Spatial transcriptomics reveals light-induced chlorenchyma cells involved in promoting shoot regeneration in tomato callus.

Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding of the cellular and molecular aspects of shoot regeneration in tomato callus and demonstrate the immense potential of spatial transcriptomics in plant biology.

Flexocatalysis Enhances Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.

Theoretical study of highly efficient VS2-based single-atom catalysts for lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries have become a research hotspot due to their high energy density. However, they also have certain disadvantages and limitations. To enhance the performance of Li-S batteries, this study focuses on the utilization of transition metal (TM)-embedded vanadium disulfide (VS2) materials as cathode catalysts. Using density functional theory (DFT), comprehensive calculations and atomic-level screening of ten TM atoms were conducted to understand the underlying mechanisms and explore the potential of TM@VS2 catalysts for enhancing battery performance. The computational results indicate that five selected catalysts possess sufficient bonding strength towards high-order lithium polysulfide intermediates by the formation of a significant covalent bond between S atoms in Li2Sn and TM atoms, thereby effectively suppressing the shuttle effect. The Ni@VS2 catalyst can effectively decrease the decomposition energy barrier of Li2S in the charge reaction and can have an optimal Gibbs free energy at the rate-determining step among TM@VS2 catalysts for the discharge reaction. This study elucidates the mechanism of VS2-based transition-metal single-atom catalysts and provides an effective reference for the anchoring of TM atoms on other materials.

Analysis of asthma incidence and mortality rates among children aged 0-14 in 204 countries from 1990 to 2019.

OBJECTIVE: Asthma is a common chronic respiratory disease in children. Understanding incidence and mortality trends is crucial for prevention and intervention strategies. METHODS: Data from the Global Burden of Disease (GBD) study were used to analyze asthma incidence and mortality trends among children aged 0-14 in 204 countries from 1990 to 2019. The 30-year trends were calculated using the Estimated Annual Percentage Change (EAPC). RESULTS: Globally, pediatric asthma cases increased from 18,857,697 in 1990 to 20,191,786 in 2019. Incidence rates for children <5, 5-9, and 10-14 years are 1509.36, 980.25, and 586.95 per 100,000, respectively. Over 30 years, pediatric asthma mortality rates significantly decreased from 1.59 to 0.51 per 100,000, with minimal gender differences. High-income North America, Tropical Latin America, and the Caribbean show the highest incidence rates at 3203.2, 2493.83, and 2314.8 per 100,000. The USA, Puerto Rico, and Haiti have the highest national rates at 3357.17, 2695.30, and 2605.38 per 100,000. Regions with higher Sociodemographic Index levels tend to have higher incidence rates. Pediatric asthma prevalence varies by region and age group. CONCLUSION: Our study of asthma incidence and mortality rates among children aged 0-14 across 204 countries from 1990 to 2019 reveals significant global disparities. These findings underscore the influence of socioeconomic and environmental factors on asthma prevalence and outcomes.

Efficient degradation of ciprofloxacin in wastewater by CuFe2O4/CuS photocatalyst activated peroxynomosulfate.

In this study, CuFe2O4/CuS composite photocatalysts were successfully synthesized for the activation of peroxynomosulfate to remove ciprofloxacin from wastewater. The structural composition and morphology of the materials were analyzed by XRD, SEM, TEM, and Raman spectroscopy. The electrochemical properties of the samples were tested by an electrochemical workstation. The band gap of the samples was calculated by DFT and compared with the experimental values. The effects of different catalysts, oxidant PMS concentrations, and coexisting ions on the experiments were investigated. The reusability and stability of the photocatalysts were also investigated. The mechanism of the photocatalytic degradation process was proposed based on the free radical trapping experiment. The results show that the p-p heterojunction formed between the two contact surfaces of the CuFe2O4 nanoparticle and CuS promoted the charge transfer between the interfaces and inhibited the recombination of electrons and holes. CuFe2O4-5/CuS photocatalyst has the best catalytic activity, and the removal rate of ciprofloxacin is 93.7%. The intermediates in the degradation process were tested by liquid chromatography-mass spectrometry (LC-MS), and the molecular structure characteristics of ciprofloxacin were analyzed by combining with DFT calculations. The possible degradation pathways of pollutants were proposed. This study reveals the great potential of the photocatalyst CuFe2O4/CuS in the activation of PMS for the degradation of ciprofloxacin wastewater.

