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As a subtype of lymphocyte, natural killer (NK) cell is the first line of defense that shows a strong function in tumor immunotherapy response and clinical outcomes. The current study aims to investigate the prognostic influence of peripheral blood absolute NK cell count after four cycles of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment (NKCC4) in diffuse large B cell lymphoma (DLBCL) patients. A total of 261 DLBCL patients treated with R-CHOP from January 2018 to September 2022 were enrolled. The low NKCC4 was observed in patients who died during the study period compared with survival individuals. A NKCC4 < 135 cells/μl had a remarkable negative influence in overall survival and progression-free survival (PFS) compared to a NKCC4 ≥ 135 cells/μl (p < 0.0001 and p < 0.0004, respectively). In addition, the OS and PFS were synergistically lower in a NKCC4 < 135 cells/μl group among DLBCL patients with GCB type or high IPI. In conclusion, this study indicates NCKK4 as a valuable marker in clinical practice and provides an insight for combination treatment of R-CHOP to improve outcomes of DLBCL patients. [ABSTRACT FROM AUTHOR]

Piper wallichii (family: Piperaceae), a folk herbal medicine with anti-inflammatory and anti-thrombotic properties, has been traditionally used to treat rheumatic arthralgia, lumbocrural pain, gastrointestinal flatulence, and other intestinal diseases in China, Thailand, and India. However, there is no scientific report on the efficacy and potential mechanisms of Piper wallichii for ulcerative colitis (UC). The study aims to investigate the therapeutic effect and possible molecular mechanisms of the ethanol extract of Piper wallichii (EEPW) on DSS-induced UC in BALB/c mice. The main components in EEPW were characterized by UPLC-QE-Orbitrap-MS. Subsequently, the anti-inflammatory effect of EEPW in vitro was preliminarily evaluated in RAW264.7 cells stimulated with LPS. UC model mice were triggered by free access to 4% DSS aqueous solution for 12 consecutive days, and simultaneously, EEPW (25, 50, and 100 mg/kg) and tofacitinib (positive control, 30 mg/kg) were orally administrated, respectively. The therapeutic efficacy of EEPW on UC was assessed by body weight, DAI, colon length, and pathological morphology. Besides, we investigated the effects of EEPW on intestinal barrier function, inflammatory factors, and immune systems of UC mice through immunohistochemistry (IHC), flow cytometry, and other techniques. Moreover, the expression of related proteins in the TLR4/NF-κB/COX-2 pathway was analyzed by Western blot. A total of 14 components were identified in the positive and negative modes, including isofutoquinol A (11), hancinone C (12), and futoquinol (14) which characterized by references. In the RAW264.7 cells experiments, the extract significantly suppressed the levels of TNF-α and IL-6. More importantly, EEPW distinctly improved the symptoms of DSS-induced UC mice as reflected by a significant recovery from body weight, colon length, pathological injuries of the colon, and so on. Further research found that EEPW remarkably restored the levels of occludin, promoted proliferation, and inhibited apoptosis in colon to maintain the integrity of intestinal barrier. In addition, the down-regulation of TNF-α and IL-1β in colon, Th1 and Th17 cells in spleen, as well as the up-regulation of IL-10 in colon and Th2 cells in spleen were distinctly observed in EEPW-treated groups. Furthermore, the protein expression of TLR4, p-IκB-α, p-p65, and COX-2 were significantly inhibited by EEPW. This study confirmed for the first time that EEPW effectively ameliorated DSS-induced UC in mice, which might be related to improving intestinal barrier function, maintaining the levels of inflammatory factors, and regulating the immune system. In addition, we found that the anti-inflammatory effect of EEPW on UC mice was involved in the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, Piper wallichii can be used as a candidate for the treatment of UC. [Display omitted] • Isofutoquinol A, hancinone C, and futoquinol with high contents were identified by references through a UPLC-QE-Orbitrap-MS method. • We investigated for the first time the therapeutic effect and possible mechanism of the ethanol extract of Piper wallichii on DSS-induced ulcerative colitis in mice. • The ethanol extract of Piper wallichii interfered with the activation of the TLR4/NF-κB/COX-2 pathway to play an anti-inflammatory activity on ulcerative colitis. [ABSTRACT FROM AUTHOR]

