A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Selection of prenatal screening with nuchal translucency > 95th centile and below 99th centile: a 4-year observational study with real-world data.

OBJECTIVE: We sought to analyze the genetic outcomes of fetuses with nuchal translucency (NT) > 95th centile, and determine whether prenatal genetic counseling, chromosomal microarray analysis (CMA) or non-invasive prenatal testing (NIPT) are truly beneficial for the outcomes of fetuses with increased NT > 95th centile and below 99th centile. MATERIALS AND METHODS: A total of 535 pregnant women were included in this study, with a fetal NT > 95th centile at 11-13+6 weeks of gestation from January 2017 to December 2020. 324 pregnant women with fetal NT > 95th centile and below 99th centile combined with other risk factors and NT > 99th centile received prenatal diagnostic karyotype analysis and CMA, and 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile were selected to carry out NIPT. RESULTS: A total of 211 pregnant women who underwent NIPT were included in the study, NIPT results showed that 8 high-risk cases were confirmed by prenatal diagnosis. Overall, the detection rate of NIPT was 3.79%. A total of 324 pregnant women with fetal NT > 95th centile and below 99th centile, along with other risk factors, and those with fetal NT > 99th centile, received karyotype analysis and CMA for prenatal diagnosis. Among them, a total of 73 genetic abnormalities were detected, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) with a size of less than 10 Mb. In addition, the 73 women with genetic abnormalities are divided into three groups based on the NT measurement (Group 1: Fetuses with NT > 95th centile and below 99th centile, Group 2: Fetuses with NT > 99th centile, and Group 3: Fetuses with NT > 99th centile). 13.11% (8/61) of pathogenic genetic abnormalities (6 chromosomal aneuploidy, 1 structural abnormality, and 1 likely pathogenic CNV) will be missed if genetic counseling and prenatal genetic testing were not conducted in fetuses with increased NT > 95th centile and below 99th centile combined with other risks. Pathogenic CNVs were the most common abnormalities in group 3, and one likely pathogenic CNV was detected in group 1 and group 3, respectively, and a total of 14 CNVs of unknown clinical significance (VOUS) were detected. CONCLUSIONS: Through this study, we demonstrated that the critical value of NT > 95th centile for invasive detection or NIPT. Invasive testing combined with CMA may be recommended for fetuses with NT > 95th centile and below 99th centile and with other risks. But when isolated NT > 95th centile and below 99th centile, NIPT would be appropriate.

Low-Triggering-Potential and Narrow-Potential-Window Electrochemiluminescence of Silver Nanoclusters for Gene Assay.

A low-triggering potential and a narrow-potential window are anticipated to decrease the electrochemical interference and cross talk of electrochemiluminescence (ECL). Herein, by exploiting the low oxidative potential (0.82 V vs Ag/AgCl) of dihydrolipoic acid-capped sliver nanoclusters (DHLA-AgNCs), a coreactant ECL system of DHLA-AgNCs/hydrazine (N2H4) is proposed to achieve efficient and oxidative-reduction ECL with a low-triggering potential of 0.82 V (vs Ag/AgCl) and a narrow-potential window of 0.22 V. The low-triggering-potential and narrow-potential-window nature of ECL can be primarily preserved upon labeling DHLA-AgNCs to probe DNA and immobilizing DHLA-AgNCs onto the Au surface via sandwiched hybridization, which eventually enables a selective ECL strategy for the gene assay at +0.82 V. This gene assay strategy can sensitively determine the gene of human papillomavirus from 10 to 1000 pM with a low limit of detection of 5 pM (S/N = 3) and would open a way to improve the applied ECL bioassay.

Organic dye-loaded reduced titanium dioxide as a broadband saturable absorber for ultrafast fiber lasers.

