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International students have the potential to contribute significantly to host countries through cultural enrichment, economic growth, and human capital development. However, their successful integration into the host society is crucial to realise these benefits. By applying the framework of the two-way integration process from acculturation theory, this study examines the employment integration of international students in Finland, a non-native English-speaking country. Our semi-structured, qualitative in-depth interviews identify several key challenges encountered by international students, including limited information about the labour market, unfamiliarity with recruitment practices, a lack of industry connections, communication gaps from recruiting companies, and host country language barriers. We provide recommendations to organisations and recruiters on how to embrace diversity in their recruitment processes, as well as suggestions to universities on how to better support international students' transition into the workforce of the host country.

This outlook explores how two different molecular imaging approaches might be combined to gain insight into dynamic, subcellular metabolic processes. Specifically, we discuss how matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and stimulated Raman scattering (SRS) microscopy, which have significantly pushed the boundaries of imaging metabolic and metabolomic analyses in their own right, could be combined to create comprehensive molecular images. We first briefly summarize the recent advances for each technique. We then explore how one might overcome the inherent limitations of each individual method, by envisioning orthogonal and interchangeable workflows. Additionally, we delve into the potential benefits of adopting a complementary approach that combines both MSI and SRS spectro-microscopy for informing on specific chemical structures through functional-group-specific targets. Ultimately, by integrating the strengths of both imaging modalities, researchers can achieve a more comprehensive understanding of biological and chemical systems, enabling precise metabolic investigations. This synergistic approach holds substantial promise to expand our toolkit for studying metabolites in complex environments.

Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

Abstract Integration of functional fillers into liquid metals (LM) induces rheology modification, enabling the free-form shaping of LM at the micrometer scale. However, integrating non-chemically modified low-dimensional materials with LM to form stable and uniform dispersions remain a great challenge. Herein, we propose a solvent-assisted dispersion (SAD) method that utilizes the fragmentation and reintegration of LM in volatile solvents to engulf and disperse fillers. This method successfully integrates MXene uniformly into LM, achieving better internal connectivity than the conventional dry powder mixing (DPM) method. Consequently, the MXene/LM (MLM) coating exhibits high electromagnetic interference (EMI) shielding performance (105 dB at 20 μm, which is 1.6 times that of coatings prepared by DPM). Moreover, the rheological characteristic of MLM render it malleable and facilitates direct printing and adaptation to diverse structures. This study offers a convenient method for assembling LM with low-dimensional materials, paving the way for the development of multifunctional soft devices.

Abstract The gap between the performance of optoelectronic components and the demands of fiber-optic communications has narrowed significantly in recent decades. Yet, the expansion of data communications traffic remains substantial, with fiber-link speeds increases anticipated in the near future. Here, we demonstrate an ultra-high-speed electro-optic waveguide modulator constructed using a thin film of lanthanum-modified lead zirconate titanate with a ferroelectric phase exhibiting a strong Pockels effect. The modulator has a wide optical window; thus, the modulation was demonstrated for 1550 and 1310 nm wavelengths. This device showed electro-optical intensity signaling with line rates of 172 Gbit s−1, in conjunction with on–off keying modulation; this performance could be increased to 304 Gbit s−1 using four-level pulse modulation. The signaling performance of this modulator was found to be robust, with stable performance at temperatures as high as 100 °C. This technology is expected to have applications in a wide range of classical optoelectronic devices and in quantum science and technology.

Abstract Background To assess the improvement of image quality and diagnostic acceptance of thinner slice iodine maps enabled by deep learning image reconstruction (DLIR) in abdominal dual-energy CT (DECT). Methods This study prospectively included 104 participants with 136 lesions. Four series of iodine maps were generated based on portal-venous scans of contrast-enhanced abdominal DECT: 5-mm and 1.25-mm using adaptive statistical iterative reconstruction-V (Asir-V) with 50% blending (AV-50), and 1.25-mm using DLIR with medium (DLIR-M), and high strength (DLIR-H). The iodine concentrations (IC) and their standard deviations of nine anatomical sites were measured, and the corresponding coefficient of variations (CV) were calculated. Noise-power-spectrum (NPS) and edge-rise-slope (ERS) were measured. Five radiologists rated image quality in terms of image noise, contrast, sharpness, texture, and small structure visibility, and evaluated overall diagnostic acceptability of images and lesion conspicuity. Results The four reconstructions maintained the IC values unchanged in nine anatomical sites (all p > 0.999). Compared to 1.25-mm AV-50, 1.25-mm DLIR-M and DLIR-H significantly reduced CV values (all p

Abstract Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.

