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Overnutrition during before and pregnancy can cause maternal obesity and raise the risk of maternal metabolic diseases during pregnancy, and in offspring. Lentinus edodes may prevent or reduce obesity. This study aimed to to assess Lentinus edodes fermented products effects on insulin sensitivity, glucose and lipid metabolism in maternal and offspring, and explore its action mechanism. A model of overnutrition during pregnancy and lactation was developed using a 60 % kcal high-fat diet in C57BL6/J female mice. Fermented Lentinus edodes (FLE) was added to the diet at concentrations of 1 %, 3 %, and 5 %. The results demonstrated that FLE to the gestation diet significantly reduced serum insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant mice. FLE can regulate maternal lipid metabolism and reduce fat deposition. Meanwhile, the hepatic phosphoinositide-3-kinase-protein kinase (PI3K/AKT) signaling pathway was significantly activated in the maternal mice. There is a significant negative correlation between maternal FLE supplementation doses and offspring body fat percentage and visceral fat content. Furthermore, FLE supplementation significantly increased offspring weaning litter weight, significantly reduced fasting glucose level, serum insulin level, HOMA-IR and serum glucose level, significantly activated liver PI3K/AKT signaling pathway in offspring, and upregulated the expression of liver lipolytic genes adipose triglyceride lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1 mRNA. Overall, FLE supplementation can regulate maternal lipid metabolism and reduce fat deposition during pregnancy and lactation, and it may improve insulin sensitivity in pregnant mothers and offspring at weaning through activation of the PI3K/AKT signaling pathway.
The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane, leading to cartilage destruction and bone erosion. Due to the complex pathogenesis of RA and the limitations of current therapies, increasing research attention has been directed towards novel strategies targeting fibroblast-like synoviocytes (FLS), which are key cellular components of the hyperplastic pannus. Recent studies have highlighted the pivotal role of FLS in the initiation and progression of RA, driven by their tumour-like transformation and the secretion of pro-inflammatory mediators, including cytokines, chemokines and matrix metalloproteinases. The aggressive phenotype of RA-FLS is marked by excessive proliferation, resistance to apoptosis, and enhanced migratory and invasive capacities. Consequently, FLS-targeted therapies represent a promising avenue for the development of next-generation RA treatments. The efficacy of such strategies – particularly those aimed at modulating FLS signalling pathways – has been demonstrated in both preclinical and clinical settings, underscoring their therapeutic potential. This review provides an updated overview of the pathogenic mechanisms and functional roles of FLS in RA, with a focus on critical signalling pathways under investigation, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), Notch and interleukin-1 receptor-associated kinase 4 (IRAK4). In addition, we discuss the emerging understanding of FLS-subset-specific contributions to immunometabolism and explore how computational biology is shaping novel targeted therapeutic strategies. A deeper understanding of the molecular and functional heterogeneity of FLS may pave the way for more effective and precise therapeutic interventions in RA.
Two-dimensional simulations incorporating detailed chemistry are conducted for detonation initiation induced by dual hot spots in a hydrogen/oxygen/argon mixture. The objective is to examine the transient behaviour of detonation initiation as facilitated by dual hot spots, and to elucidate the underlying mechanisms. Effects of hot spot pressure and distance on the detonation initiation process are assessed; and five typical initiation modes are identified. It is found that increasing the hot spot pressure promotes detonation initiation, but the impact of the distance between dual hot spots on detonation initiation is non-monotonic. During the initiation process, the initial hot spot autoignites, and forms the cylindrical shock waves. Then, the triple-shock structure, which is caused by wave collisions and consists of the longitudinal detonation wave, transverse detonation wave and cylindrical shock wave, dominates the detonation initiation behaviour. A simplified theoretical model is proposed to predict the triple-point path, whose curvature quantitatively indicates the diffraction intensity of transient detonation waves. The longitudinal detonation wave significantly diffracts when the curvature of the triple-point path is large, resulting in the failed detonation initiation. Conversely, when the curvature is small, slight diffraction effects fail to prevent the transient detonation wave from developing. The propagation of the transverse detonation wave is affected not only by the diffraction effects but also by the mixture reactivity. When the curvature of the triple-point trajectory is large, a strong cylindrical shock wave is required to compress the mixture, enhancing its reactivity to ensure the transverse detonation wave can propagate without decoupling.
