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Abstract Background Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). Methods We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. Results We identified 35 protein targets for migraine and its subtypes (p

Abstract Using e + e − annihilation data sets corresponding to an integrated luminosity of 4.5 fb −1, collected with the BESIII detector at center-of-mass energies between 4.600 and 4.699 GeV, we report the first measurements of the absolute branching fractions B Λ c + → p K L 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0\right) $$ = (1.67 ± 0.06 ± 0.04)%, B Λ c + → p K L 0 π + π − $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^{+}{\pi}^{-}\right) $$ = (1.69 ± 0.10 ± 0.05)%, and B Λ c + → p K L 0 π 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^0\right) $$ = (2.02 ± 0.13 ± 0.05)%, where the first uncertainties are statistical and the second systematic. Combining with the known branching fractions of Λ c + → p K S 0 $$ {\Lambda}_c^{+}\to p{K}_S^0 $$ , Λ c + → p K S 0 π + π − $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^{+}{\pi}^{-} $$ , and Λ c + → p K S 0 π 0 $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^0 $$ , we present the first measurements of the K S 0 $$ {K}_S^0 $$ - K L 0 $$ {K}_L^0 $$ asymmetries R Λ c + K S , L 0 X = B Λ c + → K S 0 X − B Λ c + → K L 0 X B Λ c + → K S 0 X + B Λ c + → K L 0 X $$ R\left({\Lambda}_c^{+},{K}_{S,L}^0X\right)=\frac{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)-\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)}{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)+\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)} $$ in charmed baryon decays: R Λ c + p K S , L 0 = − 0.025 ± 0.031 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0\right)=-0.025\pm 0.031 $$ , R Λ c + p K S , L 0 π + π − = − 0.027 ± 0.048 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^{+}{\pi}^{-}\right)=-0.027\pm 0.048 $$ and R Λ c + p K S , L 0 π 0 = − 0.015 ± 0.046 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^0\right)=-0.015\pm 0.046 $$ . No significant asymmetries with statistical significance are observed.

Abstract Background Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians’ understanding of the disease and to facilitate early diagnosis and treatment. Case presentation A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. infection. Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. Conclusion Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Abstract Background Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. Methods This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. Results A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1–61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1–5.7) and median overall survival was 13.1 months (95% CI 12.2–15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. Conclusions The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). Trial registration ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features. Methods Transcriptomic datasets from three independent iCCA cohorts (iCCA cohorts 1–3, n = 382) and formalin-fixed and paraffin-embedded tissues from iCCA cohort 4 (n = 31) were used. An unbiased global screening strategy was established, including the transcriptome analysis with the activated malignancy/stemness (MS) signature in iCCA cohorts 1–3 and the mass spectrometry analysis of the sorted stemness reporter-positive iCCA cells. A group of cellular assays and subcutaneous tumor xenograft assay were performed to investigate functional roles of the candidate. Immunohistochemistry was performed in iCCA cohort 4 to examine the expression and localization of the candidate. Molecular and biochemical assays were used to evaluate the membrane localization and functional protein domains of the candidate. Cell sorting was performed and the corresponding cellular molecular assays were utilized to examine cancer stem cell features of the sorted cells. Results The unbiased global screening identified RRM2 as the top candidate, with a significantly higher level in iCCA patients with the MS signature activation and in iCCA cells positive for the stemness reporter. Consistently, silencing RRM2 significantly suppressed iCCA malignancy phenotypes both in vitro and in vivo. Moreover, immunohistochemistry in tumor tissues of iCCA patients revealed an unreported cell membrane localization of RRM2, in contrast to its usual cytoplasmic localization. RRM2 cell membrane localization was then confirmed in iCCA cells via immunofluorescence with or without cell membrane permeabilization, cell fractionation assay and cell surface biotinylation assay. Meanwhile, an unclassical signal peptide and a transmembrane domain of RRM2 were revealed experimentally. They were essential for RRM2 trafficking to cell membrane via the conventional endoplasmic reticulum (ER)–Golgi secretory pathway. Furthermore, the membrane RRM2-positive iCCA cells were successfully sorted. These cells possessed significant cancer stem cell malignant features including cell differentiation ability, self-renewal ability, tumor initiation ability, and stemness/malignancy gene signatures. Patients with membrane RRM2-positive iCCA cells had poor prognosis. Conclusions RRM2 had an alternative cell membrane localization. The membrane RRM2-positive iCCA cells represented a malignant subpopulation with cancer stem cell features.