[Display omitted] • L-menthol-based products generally show the flavor loss and the inadequate release. • SFD process produced the spherical microparticles with highest porosity of 86.82 %. • SFD microparticles enhanced the flavor retention during the high humidity storage. • The porous structures caused the rapid rehydration and flavor release in liquids. • The release behaviors of L-menthol in SFD powders followed the Fickian diffusion. L-menthol-containing food products generally show the flavor loss during storage due to their high volatility. The hydrophobicity of L-menthol also causes the inadequate flavor release during rehydration. In this study, the stability of L-menthol was enhanced by microencapsulation and the effect of different powder drying techniques was also investigated. The highest efficiency (76.58–78.66 %) and loading content (18.58–28.35 mg/g) of encapsulations were obtained by using a mass ratio of 2:1(α-LA: GA). Then they were dried by non-thermal spray freeze drying (SFD) technique compared to spray drying (SD) and freeze-drying (FD) process. The SFD particles were shown to be spherical and porous with the highest porosity (86.82 %). α-LA/GA based microparticles with spherical shapes were demonstrated to largely enhance flavor retention during high humidity storage. In addition, the porous structures of SFD powders could cause rapid rehydration in liquid models, and the release behaviors of loaded L-menthol followed the Fickian diffusion. Consequently, the SFD technique shows great potential to produce microparticles by regulating the release behaviors of L-menthol during storage and rehydration. [ABSTRACT FROM AUTHOR]

• Lecithin can mediate the mineralization process of gold to form hierarchically organized gold nanoparticles. • This hierarchical structure is composed of primary gold branches, secondary bunches of gold branches, and tertiary spherical gold nanoparticles. • By regulating the reaction conditions, hierarchically organized gold nanoparticles can obtain tunable particle size from 52.6 to 549.8 nm and branch thickness from 7.4 to 16.4 nm. • Two-generation hierarchically organized gold nanoparticles with a new layer of gold branches can be received based on the lecithin-directed mineralization approach. Biomolecules have been universally used to direct the synthesis of nanomaterials, but the controllable synthesis of hierarchical structured materials remains a challenge. Herein, we show that lecithin can mediate the mineralization process of gold to form nanoparticles featuring a well-defined hierarchical structure. This structure is composed of primary gold branches, secondary bunches of gold branches, and tertiary gold nanoparticles hierarchically organized by the previous two basic structures. A molecular dynamics (MD) simulation reveals that the preferential adsorption of lecithin on the Au(111) plane directs the oriented growth and promotes the formation of the gold branch structure, and the hydrophobic force of amphiphilic lecithin leads to the spontaneous assembly of the primary gold branches into hierarchical gold nanoparticles. Specifically, hierarchical gold nanoparticles with tunable particle size from 52.6 to 549.8 nm and branch thickness from 7.4 to 16.4 nm are achieved by regulating the reaction conditions. Furthermore, two-generation HOGNPs with a new layer of gold branches growing on the one-generation HOGNPs are synthesized based on the method. This work represents an effective strategy and open an avenue for the controlled synthesis of hierarchical structured materials. Herein, a lecithin-directed mineralization approach was used to synthesize the hierarchically organized gold nanoparticles (HOGNPs), which featuring a well-defined hierarchical structure composed of rimary gold branches, secondary bunches of gold branches, and tertiary gold nanoparticles hierarchically organized by the previous two basic structures. [Display omitted] [ABSTRACT FROM AUTHOR]