As a rising star among metal oxide nanomaterials, titanium dioxide (TiO2) has been widely investigated and employed in optical applications because of its excellent optical properties. In this work, we demonstrate the efficient and broadband nonlinear photonic properties of methylene blue (MB)-loaded reduced TiO2 (TiO2-x-MB) and explore the performance of a TiO2-x-MB-microfiber photonic device in broadband ultrafast photonics. Within an erbium-doped fiber laser (EDFL) system, utilizing the TiO2-x-MB-microfiber photonic device as a saturable absorber (SA), steady mode-locked pulses together with chaotic pulses were successfully achieved at the wavelength of 1.55 µm. Furthermore, by incorporating the TiO2-x-MB SA into a thulium-doped fiber laser (TDFL) system, an ultrashort single pulse and multiple pulses were obtained at 2.0 µm. These results indicate that TiO2-x-MB is an excellent nanomaterial for use in mode-locked lasers, being an alternative candidate for ultrafast fiber lasers via exploiting the chemical and physical properties of oxide nanomaterials.

Exosomal miR-1202 mediates Brodmann Area 44 functional connectivity changes in medication-free patients with major depressive disorder: An fMRI study.

Previous large-sample postmortem study revealed that the expression of miR-1202 in brain tissues from Brodmann area 44 (BA44) was dysregulated in patients with major depressive disorder (MDDs). However, the specific in vivo neuropathological mechanism of miR-1202 as well as its interplay with BA44 circuits in the depressed brain are still unclear. Here, we performed a case-control study with imaging-genetic approach based on resting-state functional magnetic resonance imaging (MRI) data and miR-1202 quantification from 110 medication-free MDDs and 102 healthy controls. Serum-derived circulating exosomes that readily cross the blood-brain barrier were isolated to quantify miR-1202. For validation, repeated MR scans were performed after a six-week follow-up of antidepressant treatment on a cohort of MDDs. Voxelwise factorial analysis revealed two brain areas (including the striatal-thalamic region) in which the effect of depression on the functional connectivity with BA44 was significantly dependent on the expression level of exosomal miR-1202. Moreover, longitudinal change of the BA44 connectivity with the striatal-thalamic region in MDDs after antidepressant treatment was found to be significantly related to the level of miR-1202 expression. These findings revealed that the in vivo neuropathological effect of miR-1202 dysregulation in depression is possibly exerted by mediating neural functional abnormalities in BA44-striatal-thalamic circuits.

Combinational strategy using albumin-based nanoparticles to enable synergetic anti-rheumatic efficacy and reduced hepatotoxicity.

Methotrexate (MTX) is recognized as the golden standard for rheumatoid arthritis (RA) treatment. However, it can cause liver damage in long-term application. Although nanomedicines can target to inflamed sites, most of them tend to accumulate in liver. Glycyrrhizinic acid (GA) holds potential to reverse MTX-associated hepatotoxicity. The combination of GA and MTX might achieve a synergistic anti-inflammatory efficacy and reduced hepatotoxicity. As MTX and GA have totally different in vivo performance, it is necessary to co-encapsulate them in one carrier to coordinate their in vivo fates. Here, we co-delivered MTX and GA to arthritic joints using a human serum albumin-based nanoparticle (HSN). We found the dual drug-loaded albumin nanoparticles (HSN/MTX/GA) could preferentially distribute in inflamed joints, where GA can extend MTX retention by inhibiting the expression of efflux pumps for MTX, thereby exerting synergistic therapeutic effect. In liver tissues, GA was able to reverse the MTX-induced liver damage by activating anti-oxidant defense Nrf2/HO-1 and anti-apoptosis Bcl-2/Bax signaling. We offer a combinational strategy to effectively overcome the MTX-induced hepatotoxicity and enhance the anti-rheumatic efficacy simultaneously. Furthermore, we verified the underlying mechanism about how GA cooperated with MTX in vivo for the first time. Our findings can provide valuable insights for long-term treatment of RA.

Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling.