The all-d-metal Ni–Mn–Ti Heusler alloy with its good mechanical properties and colossal caloric effects has attracted significant attention for mechanocaloric refrigeration. However, the phase stability of the B2-type disordered structure at finite temperatures and the physical origin of large phase transformation entropy change in theoretical calculation remain unclear. In view of thermal and strongly anharmonic effects, we combined the first-principles and temperature dependent effective potential calculations to systematically study the phase stability, martensitic transformation mechanism, and vibrational entropy properties of B2 partial disordered structures for Ni8Mn5Ti3 and Ni8Mn6Ti2. Our results showed the austenitic structures of Ni8Mn5Ti3 and Ni8Mn6Ti2 both exhibit antiferromagnetic interaction behaviors at targeted temperatures, resolving the contradiction between previous calculations and experiments. By the analysis of phonon dispersion relations and Helmholtz free energies at low and high temperatures, we provided a deeper explanation for the underlying mechanism of martensitic transformation. Meanwhile, the phase transformation temperatures and vibrational entropy changes were accurately predicted compared with the experiment results. Specifically, we demonstrated that the large vibrational entropy change of Ni–Mn–Ti material originates from the contributions of both the tetragonal distortion ratio and volume change, which provides important theoretical guidance and has great practical significance for designing the solid-state material with large vibrational entropy change in the application of solid-state refrigeration.

Abstract The processes h c → γP (P = η′, η, π 0) are studied with a sample of (27.12 ± 0.14) × 108 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The decay h c → γη is observed for the first time with the significance of 9.0 σ, and the branching fraction is determined to be (3.77 ± 0.55 ± 0.13 ± 0.26) × 10 −4, while B $$ \mathcal{B} $$ (h c → γη′) is measured to be (1.40 ± 0.11 ± 0.04 ± 0.10) × 10 −3, where the first uncertainties are statistical, the second systematic, and the third from the branching fraction of ψ(3686) → π 0 h c . The combination of these results allows for a precise determination of R h c = B h c → γη B h c → γ η ′ , $$ {R}_{h_c}=\frac{\mathcal{B}\left({h}_c\to {\pi}^0\gamma \eta \right)}{\mathcal{B}\left({h}_c\to {\pi}^0\gamma {\eta}^{\prime}\right)}, $$ which is calculated to be (27.0 ± 4.4 ± 1.0)%. The results are valuable for gaining a deeper understanding of η − η′ mixing, and its manifestation within quantum chromodynamics. No significant signal is found for the decay h c → γπ 0, and an upper limit is placed on its branching fraction of B $$ \mathcal{B} $$ (h c → γπ 0) < 5.0 × 10 −5, at the 90% confidence level.

Abstract Background An increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there’s a lack of data regarding the long-term data on the natural course and how it’s managed in China. In this study, we offer a comprehensive overview of clinical and molecular findings, as well as treatment outcomes in the Chinese population. Methods Institutional data on all patients with dystrophinopathy from August 2011 to August 2021 were retrospectively reviewed. The data included geographic distribution, age at diagnosis, molecular findings, and treatment options, such as corticosteroids, cardiac interventions, and clinical outcomes. Results In total, 2097 patients with dystrophinopathy, including 1703 cases of Duchenne muscular dystrophy (DMD), 311 cases of Becker muscular dystrophy (BMD), 46 cases of intermediate muscular dystrophy (IMD), and 37 cases categorized as “pending” (individuals with an undetermined phenotype), were registered in the Children’s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified variants included exonic deletions (66.6%), exonic duplications (10.7%), nonsense variants (10.3%), splice-site variants (4.5%), small deletions (3.5%), small insertions/duplications (1.8%), and missense variants (0.9%). Four deep intronic variants and two inversion variants were identified. Regarding treatment, glucocorticoids were administered to 54.4% of DMD patients and 39.1% of IMD patients. The median age at loss of ambulation was 2.5 years later in DMD patients who received glucocorticoid treatment. Overall, one cardiac medicine at least was prescribed to 7.4% of DMD patients, 8.3% of IMD patients, and 2.6% of BMD patients. Additionally, ventilator support was required by four DMD patients. Eligibility for exon skipping therapy was found in 55.3% of DMD patients, with 12.9%, 10%, and 9.6% of these patients being eligible for skipping exons 51, 53, and 45, respectively. Conclusions This is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to the recruitment of eligible patients for clinical trials and the provision of real-world data to support drug development.

Abstract Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration. Graphical Abstract

Background The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights.

Abstract Astaxanthin biosynthesis in Haematococcus pluvialis is driven by energy. However, the effect of the flagella-mediated energy-consuming movement process on astaxanthin accumulation has not been well studied. In this study, the profiles of astaxanthin and NADPH contents in combination with the photosynthetic parameters with or without flagella enabled by pH shock were characterized. The results demonstrated that there was no significant alteration in cell morphology, with the exception of the loss of flagella observed in the pH shock treatment group. In contrast, the astaxanthin content in the flagella removal groups was 62.9%, 62.8% and 91.1% higher than that of the control at 4, 8 and 12 h, respectively. Simultaneously, the increased Y(II) and decreased Y(NO) suggest that cells lacking the flagellar movement process may allocate more energy towards astaxanthin biosynthesis. This finding was verified by NADPH analysis, which revealed higher levels in flagella removal cells. These results provide preliminary insights into the underlying mechanism of astaxanthin accumulation enabled by energy reassignment in movement-lacking cells.