The dark blue pigment from Vaccinium bracteatum Thunb. leaves (VBTL) is a healthy ingredient for controlling postprandial blood glucose during the stage of dietary carbohydrate digestion. Our previous study has proved that the dark blue pigment has an inhibition effect on pancreatic α-amylase. However, the influence on other digestive enzymes (α-glucosidases, trypsin, and α-chymotrypsin) is still unclear. Therefore, this research evaluated the impact of this dark blue pigment on the three digestive enzymes during in-vitro digestion. The effects of dark blue pigment on the activities and conformations of the α-glucosidase, trypsin, and α-chymotrypsin were confirmed by multi-spectroscopic techniques and molecular docking. The results showed that this pigment possessed a higher inhibition ability on the α-glucosidase. The complexes of three enzymes and the pigment all resulted in the changes in fluorescence quenching and secondary structures of these complexes. However, the interactions between two proteolytic enzymes and pigment slightly impacted their activities. Additionally, molecular docking suggested that the complex between α-glucosidase and pigment formed hydrogen bonds and hydrophobic interactions in the substrate-binding pocket. These findings provide creative insight into the VBTL dark blue pigment controlling postprandial hyperglycemia without side effects on the proteolytic enzymes. [Display omitted] • VBTL dark blue pigment exhibited stronger inhibitory activity on α-glucosidase. • VBTL dark blue pigment had no impact on the activities of trypsin and α-chymotrypsin. • Pigment molecule could lodge in the substrate-binding site of α-glucosidase. • Pigment was a mixed type inhibitor binding with α-glucosidase or their complex. [ABSTRACT FROM AUTHOR]

The starch physicochemical properties were investigated in 16 different rice accessions with different combinations of Wx , SSIIa and FLO2 alleles harvested in two environments. FLO2 , Wx and SSIIa alleles and their interaction significantly affected the starch properties. The values of apparent amylose content (AAC), gel hardness (HD), pasting temperature (PT), gelatinization temperature (GT), enthalpy of gelatinization (ΔHg), enthalpy of retrogradation (ΔHr) and percentage of retrogradation (R%) in the rice with FLO2 allele were slightly larger than those with flo2 mutant allele. The Wx × SSIIa interaction had a significant effect on breakdown (BD), setback (SB), ΔHr and R%. With Wx b allele, the influence of SSIIa allele on GT was slightly greater than that with Wx a . With SSIIa GC allele, Wx b played a greater role in the increase of PT than Wx a , but the reverse was found with SSIIa TT allele. The FLO2 × Wx interaction significantly affected the AAC, cold paste viscosity (CPV), hot paste viscosity (HPV), PT, HD, peak temperature (T p), conclusion temperature (T c) and ΔHr. FLO2 × SSIIa combination significantly affected AAC, HPV, CPV, Tc and ΔHr. This study will help us to further understand the roles of these starch synthesis-related important genes in regulating rice quality and could be better utilized in molecular breeding. [Display omitted] • Effects of Wx , SSIIa and FLO2 allele combinations on rice starch properties were analyzed. • FLO2 mutation leads to lower amylose content, gel hardness, pasting temperature and retrogradation. • FLO2 × Wx , FLO2 × SSIIa affects the amylose content, hot and cold paste viscosities. • FLO2 × Wx × SSIIa affects the amylose content and the pasting viscosities. [ABSTRACT FROM AUTHOR]

Context: Rates, patterns, and consequences of urban expansion are drawing increasing attention globally because of their profound impacts on socioeconomics, human life, and the environment. Horizontal comparative studies across multiple cities over large geographic regions are rare. Objectives: We quantified and compared the magnitude and forms of urban expansion for China's 32 major cities, and examined the spatiotemporal evolution of urban growth and trajectory of patch structure formation. Methods: Multi-temporal Landsat data of circa 1978, 1990, 1995, 2000, 2005, and 2010, patch-based analyses, and urban growth metrics were used. Results: These 32 major cities have experienced extensive expansion during the study period. Leapfrogging was the dominant urban expansion form, followed by edge-expansion and infilling in the early time periods. Interestingly, the fractions of infilling, edge-expansion, and leapfrogging has gradually reached a quasi-equilibrium condition with a ratio of 2:4:4 (the number) and 2:5:3 (the area) during recent years. Patch analysis suggested that these cities evolved under a nationally-consistent converged urban patch structure regardless of city size, location, and history. The dynamics of urban growth in China corresponded well with its socioeconomic and political geography and the phased implementation of various regional and national policies. Conclusions: Our results generally supported the continuum of diffusion-coalescence urbanization process and a spatial self-organization of urban land patches during urbanization. More studies are needed to test the generality of urban growth hypothesis and examine the universality of converged urban patch structure across regions and countries and to understand their implications to city organization, metabolism, and evolution. [ABSTRACT FROM AUTHOR]