Status of Professional Identity, Self-Directed Learning Competence, and Self-Efficacy Among Central Sterile Supply Department Nurses.

BACKGROUND Previous studies on professional identity, self-directed learning competence, and self-efficacy among central sterile supply department (CSSD) nurses are rare. We investigated the status of these 3 characteristics among CSSD nurses and offered suggestions, to provide a reference for CSSD talent development. MATERIAL AND METHODS CSSD nurses working in 45 hospitals in southwest China were invited to participate in a questionnaire survey in August 2021. The survey comprised a general information questionnaire, a self-directed learning competence rating scale, a professional identity scale, and a general self-efficacy scale. RESULTS The CSSD nurses' scores for professional identity, self-directed learning competence, and self-efficacy were 109.92±17.161, 125.77±21.316, and 26.92±6.633, respectively. For professional identity, statistically significant differences were identified (P≤0.05) for 3 factors: monthly income, reason for studying nursing, and reason for working in the CSSD. For self-directed learning competence, statistically significant differences (P≤0.05) were identified for 5 factors: age, hospital grade, type of employee, monthly income, and reason for working in the CSSD. For self-efficacy, statistically significant differences were identified (P≤0.05) for 3 factors: age, reason for studying nursing and working in the CSSD, and whether the CSSD nurses wished their children to become nurses. CONCLUSIONS The professional identity, self-directed learning competence, and self-efficacy of the CSSD nurses in this study were at the medium level. More attention should be paid to career planning of young nurses and improvement of their professional identity and self-directed learning competence.

Liver fat volume fraction measurements based on multi-material decomposition algorithm in patients with nonalcoholic fatty liver disease: the influences of blood vessel, location, and iodine contrast.

BACKGROUND: In recent years, spectral CT-derived liver fat quantification method named multi-material decomposition (MMD) is playing an increasingly important role as an imaging biomarker of hepatic steatosis. However, there are various measurement ways with various results among different researches, and the impact of measurement methods on the research results is unknown. The aim of this study is to evaluate the reproducibility of liver fat volume fraction (FVF) using MMD algorithm in nonalcoholic fatty liver disease (NAFLD) patients when taking blood vessel, location, and iodine contrast into account during measurement. METHODS: This retrospective study was approved by the institutional ethics committee, and the requirement for informed consent was waived because of the retrospective nature of the study. 101 patients with NAFLD were enrolled in this study. Participants underwent non-contrast phase (NCP) and two-phase enhanced CT scanning (late arterial phase (LAP) and portal vein phase (PVP)) with spectral mode. Regions of interest (ROIs) were placed at right posterior lobe (RPL), right anterior lobe (RAL) and left lateral lobe (LLL) to obtain FVF values on liver fat images without and with the reference of enhanced CT images. The differences of FVF values measured under different conditions (ROI locations, with/without enhancement reference, NCP and enhanced phases) were compared. Friedman test was used to compare FVF values among three phases for each lobe, while the consistency of FVF values was assessed between each two phases using Bland-Altman analysis. RESULTS: Significant difference was found between FVF values obtained without and with the reference of enhanced CT images. There was no significant difference about FVF values obtained from NCP images under the reference of enhanced CT images between any two lobes or among three lobes. The FVF value increased after the contrast injection, and there were significant differences in the FVF values among three scanning phases. Poor consistencies of FVF values between each two phases were found in each lobe by Bland-Altman analysis. CONCLUSION: MMD algorithm quantifying hepatic fat was reproducible among different lobes, while was influenced by blood vessel and iodine contrast.

Exposure to high concentrations of triphenyl phosphate altered functional performance, liver metabolism and intestinal bacterial composition of aquatic turtles.

Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.

Environmentally Relevant Levels of Antiepileptic Carbamazepine Altered Intestinal Microbial Composition and Metabolites in Amphibian Larvae.