Abstract Fractional tree cover facilitates the depiction of forest density and its changes. However, it remains challenging to estimate tree cover from satellite data, leading to substantial uncertainties in forest cover changes analysis. This paper generated a global annual fractional tree cover dataset from 2000 to 2021 with 250 m resolution (GLOBMAP FTC). MODIS annual observations were realigned at the pixel level to a common phenology and used to extract twelve features that can differentiate between trees and herbaceous vegetation, which greatly reduced feature dimensionality. A massive training data, consisting of 465.88 million sample points from four high-resolution global forest cover products, was collected to train a feedforward neural network model to predict tree cover. Compared with the validation datasets derived from the USGS circa 2010 global land cover reference dataset, the R2 value, MAE, and RMSE were 0.73, 10.55%, and 17.98%, respectively. This dataset can be applied for assessment of forest cover changes, including both abrupt forest loss and gradual forest gain.

Abstract Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

Abstract Using e + e − collision data collected with the BESIII detector at the BEPCII collider at center-of-mass energies between 3.510 and 4.914 GeV, corresponding to an integrated luminosity of 25 fb −1, we measure the Born cross sections for the process e + e − → K − Ξ ¯ + Λ / Σ 0 $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ at thirty-five energy points with a partial-reconstruction strategy. By fitting the dressed cross sections of e + e − → K − Ξ ¯ + Λ / Σ 0 $$ {e}^{+}{e}^{-}\to {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ , evidence for ψ 4160 → K − Ξ ¯ + Λ $$ \psi (4160)\to {K}^{-}{\overline{\Xi}}^{+}\Lambda $$ is found for the first time with a significance of 4.4σ, including systematic uncertainties. No evidence for other possible resonances is found. In addition, the products of electronic partial width and branching fraction for all assumed resonances decaying into K − Ξ ¯ + Λ / Σ 0 $$ {K}^{-}{\overline{\Xi}}^{+}\Lambda /{\Sigma}^0 $$ are determined.

Objective To investigate the predictive value of glycemic gap in the conservative medicine treatment of symptomatic intracranial hemorrhage in stroke patients. Methods A retrospective analysis was conducted on 133 elderly stroke patients who received conservative drug treatment in Xuanwu Hospital, Capital Medical University from January 2021 to January 2023. According to whether symptomatic intracranial hemorrhage occurred, they were divided into the occurrence group (33 cases) and the non-occurrence group (100 cases), and relevant clinical data of the two groups were collected. Multivariate logistic regression was used to analyze the related factors affecting the occurrence of symptomatic intracranial hemorrhage, and ROC curve was drawn to analyze the predictive value of glycemic gap on the occurrence of symptomatic intracranial hemorrhage. Results There were significant differences in age, drinking history, National Institutes of Health Stroke Scale (NIHSS) score, combined hypertension and glycemic gap between the two groups (P

Abstract With a sample of (10087 ± 44) × 106 J/ψ events accumulated with the BESIII detector, we analyze the decays η′ → π + π − l + l − (l = e, μ) via the process J/ψ → γη′. The branching fractions are measured to be B $$ \mathcal{B} $$ (η′ → π + π − e + e − ) = (2.45 ± 0.02(stat.) ± 0.08(syst.)) × 10 −3 and B $$ \mathcal{B} $$ (η′ → π + π − μ + μ − ) = (2.16 ± 0.12(stat.) ± 0.06(syst.)) × 10 −5, and the ratio is B η ′ → π + π − e + e − B η ′ → π + π − μ + μ − = 113.4 ± 0.9 stat . ± 3.7 syst . $$ \frac{\mathcal{B}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{e}^{+}{e}^{-}\right)}{\mathcal{B}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{\mu}^{+}{\mu}^{-}\right)}=113.4\pm 0.9\left(\textrm{stat}.\right)\pm 3.7\left(\textrm{syst}.\right) $$ . In addition, by combining the η′ → π + π − e + e − and η′ → π + π − μ + μ − decays, the slope parameter of the electromagnetic transition form factor is measured to be b η′ = 1.30 ± 0.19 (GeV/c 2) −2, which is consistent with previous measurements from BESIII and theoretical predictions from the VMD model. The asymmetry in the angle between the π + π − and l + l − decay planes, which has the potential to reveal the CP-violation originating from an unconventional electric dipole transition, is also investigated. The asymmetry parameters are determined to be A CP η ′ → π + π − e + e − = − 0.21 ± 0.73 stat . ± 0.01 syst . % $$ {\mathcal{A}}_{CP}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{e}^{+}{e}^{-}\right)=\left(-0.21\pm 0.73\left(\textrm{stat}.\right)\pm 0.01\left(\textrm{syst}.\right)\right)\% $$ and A CP η ′ → π + π − μ + μ − = 0.62 ± 4.71 stat . ± 0.08 syst . % $$ {\mathcal{A}}_{CP}\left({\eta}^{\prime}\to {\pi}^{+}{\pi}^{-}{\mu}^{+}{\mu}^{-}\right)=\left(0.62\pm 4.71\left(\textrm{stat}.\right)\pm 0.08\left(\textrm{syst}.\right)\right)\% $$ , implying that no evidence of CP-violation is observed at the present statistics. Finally, an axion-like particle is searched for via the decay η′ → π + π − a, a → e + e − , and upper limits of the branching fractions are presented for the mass assumptions of the axion-like particle in the range of 0 − 500 MeV/c 2.