We presented an attosecond-precision timing detector based on linear optics. The minimum measurement floor is 1×10–10 fs2/Hz with only 1 mW input optical power. With this novel technique, the residual dispersion of a 5.2 km fiber link is characterized and precisely compensated. Finally, a comprehensive feedback model has been developed to analyze the noise coupling in a long-distance link stabilization system. The simulation results demonstrate an out-of-loop jitter of merely 359 as, integrated at [1 Hz, 1 MHz], at 1 mW input power per photodetector of our timing detector. Remarkably, the system is capable of maintaining sub-femtosecond precision even at optical power levels as low as 240 nW (for a 5.2 km link length), or link lengths as long as 20 km (with 1 μW optical power), respectively.
This paper presents an investigation of the secondary saturation characteristics of a HfTe2 saturable absorber. Pulse energies of 5.85 and 7.4 mJ were demonstrated with a high-order Hermite–Gaussian (HG) laser and a vortex laser, respectively, using alexandrite as the gain medium. To the best of our knowledge, these are the highest pulse energies directly generated with HG and vortex lasers. To broaden the applications of high-energy pulsed HG and vortex lasers, wavelength tuning in the region of 40 nm was achieved using an etalon.
This study investigates the effects of fat emulsion-based early parenteral nutrition in patients following hemihepatectomy, addressing a critical gap in clinical knowledge regarding parenteral nutrition after hemihepatectomy. We retrospectively analysed clinical data from 274 patients who received non-fat emulsion-based parenteral nutrition (non-fatty nutrition group) and 297 patients who received fat emulsion-based parenteral nutrition (fatty nutrition group) after hemihepatectomy. Fat emulsion-based early parenteral nutrition significantly reduced levels of post-operative aspartate aminotransferase, total bilirubin and direct bilirubin, while minor decreases in red blood cell and platelet counts were observed in the fatty nutrition group. Importantly, fat emulsion-based early parenteral nutrition shortened lengths of post-operative hospital stay and fasting duration, but did not affect the incidence of short-term post-operative complications. Subgroup analyses revealed that the supplement of n-3 fish oil emulsions was significantly associated with a reduced inflammatory response and risk of post-operative infections. These findings indicate that fat emulsion-based early parenteral nutrition enhances short-term post-operative recovery in patients undergoing hemihepatectomy.
This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.
The intrinsic uncertainty of fluid properties, including the equation-of-state, viscosity and thermal conductivity, on boundary layer stability has scarcely been addressed. When a fluid is operating in the vicinity of the Widom line (defined as the maximum of isobaric specific heat) in supercritical state, its properties exhibit highly non-ideal behavior, which is an ongoing research field leading to refined and more accurate fluid property databases. Upon crossing the Widom line, new mechanisms of flow instability emerge, feasibly leading to changes in dominating modes that yield turbulence. The present work investigates the sensitivity of three-dimensional boundary layer modal instability to these intrinsic uncertainties in fluid properties. The uncertainty, regardless of its source and the fluid regimes, gives rise to distortions of all profiles that constitute the inputs of the stability operator. The effect of these distortions on flow stability is measured by sensitivity coefficients, which are formulated with the adjoint operator and validated against linear modal stability analysis. The results are presented for carbon dioxide at a representative supercritical pressure of approximately 80 bar. The sensitivity to different inputs of the stability operator across various thermodynamic regimes shows an immense range of sensitivity amplitude. A balancing relationship between the density gradient and its perturbation leads to a quadratic effect across the Widom line, provoking significant sensitivity to distortions of the second derivative of the pressure with respect to the density, $\partial ^2 p/\partial \rho ^2$. From an application-oriented point of view, one important question is whether the correct baseflow profiles can be meaningfully analysed by the simplified ideal-fluid model. The integrated modal disturbance growth – the N factor calculated with different partly idealised models – indicates that the answer depends strongly on the thermodynamic regime investigated.
This study investigates the spatial distribution of inertial particles in turbulent Taylor–Couette flow. Direct numerical simulations are performed using a one-way coupled Eulerian–Lagrangian approach, with a fixed inner-wall Reynolds number of 2500 for the carrier flow, while the particle Stokes number ($St$) varies from 0.034 to 1 for the dispersed phase. We first examine the issue of preferential concentration of particles near the outer-wall region. Employing two-dimensional Voronoï analysis, we observe a pronounced particle clustering with increasing $St$, particularly evident in regions of low fluid velocity. Additionally, we investigate the concentration balance equation, inspired by the work of Johnson et al. (J. Fluid Mech., vol. 883, 2020, A27), to examine the particle radial distribution. We discern the predominant sources of influence, namely biased sampling, turbophoresis and centrifugal effects. Across all cases, centrifugal force emerges as the primary driver, causing particle migration toward the outer wall. Biased sampling predominantly affects smaller inertial particles, driving them toward the inner wall due to sampling within Taylor rolls with inward radial velocity. Conversely, turbophoresis primarily impacts larger inertial particles, inducing migration towards both walls where turbulent intensity is weaker compared with the bulk. With the revealed physics, our work provides a basis for predicting and controlling particle movement and distribution in industrial applications.
