Immune cell traits and causal relationships with cholecystitis: a mendelian randomization analysis.

Cholecystitis, characterized by inflammation of the gallbladder, is intricately linked to immune cells and the cytokines they produce. Despite this association, the specific contributions of immune cells to the onset and progression of cholecystitis remain to be fully understood. To delineate this relationship, we utilized the Mendelian randomization (MR) method to scrutinize the causal connections between 731 immune cell phenotypes and cholecystitis. By conducting MR analysis on 731 immune cell markers from public datasets, this study seeks to understand their potential impact on the risk of cholecystitis. It aims to elucidate the interactions between immune phenotypes and the disease, aiming to lay the groundwork for advancing precision medicine and developing effective treatment strategies for cholecystitis. Taking immune cell phenotypes as the exposure factor and cholecystitis as the outcome event, this study used single nucleotide polymorphisms (SNPs) closely associated with both immune cell phenotypes and cholecystitis as genetic instrumental variables. We conducted a two-sample MR analysis on genome-wide association studies (GWAS) data. Our research thoroughly examined 731 immune cell markers, to determine potential causal relationships with susceptibility to cholecystitis. Sensitivity analyses were performed to ensure the robustness of our findings, excluding the potential impacts of heterogeneity and pleiotropy. To avoid reverse causality, we conducted reverse MR analyses with cholecystitis as the exposure factor and immune cell phenotypes as the outcome event. Among the 731 immune phenotypes, our study identified 21 phenotypes with a causal relationship to cholecystitis (P < 0.05). Of these, eight immune phenotypes exhibited a protective effect against cholecystitis (odds ratio (OR) < 1), while the other 13 immune phenotypes were associated with an increased risk of developing cholecystitis (OR > 1). Additionally, employing the false discovery rate (FDR) method at a significance level of 0.2, no significant causal relationship was found between cholecystitis and immune phenotypes. Our research has uncovered a significant causal relationship between immune cell phenotypes and cholecystitis. This discovery not only enhances our understanding of the role of immune cells in the onset and progression of cholecystitis but also establishes a foundation for developing more precise biomarkers and targeted therapeutic strategies. It provides a scientific basis for more effective and personalized treatments in the future. These findings are expected to substantially improve the quality of life for patients with cholecystitis and mitigate the impact of the disease on patients and their families.

Exploring the causes of variability in quality of oropharyngeal swab sampling for SARS-CoV-2 nucleic acid testing and proposed improvement measures: a multicenter, double-blind study.

Although coronavirus disease 2019 (COVID-19) has not been considered a public health emergency of international concern since last year, intermittent regional impacts still persist, and accurate testing remains crucial. Ribonuclease P protein subunit P30 (RPP30) RNA, known for its broad and stable expression in tissue cells, was used to evaluate samples from 10 hospitals with over 3,000 negative nucleic acid tests. The results revealed that the overall pass rate for the collected samples was consistently low and exhibited significant heterogeneity. After reassessing the evaluative effectiveness of RPP30 RNA Ct values from the samples of 132 positive individuals under quarantine observation, it was used to identify factors affecting sampling quality. These factors included different stages ranging from sample collection to PCR processing, various characteristics of both samplers and individuals being sampled, as well as sampling season and location. The results indicated that post-sampling handling had minimal impact, winter and fever clinic samples showed higher quality, whereas children's samples had lower quality. The key finding was that the characteristics of samplers were closely related to sampling quality, emphasizing the role of subjectivity. Quality control warnings led to substantial improvements, confirming this finding. Consequently, although there are various factors during the testing process, the most critical aspect is to improve, supervise, and maintain standardized practices among sampling staff.IMPORTANCEThis study further confirmed the reliability of internal references (IRs) in assessing sample quality, and utilized a large sample IR data to comprehensively and multidimensionally identify significant interference factors in nucleic acid test results. By further reminding and intervening in the subjective practices of specimen collectors, good results could be achieved.

A neural circuit for lavender-essential-oil-induced antinociception.

Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPirGlu) innervate GABAergic neurons in the IC (ICGABA) to inhibit local glutamatergic neurons (ICGlu) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPirGlu→ICGABA→Glu pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPirGlu neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain.

Effect of Cr Element in Gas-Shielded Solid Wire for Oil and Gas Long-Distance Pipeline on Microstructure and Low Temperature Toughness of Weld.