Abstract We measured the Born cross sections for the process e + e − → ωη′ at 22 center-of-mass energies from 2.000 to 3.080 GeV with the BESIII detector at the BEPCII collider. We observed a resonant structure with a statistical significance of 9.6σ. A Breit-Wigner fit determines its mass to be M R = (2153 ± 30 ± 31) MeV/c 2 and its width to be Γ R = (167 ± 77 ± 7) MeV, where the first uncertainties are statistical and the second are systematic.

Abstract Objectives This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. Methods 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Results Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p

To investigate the interfacial reaction of metal powder after absorbing microwave radiation, pure metal powder composed of five elements, Fe, Co, Ni, Cr, and Mn, was microwave heated at four temperature gradients of 500, 800, 1000, and 1200 °C. At 1200 °C, the powder particles diffused to form an alloy. Mechanical alloying of the mixed metal powder was performed for 5, 10, 24, and 48 h to observe the changes of the powder. The size of the alloy particles first increased, then decreased, and then increased again. The powder mechanically alloyed for 48 h was microwave heated at 700, 800, 900, 1000, and 1200 °C. The alloy only formed at 1200 °C.

Abstract The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration.

Abstract Background and aim Conflicting results have been reported on the association between Parkinson's disease (PD) and cardiovascular disease (CVD) mortality in different populations. Therefore, studying the relationship between PD and CVD mortality is crucial to reduce mortality caused by the former. Methods In this cohort investigation, we enrolled 28,242 participants from the National Health and Nutrition Examination Survey spanning from 2003 to 2018. The 380 cases of PD in the cohort were identified by documenting ‘ANTIPARKINSON AGENTS’ in their reported prescription medications. Mortality outcomes were ascertained by cross-referencing the cohort database with the National Death Index, which was last updated on 31 December 2019. Cardiovascular disease mortality was categorised according to the 10th revision of the International Classification of Diseases by using a spectrum of diagnostic codes. Weighted multivariable Cox regression analysis was used to examine the association between PD and the risk of CVD mortality. Results A total of 28,242 adults were included in the study [mean age, 60.156 (12.55) years, 13,766 men (48.74%)], and the median follow-up period was 89 months. Individuals with PD had an adjusted HR of 1.82 (95% CI, 1.24–2.69; p = 0.002) for CVD mortality and 1.84 (95% CI, 1.44–2.33; p

Currently, practical applications of shape memory alloy (SMA) solid elastocaloric refrigeration materials are limited by low elastocaloric effect (eCE), high applied stress, and large stress hysteresis (Δσhys). Here, we introduce a composition design strategy using Ti-doped Co–V-Ga SMAs to address these challenges. We combine first-principles calculations and experiments to verify this strategy. Our results show that the lattice distortion caused by the significant difference in atomic radius after Ti doping produces a solid solution strengthening effect inside the alloy, which significantly improves the superelasticity of the alloy, delays the plastic deformation of the austenite phase, and the volume fraction of martensitic transformation increases significantly. The newly developed Co51.7V31.3Ga16Ti1 bulk polycrystalline alloy exhibits a remarkable adiabatic temperature change (ΔTad) of −10 K at room temperature under a low stress of 400 MPa, a minimum Δσhys of 18 MPa, and a high coefficient of performance COPmat of 31.9. Importantly, the 100-cycle loading-unloading test at 350 MPa is done, and it reveals that the ΔTad for the Ti0 alloy was only 3.9 K, while it reached 6.2 K for the Ti1 alloy, marking a noteworthy 59 % performance enhancement. From the simplicity of the fabrication process to the comprehensive performance of the material, it exhibits a promising advantage for practical cooling applications This study presents a feasible design strategy for large-scale production of high-performance bulk polycrystalline alloys with high eCE, low stress, and Δσhys.