There is growing concern about the potential ecological risks posed by pharmaceutical residues in the aquatic environment. However, our understanding of the toxic effects of antiepileptic pharmaceuticals, such as carbamazepine (CBZ), on aquatic animal larvae is still limited. In this study, the tadpoles of the black-spotted pond frog (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of CBZ (0.3 and 3.0 µg/L) for 30 days, and their growth, intestinal microbial composition, and metabolites were investigated to assess the potential toxic effects of CBZ in non-targeted aquatic organisms. Some tadpoles died during exposure, but there was no significant among-group difference in the survival and growth rates. CBZ exposure significantly altered the composition of tadpole intestinal microbiota. Relative abundances of some bacterial genera (e.g., Blautia, Prevotella, Bacillus, Microbacterium, etc.) decreased, while others (e.g., Paucibacter, etc.) increased in CBZ-exposed tadpoles. Interestingly, CBZ-induced alterations in some bacteria might not necessarily lead to adverse outcomes for animals. Meanwhile, small molecular intestinal metabolites related to energy metabolism, and antioxidant and anti-inflammatory activities were also altered after exposure. Taken together, environmentally relevant levels of CBZ might alter the metabolic and immune performances of amphibian larvae by modifying the abundance of some specific bacteria and the level of metabolites in their intestines, thereby potentially causing a long-term effect on their fitness.

Predicting and analyzing the algal population dynamics of a grass-type lake with explainable machine learning.

Algal blooms, exacerbated by climate change and eutrophication, have emerged as a global concern. In this study, we introduce a novel interpretable machine learning (ML) workflow tailored for investigating the dynamics of algal populations in grass-type lakes, Liangzi lake. Utilizing seven ML methods and incorporating the covariance matrix adaptation evolution strategy (CMA-ES), we predict algal density across three distinct time periods, resulting in the construction of a total of 30 ML models. The CMA-ES-CatBoost model consistently demonstrates superior predictive accuracy and generalization capability across these periods. Through the collective validation of various interpretable tools, we identify water temperature and permanganate index as the two most critical water quality parameters (WQIs) influencing algal density in Liangzi Lake. Additionally, we quantify the independent and interactive effects of WQIs on algal density, pinpointing key thresholds and trends. Furthermore, we determine the minimum combination of WQIs that achieves near-optimal predictive performance, striking a balance between accuracy and cost-effectiveness. These findings offer a scientific and economically efficient foundation for governmental agencies to formulate strategies for water quality management and sustainable development.

Similarity and diversity of genetic architecture for complex traits between East Asian and European populations.

BACKGROUND: Genome-wide association studies have detected a large number of single-nucleotide polymorphisms (SNPs) associated with complex traits in diverse ancestral groups. However, the trans-ethnic similarity and diversity of genetic architecture is not well understood currently. RESULTS: By leveraging summary statistics of 37 traits from East Asian (Nmax=254,373) or European (Nmax=693,529) populations, we first evaluated the trans-ethnic genetic correlation (ρg) and found substantial evidence of shared genetic overlap underlying these traits between the two populations, with [Formula: see text] ranging from 0.53 (se = 0.11) for adult-onset asthma to 0.98 (se = 0.17) for hemoglobin A1c. However, 88.9% of the genetic correlation estimates were significantly less than one, indicating potential heterogeneity in genetic effect across populations. We next identified common associated SNPs using the conjunction conditional false discovery rate method and observed 21.7% of trait-associated SNPs can be identified simultaneously in both populations. Among these shared associated SNPs, 20.8% showed heterogeneous influence on traits between the two ancestral populations. Moreover, we demonstrated that population-common associated SNPs often exhibited more consistent linkage disequilibrium and allele frequency pattern across ancestral groups compared to population-specific or null ones. We also revealed population-specific associated SNPs were much likely to undergo natural selection compared to population-common associated SNPs. CONCLUSIONS: Our study provides an in-depth understanding of similarity and diversity regarding genetic architecture for complex traits across diverse populations, and can assist in trans-ethnic association analysis, genetic risk prediction, and causal variant fine mapping.

