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Pump–probe experiments with subfemtosecond resolution are the key to understanding electronic dynamics in quantum systems. Here we demonstrate the generation and control of subfemtosecond pulse pairs from a two-colour X-ray free-electron laser. By measuring the delay between the two pulses with an angular streaking diagnostic, we characterize the group velocity of the X-ray free-electron laser and show control of the pulse delay down to 270 as. We confirm the application of this technique to a pump–probe measurement in core-ionized para-aminophenol. These results reveal the ability to perform pump–probe experiments with subfemtosecond resolution and atomic site specificity.

Abstract Cachexia, which affects 50–80% of cancer patients, is a debilitating syndrome that leads to 20% of cancer-related deaths. A key feature of cachexia is adipose tissue atrophy, but how it contributes to the development of cachexia is poorly understood. Here, we demonstrate in mouse models of cancer cachexia that white adipose tissue browning, which can be a characteristic early-onset manifestation, occurs prior to the loss of body weight and skeletal muscle wasting. By analysing the proteins differentially expressed in extracellular vesicles derived from cachexia-inducing tumours, we identified a molecular chaperone, Glucose-regulated protein 75 (GRP75), as a critical mediator of adipocyte browning. Mechanistically, GRP75 binds adenine nucleotide translocase 2 (ANT2) to form a GRP75–ANT2 complex. Strikingly, stabilized ANT2 enhances its interaction with uncoupling protein 1, leading to elevated expression of the latter, which, in turn, promotes adipocyte browning. Treatment with withanone, a GRP75 inhibitor, can reverse this browning and alleviate cachectic phenotypes in vivo. Overall, our findings reveal a novel mechanism by which tumour-derived GRP75 regulates white adipose tissue browning during cachexia development and suggest a potential white adipose tissue-centred targeting approach for early cachexia intervention.

BackgroundPer- and poly-fluoroalkyl substances (PFAS) are a class of emerging persistent organic pollutants, and their negative health impacts have been widely concerned. There is a lack of epidemiological studies on the associations of PFAS exposure with lipid homeostasis. ObjectiveTo investigate the associations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure with blood lipid levels and dyslipidemia in middle-aged and elderly women. MethodsThis study was based on 795 middle-aged and elderly women from a female sub-cohort of the Dongfeng-Tongji cohort study, excluding the participants without blood lipid measurements and/or reported use of lipid-lowering drugs at baseline. The concentrations of plasma PFOS and PFOA were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured using an automatic analyzer. The normally distributed continuous variables were presented as mean ± standard deviation (\begin{document}$ \bar{x}\pm s) $\end{document}, while the skewedly distributed continuous variables were presented as median (M) and the 25th and 75th percentiles (P25, P75). Generalized linear models (GLM), generalized additive models (GAM), and logistic regression models were applied to evaluate the associations of PFOS and PFOA exposure with blood lipid levels and the risk of dyslipidemia. Stratified analyses were also implemented to explore potential modification effects of sociodemographic characteristics, lifestyles, and menopause on associations of PFOS and PFOA exposure and blood lipids. ResultsThe \begin{document}$ \bar{x}\pm s $\end{document} of baseline age for the study participants was (59.4±8.6) years old, and their baseline body mass index (BMI) was (24.3±3.4) kg·m−2. The M (P25, P75) of baseline plasma concentrations for PFOS and PFOA were 9.96 (6.24, 15.09) μg·L−1 and 1.20 (0.84, 1.80) μg·L−1 respectively. The GLM analysis showed that plasma concentration of PFOS was positively associated with serum HDL-C [b (95%CI): 0.04 (0.01, 0.07)]. The plasma concentration of PFOA was also positively associated with serum TC [b (95%CI): 0.05 (0.02, 0.08)] and serum LDL-C [b (95%CI): 0.05 (0.01, 0.09)]. No significant association was observed between plasma PFOS and serum TC, TG, or LDL-C, nor between plasma PFOA and serum TG or HDL-C. The stratified analyses showed that the association between PFOA and LDL-C was significant among the participants aged