The previous study indicated that ubiquitination is involved in the freezing tolerance of hydrated seeds. Parthenolide (PN), inducing the ubiquitination of MDM2, an E3 ring-finger ubiquitin ligase, adversely affects the freezing tolerance of hydrated lettuce seeds. Therefore, a proteomics analysis was conducted to identify PN's targets in hydrated seeds exposed to cooling conditions. Several pathways, including oxidative phosphorylation (KEGG00190), amino sugar and nucleotide sugar metabolism (KEGG00520), and biosynthesis of nucleotide sugars (KEGG01250), were enriched in the PN treatment under slow-cooling conditions (3°C h−1, P < 0.05). Among the proteins in oxidative phosphorylation, the expression of NADH dehydrogenases and ATP synthases (ATPsyn) decreased in PN treatment. In contrast, uncoupling proteins increased after PN treatment, which led to the dissociation of the electron transport chain from ATP synthesis. Treatments with rotenone, dicoumarol, and oligomycin (i.e., oxidative phosphorylation inhibitors) decreased the survival rate of hydrated seeds under freezing conditions, which indicated that energy metabolism was related to the freezing tolerance of hydrated seeds. The predicted interactions between PN and MDM2-like proteins of Lactuca indicated that LsMDM2-5 forms two potential hydrogen bonds with PN. Furthermore, based on AlphaFold predictions and yeast 2-hybrid results, MDM2-5 might interact directly with NADH2. The knockdown of MDM2-5 by RNAi caused a higher level of NADH2 and ATPsyn and a higher freezing tolerance of hydrated seeds. This indicated that MDM2 played negative roles in regulating ATP synthesis and freezing tolerance of hydrated seeds.
Rhopalosiphum padi is an important grain pest, causing severe losses during crop production. As a systemic insecticide, flonicamid can control piercing-sucking pests efficiently. In our study, the lethal effects of flonicamid on the biological traits of R. padi were investigated via a life table approach. Flonicamid is highly efficiently toxic to R. padi, with an LC50 of 9.068 mg L−1. The adult longevity and fecundity of the R. padi F0 generation were markedly reduced under the LC25 and LC50 concentrations of flonicamid exposure. In addition, negative transgenerational effects on R. padi were observed under exposure to lethal concentrations of flonicamid, with noticeable decreases in the reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation under the LC25 concentration of flonicamid. Furthermore, the third nymph stage (N3), preadult stage, duration of the adult pre-reproductive period, duration of the total pre-reproductive period, reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation were significantly lower under treatment with the LC50 concentration of flonicamid. The life table parameters were subsequently analysed, revealing that the intrinsic rate of increase (rm) and the net reproductive rate (R0) were significantly lower but that the finite rate of increase (λ) and the mean generation time (T) were not significantly different under the LC25 and LC50 concentrations of flonicamid. These data are beneficial for grain aphid control and are critical for exploring the role of flonicamid in the integrated management of this key pest.
Working memory deficit, a key feature of schizophrenia, is a heritable trait shared with unaffected siblings. It can be attributed to dysregulation in transitions from one brain state to another.
Aims
Using network control theory, we evaluate if defective brain state transitions underlie working memory deficits in schizophrenia.
Method
We examined average and modal controllability of the brain's functional connectome in 161 patients with schizophrenia, 37 unaffected siblings and 96 healthy controls during a two-back task. We use one-way analysis of variance to detect the regions with group differences, and correlated aberrant controllability to task performance and clinical characteristics. Regions affected in both unaffected siblings and patients were selected for gene and functional annotation analysis.
Results
Both average and modal controllability during the two-back task are reduced in patients compared to healthy controls and siblings, indicating a disruption in both proximal and distal state transitions. Among patients, reduced average controllability was prominent in auditory, visual and sensorimotor networks. Reduced modal controllability was prominent in default mode, frontoparietal and salience networks. Lower modal controllability in the affected networks correlated with worse task performance and higher antipsychotic dose in schizophrenia (uncorrected). Both siblings and patients had reduced average controllability in the paracentral lobule and Rolandic operculum. Subsequent out-of-sample gene analysis revealed that these two regions had preferential expression of genes relevant to bioenergetic pathways (calmodulin binding and insulin secretion).
Conclusions
Aberrant control of brain state transitions during task execution marks working memory deficits in patients and their siblings.