Evaluating significance of European-associated index SNPs in the East Asian population for 31 complex phenotypes.

BACKGROUND: Genome-wide association studies (GWASs) have identified many single-nucleotide polymorphisms (SNPs) associated with complex phenotypes in the European (EUR) population; however, the extent to which EUR-associated SNPs can be generalized to other populations such as East Asian (EAS) is not clear. RESULTS: By leveraging summary statistics of 31 phenotypes in the EUR and EAS populations, we first evaluated the difference in heritability between the two populations and calculated the trans-ethnic genetic correlation. We observed the heritability estimates of some phenotypes varied substantially across populations and 53.3% of trans-ethnic genetic correlations were significantly smaller than one. Next, we examined whether EUR-associated SNPs of these phenotypes could be identified in EAS using the trans-ethnic false discovery rate method while accounting for winner's curse for SNP effect in EUR and difference of sample sizes in EAS. We found on average 54.5% of EUR-associated SNPs were also significant in EAS. Furthermore, we discovered non-significant SNPs had higher effect heterogeneity, and significant SNPs showed more consistent linkage disequilibrium and allele frequency patterns between the two populations. We also demonstrated non-significant SNPs were more likely to undergo natural selection. CONCLUSIONS: Our study revealed the extent to which EUR-associated SNPs could be significant in the EAS population and offered deep insights into the similarity and diversity of genetic architectures underlying phenotypes in distinct ancestral groups.

A Spike-Control Approach that Evaluates High Resolution Mass Spectrometry-Based Sequence Variant Analytical Method Performance for Therapeutic Proteins.

An amino acid sequence variant (SV) is defined as an unintended amino acid substitution in protein drug products. SVs contribute to product heterogeneity and can potentially impact product quality, safety, immunogenicity, and efficacy. The analysis of biotherapeutics for SVs is important throughout the product life cycle including clone selection, development of nutrient feed strategies, commercial manufacturing process, and post-approval changes to monitor product quality. The proposed analytical procedure for SVs consists of both qualitative (identification of SVs) and quantitative (quantitation of identified SVs) components. The complexities of SV analysis and the variety of current procedures highlight the need for a systematic approach for assessing the capability of these methodologies to reliably identify and quantitate SVs in biotherapeutics. We described here a "spike-control" approach for evaluating SV analytical procedure. The concept was adopted from quality control samples routinely used in analytical procedure validation. One FDA approved monoclonal antibody (mAb) was spiked with accurate amounts of highly homologous mAb to create mAb samples containing low yet accurate levels of "artificial" SVs. Spike-control samples were denatured, reduced, alkylated, digested and then analyzed by high resolution Orbitrap mass spectrometry. In silico analysis revealed four single amino acid differences between the two mAbs that could be used to represent SVs in the spike-control samples. All four "artificial" SVs were reliably identified by the current workflow. Analytical range (0.01% to 2%), accuracy and precision of identified SVs have also been evaluated. Overall, spike-control sample(s) helped to demonstrate that the SV analytical procedure (i.e., sample preparation, LC separation, mass spectrometry determinations and bioinformatic software) was fit for purpose and suitable for the identification and quantitation of SVs at a pre-determined threshold.

TRCCBP: Transformer Network for Radar-Based Contactless Continuous Blood Pressure Monitoring.

Contactless continuous blood pressure (BP) monitoring is of great significance for daily healthcare. Radar-based continuous monitoring methods typically extract time-domain features manually such as pulse transit time (PTT) to calculate the BP. However, breathing and slight body movements usually distort the features extracted from pulse-wave signals, especially in long-term continuous monitoring, and manually extracted features may have limited performance for BP estimation. This article proposes a Transformer network for Radar-based Contactless Continuous Blood Pressure monitoring (TRCCBP). A heartbeat signal-guided single-beat pulse wave extraction method is designed to obtain pure pulse-wave signals. A transformer network-based blood pressure estimation network is proposed to estimate BP, which utilizes convolutional layers with different scales, a gated recurrent unit (GRU) to capture time-dependence in continuous radar signal and multi-head attention modules to capture deep temporal domain characteristics. A radar signal dataset captured in an indoor environment containing 31 persons and a real medical situation containing five persons is set up to evaluate the performance of TRCCBP. Compared with the state-of-the-art method, the average accuracy of diastolic blood pressure (DBP) and systolic blood pressure (SBP) is 4.49 mmHg and 4.73 mmHg, improved by 12.36 mmHg and 8.80 mmHg, respectively. The proposed TRCCBP source codes and radar signal dataset have been made open-source online for further research.