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a ''semi-extended and pronated'' elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

Hirschsprung-associated enterocolitis (HAEC) is an important cause of morbidity and the leading cause of mortality in patients with Hirschsprung disease. The pathophysiology of disease includes dysmotility of the enteric nervous system, dysbiosis of the microbiota, failure of the intestinal barrier, and impaired immunity. Common manifestations include fever, abdominal distension, lethargy, vomiting, and diarrhea. Given the non-specific signs and symptoms of HAEC, high clinical suspicion is warranted, especially in patients with risk factors. Diagnosis and management of HAEC depend on the severity of disease presentation. Several preoperative and postoperative modalities have been explored to prevent HAEC. The current review elaborates on the risk factors, pathogenesis, diagnosis, treatment, and prevention of HAEC.

Objective: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. Methods: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. Results: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standard deviation increase in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer’s disease (AD), but no significant modification effects are found for sleep patterns or smoking status. Conclusion: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

The measurement of flame temperature and velocity is crucial to combustion research, hence it is of great significance to develop a non-invasive diagnosis technology for the measurement of flame temperature and velocity. In this study, a single-camera simultaneous non-invasive diagnosis technology for flame temperature and velocity field was developed, based on radiation self-calibration and optical flow method. The diagnosis method was applied to two case studies, propane diffusion flame and solid surface spread flame. The reconstructed flame temperature field was compared with measuring results by thermocouples. Results show that the reconstructed temperature field can accurately describe the symmetrical distribution characteristics and the clear high-temperature front. The combustion zone reconstruction temperature was 1250–1380 K for propane diffusion flame and the maximum reconstruction temperature was 1400 K for solid spread flame. The maximum relative error between the reconstructed temperature and the measured values by thermocouples is less than 15 %. Additionally, the flow velocity field at the flame edge was also measured, which could provide a good qualitative characterization of flame kinematic.

Abstract Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive “transient” and “durable” expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.

ABSTRACT Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).

Introduction Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI.Methods and analysis This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year.Ethics and dissemination This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences.Trial registration number ChiCTR2300077633.

Abstract The southwest vortices (SWVs) are a unique type of mesoscale vortex that frequently induce torrential rainfall in China. In this study, we focused a long‐lived quasi‐stationary SWV, which was the primary system for producing an extremely heavy rainstorm within/around Sichuan (the maximum hourly precipitation was ~103.8 mm) in Mid July 2021. After reproduced the SWV's formation by using Weather Research and Forecasting model, we conducted trajectory analyses and topography sensitivity simulations to understand the effects of complicated topography on the vortex's formation. It is found that, the regions south and southwest of the SWV acted as the most important source regions for the air clusters that formed the SWV (proportion ≥ 65%), and the air clusters originated from the upper layer contributed the most (≥60%). Of these, the air clusters sourced from the upper layer southwest and south of the SWV played the most important role in the SWV's formation, as their increase in cyclonic vorticity and their contributions to trajectory number and vorticity were all much larger than those of the others. Sensitivity simulations indicated that, detailed topography features around the Sichuan Basin were crucial in determining the structure, intensity and precipitation of the SWV, whereas, the topography features were not a decisive factor for the SWV's formation. In summary, our findings are useful to enrich the current understanding of the SWVs' formation, which would be helpful to improve the related forecasts.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Respiratory infectious diseases can cause public health emergencies, threatening human well-being, social operation, and economic development. Clarifying the transmission mechanism of respiratory infectious diseases is essential for control measures. We review the main research findings on the transmission mechanism of respiratory infectious diseases in recent decades. The source characteristics of respiratory infectious diseases, the airborne transmission mechanism, the exposure of susceptible persons, and the infection risk assessment methods are discussed. Given that the dynamic scenario of respiratory infectious disease transmission has attracted wide attention in recent years, we summarize the effects of human movement on indoor airflow, pathogen diffusion, and human exposure. Considering the everyday use of facemasks, the effects of facemasks on source characteristics and infection risk are also discussed. Finally, future research prospects are proposed. The transmission mechanism of infectious diseases can be comprehensively explored by delving into patients' pathological characteristics and personnel protection measures. This exploration can be facilitated by establishing a multi-pose manikin database, enabling personalized and refined evaluations. Interdisciplinary cooperation will play a pivotal role in fostering a holistic understanding. Furthermore, it is crucial to account for the impact of individuals' activity patterns on disease transmission dynamics. This review is expected to reference public health emergency management.