Abstract This study aimed to develop a machine learning (ML)-based tool for early and accurate prediction of in-hospital mortality risk in patients with spontaneous intracerebral hemorrhage (sICH) in the intensive care unit (ICU). We did a retrospective study in our study and identified cases of sICH from the MIMIC IV (n = 1486) and Zhejiang Hospital databases (n = 110). The model was constructed using features selected through LASSO regression. Among five well-known models, the selection of the best model was based on the area under the curve (AUC) in the validation cohort. We further analyzed calibration and decision curves to assess prediction results and visualized the impact of each variable on the model through SHapley Additive exPlanations. To facilitate accessibility, we also created a visual online calculation page for the model. The XGBoost exhibited high accuracy in both internal validation (AUC = 0.907) and external validation (AUC = 0.787) sets. Calibration curve and decision curve analyses showed that the model had no significant bias as well as being useful for supporting clinical decisions. XGBoost is an effective algorithm for predicting in-hospital mortality in patients with sICH, indicating its potential significance in the development of early warning systems.

Abstract Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The “Atyp.C” parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case–control study identified clinical primary or newly recurrent BC (study period, 2022–2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman’s rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P

The oxidation of coal at room temperature provides the initial heat source for spontaneous coal combustion (CSC). In the CSC theoretical study, exploring the active substances in coal that can be oxidized at room temperature is a complex problem. Previous thermal decomposition experiments have found that coal after pyrolysis contains active sites that can exist stably in inert gases and be oxidized at room temperature. Thus it is speculated that there may also be primary active sites that are forced to be stored under inert media in coal. In order to explore the primary active sites of coal, the vacuum drying technology is applied. Based on that, the water in the raw coal can reach the boiling point under the low-temperature environment of negative vacuum pressure to complete the removal of water and gas. Under different experimental conditions (coal, desorption temperature, oxidation temperature, particle size), the cyclic oxidation online monitoring technology is used to design and implement the room temperature oxidation experiment of the desorbed coal samples. At the same time, the reaction mechanism is analyzed by the corresponding low-temperature nitrogen adsorption, XPS, ESR experiments. After vacuum desorbed, the oxidation experiments under cyclic conditions show that the massive gaseous oxidation products such as CO and CO2 will be formed in the process of raw oxidation at room temperature, and the gases appear and accumulate soon after oxygen is introduced, which proves that coal oxidation can occur at room temperature. The room temperature oxidation experiment after the desorption of raw coal indicates that there are a large number of active sites affected by water-gas masking in the raw coal. They are unable to undergo the oxidation exothermic processes, while the coal after the desorption of water and gas under negative pressure exposes massive active sites and forms a channel conducive to oxygen transport and reaction, which rapidly occur oxidation exothermic phenomenon and lead to the rise of coal temperature. Therefore, the active structure leading to the spontaneous warming of the raw coal is found, and the experiments extend the view of room temperature oxidation of the active sites from the particular case state of the pyrolysis to the general state. From the comparison of gas product generation, it can be seen that CO, which is not easy to be adsorbed by pores, is produced quickly at the moment of contact between the primary active site and oxygen. Therefore, it can be concluded that CO is more suitable as an intuitive gas evaluation index of the concentration of the active sites compared with CO2. The room temperature oxidation of the primary active sites of coal helps reveal the mechanism of coal spontaneous combustion and provides a solution to the problem of spontaneous combustion during gas extraction in high-gas mines and the problem of CO over-limit in low-rank coal mines.

Abstract Introduction Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi’an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi’an, China Methods The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. Results Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. Conclusions When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Abstract While strategies to enhance the quantum coherence of plasmonic resonances have attracted a lot of attention in the past, the advent of non-Hermitian optics carries promising possibilities in this direction, mostly of which are still unexplored. In this work, we show that the quantum coherence of plasmonic resonances can be enhanced by integrating a plasmonic antenna in a photonic cavity operated at a chiral exceptional point (CEP), where the phase of light offers an additional degree of freedom for flexibly manipulating the quantum dynamics. The few-mode quantization theory is employed to demonstrate the advantages and related quantum-optics applications of the proposed hybrid cavity in both off- and on-resonance plasmon-photon coupling. For the former case, the local density of states evolves into sub-Lorentzian lineshape, resulting in reduced dissipation of polaritonic states. On resonance, we identify two mechanisms improving the quantum yield by two orders of magnitude at room temperature: the reduction of plasmonic absorption through Fano interference and the enhancement of cavity radiation through superscattering. Our results establish CEP-engineered plasmonic resonances as a promising platform for controlling quantum states and building high-performance quantum devices.