On January 23, 2024, an MW7.0 earthquake occurred in Wushi County. This earthquake was the largest earthquake event in the south Tianshan Fault Zone in the past century. In order to determine the seismogenic structure of the Wushi earthquake and analyze the regional tectonic stress characteristics, we obtained the coseismic deformation field using radar interferometry and pixel offset based on Sentinel-1A data, and estimated the optimal fault geometric parameters applying the Bayesian nonlinear inversion. The results show that the maximum ascending line-of-sight uplift displacement is ~80 cm, and the maximum line-of-sight subsidence is ~16 cm. The line-of-sight coseismic deformation and pixel offsets indicate the significant vertical deformation characteristics of the Wushi earthquake, while the reverse pixel offset results in the azimuth direction of the ascending and descending orbit indicate obvious left-lateral strike-slip on the seismogenic fault. The inversion results show that the seismogenic fault of the Wushi earthquake is SW trending, NW dipping, with an optimal fault dip angle of ~67° and an average rake angle of ~60°, indicating that the coseismic slip is mainly driven by thrust-slip motion with a minor left-lateral strike-slip component. The deformation pattern and fault geometry parameters of the Wushi earthquake are consistent with the kinematics and geometry of the Maidan-Shayilamu fault at the basin-mountain boundary in the southern margin of the Tianshan Mountains. The high dip angle fault with strike- and thrust-slip activity of the Wushi earthquake indicates oblique convergence between the southern Tianshan Mountains and the Tarim Basin, and emphasizes that crustal shortening in the Tianshan region is absorbed by the nascent thrust nappe belts in the piedmont areas and the reverse faults with high dip angles in the orogenic regions.

AbstractContext Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota.Objective This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation.Methods We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD.Results Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD.Conclusion This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

ABSTRACTAmidst the rapid urbanisation, the ecological environment of plateau lake basins faces significant challenges. To better coordinate the relationship between urbanisation development and ecological environment construction, this paper conducts an analysis and assessment of the ecological resilience and urbanisation coupling coordination in Dali Prefecture based on socio-geographical spatial data. Initially, an assessment model for ecological resilience is established using resilience theory. Subsequently, the urbanisation development level is evaluated based on panel data. Finally, a coupling coordination model is employed to calculate the coupling coordination between the two aspects. The results indicate: (1) a rapid increase in basin urbanisation from 2010 to 2019, particularly between 2010 and 2015; (2) a continuous expansion of low-value ecological resilience areas across the entire basin, with a predominance of townships experiencing fluctuating decreases or stagnation, leading to an overall negative trend in ecological resilience indices; (3) evident spatial and temporal disparities in coupling coordination between the two systems in the basin’s villages and towns, primarily reflected in differences in coupling coordination types, with a few towns consistently exhibiting environmental lag. This study introduces a customised ecological resilience model for the Erhai Basin, enhancing comprehension of urbanisation-ecological resilience dynamics in plateau lake basins.

Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.

Abstract Aims The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. Methods RNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. Results HFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P

Oscillating laser-arc hybrid welding of AZ31B magnesium alloy was carried out, the effects of beam oscillation parameters on pore inhibition, microstructure, grain boundary characteristics and tensile properties were investigated. The results showed that the pore formation can be inhibited with oscillating frequency higher than 75 Hz and radius smaller than 0.5 mm. The columnar grains neighboring the fusion line can be broken by the beam oscillation behavior, while the grain growth was promoted with the increase of frequency or radius. It should be noted that the coincidence site lattice (CSL) boundaries were mainly Σ13b and Σ29 boundaries, which were contributed by {101¯2} tensile twins and {112¯2} compression twins, respectively. The total fraction of CSL boundaries reached maximum at radius of 0.25 mm and frequency of 75 Hz, which was also confirmed as the optimized parameters. In this case, the elongation rate increased up to 13.2%, 12.8% higher than that of the weld without beam oscillation. Finally, the pore formation and inhibition mechanisms were illustrated according to the state of melt flow and keyhole formation, the abnormal growth was discussed basing on secondary recrystallization, and the relationship among the pore formation, grain size, boundary characteristics and weld toughness were finally established.

Abstract Immunotherapies are revolutionizing cancer care, but many patients do not achieve durable responses and immune-related adverse events are difficult to predict. Quantifying the hundreds of proteins involved in cancer immunity has the potential to provide biomarkers to monitor and predict tumor response. We previously developed robust, multiplexed quantitative assays for immunomodulatory proteins using targeted mass spectrometry, providing measurements that can be performed reproducibly and harmonized across laboratories. Here, we expand upon those efforts in presenting data from a multiplexed immuno-oncology (IO)-3 assay panel targeting 43 peptides representing 39 immune- and inflammation-related proteins. A suite of novel monoclonal antibodies was generated as assay reagents, and the fully characterized antibodies are made available as a resource to the community. The publicly available dataset contains complete characterization of the assay performance, as well as the mass spectrometer parameters and reagent information necessary for implementation of the assay. Quantification of the proteins will provide benefit to correlative studies in clinical trials, identification of new biomarkers, and improve understanding of the immune response in cancer.