Heteroatomic mesoporous ZSM-5 (Zeolite Socony Mobil–5) as an important catalyst is widely applied in catalytic field, however, its catalytic performance in VOCs oxidation is not clear. Particularly, the effects of the metal ionic radius at lattice site on surface active oxygen and reducibility of ZSM-5 are confused. Herein, Cu-, Mn-, Cr- and Co-doped mesoporous ZSM-5 were synthesized by a hydrothermal method to investigate the effects and altered mechanisms for hexane oxidation via the catalysts containing transition metals with different ionic radii at lattice sites in mesoporous ZSM-5, and the physical/chemical characteristics of all the catalysts were characterized. The results show that surface active oxygen species and low-temperature reducibility as critical factors in hexane oxidation are relevant to the transition metal ion radius. And, moderate-length ionic radius can significantly facilitate the increase in the amount and transfer capacity of the surface reactive oxygen species and the reducibility of catalysts, which exhibits a typical volcano-type curve relationship. Among the prepared catalysts, Cu-HZ (tetra-coordination Cu2+ radius: 0.57 Å), which possesses the largest concentration of superficial lattice oxygen, the highest reducibility and an adequate degree and strength for surface acidity, exhibits the highest catalytic activity, the highest CO 2 yield and selectivity. Additionally, compared with the supported mesoporous ZSM-5, the reaction mechanism of hexane oxidation over doped mesoporous ZSM-5 can be intensified by the synergistic effects between the lattice transition metal atom as the acidic adsorption site and the surface reactive oxygen generated by lattice doping of transition metal. We believe that this work can provide new insights into the design of catalysts for VOC degradation. [Display omitted] •The lattice doping of transition metal over mesoporous ZSM-5 can significantly facilitate the increase of catalytic activity. •Cu doped mesoporous ZSM-5 exhibits the best reaction activity for hexane oxidation. •An appropriate metal ionic radius can clearly promote an increase in the degree and transfer capacity of the surface reactive oxygen species and the reducibility of catalysts. •The hexane oxidation process can be intensified by the surface reactive oxygen species generated by the transition metal doped nearly the acidic adsorption sites over the mesoporous ZSM-5. •The superficial lattice oxygen and the low-temperature reducibility both play the key roles in hexane oxidation process. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the magnetic field perturbation method is used to study the effects of the Lorentz force and the gradient magnetic force on the anodic dissolution of Ni in 0.50mol dm-3 HNO3 +5.0mmol dm-3 NaCl solution. During the anodic dissolution process, magnetic fields are applied in two directions: parallel (B//) and perpendicular (B⊥) to the surface of the electrode. Thus, the effects of different magnetic forces on the anodic dissolution can be analyzed. After the application of B//, the current may increase, decrease or remain stable under different potentials, while the peak potential, the oscillatory region and the passive potential shift positively. These are always caused by the Lorentz force, which enhances the mass-transport processes. However, after the application of B⊥, the peak potential, the oscillatory region and the passive potential shift negatively. The currents always tend to decrease under the different potentials, which can be explained as follows: the gradient magnetic force suppresses convection to increase the concentration of corrosion products, such as the paramagnetic Ni(II) species, in local positions at the electrode|electrolyte interface. However, neither B// nor B⊥ affects the anodic dissolution in the passive region for the oxide film on the electrode surface inhibits the MF effects. If Ni dissolves in 0.50mol dm-3 HNO3 with different chloride ions containing solution at the same potential, the effects caused by B// are different for it is in different regions and the rate-determining steps are different, however, the currents still tend to decrease with application of B⊥. [Copyright &y& Elsevier]