Nonlinear compression experiments based on multiple solid thin plates are conducted in an ultra-high peak power Ti:sapphire laser system. The incident laser pulse, with an energy of 80 mJ and a pulse width of 30.2 fs, is compressed to 10.1 fs by a thin-plate based nonlinear compression. Significant small-scale self-focusing is observed as ring structures appear in the near-field of the output pulse at high energy. Numerical simulations based on the experimental setup provide a good explanation for the observed phenomena, offering quantitative predictions of the spectrum, pulse width, dispersion and near- and far-field distributions of the compressed laser pulse.
Stimulated Raman scattering is a third-order nonlinear optical effect that is not only effective for wavelength converting laser output, but also for single longitudinal-mode output due to the absence of spatial hole burning. Diamond is a prominent Raman-active medium that has significant potential for linewidth narrowing and wavelength converting lasers at high power levels due to its high thermal conductivity, long Raman frequency shift and wide spectral transmission range. In this work we utilize diamond in a resonantly mode-matched external cavity to achieve cascaded Raman conversion of a 1064 nm laser. By fine-tuning the length of this external cavity, we can obtain narrow linewidth emission at 1240 and 1485 nm. When operating at maximum power, the measured linewidths were more than twofold narrower than the linewidth of the fundamental field. In addition, the noise levels of the Stokes fields are lower than that of the fundamental field throughout the entire noise frequency range, and the intrinsic linewidth of the second Stokes field, which is expressed at the hertz level (~3.6 Hz), is decreased by approximately three orders of magnitude compared to that of the pump. This work represents the first measurement and analysis of the linewidth and noise characteristics of cascaded diamond Raman lasers and, significantly, offers a new means by which high-power, narrow linewidth laser output can be produced from wavelength-converted laser systems.
Modern fluvial sediments provide important information about source-to-sink process and regional tectono-magmatic events in the source area, but many factors, e.g., chemical weathering, sedimentary cycles and source-rock types, can interfere with the establishment of the source-sink system. The Lalin River (LR) and the Jilin Songhua River (JSR) are two important tributaries of the Songhua River in the Songnen Plain in NE China. They have similar flow direction, topography and identical climate backgrounds, but have notably different parent-rock types in the headwater, which provides an opportunity to explore the influencing factors of river sediment composition. To this end, the point bar sediments in the two rivers were sampled for an analysis of geochemistry (including element and Sr-Nd isotopic ratios), heavy mineral and detrital zircon U-Pb dating. The results are indicative of the fact that the two rivers have the similar geochemical composition (e.g., elements and Sr isotopes) as well as chemical weathering (CIA = 51.41–57.60, CIW = 59.68–66.11, PIA = 51.95–60.23, WIP = 56.00–65.47, Rb/Sr = 0.38–0.42) and recycling (SiO2/Al2O3 = 5.79 and 5.03, ICV = 1.0 and 1.2, CIA/WIP = 0.81–1.03) characteristics, showing a major control of climate on the low-level weathering and recycling of the river sediments. However, there are significant differences in the detrital zircon U-Pb age (a significant Mesozoic age peak for the LR but an additional Precambrian peak for the JSR), Nd isotope ratio (−6.2812–8.5830 and −8.1149–10.2411 for the LR and the JSR, respectively) and to a certain extent heavy mineral composition (e.g., for the < 63 μm fraction, a dominance of hornblende and magnetite in the LR, but haematite-limonite in the JSR) in the two river sediments, indicating that source rocks largely control the composition of the river sediments. Some of the major tectono-magmatic events (e.g., crustal growth and cratonisation of the North China Craton, closure of the Paleo-Asian Ocean, subduction and rollback of the Paleo-Pacific plate) occurring in the eastern Songnen Plain are well documented in the JSR sediments but not in the LR, the difference of which is largely regulated by the source rocks in the source area.
This study aimed to develop a predictive tool for identifying individuals with high antibody titers crucial for recruiting COVID-19 convalescent plasma (CCP) donors and to assess the quality and storage changes of CCP. A convenience sample of 110 plasma donors was recruited, of which 75 met the study criteria. Using univariate logistic regression and random forest, 6 significant factors were identified, leading to the development of a nomogram. Receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA) evaluated the nomogram’s discrimination, calibration, and clinical utility. The nomogram indicated that females aged 18 to 26, blood type O, receiving 1 to 2 COVID-19 vaccine doses, experiencing 2 symptoms during infection, and donating plasma 41 to 150 days after symptom onset had higher likelihoods of high antibody titres. Nomogram’s AUC was 0.853 with good calibration. DCA showed clinical benefit within 9% ~ 90% thresholds. CCP quality was qualified, with stable antibody titres over 6 months (P > 0.05). These findings highlight developing predictive tools to identify suitable CCP donors and emphasize the stability of CCP quality over time, suggesting its potential for long-term storage.