Quantitative Analysis of Primary Compressive Trabeculae Distribution in the Proximal Femur of the Elderly.

OBJECTIVE: As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load-bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. METHODS: This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck-shaft angle (NSA), the angle between the PCT-axis and the head-neck axis (α), the distance from the femoral head center to the PCT-axis (δ), and the lengths of the PCT's bottom and top boundaries (L-bottom and L-top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t-test or Mann-Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. RESULTS: PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = -0.689, p < 0.001), and R and L-top (r = 0.623, p < 0.001), with mild correlations observed between δ and NSA (r = -0.487, p < 0.001), and R and L-bottom (r = 0.427, p < 0.001). Importantly, our study establishes a method to accurately localize PCT distribution in true anteroposterior (AP) radiographs of the hip joint, facilitating precise screw placement in proximal femur fixation procedures. CONCLUSION: Our study provided unprecedented insights into the distribution patterns of PCT in the proximal femur of the elderly population. The distribution of PCT in the proximal femur is predominantly influenced by anatomical and geometric factors, such as NSA and femoral head size, rather than demographic factors like gender. These insights have crucial implications for the design of internal fixation devices and surgical planning, offering objective guidance for the placement of screws in hip fracture treatments.

Macrophages and pulmonary fibrosis: a bibliometric and visual analysis of publications from 1990 to 2023.

Background: The role of macrophages in the symptomatic and structural progression of pulmonary fibrosis (PF) has garnered significant scholarly attention in recent years. This study employs a bibliometric approach to examine the present research status and areas of focus regarding the correlation between macrophages and PF, aiming to provide a comprehensive understanding of their relationship. Methodology: The present study employed VOSviewer, CiteSpace, and Microsoft Excel software to visualize and analyze various aspects such as countries, institutions, authors, journals, co-cited literature, keywords, related genes, and diseases. These analyses were conducted using the Web of Science core collection database. Results: A comprehensive collection of 3,479 records pertaining to macrophages and PF from the period of 1990 to 2023 was obtained. Over the years, there has been a consistent increase in research literature on this topic. Notably, the United States and China exhibited the highest level of collaboration in this field. Through careful analysis, the institutions, authors, and prominent journals that hold significant influence within this particular field have been identified as having the highest publication output. The pertinent research primarily concentrates on the domains of Biology and Medicine. The prevailing keywords encompass pulmonary fibrosis, acute lung injury, idiopathic pulmonary fibrosis, and others. Notably, TGFß1, TNF, and CXCL8 emerge as the most frequently studied targets, primarily associated with signaling pathways such as cytokine-cytokine receptor interaction. Additionally, cluster analysis of related diseases reveals their interconnectedness with ailments such as cancer. Conclusion: The present study employed bibliometric methods to investigate the knowledge structure and developmental trends in the realm of macrophage and PF research. The findings shed light on the introduction and research hotspots that facilitate a more comprehensive understanding of macrophages and PF.

Mn/carbon aerogels derived from the water-induced self-assembly of UIO-66 (Mn) for the thermal decomposition of ammonium perchlorate.

In solid propellants, combustion catalysts play a crucial role. Here, we introduce a convenient method for the self-assembly of UIO-66 (Mn) in the presence of water, leading to the preparation of Mn/C aerogels. The aerogels were successfully utilized in the thermocatalytic decomposition of ammonium perchlorate (AP). The results indicate that the incorporation of 2% mass fraction of Mn/C aerogels enhances the peak temperature of AP decomposition by approximately 87.5°C. Mn/C aerogels demonstrate excellent catalytic performance. In combination with kinetics, we propose a thermal catalytic mechanism.

Diisodecyl phenyl phosphate promotes foam cell formation by antagonizing Liver X receptor alpha.

While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 µM. We showed that treatment of an in vitro macrophage model with 1 to 10 µM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.