Generalization of visual aversion is a critical function of the brain that supports survival, but the underlying neurobiological mechanisms are unclear. We establish a rapid generalization procedure for inducing visual aversion by dynamic stripe images. By using fiber photometry, apoptosis, chemogenetic and optogenetic techniques, and behavioral tests, we find that decreased cholinergic neurons' activity in the medial septum (MS) leads to generalization loss of visual aversion. Strikingly, we identify a projection from MS cholinergic neurons to the medial habenula (MHb) and find that inhibition of the MS→MHb cholinergic circuit disrupts aversion-generalization formation while its continuous activation disrupts subsequent extinction. Further studies show that MS→MHb cholinergic projections modulate the generalization of visual aversion possibly via M1 muscarinic acetylcholine receptors (mAChRs) of downstream neurons coreleasing glutamate and acetylcholine. These findings reveal that the MS→MHb cholinergic circuit is a critical node in aversion-generalization formation and extinction and potentially provides insight into the pathogenesis of affective disorders. [Display omitted] • MS cholinergic neurons participate in generalization of visual aversion • MS→MHb cholinergic circuits control generalization of visual aversion • MHb M1 mAChRs in the circuit mediate aversion generalization • MHb glutamatergic/cholinergic neurons in the circuit regulate aversion generalization Mu at al. identify the critical roles of the MS cholinergic neuron and MS→MHb circuit that regulate generalization of visual aversion, revealing that the pathway modulation for controlling aversion generalization and extinction might be via M1 mAChRs of MHb glutamatergic/cholinergic neurons. [ABSTRACT FROM AUTHOR]

Plants of genus Chrysosplenium have a long history of application and are distributed in many countries, especially in Tibetan regions of China. The genus has been used locally in the treatment of various hepatobiliary diseases such as "Chiba disease" (related to cholecystitis, cholelithiasis, acute icteric hepatitis, and acute liver necrosis in modern medicine). This review summarizes and critically analyzes the aspects of the botanical morphology and distribution, traditional uses, phytochemistry, pharmacological activities, quality control, and development status of preparations of the genus Chrysosplenium. Moreover, the future research direction and focus of the genus are also discussed. We hope to provide a valuable reference for researchers who are interested in the genus Chrysosplenium. The relevant information of the genus Chrysosplenium was gathered through electronic databases from 1968 to 2021, including PubMed, Web of Science, ScienceDirect, Google Scholar, Springer, CNKI, and Wan Fang, as well as PhD, MSc thesis, Chinese Pharmacopoeia (2020 edition), Tibetan medicine monographs. In addition, plant names were verified by "The Plant List" (The Plant List Database, http://www.theplantlist.org). Based on existing studies of chemical compositions, more than 90 compounds have been identified from Chrysosplenium species, including flavonoids, triterpenoids, volatile oils, steroids, alkaloids, and other compounds. The highly hydroxylated and methoxylated flavonoids and triterpenoids are the main active components. In addition, many studies have shown that the extracts and some components isolated from the genus Chrysosplenium have a variety of pharmacological activities, such as anti-tumor, antibacterial, anti-viral, hepatoprotective, and insecticidal properties. Furthermore, there are only 9 preparations with Chrysosplenium species as one of the medicinal materials. Among these preparations, C. nudicaule is used more and other Chrysosplenium species are rarely involved. Most medicinal species of Chrysosplenium have not only good therapeutic effects in traditional uses, but also a great potential for development in modern pharmaceutical studies. However, the material basis and mechanism of action of this genus have not been well explained. Therefore, further systematic and comprehensive research on the genus Chrysosplenium is still required to provide a scientific basis for its clinical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

The effects of triticale bran pretreatments on rheological and functional properties of triticale whole-wheat flour (TWWF), such as pasting properties, thermomechanical properties, dynamic rheological properties, fermentation properties, water distribution states, disulfide bonds (SS), glutenin macropolymer (GMP), and protein secondary structure were investigated. Eight different pretreatments of triticale bran (microwaving, roasting, air frying, stir-frying, atmospheric-pressure steaming, high-pressure steaming, enzymolysis, and solid-state fermentation) were used in the study. The results showed that the pasting properties were improved, where the breakdown and setback values of TWWF were significantly reduced after solid-state fermentation. Solid-state fermentation strengthened the dough elasticity by increasing the storage modulus (G′) and loss modulus (G″) and decreasing the loss tangent (tanδ). The fermentation tolerance and gas retention capacity were enhanced, and the water distribution states were significantly improved. Moreover, the contents of SS, GMP, α-helix, and β-sheet were higher as compared with other pretreatments. In conclusion, solid-state fermentation pretreatment of triticale bran had the most significant improvement in the rheological and functional properties of TWWF. The results could be helpful in selecting the pretreatment for triticale bran that contributes to the development of TWWF-based bakery products. [ABSTRACT FROM AUTHOR]