Application of bridge-link type combined fixation system in the treatment of trifocal femoral fractures.

PURPOSE: Ipsilateral combined fractures of the proximal femur, femoral shaft, and distal femur, though uncommon, present significant treatment challenges for orthopaedic surgeons. This retrospective study aims to investigate the intraoperative and long-term postoperative outcomes of this combination fracture when treated using a bridge-link type combined fixation system (BCFS). PATIENTS AND METHODS: Four individuals received treatment at a level 1 trauma centre between January 2013 and December 2017 for combined fractures of the proximal femur, femoral shaft, and distal femur. The medical records of these patients were retrospectively examined. In addition to minimally invasive percutaneous plate osteosynthesis (MIO), all patients underwent BCFS. RESULTS: The median follow-up period for each patient was 28.5 months. The median duration of the surgical procedure was 176.0 min, with intraoperative haemorrhage measured at 470.0 ml. Among the cases, three patients showed firm union of the femoral shaft fractures. However, one patient experienced nonunion 12 months after the procedure, while another patient suffered from refracture of the femoral shaft and postoperative avascular necrosis of the femoral head. At the time of the last follow-up, the Friedman-Wyman functional scores were excellent in one case, good in two cases, and fair in one case. CONCLUSIONS: Trifocal femoral fractures lack a widely approved therapeutic strategy. Nonetheless, BCFS may present itself as a viable alternative for treating this type of fracture, offering positive clinical outcomes.

Comparative Analysis of Water-Soluble Polysaccharides from Dendrobium Second Love 'Tokimeki' and Dendrobium nobile in Structure, Antioxidant, and Anti-Tumor Activity In Vitro.

With potential anti-tumor and antioxidant properties, the polysaccharide content of D. nobile is relatively lower than that of the other medicinal Dendrobium. To find high-content polysaccharide resources, the polysaccharide (DHPP-Ⅰs) was prepared from D. Second Love 'Tokimeki' (a D. nobile hybrid) and compared with DNPP-Ⅰs from D. nobile. DHPP-Is (Mn 31.09 kDa) and DNPP-Is (Mn 46.65 kDa) were found to be O-acetylated glucomannans (-Glcp-(1,4) and O-acetylated-D-Manp-(1,4) backbones), analogous to other Dendrobium polysaccharides. DHPP-Ⅰs had higher glucose content (31.1%) and a lower degree (0.16) of acetylation than DNPP-Ⅰs (15.8%, 0.28). Meanwhile, DHPP-Ⅰs and DNPP-Ⅰs had the same ability in the radical scavenging assay, which was milder than the control of Vc. Both DHPP-Is and DNPP-Is inhibited SPC-A-1 cell proliferation in vitro, with obvious differences in dose concentrations (0.5-2.0 mg/mL) and treatment times (24-72 h). Therefore, the antioxidant activity of DHPP-Ⅰs and DNPP-Ⅰs is not associated with distinction in anti-proliferative activity. As a glucomannan derived from non-medicinal Dendrobium, DHPP-Ⅰs has similar bioactivity to other medicinal Dendrobium, and this could serve as a starting point for studying the conformational-bioactivity relationship of Dendrobium polysaccharides.

[Analysis of phenotype and pathogenic variants in a Chinese pedigree affected with Multiple synostoses syndrome type 1].