Abnormal platelet parameters in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet parameters among IBD patients, inconsistencies persist, and these parameters lack standardization for diagnosis or clinical assessment. METHODS: A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for relevant articles published up to December 16th, 2023. A random-effects model was employed to pool the weighted mean difference (WMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) between IBD patients and healthy controls, and subgroup analyses were performed. RESULTS: The meta-analysis included 79 articles with 8,350 IBD patients and 13,181 healthy individuals. The results revealed significantly increased PLT and PCT levels (WMD: 69.910, 95% CI: 62.177, 77.643 109/L; WMD: 0.046%, 95% CI: 0.031%, 0.061%), and decreased MPV levels (WMD: -0.912, 95% CI: -1.086, -0.739 fL) in IBD patients compared to healthy individuals. No significant difference was found in PDW between the IBD and control groups (WMD: -0.207%, 95% CI: -0.655%, 0.241%). Subgroup analysis by disease type and disease activity showed no change in the differences for PLT, PCT, and MPV in the ulcerative colitis and Crohn's disease groups, as well as the active and inactive groups. Notably, the active group exhibited significantly lower PDW levels than the control group (WMD: -1.138%, 95% CI: -1.535%, -0.741%). CONCLUSIONS: Compared with healthy individuals, IBD patients display significantly higher PLT and PCT and significantly lower MPV. Monitoring the clinical manifestations of platelet abnormalities serves as a valuable means to obtain diagnostic and prognostic information. Conversely, proactive measures should be taken to prevent the consequences of platelet abnormalities in individuals with IBD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023493848.

Seasonal variation in BCG-induced trained immunity.

The Bacille Calmette-Guerin (BCG) vaccine is a well-established inducer of innate immune memory (also termed trained immunity), causing increased cytokine production upon heterologous secondary stimulation. Innate immune responses are known to be influenced by season, but whether seasons impact induction of trained immunity is not known. To explore the influence of season on innate immune memory induced by the BCG vaccine, we vaccinated healthy volunteers with BCG either during winter or spring. Three months later, we measured the ex vivo cytokine responses against heterologous stimuli, analyzed gene expressions and epigenetic signatures of the immune cells, and compared these with the baseline before vaccination. BCG vaccination during winter induced a stronger increase in the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) upon stimulation with different bacterial and fungal stimuli, compared to BCG vaccination in spring. In contrast, winter BCG vaccination resulted in lower IFNγ release in PBMCs compared to spring BCG vaccination. Furthermore, NK cells of the winter-vaccinated people had a greater pro-inflammatory cytokine and IFNγ production capacity upon heterologous stimulation. BCG had only minor effects on the transcriptome of monocytes 3 months later. In contrast, we identified season-dependent epigenetic changes in monocytes and NK cells induced by vaccination, partly explaining the higher immune cell reactivity in the winter BCG vaccination group. These results suggest that BCG vaccination during winter is more prone to induce a robust trained immunity response by activating and reprogramming the immune cells, especially NK cells. (Dutch clinical trial registry no. NL58219.091.16).

Machine learning-based diagnosis and prognosis of IgAN: A systematic review and meta-analysis.

Purpose: Plenty of studies have explored the diagnosis and prognosis of IgA nephropathy (IgAN) based on machine learning (ML), but the accuracy lacks the support of evidence-based medical evidence. We aim at this problem to guide the precision treatment of IgAN. Methods: Embase, Pubmed, Cochrane Library, and Web of Science were searched systematically until February 24th, 2024, for publications on ML-based diagnosis and prognosis of IgAN. Subgroup analysis or meta-regression was conducted according to modeling method, follow-up time, endpoint definition, and variable type. Further, the rank sum test was applied to compare the discrimination ability of prognosis. Results: A total of 47 studies involving 51,935 patients were eligible. Among the 38 diagnostic models, the pooled C-index was 0.902 (95 % CI: 0.878-0.926) in 27 diagnostic models. Of the 162 prognostic models, the C-index for model discrimination of 144 prognostic models was 0.838 (95 % CI: 0.827-0.850) in training. The overall discrimination ability of prognosis was as follows: COX regression > new ML models (e.g. ANN, DT, RF, SVM, XGBoost) > traditional ML models (logistic regression) > Naïve Bayesian network (P < 0.05). External validation of IIgAN-RPT in 19 models showed a pooled C-index of 0.801 (95 % CI: 0.784-0.817). Conclusions: New ML models have shown application values that are as good as traditional ML models, both in diagnosis and prognosis. In addition, future models are desired to use a more sensitive prognostic endpoint (albuminuria), improve predictive ability in moderate progression risk, and ultimately translate into clinically applicable intelligent tools.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

Differentiation of glioma and solitary brain metastasis: a multi-parameter magnetic resonance imaging study using histogram analysis.