• The synthesized mesoporous organosilicon nanoparticles have three independent interfaces and each interface is hybridized with three different functional groups. • It has excellent physical properties such as uniform size (320 nm), large specific surface area (458 m2g−1), large pore volume (0.82 cm3g−1), and uniform mesoporous channels (4.20 nm). • The size of nanoparticles can be controlled between 190 and 330 nm. Multilayer hollow materials have attracted considerable attention as potentially valuable in drug delivery, catalysis, and nanoreactors. The main purpose of this work is to synthesize hybridized triple-shelled hollow mesoporous organosilica nanoparticles (ht HMONs) with ethane-, benzene-, and thioether groups. The nanoparticles are prepared using a surfactant-directed co-assembly process and a following hydrothermal etching strategy. First, hybridized mesostructured organosilica nanoparticles were synthesized via step-by-step adding multiple organosilica in a surfactant solution. The mesostructured organosilica nanoparticles are then transformed into ht HMONs by hydrothermal treatment at 160 °C for 3 h. The prepared typical ht HMONs possess a uniform diameter (320 nm), independent core (107 nm), and three separate shells (10, 13, and 23 nm from outside to inside). In addition, ht HMONs possess typical properties of mesoporous materials, including uniform mesopore (4.20 nm), large specific surface area (SSA) (458 m2g−1), and huge pore volume (0.82 cm3g−1). Furthermore, ht HMONs with various sizes (190–330 nm) are also prepared by varying the amount of structure-directing agent or volume ratio of water to ethanol. The ethane-, thioether- and benzene-hybridized triple-shelled hollow mesoporous organosilica nanoparticles are successfully prepared by a surfactant-directed co-assembly process and a following multi-interface transformation via hydrothermal etching. Insets are the models of the hybridized triple-shelled HMONs to illustrate the structural transformation process. [Display omitted] [ABSTRACT FROM AUTHOR]

Precision double-nut ball screws are key functional parts in machine tools. The positioning accuracy of a ball screw can directly affect the machining accuracy of a machine tools. During actual use, the preload degradation and the large axial clearance of the double-nut ball screw are caused by the contact wear, which directly affects the transmission positioning accuracy. The contact wear is focused on the ball and the rough raceway surface of the ball screw. Therefore, a novel method is proposed in this paper to characterize the rough spherical morphology of raceways for ball screws based on fractal theory, and the fractal parameters of the screw and nut raceways are identified. A fractal contact model of the asperity on the raceway surface is established. By introducing contact parameters to modify the contact area, an area distribution function suitable for the coordinated contact is obtained. A mathematical model for calculating the normal contact load of the ball screw in three states is established by considering the friction factor. A precision loss model of the ball screw is established based on the full ball load distribution model and the multiscale contact load model, and the proposed model is verified by experiments. The surface contact coefficient of the inner and outer raceways is discussed. The influence of raceway fractal parameters on the wear rate is analyzed, and coupling research on precision loss and preload degradation for the ball screw is carried out. The initial wear rate under different axial load is discussed, and the change trend of wear rate with time is analyzed. The precision loss model of the preload double-nut ball screw based on fractal theory provides a new theoretical basis for accurately predicting the precision degradation and provides method support for establishing the wear life prediction of a ball screw. • Raceway wear considering surface fractal can lead to precision loss of ball screw. • Wear volume of the work nut is different from the preload nut under axial load. • Preload of ball screw degenerates with the increasing contact wear of raceways. • Time-varying wear rate affected by operating parameters is coupled to preload loss. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum L.) is a crucial cereal crop, contributing around 20% of global caloric intake. However, challenges such as diminishing arable land, water shortages, and climate change threaten wheat production, making yield enhancement crucial for global food security. The heading date (HD) is a critical factor influencing wheat's growth cycle, harvest timing, climate adaptability, and yield. Understanding the genetic determinants of HD is essential for developing high-yield and stable wheat varieties. This study used a doubled haploid (DH) population from a cross between Jinmai 47 and Jinmai 84. QTL analysis of HD was performed under three phosphorus (P) treatments (low, medium, and normal) across six environments, using Wheat15K high-density SNP technology. The study identified 39 QTLs for HD, distributed across ten chromosomes, accounting for 2.39% to 29.52% of the phenotypic variance. Notably, five stable and major QTLs (Qhd.saw-3A.7, Qhd.saw-3A.8, Qhd.saw-3A.9, Qhd.saw-4A.4, and Qhd.saw-4D.3) were consistently detected across varying P conditions. The additive effects of these major QTLs showed that favorable alleles significantly delayed HD. There was a clear trend of increasing HD delay as the number of favorable alleles increased. Among them, Qhd.saw-3A.8, Qhd.saw-3A.9, and Qhd.saw-4D.3 were identified as novel QTLs with no prior reports of HD QTLs/genes in their respective intervals. Candidate gene analysis highlighted seven highly expressed genes related to Ca2+ transport, hormone signaling, glycosylation, and zinc finger proteins, likely involved in HD regulation. This research elucidates the genetic basis of wheat HD under P stress, providing critical insights for breeding high-yield, stable wheat varieties suited to low-P environments. [ABSTRACT FROM AUTHOR]