In this paper, the influence of Cr element on the mechanical properties of welded joints of gas-shielded solid wire used in oil and gas long-distance pipelines was studied by means of tensile test, impact test, and hardness test, and the microstructure and crack propagation path of weld were characterized by means of an optical microscope, scanning electron microscope, and electron backscattering diffraction. The results show that with the addition of Cr, the strength and toughness of the weld are significantly improved, in which the tensile strength is increased from 607 MPa to 656 MPa, and the impact toughness is increased from 126.37 J to 223.79 J. The proportion of the ferrite side plate in the weld structure is reduced by about 20%, and the effective grain size of acicular ferrite is reduced by about 15%. The reason is that the addition of the Cr element improves the hardenability of the weld structure, inhibits the formation of the ferrite side plate, and promotes the effective refinement of acicular ferrite, which increases the proportion of high-angle grain boundaries in the weld, effectively hindering the crack propagation, improves the crack propagation work, and thus improves the strength and toughness of the weld.

A neural circuit for alcohol withdrawal-induced hyperalgesia in a nondependent state.

Alcohol use disorder is highly prevalent worldwide, with characteristically severe pain sensitivity during withdrawal. Here, we established a mouse model of hyperalgesia during ethanol withdrawal (EW) before addiction to investigate the window for onset and underlying mechanisms. Viral tracing with in vivo microendoscopic and two-photon calcium imaging identified a circuit pathway from dorsal hippocampal CA1 glutamatergic neurons (dCA1Glu) to anterior cingulate cortex glutamatergic neurons (ACCGlu) activated in EW mice with hyperalgesia. Chemogenetic inhibition of this pathway can alleviate hyperalgesia in EW mice, whereas artificial activation recapitulates EW-induced hyperalgesia in naïve mice. These findings demonstrate that the dCA1Glu → ACCGlu neuronal pathway participates in driving EW-induced hyperalgesia before ethanol dependence in mice.

Structural and Functional Differences in Small Intestinal and Fecal Microbiota: 16S rRNA Gene Investigation in Rats.

To compare the differences in floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats fed in a conventional or specific-pathogen free (SPF) environment and rats fed a high-fat diet (HFD), and the V3-V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was then amplified and sequenced. Compared with feces, about 60% of the bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units (OTUs) < 1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). The dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater ß-diversity, and the distance between in-group samples was nearer than that between paired ileum-feces samples. Moreover, the ileum shared various biomarkers and functions with feces (p < 0.05). The HFD and SPF conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or ß-diversity of samples. The present findings suggested that, under conventional circumstances, fecal bacteria can represent approximately 40% of the low abundant ileal bacterial genera and that dominant fecal bacteria failed to represent the ileal dominant flora. Moreover, fecal flora diversity does not reflect ß-diversity in the ileum.

Global prevalence of liver disease in human and domestic animals caused by Fasciola: A systematic review and meta-analysis.

Background: Liver disease caused by Fasciola is a significant zoonotic and parasitic disease with substantial economic impacts on humans and animals. Many studies have looked at the prevalence of fasciolis worldwide, yet the overall prevalence and risk factors in cattle, ruminants, and humans remains unknown. Methods: We conducted a systematic review and meta-analysis to estimate the global prevalence and risk factors of fascioliasis in humans and domestic ruminants. With this aim, we searched PubMed, ScienceDirect, Web of Science, and Scopus from inception to 8 December 2022 for studies reporting the prevalence of fascioliasis in humans or domestic ruminants post-2000. We then used random effects models to describe the prevalence of fascioliasis; trim-and-fill analysis and Egger's test to assess publication bias; and meta-regression and sensitivity analyses to examine the risk factors for prevalence and heterogeneity. Results: We retrieved 4422 articles, with 371 being included in the analysis, as they concerned fascioliasis in humans and ruminants globally. The pooled prevalence of bovine fasciolosis was 17%, while ovine fasciolosis and human fascioliasis had pooled prevalences of 13% and 5%, respectively. We also conducted subgroup analyses by continents, countries, Fasciola species, sampling years, altitude, rainfall, temperature, humidity, age, sex, feeding mode, and residence. Here, altitude and age emerged as risk factors associated with an increased prevalence of fascioliasis. Both the trim-and-fill analysis and Egger's test confirmed the presence of publication bias, while the sensitivity analysis showed that the omission of any single study did not significantly influence the combined pooled prevalence. Conclusions: Fascioliasis is a widely prevalent zoonosis among humans and livestock worldwide. Strategies targeting risk factors such as altitude and age are urgently needed for prevention and control of this disease, which will consequently reduce Fasciola infection. Additionally, given the inadequacy or absence of data in some countries, greater attention should be paid to Fasciola infection, with further epidemiological studies focussing on improving data quality.