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1). METHODS: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were carried out for the proband and her parents. RESULTS: The pedigree has comprised of 14 members from three generations, of whom six had manifested hearing loss, with other symptoms including proximal symphalangism, hemicylindrical nose, amblyopia, strabismus, brachydactyly, incomplete syndactyly, which fulfilled the diagnostic criteria for SYNS1. WES had detected no pathogenic single nucleotide variants and insertion-deletion (InDel) in the coding region of the NOG gene, whilst copy number variation (CNV) analysis indicated that there was a heterozygous deletion involving the NOG gene. WGS revealed a heterozygous deletion (54171786_55143998) in 17q22 of the proband. The CNV was classified as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION: The heterozygous deletion in 17p22 involving the NOG gene probably underlay the pathogenesis of SYNS1 in this pedigree. Above finding has enriched the mutational spectrum of NOG. CNV should be considered when conventional sequencing has failed to detect any pathogenic variants in such patients.

Application of Cortical Bone Plate Allografts Combined with Less Invasive Stabilization System (LISS) Plates in Fixation of Comminuted Distal Femur Fractures.

Background and Objectives: At present, the management of comminuted distal femur fractures remains challenging for orthopedic surgeons. The aim of this study is to report a surgical treatment for comminuted distal femur fractures using supplementary medial cortical bone plate allografts in conjunction with the lateral less invasive stabilization system (LISS) plates. Materials and Methods: From January 2009 to January 2014, the records of thirty-three patients who underwent supplementary medial cortical bone plate allografts combined with lateral LISS plates fixation were reviewed. Clinical and radiographic data were collected during regular postoperative follow-up visits. Functional outcomes were determined according to the special surgery knee rating scale (HSS) used at the hospital. Results: Thirty patients were followed for 13 to 73 months after surgery, with an average follow-up time of 31.3 months. The mean time to bone union was 5.4 months (range of 3-12 months) and the mean range of knee flexion was 105.6° (range of 80-130°). Of the remaining patients, 10 had a score of "Excellent", while 10 had a score of "Good". Three patients had superficial or deep infections, one patient had nonunion that required bone grafting, and one patient had post-traumatic knee arthritis. Conclusions: Based on these promising results, we propose that supplementary medial cortical bone plate allografts combined with lateral LISS plate fixation may be a good treatment option for comminuted distal femur fractures. This treatment choice not only resulted in markedly improved stability on the medial side of the femur, but also satisfactory outcomes for distal femoral fractures.

Matrix Gla protein (MGP), GATA3, and TRPS1: a novel diagnostic panel to determine breast origin.

BACKGROUND: Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs. RESULTS: MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas. CONCLUSIONS: Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.

Aqueous metabolome of tissue-specific conditional Pten-knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma.

BACKGROUND: Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of Pten-KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa). METHODS: Three matched pairs of tissue-specific conditional Pten-KO mouse prostate and WT prostate of litter/cage-mates at 20-22 weeks of age and three pairs of TRAMP NECa versus WT (28-31 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography-tandem mass spectrometry. RESULTS: The Pten-KO prostate increased purine nucleotide pools, cystathionine, and both reduced and oxidized glutathione (GSH, GSSG), and gluconate/glucuronate species in addition to cholesteryl sulfate and polyamine precursor ornithine. On the contrary, Pten-KO prostate contained diminished pools of glycolytic intermediates and phosphorylcholine derivatives, select amino acids, and their metabolites. Bioinformatic integration revealed a significant shunting of glucose away from glycolysis-citrate cycle and glycerol-lipid genesis to pentose phosphate cycle for NADPH/GSH/GSSG redox and pentose moieties for purine and pyrimidine nucleotides, and glycosylation/glucuronidation. Implicit arginine catabolism to ornithine was consistent with immunosuppression in Pten-KO model. While also increased in cystathionine-GSH/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at the expense of glycolysis-citrate cycle, the TRAMP NECa increased abundance of many amino acids, methyl donor S-adenosyl-methionine, and intermediates for phospholipids without increasing cholesteryl sulfate or ornithine. CONCLUSIONS: The aqueous metabolomic patterns in Pten-KO prostate and TRAMP NECa shared similarities in the greater pools of cystathionine, GSH/GSSG redox pair, and nucleotides and shunting away from glycolysis-citrate cycle in both models. Remarkable metabolic distinctions between them included metabolisms of many amino acids (protein synthesis; arginine-ornithine/immune suppression) and cholesteryl sulfate and methylation donor for epigenetic regulations.