Key gene mutations are essential for colorectal cancer (CRC) development; however, how the mutated tumor cells impact the surrounding normal cells to promote tumor progression has not been well defined. Here, we report that PIK3CA mutant tumor cells transmit oncogenic signals and result in malignant transformation of intestinal epithelial cells (IECs) via paracrine exosomal arachidonic acid (AA)-induced H3K4 trimethylation. Mechanistically, PIK3CA mutations sustain SGK3-FBW7-mediated stability of the cPLA2 protein, leading to the synthetic increase in AA, which is transported through exosome and accumulated in IECs. Transferred AA directly binds Menin and strengthens the interactions of Menin and MLL1/2 methyltransferase. Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Leaf Senescence Regulation Mechanism Based on Comparative Transcriptome Analysis in Foxtail Millet.

Leaf senescence, a pivotal process in plants, directly influences both crop yield and nutritional quality. Foxtail millet (Setaria italica) is a C4 model crop renowned for its exceptional nutritional value and stress tolerance characteristics. However, there is a lack of research on the identification of senescence-associated genes (SAGs) and the underlying molecular regulatory mechanisms governing this process. In this study, a dark-induced senescence (DIS) experimental system was applied to investigate the extensive physiological and transcriptomic changes in two foxtail millet varieties with different degrees of leaf senescence. The physiological and biochemical indices revealed that the light senescence (LS) variety exhibited a delayed senescence phenotype, whereas the severe senescence (SS) variety exhibited an accelerated senescence phenotype. The most evident differences in gene expression profiles between these two varieties during DIS included photosynthesis, chlorophyll, and lipid metabolism. Comparative transcriptome analysis further revealed a significant up-regulation of genes related to polysaccharide and calcium ion binding, nitrogen utilization, defense response, and malate metabolism in LS. In contrast, the expression of genes associated with redox homeostasis, carbohydrate metabolism, lipid homeostasis, and hormone signaling was significantly altered in SS. Through WGCNA and RT-qPCR analyses, we identified three SAGs that exhibit potential negative regulation towards dark-induced leaf senescence in foxtail millet. This study establishes the foundation for a further comprehensive examination of the regulatory network governing leaf senescence and provides potential genetic resources for manipulating senescence in foxtail millet.

A convolutional neural network prediction model for aviation nitrogen oxides emissions throughout all flight phases.

In recent years, there has been an increasing amount of research on nitrogen oxides (NOx) emissions, and the environmental impact of aviation NOx emissions at cruising altitudes has received widespread attention. NOx may play a crucial role in altering the composition of the atmosphere, particularly regarding ozone formation in the upper troposphere. At present, the ground emission database based on the landing and takeoff (LTO) cycle is more comprehensive, while high-altitude emission data is scarce due to the prohibitively high cost and the inevitable measurement uncertainty associated with in-flight sampling. Therefore, it is necessary to establish a comprehensive NOx emission database for the entire flight envelope, encompassing both ground and cruise phases. This will enable a thorough assessment of the impact of aviation NOx emissions on climate and air quality. In this study, a prediction model has been developed via convolutional neural network (CNN) technology. This model can predict the ground and cruise NOx emission index for turbofan engines and mixed turbofan engines fueled by either conventional aviation kerosene or sustainable aviation fuels (SAFs). The model utilizes data from the engine emission database (EEDB) released by the International Civil Aviation Organization (ICAO) and results obtained from several in-situ emission measurements conducted during ground and cruise phases. The model has been validated by comparing measured and predicted data, and the results demonstrate its high prediction accuracy for both the ground (R2 > 0.95) and cruise phases (R2 > 0.9). This surpasses traditional prediction models that rely on fuel flow rate, such as the Boeing Fuel Flow Method 2 (BFFM2). Furthermore, the model can predict NOx emissions from aircrafts burning SAFs with satisfactory accuracy, facilitating the development of a more complete and accurate aviation NOx emission inventory, which can serve as a basis for aviation environmental and climatic research. SYNOPSIS: The utilization of the ANOEPM-CNN offers a foundation for establishing more precise emission inventories, thereby reducing inaccuracies in assessing the impact of aviation NOx emissions on climate and air quality.

Quantitatively assessing the effect of cervical sagittal alignment on dynamic intervertebral kinematics by video-fluoroscopy technique.