The Asymmetrical Fe-O-Se Bonds in Fe2O(SeO3)2 Boosting Bifunctional Oxygen Electrocatalytic Performance for Zinc-Air Battery.

Here Fe2O(SeO3)2/Fe3C@NC catalysts with high performance were fabricated for zinc-air batteries (ZABs). The experimental results confirmed that the existence of Fe-O-Se bonds in Fe2O(SeO3)2 crystal phase, and the Fe-O-Se bonds could obviously enhance ORR and OER catalytic performance of Fe2O(SeO3)2/Fe3C@NC. Density functional theoretical calculations (DFT) confirmed that the Fe2O(SeO3)2 in Fe2O(SeO3)2/Fe3C@NC had a higher d-band center of Fe atom and a lower p-orbital coupling degree with its own lattice O atom than Fe2O3, which leads to Fe site of Fe2O(SeO3)2 being more likely to adsorb external oxygen intermediates. The Fe-O-Se bonds in Fe2O(SeO3)2 results in the modification of coordination environment of Fe atoms and optimizes the adsorption energy of Fe site for oxygen intermediates. Compared with Fe2O3/Fe3C@NC, the Fe2O(SeO3)2/Fe3C@NC showed obvious enhancements of ORR/OER catalytic activities with a half-wave potential of 0.91 V for ORR in 0.1 M KOH electrolyte and a low overpotential of 345 mV for OER at 10 mA cm-2 in a 1.0 M KOH electrolyte. The peak power density and specific capacity of Fe2O(SeO3)2/Fe3C@NC-based ZABs are higher than those of Pt/C+RuO2-ZABs. The above results demonstrate that the asymmetrical Fe-O-Se bonds in Fe2O(SeO3)2 plays a key role in improving the bifunctional catalytic activities of ORR/OER for ZABs.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study.

BACKGROUND: Regarding when to treat gastric cancer and ovarian metastasis (GCOM) and whether to have metastatic resection surgery, there is presently debate on a global scale. The purpose of this research is to examine, in real-world patients with GCOM, the survival rates and efficacy of metastatic vs non-metastasized resection. AIM: To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM. METHODS: This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People's Hospital from June 2009 to July 2023. The diagnosis of all patients was confirmed by pathology. The primary study endpoints included overall survival (OS), ovarian survival, OS after surgery (OSAS), disease-free survival (DFS), differences in efficacy. RESULTS: This study had 41 patients in total. The surgical group (n = 27) exhibited significantly longer median OS (mOS) and median overall months (mOM) compared to the nonoperative group (n = 14) (mOS: 23.0 vs 6.9 months, P = 0.015; mOM: 18.3 vs 3.8 months, P = 0.001). However, there were no significant differences observed in mOS, mOM, median OSAS (mOSAS), and median DFS (mDFS) between patients in the surgical resection plus neoadjuvant therapy group (n = 11) and those who surgical resection without neoadjuvant therapy group (n = 16) (mOS: 26.1 months vs 21.8 months, P = 0.189; mOM: 19.8 vs 15.2 months, P = 0.424; mOSAS: 13.9 vs 8.7 months, P = 0.661, mDFS: 5.1 vs 8.2 months, P = 0.589). CONCLUSION: Compared to the non-surgical group, the surgical group's survival duration and efficacy are noticeably longer. The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.

Regio- and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes.

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

Murine exosomal miR-30a aggravates cardiac function after acute myocardial infarction via regulating cell fate of cardiomyocytes and cardiac resident macrophages.

After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.

Amorphous P-CoOX Promotes the Formation of Hypervalent Ni Species in NiFe LDHs by Amorphous/Crystalline Interfaces for Excellent Catalytic Performance of Oxygen Evolution Reaction.

Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoOX/NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoOX/NiFe LDHs heterointerfaces are easily transferred from Ni2+ to Co3+ because that the amorphous configuration of P-CoOX can well induce Ni-O-Co orbital coupling. The electron transfer of Ni2+ to the surrounding Fe3+ and Co3+ will lead to the unoccupied eg orbitals of Ni3+ that can promote water dissociation and accelerate *OOH migration to improve OER catalytic performance. The optimized P-CoOX/NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm-2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm-2. This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER.

Glycomol: A pervasive tool for structure predication of natural saponin products basing on MS data.