Abstract Objectives Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). Methods The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. Results Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p

In the process of water treatment, the coagulation process is a complex system characterized by significant lag and non-linearity. To address its characteristics and based on the current research status of dosing control, a forward-cascade intelligent dosing system based on floc image processing and fuzzy logic control was developed. Through the acquisition and processing of water sample images, key parameters of floc characteristics were extracted, and the equivalent diameters were calculated to establish a dosing model to determine the coagulant dosage. Subsequently, automatic adjustment and precise dosing of coagulants were achieved through fuzzy PID control and feedforward compensation. System monitoring and performance analysis showed that compared with traditional manual dosing, the intelligent dosing system reduced the standard deviation of the sedimentation effluent turbidity by 27%, with the relative error controlled within 10% of the set value. The dosage of coagulants was reduced by 11.04%. The intelligent dosing system demonstrated significant advantages in coagulant dosage and treatment effects, which showed promising feasibility and potential for dissemination.

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. Methods 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1–2, and the moderate neuromuscular block group maintained TOF = 1–2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. Results MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg−1·h−1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), μg·kg−1·min−1, P

Abstract Background Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). Methods We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer’s disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. Results The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. Discussion This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients.

Abstract Background Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD. Methods A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis. Results Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies. Conclusions Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.

Chicken breast as the raw material was fully sheared and then the obtain minced meat was rested at 4 ℃ for different time (0~48 h). The thixotropy and rheological properties of the chicken minced meat was further analyzed, and the effect of resting time on the properties of the chicken minced meat gel was also investigated. The results showed that the chicken minced meat exhibited pseudoplasticity, thixotropy and weak gel properties (G'>G''), and the viscosity, thixotropy, elasticity (G') and viscosity (G'') of the chicken minced meat gradually increased with the increase of resting time. The cooking loss rate of the chicken minced meat gel significantly increased (P

Objective To investigate the correlation between bone metabolism indicators and cerebrovascular diseases in patients with diabetic nephropathy and their impact on survival rate. Methods A total of 996 elderly patients with type 2 diabetic nephropathy who visited the department of endocrinology,Xuanwu Hospital,Capital Medical University from January 2014 to December 2019 were selected as the study subjects and divided into the combined group(n=599) and the uncombined group(n=397) according to the presence or absence of cerebrovascular disease.General data,clinical data,laboratory data,bone metabolism data and follow-up data of the patients were collected.Logistic regression was used to analyze the association between bone metabolism indicators(bone mineral density,osteocalcin,bone alkaline phosphatase,vitamin D,parathyroid hormone,etc.) and cerebrovascular disease. Results Bone mineral density and vitamin D in the combined group were lower than those in the uncombined group;osteocalcin and bone alkaline phosphatase were higher than those in the uncombined group;serum calcium and phosphorus levels in the combined group were lower than those in the uncombined group,and the differences were statistically significant(P

Laser-arc hybrid welding of AZ31B magnesium alloy was carried out, the effects of welding parameters on weld formation, microstructure homogeneity and mechanical properties were investigated. The results showed that laser-arc hybrid welding was beneficial to improve the weld formation of magnesium alloy by inhibiting the defect of undercut and pores. The weld microstructure was mainly columnar grains neighboring the fusion line and equiaxed grains at the weld center. It was interesting that the grain size at the upper arc zone was smaller than that at the lower laser zone, with the difference mainly affected by laser power rather than welding current and welding speed. The welding parameters were optimized as laser power of 3.5 kW, welding current of 100 A and welding speed of 1.5 m/min. In this case, the weld was free of undercut and pores, and the tensile strength and elongation rate reached 252 MPa and 11.2%, respectively. Finally, the microstructure homogeneity was illustrated according to the heat distribution, and the evolution law of tensile properties was discussed basing on the weld formation and microstructure characteristics.

Abstract Using e + e − collision data collected at the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, corresponding to an integrated luminosity of 7.33 fb −1, we determine the absolute branching fractions of fifteen hadronic D s + $$ {D}_s^{+} $$ decays with a double-tag technique. In particular, we make precise measurements of the branching fractions B D s + → K + K − π + = 5.49 ± 0.04 ± 0.07 % $$ \mathcal{B}\left({D}_s^{+}\to {K}^{+}{K}^{-}{\pi}^{+}\right)=\left(5.49\pm 0.04\pm 0.07\right)\% $$ , B D s + → K S 0 K + = 1.50 ± 0.01 ± 0.01 % $$ \mathcal{B}\left({D}_s^{+}\to {K}_S^0{K}^{+}\right)=\left(1.50\pm 0.01\pm 0.01\right)\% $$ and B D s + → K + K − π + π 0 = 5.50 ± 0.05 ± 0.11 % $$ \mathcal{B}\left({D}_s^{+}\to {K}^{+}{K}^{-}{\pi}^{+}{\pi}^0\right)=\left(5.50\pm 0.05\pm 0.11\right)\% $$ , where the first uncertainties are statistical and the second ones are systematic. The CP asymmetries in these decays are also measured and all are found to be compatible with zero.