Abstract Experimental realization of strong coupling between a single exciton and plasmons remains challenging as it requires deterministic positioning of the single exciton and alignment of its dipole moment with the plasmonic fields. This study aims to combine the host–guest chemistry approach with the cucurbit[7]uril-mediated active self-assembly to precisely integrate a single methylene blue molecule in an Au nanodimer at the deterministic position (gap center of the nanodimer) with the maximum electric field (EFmax) and perfectly align its transition dipole moment with the EFmax, yielding a large spectral Rabi splitting of 116 meV for a single-molecule exciton—matching the analytical model and numerical simulations. Statistical analysis of vibrational spectroscopy and dark-field scattering spectra confirm the realization of the single exciton strong coupling at room temperature. Our work may suggest an approach for achieving the strong coupling between a deterministic single exciton and plasmons, contributing to the development of room-temperature single-qubit quantum devices.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

To improve the thermal barrier properties of epoxy resin coatings, a composite waterborne aerogel multifunctional coating that possesses both mechanical properties and controllable barrier ability was prepared in this study. This coating incorporates granular silica aerogel, organic montmorillonite, and two flame retardants: aluminum hydroxide (ATH) and magnesium hydroxide (MH). The results showed that montmorillonite, modified with stearyl trimethyl ammonium bromide (STAB), exhibited antisymmetric and symmetric stretching vibrational infrared spectral absorption peaks of –CH3, –CH2, characteristic of the long-chain alkane quaternary ammonium salt. This indicated that the quaternary ammonium salt was intercalated into the montmorillonite interlayer, enhancing the surface lamellae. The coating effectively absorbed energy when stressed, resulting in a strength increase of 146.3%. Incorporating high porosity silica aerogel significantly improved the barrier behavior of the composite coating, enabling controlled thermal insulation and excellent corrosion resistance. The coating reduced heat transfer paths and effectively impeded heat transfer, maintaining a high corrosion inhibition efficiency (99.9%) in a 3.5% NaCl solution. Additionally, the individual actions of the two flame retardants led to highly effective flame retardant properties, with the total heat release rate (THR) reduced by about 43.5% and the total smoke production (TSP) by 40.1%.

Abstract Avalanche or carrier-multiplication effect, based on impact ionization processes in semiconductors, has a great potential for enhancing the performance of photodetector and solar cells. However, in practical applications, it suffers from high threshold energy, reducing the advantages of carrier multiplication. Here, we report on a low-threshold avalanche effect in a stepwise WSe2 structure, in which the combination of weak electron-phonon scattering and high electric fields leads to a low-loss carrier acceleration and multiplication. Owing to this effect, the room-temperature threshold energy approaches the fundamental limit, E thre ≈ E g, where E g is the bandgap of the semiconductor. Our findings offer an alternative perspective on the design and fabrication of future avalanche and hot-carrier photovoltaic devices.

Abstract Background We explored the clinical significance of miR-28-5p pre- and post-endovascular abdominal aortic aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA) patients. Methods Subjects included AAA patients receiving EVAR and non-AAA people without statistical differences from AAA patient in comorbidities/Framingham risk score. Fasting elbow venous blood (4 mL) was collected in the morning of the day of EVAR surgery and in the morning of 3 months post-EVAR. Pre-/post-EVAR serum miR-28-5p expression, AAA maximum diameter alterations, CD3+/CD4+/CD8+/TC/TG pre-/post-EVAR, and the correlations between miR-28-5p and AAA maximum diameter were investigated. Prediction of miR-28-5p on post-EVAR mortality, prognosis, and independent factors of post-EVAR death were analyzed using receiver operating characteristic curve (ROC)/Kaplan-Meier curve/univariable and multivariable Cox regression. According to the cut-off value of ROC curve for postoperative miR-28-5p was the cut-off value, and the patients were classified into the miR-28-5p high- and low-expression groups. The survival or death of both groups were compared after 48-month follow-up. Results Serum miR-28-5p levels in AAA patients dropped post-EVAR. AAA patients showed notable differences in CD3+/CD4+/CD8+/TC/TG levels pre-/post-EVAR. The miR-28-5p low-expression group exhibited higher CD3+/CD4+ and lower CD8+/TC/TG levels. We observed a positive correlation between post-EVAR miR-28-5p and AAA maximum diameter and between the pre-/post-EVAR miR-28-5p fold change and the AAA maximum diameter change. Postoperative miR-28-5p demonstrated good predictive value for postoperative death. Hypertension, Framingham risk score, TC, TG, and miR-28-5p were independent influencing factors of post-EVAR death. Conclusion EVAR decreased serum miR-28-5p expression in AAA patients. Post-operative miR-28-5p level and pre-/post-operative fold change level are positively-correlated with AAA diameter.