Anthomyiidae is a cosmopolitan and diverse family of Calyptratae, and is routinely considered to play key roles in both ecology and agriculture. The higher-level phylogenetic classification of Anthomyiidae has been highly controversial, necessitating further molecular data for precise reconstruction of phylogenetic relationships. In this study, we successfully acquired and annotated 18 new mitogenomes of anthomyiids. Moreover, the mitogenomes of the following genera Eustalomyia, Hyporites, Leucophora, Emmesomyia and Eutrichota are reported for the first time. The 18 mitogenomes are compared with confamilial species to assess genetic variation and to better understand evolutionary relationships within the family Anthomyiidae. In comparisons among 13 mitochondrial protein coding genes (PCG), the calculation of evolutionary rate exhibited nad1 as the fastest evolving gene in Anthomyiidae. Among the anthomyiids investigated, cox2 and nad4 had the lowest genetic distance across the 13 PCGs, suggesting a high degree of conservation for these two genes. Herein, we conducted phylogenetic analyses of the newly sequenced mitogenomes along with 11 known anthomyiids to investigate the interrelationships of Anthomyiidae. Our results indicate that Anthomyiidae is a monophyletic lineage and sister group to Scathophagidae, confirming prior findings based on morphological and molecular analyses. We recovered two subfamilies as monophyletic (Myopininae, Pegomyinae) while Anthomyiinae was polyphyletic. The great species diversity of anthomyiid flies limits the availability of mitogenomes for accurately resolving the phylogeny of Anthomyiidae. Nonetheless, our study provides novel insight into the molecular taxonomy, evolution, and phylogeny of the family Anthomyiidae.

Objective: To isolate Lactobacillus acidophilus M6 from the feces of long-distance runners in the early stage. The aim of this study was to investigate the effect of Lactobacillus acidophilus M6 on improving exercise ability and alleviating fatigue function in mice. Methods: Sixty C57BL/6N male mice were randomly divided into 4 groups: Control, low, medium and high dose groups of L. acidophilus M6, L. acidophilus M6 was given daily for four weeks, muscle strength, exercise endurance, fatigue related indicators, energy related indicators and antioxidant related indicators were measured. Results: The low, medium and high dose of L. acidophilus M6 significantly (P

Abstract Knowledge of x-ray free electron lasers’ (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs’ self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator’s configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties.

Polycrystalline silicon carbide (SiC) is a highly valuable material with crucial applications across various industries. Despite its benefits, processing this brittle material efficiently and with high quality presents significant challenges. A thorough understanding of the mechanisms involved in processing and removing SiC is essential for optimizing its production. In this study, we investigated the sawing characteristics and material removal mechanisms of polycrystalline silicon carbide (SiC) ceramic using a diamond wire saw. Experiments were conducted with high wire speeds of 30 m/s and a maximum feed rate of 2.0 mm/min. The coarseness value (Ra) increased slightly with the feed rate. Changes in the diamond wire during the grinding process and their effects on the grinding surface were analyzed using scanning electron microscopy (SEM), laser confocal microscopy, and focused ion beam (FIB)-transmission electron microscopy (TEM). The findings provide insights into the grinding mechanisms. The presence of ductile grinding zones and brittle fracture areas on the ground surface reveals that external forces induce dislocation and amorphization within the grain structure, which are key factors in material removal during grinding.