The crack growth behavior and microstructural evolution of 316H austenitic stainless steel welded joints subjected to load-controlled creep-fatigue crack growth at 550 °C was investigated in this study. A comprehensive analysis of the fracture mechanisms in both the base metal (BM) and weld metal (WM) was conducted employing advanced characterization. The results revealed that cracks in both BM and WM preferentially propagate along paths of high energy and low resistance, characterized by substructured and deformed grains. In the BM, twin boundaries demonstrated high fracture resistance; however, with increased dwell time, the interaction between planar slip bands and twins induced a detwinning effect, thereby reducing the fracture resistance. In contrast, the WM exhibited interdendritic cracking primarily due to the precipitation of carbide and σ phase at the δ/γ interface, causing cracks to propagate along the ferrite network during extended dwell times. Furthermore, the formation of subgrains in austenitic dendrites and the transition of ferrite in the WM significantly reduced the texture strength of the original columnar crystals, impacting the overall creep-fatigue crack growth behavior. These results underscore the critical role of microstructural evolution in determining fracture resistance and crack propagation behavior in 316H austenitic stainless steel welded joints under creep-fatigue loading. The insights gained from this study are essential for improving the design and durability of high-temperature components in advanced reactors.

Abstract Using (27.12 ± 0.14) × 108 ψ(3686) events collected by the BESIII detector at the center-of-mass energy of s $$ \sqrt{s} $$ = 3.686 GeV, we search for the first time for two nonleptonic hyperon decays that change strangeness by two units, Ω − → Σ0 π − and Ω − → nK − . No significant signal is observed. The upper limits on their decay branching fractions are determined to be B $$ \mathcal{B} $$ (Ω − → Σ0 π − ) < 5.4 × 10 −4 and B $$ \mathcal{B} $$ (Ω − → nK − ) < 2.4 × 10 −4 at the 90% confidence level.

Abstract Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02–1.09), vascular dementia (HR, 1.08; 95% CI 1.01–1.15), and non-Alzheimer’s disease non-vascular dementia (HR, 1.09; 95% CI 1.03–1.14). No significant association was observed for Alzheimer’s disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Highlights A novel photoelectrochemical (PEC) photosensor composed of GaN nanowire-on-Si platform demonstrates record-high responsivity of 247.8 mA W−1 with ultra-stable operation characteristics. Strategic internal and external band structure engineering of semiconductor nanowires promotes efficient PEC reaction via controlling carrier dynamics while preserving nanowires from material degradation. The glucose sensing system is constructed to successfully analyze blood glucose levels in real human serum samples, featuring a high sensitivity of 0.173 µA µM−1 cm−2 and a low detection limit of 0.07 µM.

Abstract Using 24.1 fb −1 of e + e − collision data collected with the BESIII detector at the BEPCII collider, the Born cross sections and effective form factors of the e + e − → Σ + Σ ¯ − $$ {e}^{+}{e}^{-}\to {\Sigma}^{+}{\overline{\Sigma}}^{-} $$ reaction are measured. The measurements are performed at center-of-mass energies ranging from 3.510 to 4.951 GeV. No significant evidence for the decay of the charmonium(-like) states, ψ(3770), ψ(4040), ψ(4160), Y(4230), Y(4360), ψ(4415), and Y(4660), into a Σ + Σ ¯ − $$ {\Sigma}^{+}{\overline{\Sigma}}^{-} $$ final state is observed. Consequently, upper limits for the products of the branching fractions and the electronic partial widths at the 90% confidence level are reported for these decays.

The objective of this study was to investigate the optimal preparation process and digestive properties of sulforaphane from Raphanus sativus seeds prepared by enzymatic method. Single factor experiment and response surface methodology were employed to optimize the enzymolysis conditions for extracting sulforaphane from red Raphanus sativus seeds, with sulforaphane yield as index. Additionally, an in vitro simulated gastrointestinal digestion model was used to evaluate the changes in content and antioxidant activity of sulforaphane in ethyl acetate extracts of Raphanus sativus seeds. The results revealed that the optimal preparation conditions were as follows: The enzymolysis time was 22 minutes, the enzymolysis temperature was 40 ℃, the vitamin C concentration was 0.8 mg/g. Under these conditions, the sulforaphane yield was 2.11±0.02 mg/g, which closely matched the predicted value of 2.14 mg/g. The relative error for the enzymolysis process was 1.4%, demonstrating its feasibility. Furthermore, in vitro digestion simulation showed that the retention rate of sulforaphane was 79.64% and 76.22% in gastric and intestinal fluids, respectively. The free radical scavenging rates of ABTS+, DPPH and OH in gastric fluid reached 54.23%, 33.90% and 15.07%, respectively, and all the values had significant (P0.05) difference in the three radical scavenging rates was observed in intestinal and gastric digestive fluids. This study enriched the research on the preparation of sulforaphane by enzymolysis method, and provided experimental basis for the development and high value-added utilization of Raphanus sativus seeds.