Abstract Background This study aimed to investigate the differences in the microbiota composition of serum exosomes from patients with acute and chronic cholecystitis. Method Exosomes were isolated from the serum of cholecystitis patients through centrifugation and identified and characterized using transmission electron microscopy and nano-flow cytometry. Microbiota analysis was performed using 16S rRNA sequencing. Results Compared to patients with chronic cholecystitis, those with acute cholecystitis exhibited lower richness and diversity. Beta diversity analysis revealed significant differences in the microbiota composition between patients with acute and chronic cholecystitis. The relative abundance of Proteobacteria was significantly higher in exosomes from patients with acute cholecystitis, whereas Actinobacteria, Bacteroidetes, and Firmicutes were significantly more abundant in exosomes from patients with chronic cholecystitis. Furthermore, functional predictions of microbial communities using Tax4Fun analysis revealed significant differences in metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and membrane transport between the two patient groups. Conclusions This study confirmed the differences in the microbiota composition within serum exosomes of patients with acute and chronic cholecystitis. Serum exosomes could serve as diagnostic indicators for distinguishing acute and chronic cholecystitis.

Abstract In this work, an invasive plant (Aster subulatus Michx) mesopore laminar biochar loaded with transition metal Co (CoS@MLBC) was synthesized by a one-step hydrothermal carbonization way for activating peroxymonosulfate (PMS) to remove antibiotics in water. We characterized the structure and morphology of CoS@MLBC and tested its performance. The results showed that the carbon nitride structure was formed on CoS@MLBC, which improved its adsorption capacity for antibiotics and PMS. In addition, Co-doping significantly enhanced the PMS activity and efficiently degraded ciprofloxacin (CIP) over a wide pH range. It was identified that radical and non-radical synergistic action had a critical effect on the CIP degradation process. Furthermore, CoS@MLBC could completely remove CIP within 10 min and had a high removal efficiency (98%) after four cycles. Three possible pathways of the CIP degradation process with 12 intermediates were proposed and their ecotoxicity was analyzed. This work provides a new perspective for preparing biochar from invasive plants for the degradation of antibiotics in water, realizing the concept of “treating the wastes with wastes”. Graphical Abstract

Abstract Background Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin’s clinical application is limited due to its poor water solubility and low bioavailability. Results In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA——miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. Conclusion In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment. Graphical Abstract

Abstract Background Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C‐reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. Methods A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. Results Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45–74%]) and 78% (95% CI [69–86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86–10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26–83%]) and 75% (95% CI [68–82%]), and those for CRP were 67% (95% CI [35–88%]) and 73% (95% CI [69–77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61–0.91 vs. 0.74, CI = 0.61–0.95, p = 0.93). Conclusion While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.

Abstract Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Abstract Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Abstract Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

The grain refinement and texture regulation mechanism of spin-formed commercially pure titanium (CP–Ti) cathode during annealing were studied by electron back scatter diffraction (EBSD) and transmission electron microscopy (TEM). The results show that the CP-Ti is seriously deformed after spinning, and the internal strain forms are mainly tension in spinning direction (SD), compression in normal direction (ND), and shear in transverse direction (TD). The dynamic recrystallization occurs during the spinning process, and the recrystallization nucleation mechanism is mainly subgrain nucleation. When spin-formed CP-Ti is annealed at 500 °C, the well-defined substructures generated by fragmentation of primary grains during deformation, as well as the cellular substructures formed by rearrangement of high-density entangled dislocations during annealing can evolve into a large number of fine equiaxed and randomly oriented recrystallized grains. In this case, the subgrain nucleation-dominated recrystallization nucleation mechanism can significantly refine grains. When annealed at 560 °C, a large number of tongue-shaped nuclei with similar orientation to the original grain generated at the grain boundaries, the recrystallization nucleation is inferred to be dominated by grain boundary bulge mechanism. Different recrystallization nucleation mechanisms result in different annealing texture evolution behaviors. When annealed at 500 °C, in the rapid nucleation stage of recrystallization (before 30 min), the texture strength is gradually weakened due to many randomly oriented recrystallized nuclei. With increasing the time from 30 min to 60 min, the recrystallization nucleation and growth reach a dynamic equilibrium, the texture strength tends to be stable. When annealed at 560 °C, a large number of recrystallized grains with similar orientation to the original deformed grains are formed. Oriented nucleation results in a strong texture at the short annealing time (5 min), but the competitive growth of different orientations makes the texture strength gradually decrease with the prolongation of annealing time. In any case, the overall texture strength annealed at 560 °C is higher than that annealed at 500 °C under the same annealing time.