BACKGROUND: Differentiation of glioma and solitary brain metastasis (SBM), which requires biopsy or multi-disciplinary diagnosis, remains sophisticated clinically. Histogram analysis of MR diffusion or molecular imaging hasn't been fully investigated for the differentiation and may have the potential to improve it. METHODS: A total of 65 patients with newly diagnosed glioma or metastases were enrolled. All patients underwent DWI, IVIM, and APTW, as well as the T1W, T2W, T2FLAIR, and contrast-enhanced T1W imaging. The histogram features of apparent diffusion coefficient (ADC) from DWI, slow diffusion coefficient (Dslow), perfusion fraction (frac), fast diffusion coefficient (Dfast) from IVIM, and MTRasym@3.5ppm from APTWI were extracted from the tumor parenchyma and compared between glioma and SBM. Parameters with significant differences were analyzed with the logistics regression and receiver operator curves to explore the optimal model and compare the differentiation performance. RESULTS: Higher ADCkurtosis (P = 0.022), frackurtosis (P<0.001),and fracskewness (P<0.001) were found for glioma, while higher (MTRasym@3.5ppm)10 (P = 0.045), frac10 (P<0.001),frac90 (P = 0.001), fracmean (P<0.001), and fracentropy (P<0.001) were observed for SBM. frackurtosis (OR = 0.431, 95%CI 0.256-0.723, P = 0.002) was independent factor for SBM differentiation. The model combining (MTRasym@3.5ppm)10, frac10, and frackurtosis showed an AUC of 0.857 (sensitivity: 0.857, specificity: 0.750), while the model combined with frac10 and frackurtosis had an AUC of 0.824 (sensitivity: 0.952, specificity: 0.591). There was no statistically significant difference between AUCs from the two models. (Z = -1.14, P = 0.25). CONCLUSIONS: The frac10 and frackurtosis in enhanced tumor region could be used to differentiate glioma and SBM and (MTRasym@3.5ppm)10 helps improving the differentiation specificity.

Yb/Si frustrated Lewis pairs with a labile naphthalenyl bridge.

The first examples of RE/Si FLPs (RE: rare-earth metal, FLPs: frustrated Lewis pairs), namely Yb/Si FLPs were synthesized, where Yb⋯Si distances are in the range of 3.55 to 3.72 Å. These FLPs react with triphenylphosphine sulfide and aryl isocyanide to produce novel silylyne group transfer products through dissociation of naphthalene.

Inhibition of HMOX1 by MAFG potentiates the development of depression­like behavior in mice associated with astrocyte-mediated neuroinflammation.

MAF bZIP transcription factor G (MAFG)-driven astrocytes have been reported to promote inflammation in the CNS. However, its function in depression, the primary cause of disability worldwide, has not been well characterized. This study investigated the possible perturbation of heme oxygenase 1 (HMOX1, also known as HO1) by the transcription factor MAFG as an underlying mechanism of the development of depression. The GSE98793 dataset was included for gene expression analysis of whole blood from donors with major depressive disorder and controls, and the target of MAFG was predicted by multiple database mining. Mouse and cellular models of depression were established by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment of astrocytes, which were treated with MAFG and HMOX1 knockdown plasmids. MAFG was highly expressed in the hippocampal tissues of CUMS-challenged mice and LPS-induced astrocytes. MAFG knockdown alleviated depression-like behaviors in mice. MAFG bound to the HMOX1 promoter and repressed its transcription. Knockdown of HMOX1 exacerbated neuroinflammation in astrocytes and accelerated depression-like behavior in mice. In conclusion, MAFG knockdown attenuated CUMS-stimulated depression-like behaviors in mice by astrocyte-mediated neuroinflammation via restoration of HMOX1.

Interactions of peroxy radicals from monoterpene and isoprene oxidation simulated in the radical volatility basis set.

Isoprene affects new particle formation rates in environments and experiments also containing monoterpenes. For the most part, isoprene reduces particle formation rates, but the reason is debated. It is proposed that due to its fast reaction with OH, isoprene may compete with larger monoterpenes for oxidants. However, by forming a large amount of peroxy-radicals (RO2), isoprene may also interfere with the formation of the nucleating species compared to a purely monoterpene system. We explore the RO2 cross reactions between monoterpene and isoprene oxidation products using the radical Volatility Basis Set (radical-VBS), a simplified reaction mechanism, comparing with observations from the CLOUD experiment at CERN. We find that isoprene interferes with covalently bound C20 dimers formed in the pure monoterpene system and consequently reduces the yields of the lowest volatility (Ultra Low Volatility Organic Carbon, ULVOC) VBS products. This in turn reduces nucleation rates, while having less of an effect on subsequent growth rates.