Abstract The 6th member of the Triassic Yanchang Formation, hereafter referred to as Chang 6 reservoir, in the Wuqi area of the Ordos Basin presents formidable obstacles for efficient tight oil development. This reservoir is known for its tight lithology, strong heterogeneity, inadequate oil saturation, and abnormally low reservoir pressure, which collectively contribute to the highly differentiated mobility of tight oil within the formation. To overcome these challenges, a comprehensive understanding of the factors influencing oil mobility is essential. This study investigates the occurrence characteristics of movable fluids in different diagenetic facies and the corresponding influential factors by employing various microscopic experiments, including high-pressure mercury intrusion, constant-rate mercury intrusion, nuclear magnetic resonance test, scanning electron microscopy, pore-casted thin section analysis, and X-ray diffraction measurement. There is a weaker correlation between the pore-throat radius ratio and the movable fluid saturation in reservoirs of various diagenetic facies (R 2 = 0.6104), whereas there is a stronger correlation between movable fluid saturation and throat radius (R 2 = 0.9415). Among the seven types of diagenetic facies, chlorite membrane cementation-intergranular pore facies (Facies I) and chlorite and illite membrane cementation-intergranular pore facies (Facies II) have the best-developed throats and the highest coordination number. Illite cementation-intergranular pore facies (Facies III) and illite and chlorite membrane cementation-dissolution facies (Facies IV) demonstrate smaller pore-throat radii and moderate to poor reservoir connectivity. The other three facies, namely illite cementation-dissolution facies (Facies V), illite cementation facies (Facies VI), and carbonate tight cementation facies (Facies VII) exhibit underdeveloped pore structures and lower recovery rates. Pore-throat radius emerges as the principal factor influencing reservoir permeability and storage capacity. The distribution of favorable diagenetic facies is influenced by depositional environments, diagenetic processes, and microscopic pore-throat characteristics. This study significantly enhances our understanding of the differential occurrence characteristics of fluids in different diagenetic facies in the Chang 6 reservoir, providing valuable insights for future exploration and production endeavors aimed at optimizing oil recovery in tight sandstone reservoirs.

Abstract This paper proposes a prediction method for the tension force of support ropes in flexible rockfall barriers. The method is based on two full-scale model tests with an impact energy of 3000 kJ, as well as 36 set numerical models featuring varying lengths and impact energies. From the results of full scale tests and numerical models, it is inferred that the tension force at the end of the support rope is significantly less than that at the point of impact, exhibiting an approximate Gaussian attenuation distribution with propagation distance. To account for the attenuation of tensile forces in support ropes, a tensile attenuation coefficient is defined. Through comparative analysis of data obtained from 36 models with varying impact energies and propagation distances, the average attenuation coefficient for the upper support rope is determined to be approximately 0.7, while the average coefficient for the lower support rope is around 0.8. Utilizing the least squares method, a prediction method for the tension force of support ropes in flexible rockfall barriers is established. This method takes into account both the propagation distance and impact energy, enabling accurate predictions of the tensile behavior of the ropes under different conditions. This prediction model provides valuable insights for engineers in the design and optimization of these flexible barriers for rockfall mitigation.

Abstract The transmission bottleneck describes the number of viral particles that initiate an infection in a new host. Previous studies have used genome sequence data to suggest that transmission bottlenecks for influenza and SARS-CoV-2 involve few viral particles, but the general principles of virus transmission are not fully understood. Here we show that, across a broad range of circumstances, tight transmission bottlenecks are a simple consequence of the physical process of airborne viral transmission. We use mathematical modelling to describe the physical process of the emission and inhalation of infectious particles, deriving the result that that the great majority of transmission bottlenecks involve few viral particles. While exceptions to this rule exist, the circumstances needed to create these exceptions are likely very rare. We thus provide a physical explanation for previous inferences of bottleneck size, while predicting that tight transmission bottlenecks prevail more generally in respiratory virus transmission.

In order to investigate the changes in structure and properties of waxy maize starch (WMS) after its nano-starch was prepared by pullulanase enzymolysis-dynamic high pressure micro-fluidization technology (P-DHPM), this paper explored the trends of changes in starch microstructure, crystalline structure, molecular structure, particle size, molecular weight, and thermal properties before and after the treatment. The results showed that spherical starch particles were turned into fragmentization, and the crystalline structures were transferred into amorphous states, the short-range ordered structure was increased, and the molecular weight of starch was decreased with the increment of enzymatic hydrolysis time. In the meantime, the peak gelatinization temperature (Tp) of treated starch was decreased from 71.23 ℃ to 55.81 ℃, and the enthalpy value of pasting (ΔH) was decreased to 4.68 J/g significantly (P

Abstract Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 $$\times $$ × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Abstract Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.