questions in this paper. First, what are the relationships between stresses (COVID-19 and "social event" related stresses) and psychological well-being indexed by depressive symptoms? Based on the stress and coping perspective, we predicted that there would be positive relationships between both types of stress and depression. Second, what are the relationships between different positive psychological factors (including life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity) and depression? Based on different theoretical models of positive psychology, we hypothesized that negative relationships would exist between positive psychological factors and depressive symptoms. Third, do positive psychological attributes moderate the associations between stresses (COVID-19 and "social event" related stresses) and depressive symptoms? Based on the positive psychology literature, we hypothesized that positive psychological attributes would buffer the negative impact of stresses on depression. Methods: We recruited university students roughly one year after the first wave of the pandemic (N = 1,648) in early 2021. We used 25 items to measure COVID-19-related stress and "social event" related stress. For psychological well-being indexed by depressive symptoms, we used the "Centre for Epidemiologic Studies Depression Scale Revised (CESD-R)". For positive psychological attributes, we employed established measures of life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity. Results: Regarding the relationship between stress and depression, we found positive relationships between both types of stress and depressive symptoms. As predicted, negative relationships existed between all positive psychological attributes and depressive symptoms. Besides, the positive psychological attributes significantly moderated the effects of stresses on depression, suggesting that these factors can reduce the negative impacts of stresses on depression. The present findings provide support for those models, highlighting the importance of positive psychological attributes as protective factors for university students' depression. Discussion: The findings of this study underscore the important role of positive psychological attributes in the stress-depression relationship in university students under the pandemic. The findings also generalize the positive youth development theory in the Chinese context. In terms of practice, university administrators and service providers should consider cultivating positive psychological attributes in university students with the purpose of promoting their psychological well-being.