BACKGROUND: Cervical sagittal alignment is crucial for distributing the head load to lower cervical segments and maintaining normal cervical spine function, but its biomechanical effect on the cervical spine was not fully elucidated. OBJECTIVE: To investigate the effect of cervical sagittal alignment on dynamic intervertebral kinematics. DESIGN: Cross-sectional study. METHODS: Healthy participants without neck pain were recruited and divided into lordosis, straight and kyphosis groups according to the C2-C7 Cobb angle at the neutral position. The anti-directional and total joint motions were extracted across 10 epochs of dynamic cervical flexion and extension movements. RESULTS: /findings: The overall anti-directional joint motion during flexion is larger in the kyphosis group when compared with the lordosis group (p = 0.021), while the range of flexion is smaller in the kyphosis group than that in the lordosis group (p = 0.017). The C2/C3 anti-directional joint motion during extension in the straight group is larger than that in the lordosis group (p = 0016). The range of extension in the kyphosis group (p < 0.001) and the straight group (p = 0.002) are larger than that in the lordosis group. The increased range of extension in the kyphosis and straight groups were mainly from the C3/C4, C4/C5, and C5/C6 joints(p < 0.05). CONCLUSION: Changes in cervical sagittal alignment alter both the quality and quantity of the individual joint motions. More adjustments are required by the cervical joints to complete neck movements with the loss of lordosis. The lordotic curvature is a relatively effort-saving mode for the cervical spine from a biomechanical perspective.

Potential-selective electrochemiluminescence of AgInS2/ZnS nanocrystals and its immunoassay application.

Potential-selective electrochemiluminescence (ECL) with tunable maximum-emission-potential ranging from 0.95 to 0.30 V is achieved using AgInS2/ZnS nanocrystals, which is promising in the design of multiplexed bioassay on commercialized ECL setups. The model system AgInS2/ZnS/N2H4 exhibits efficient ECL around 0.30 V and can be exploited for sensitive immunoassays with less electrochemical interference and crosstalk.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

Background: Liver fibrosis is an important clinical endpoint of progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. Objective: To assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. Methods: This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD [primary sclerosing cholangitis (PSC), ASC (autoimmune sclerosing cholangitis), or AIH (autoimmune hepatitis)]. The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within a 6-month interval. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (kPa) for each examination. Laboratory markers of liver fibrosis [aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4)] were recorded. For investigational purposes, one pathologist determined histologic METAVIR liver fibrosis stage, blinded to clinical and MRI data. Spearman rank-order correlation was calculated between MRE liver stiffness and METAVIR liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating METAVIR F0-F1 from F2-F4 fibrosis), calculating sensitivity and specificity at the Youden's index. Results: The study included 46 patients (median [IQR] age, 16.6 [13.7-17.8] years; 20 female, 26 male); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR: 2.2-4.0 kPa). MRE liver stiffness and METAVIR fibrosis stage showed strong positive correlation (rho=0.68). For identifying advanced liver fibrosis, MRE liver stiffness had AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had AUC of 0.72, with sensitivity of 60.0% and specificity of 85.0%; and FIB-4 had AUC of 0.71, with sensitivity of 64.0% and 85.0%. Conclusion: MRE liver stiffness measurements were associated with histologic liver fibrosis severity. Clinical Impact: The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD.

A combined nomogram based on radiomics and hematology to predict the pathological complete response of neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. METHODS: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). RESULTS: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819-0.928) and 0.772 (95% CI: 0.699-0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896-0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models. CONCLUSIONS: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making.

Using the Photo-Piezoelectric Effect of AuPt@BaTiO3 Oxidase Mimetics for Colorimetric Detection of GSH in Serum.