Abstract Background The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). Methods This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. Results The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07–0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P

Abstract While significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they’re computationally demanding due to rare transitions between biologically relevant equilibrium states. In this study, we present DynamicBind, a deep learning method that employs equivariant geometric diffusion networks to construct a smooth energy landscape, promoting efficient transitions between different equilibrium states. DynamicBind accurately recovers ligand-specific conformations from unbound protein structures without the need for holo-structures or extensive sampling. Remarkably, it demonstrates state-of-the-art performance in docking and virtual screening benchmarks. Our experiments reveal that DynamicBind can accommodate a wide range of large protein conformational changes and identify cryptic pockets in unseen protein targets. As a result, DynamicBind shows potential in accelerating the development of small molecules for previously undruggable targets and expanding the horizons of computational drug discovery.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit’s response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit’s sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit’s defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.

Summary: Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48−LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN− LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN− LT-HSCs. Emcn−/− and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn−/− LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn−/− or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant.

Scrophularia ningpoensis Hemsl. (SN) is an herbal medicine used as a functional food in China. SN has traditionally been used to treat diabetes mellitus (DM), but its mechanism of action is not well understood. Our previous study indicated that the aqueous extract of SN can reduce hepatic insulin resistance and correct the irregular shape of pancreatic islets in diabetic mice. This study aims to investigate whether the aqueous extract of SN can regulate pyroptosis in pancreatic β-cells and explore its underlying mechanisms. Db/db mice were orally given an aqueous extract of SN for eight weeks. Subsequently, their pancreatic tissues were collected for histopathological analysis and immunoblotting. Rat insulinoma (INS-1) cells were cultured either alone or with the aqueous extract of SN and evaluated for cell viability, pyroptotic body formation, AMP-activated protein kinase (AMPK) activity, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD) activation, and reactive oxygen species (ROS) production under high glucose (HG) exposure conditions. The aqueous extract of SN reduced insulitis and pancreatic β-cell death in db/db mice. Increased AMPK phosphorylation and decreased NLRP3 inflammasome and GSDMD activation were observed in pancreatic tissues after administration of the aqueous extract of SN. In vitro, the aqueous extract of SN increased cell viability and AMPK phosphorylation in a concentration-dependent manner. Additionally, the aqueous extract of SN corrected excessive ROS generation, NLRP3 inflammasome and GSDMD activation, and pyroptotic body formation. Inhibition of AMPK negated these beneficial effects of the aqueous extract of SN on INS-1 cells. The study concluded that the aqueous extract of SN alleviates β-cell pyroptosis by inhibiting NLRP3/GSDMD activation in an AMPK-dependent manner.

In order to investigate the effect of different water filling times on the compression deformation of filled gangue, a large-scale crushed gangue deformation testing system was utilized, and two sets of gradient loading experiments were designed. Through rigorous experimental analysis, distinct patterns of deformation during loading and constant load stages are elucidated, with a particular focus on the influence of water filling timing. Quantitative assessment reveals that early water filling induces rapid gangue deformation, primarily during loading stages, while later water filling stages exhibit a heightened impact on constant load stages. Moreover, the study identifies a stepped deformation phenomenon attributed to the irregularities in crushed gangue particles, shedding light on the underlying mechanisms governing gangue behavior under varying water filling conditions. Notably, an in-depth analysis of energy consumption patterns underscores the dominant role of strain, especially in later water filling stages, significantly influencing deformation characteristics. The study further explores the implications of water filling timing on mining subsidence effects, offering quantitative insights into the stability of gangue backfilling. Under the action of the cumulative deformation and concentrated filling effect, the equivalent filling height is slightly higher than that of the early water filling state, but this trend weakens with the increase of mining height. The conclusions of this study can provide experimental data for stability analysis of crushed gangue filling the abandoned mines with different water filling timing.