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Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

Improving quantitative prediction of protein subcellular locations in fluorescence images through deep generative models.

Machine learning has been employed in recognizing protein localization at the subcellular level, which highly facilitates the protein function studies, especially for those multi-label proteins that localize in more than one organelle. However, existing works mostly study the qualitative classification of protein subcellular locations, ignoring fraction of one multi-label protein in different locations. Actually, about 50 % proteins are multi-label proteins, and the ignorance of quantitative information highly restricts the understanding of their spatial distribution and functional mechanism. One reason of the lack of quantitative study is the insufficiency of quantitative annotations. To address the data shortage problem, here we proposed a generative model, PLocGAN, which could generate cell images with conditional quantitative annotation of the fluorescence distribution. The model was a conditional generative adversarial network, in which the condition learning utilized partial label learning to overcome the lack of training labels and allowed training with only qualitative labels. Meanwhile, it used contrastive learning to enhance diversity of the generated images. We assessed the PLocGAN on four pixel-fused synthetic datasets and one real dataset, and demonstrated that the model could generate images with good fidelity and diversity, outperforming existing state-of-the-art generative methods. To verify the utility of PLocGAN in the quantitative prediction of protein subcellular locations, we replaced the training images with generated quantitative images and built prediction models, and found that they had a boosting effect on the quantitative estimation. This work demonstrates the effectiveness of deep generative models in bioimage analysis, and provides a new solution for quantitative subcellular proteomics.

Computed tomography-based radiomics machine learning models for differentiating enchondroma and atypical cartilaginous tumor in long bones.

To explore the value of CT-based radiomics machine learning models for differentiating enchondroma from atypical cartilaginous tumor (ACT) in long bones and methods to improve model performance.59 enchondromas and 53 ACTs in long bones confirmed by pathology were collected retrospectively. The features were extracted from preoperative CT images of these patients, and least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and dimensionality reduction. The selected features were used to construct classification models by thirteen machine learning algorithms. The data set was randomly divided into a training set and a test set at a proportion of 7:3 by ten-fold cross-validation to evaluate the performance of these models.A total of 1199 features were extracted, 9 features were selected, and 13 radiomics machine learning models were constructed. The area under the curve (AUC) of 11 models was more than 0.8, and that of 3 models was more than 0.9. The Extremely Randomized Trees model achieved the best performance (AUC = 0.9375 ± 0.0884), followed by the Adaptive Boosting model (AUC = 0.9188 ± 0.1010) and the Linear Discriminant Analysis model (AUC = 0.9062 ± 0.1459).CT-based radiomics machine learning models had great ability to distinguish enchondroma and ACT in long bones. By using filters to deeply mine high-order features in the original image and selecting appropriate machine learning algorithms, the performance of the model can be improved. · CT-based radiomics machine learning models can distinguish enchondroma and ACT in long bones.. · Using filters and selecting advanced machine learning algorithms can improve model performance.. · Clinical features have limited utility in distinguishing enchondroma and ACT in long bones.. · Hong R, Li Q, Ma J et al. Computed tomography-based radiomics machine learning models for differentiating enchondroma and atypical cartilaginous tumor in long bones. Fortschr Röntgenstr 2024; DOI 10.1055/a-2344-5398.

BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Direct detection Φ-OTDR based on UWFBG array using linear-phase-modulated double-pulse.

We propose what we believe to be a novel direct detection phase-sensitive optical time-domain reflectometry (Φ-OTDR) based on ultra-weak fiber Bragg grating (UWFBG) array to achieve distributed vibration measurements with exceptional sensitivity and remarkable stability. Our system employs a pulse modulator to generate a double pulse and achieves linear phase modulation of one pulse by one cycle through a phase modulator. The phase change can be quantitatively demodulated using our proposed N-step phase-shifted demodulation algorithm. This method effectively mitigates the influence of phase noise of the laser and the pulse modulator, while also eliminating fluctuations in the half-voltage of the phase modulator. Compared with the existing phase modulation methods, our method avoids stringent requirements for the stability and precision of phase modulation. Moreover, we propose a phase-shifted approximation method, breaking the limitation of sensing length on the traditional differential approximation method and improving the accuracy significantly. The technique's effectiveness is experimentally demonstrated on a 1 km UWFBG array with a reflectivity of -40 dB to -45 dB and a spatial resolution of 10 m. Vibrations with different amplitudes are measured quantitatively with good linearity. The low-frequency self-noise is greatly suppressed and the overall self-noise is -54.3 dB rad2/Hz.

Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study.

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.