Nanozymes possess major advantages in catalysis and biosensing compared with natural nanozymes. In this study, the AuPt@BaTiO3 bimetallic alloy Schottky junction is prepared to act as oxidase mimetics, and its photo-piezoelectric effect is investigated. The synergy between the photo-piezoelectric effect and the local surface plasmon resonance enhances the directional migration and separation of photogenerated electrons, as well as hot electrons induced by the AuPt bimetallic alloy. This synergy significantly improves the oxidase-like activity. A GSH colorimetric detection platform is developed based on this fading principle. Leveraging the photo-piezoelectric effect allows for highly sensitive detection with a low detection limit (0.225 µM) and reduces the detection time from 10 min to 3 min. The high recovery rate (ranging from 99.91% to 101.8%) in actual serum detection suggests promising potential for practical applications. The development of bimetallic alloy heterojunctions presents new opportunities for creating efficient nanozymes.

Effects of Heating Treatment on the Physicochemical and Volatile Flavor Properties of Argentinian Shortfin Squid (Illex argentinus).

In this study, the effect of different heating temperatures (80, 90, 100, and 121 °C) on the physicochemical and volatile flavor properties of fried mantles (Argentinian shortfin) was investigated. The squid mantles were soaked in a maltose syrup solution (20% w/v) for 10 s and fried in soybean oil for 10 s (160 °C), vacuum-packed, and processed at different temperatures for 10 min. Then, the squid mantles were subjected to colorimetric analysis, sensory evaluation, free amino acid analysis, and texture profile analysis. In addition, the volatile organic compounds (VOCs) in the squid mantles were analyzed. The results revealed that lower treating temperatures (80 and 90 °C) improved the chromatic and textural properties, along with organoleptic perception. Additionally, the content of amino acid in the squid mantles treated at 121 °C was significantly lower than that of the samples treated at other temperatures (p < 0.05). Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was used to detect 41 VOCs, including their monomers and dimers. Among these detected VOCs, the contents of alcohols, ketones, and pyrazines were positively correlated with temperature. However, the content of aldehydes in the squid mantles gradually decreased as the heating temperature increased (p < 0.05). The combined HS-GC-IMS and E-nose results revealed that the lower temperatures (80 and 90 °C) were more suitable for flavor development and practical processing. This study provides valuable information for properly controlling the heating process of squid products, as well as flavor and practical applications for the aquatic industry.

Towards molecular alloys: computational and experimental studies on (p-NCC6F4CNSeSeN)x(p-NCC6F4CNSSN)1-x.

The ß-phase of the radical p-NCC6F4CNSSN (1ß) crystallizes in the orthorhombic space group Fdd2 and orders as a canted antiferromagnet with TN = 36 K. Computational studies (B3LYP or M06-2X functional with the cc-pVTZ-PP(-F)+basis set) of the microscopic nearest-neighbour magnetic exchange coupling in 1ß and in the hypothetical isomorphous phase of the selenium radical p-NCC6F4CNSeSeN (2ß) revealed that replacement of S by Se should lead to a significant enhancement in the magnetic ordering temperature by ca. 20% (B3LYP) - 30% (M06-2X). Recrystallization of 2 from solution or via vacuum sublimation afforded only the known diamagnetic, dimeric phase, 2α. Computational studies indicated that both the molecular geometry and charge distribution for 1 and 2 are extremely similar and experimental approaches to form alloys of the general form 11-x2x were explored: attempts to cosublime 1 and 2in vacuo were unsuccessful, forming only 1ß due to the low volatility of 2. Crystallization of pure 1 by solution evaporation was found to afford polymorph 1α (triclinic, P1̄) selectively, irrespective of the solvent employed (CH2Cl2, MeCN, PhMe or THF) but 1α transformed to 1ß upon subsequent vacuum sublimation. Crystallization of 1 in the presence of 2 (up to 20 mol%) from solution evaporation was examined. At 20 mol% there was clear evidence for formation of both 1α and 2α as distinct crystallographic phases by powder X-ray diffraction (PXRD) but some evidence for doping of 2 into 1α at low concentration (≤15 mol percent) was observed. Attempts to sublime a sample of 10.920.1 led to phase separation with the isolation of needle-shaped crystals of pure 1ß characterized by X-ray diffraction.

Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study.

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging.

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.

Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.