[Ce3+-OV-Ce4+] Located Surface-Distributed Sheet Cu-Zn-Ce Catalysts for Methanol Production by CO2 Hydrogenation.

The metal-support interaction is crucial for the performance of Cu-based catalysts. However, the distinctive properties of the support metal element itself are often overlooked in catalyst design. In this paper, a sheet Cu-Zn-Ce with [Ce3+-OV-Ce4+] located on the surface was designed by the sol-gel method. Through EPR and X-ray photoelectron spectroscopy (XPS), the relationship between the content of oxygen vacancies and Ce was revealed. Ce itself induces the generation of [Ce3+-OV-Ce4+]. Through ICP-MS, XPS, and SEM-mapping, the Ce-induced formation of [Ce3+-OV-Ce4+] located on the catalyst surface was demonstrated. CO2-TPD and DFT calculations further revealed that [Ce3+-OV-Ce4+] enhanced CO2 adsorption, leading to a 10% increase in methanol selectivity compared to Cu-Zn-Ce synthesized via the coprecipitation method.

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Impdh2 deficiency suppresses osteoclastogenesis through mitochondrial oxidative phosphorylation and alleviates ovariectomy-induced osteoporosis.

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.

Systematic dissection of sequence features affecting binding specificity of a pioneer factor reveals binding synergy between FOXA1 and AP-1.

Despite the unique ability of pioneer factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called chromatin immunoprecipitation with integrated synthetic oligonucleotides (ChIP-ISO) to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1, in human A549 cells. Combining ChIP-ISO with in vitro and neural network analyses, we find that (1) FOXA1 binding is strongly affected by co-binding transcription factors (TFs) AP-1 and CEBPB; (2) FOXA1 and AP-1 show binding cooperativity in vitro; (3) FOXA1's binding is determined more by local sequences than chromatin context, including eu-/heterochromatin; and (4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.

Noninvasive reconstruction of internal heat source in biological tissue using adaptive simulated annealing algorithm.

The heat distribution information of human lesions is of great value for disease analysis, diagnosis, and treatment. It is a typical inverse problem of heat conduction that deriving the distribution of internal heat sources from the temperature distribution on the body surface. This paper transforms such an inverse problem of bio-heat transfer into a direct one, thereby avoiding complex boundary conditions and regularization processes. To noninvasively reconstruct the internal heat source and its corresponding 3D temperature field in biological tissue, the adaptive simulated annealing (ASA) algorithm is used in the simulation module, where the position P(x, y, z) of point heat source in biological tissue and its corresponding temperature T are set as the optimization variables. Under a certain optimized sample, one can obtain the simulated temperature distributing on the surface of the module, then subtract the simulated temperature from the measured temperature of the same surface which was measured using a thermal infrared imager. If the sum of absolute values of the difference is smaller, it indicates that the current sample is closer to the true location and temperature of the heat source. When the values of optimization variables are determined, the corresponding 3D temperature field is also confirmed. The simulation results show the simulated position and temperature of the heat source are very approximate with those of the real experimental module. The method presented in this paper has enormous potential and promising prospects in clinical research and application, such as tumor hyperthermia, disease thermal diagnosis technology, etc.

Assembly-Induced Membrane Selectivity of Artificial Model Peptides through Entropy-Enthalpy Competition.

Peptide design and drug development offer a promising solution for combating serious diseases or infections. In this study, using an AI-human negotiation approach, we have designed a class of minimal model peptides against tuberculosis (TB), among which K7W6 exhibits potent efficacy attributed to its assembly-induced function. Comprising lysine and tryptophan with an amphiphilic α-helical structure, the K7W6 sequence exhibits robust activity against various infectious bacteria causing TB (including clinically isolated and drug-resistant strains) both in vitro and in vivo. Moreover, it synergistically enhances the effectiveness of the first-line antibiotic rifampicin while displaying low potential for inducing drug resistance and minimal toxicity toward mammalian cells. Biophysical experiments and simulations elucidate that K7W6's exceptional performance can be ascribed to its highly selective and efficient membrane permeabilization activity induced by its distinctive self-assembly behavior. Additionally, these assemblies regulate the interplay between enthalpy and entropy during K7W6-membrane interaction, leading to the peptide's two-step mechanism of membrane interaction. These findings provide valuable insights into rational design principles for developing advanced peptide-based drugs while uncovering the functional role played by assembly.