• The dynamical function connectivity consists of three main states in resting state. • These three states were labeled as sensory, somatomotor, and internal mentation networks. • The transitions between the three states reveal the relationship with aging. • Higher appearance of the "internal mentation network" is found as aging progresses. Age-related changes in the brain are associated with a decline in functional flexibility. Intrinsic functional flexibility is evident in the brain's dynamic ability to switch between alternative spatiotemporal states during resting state. However, the relationship between brain connectivity states, associated psychological functions during resting state, and the changes in normal aging remain poorly understood. In this study, we analyzed resting-state functional magnetic resonance imaging (rsfMRI) data from the Human Connectome Project (HCP; N = 812) and the UK Biobank (UKB; N = 6,716). Using signed community clustering to identify distinct states of dynamic functional connectivity, and text-mining of a large existing literature for functional annotation of each state, our findings from the HCP dataset indicated that the resting brain spontaneously transitions between three functionally specialized states: sensory, somatomotor, and internal mentation networks. The occurrence, transition-rate, and persistence-time parameters for each state were correlated with behavioural scores using canonical correlation analysis. We estimated the same brain states and parameters in the UKB dataset, subdivided into three distinct age ranges: 50–55, 56–67, and 68–78 years. We found that the internal mentation network was more frequently expressed in people aged 71 and older, whereas people younger than 55 more frequently expressed sensory and somatomotor networks. Furthermore, analysis of the functional entropy — a measure of uncertainty of functional connectivity — also supported this finding across the three age ranges. Our study demonstrates that dynamic functional connectivity analysis can expose the time-varying patterns of transition between functionally specialized brain states, which are strongly tied to increasing age. [ABSTRACT FROM AUTHOR]

Ablation resistance as an important factor affecting the service life of SiC ceramic matrix composites that is highly valued. In this study, Three C/SiC composites reinforced by high thermal conductivity (HTC) graphite films and carbon fiber cloth were fabricated by precursor infiltration and pyrolysis (PIP) technology, to improve the ablation resistance of C/SiC composites. The quantity ratios of carbon fiber cloth to HTC graphite film was 1:0, 1:1, and 1:10. The microstructure, mechanical properties, thermal conductivity and ablation performance of C/SiC composites after plasma ablation test at 1500 °C for 600 s were investigated. The results indicated that with the increase of graphite films' contents, the in-plane thermal conductivity of composites was increased from 9.78 W/(m·K) to 333.34 W/(m·K). Meantime, the mass loss rate reduced from 1.18 to 0.74 mg/s and the linear ablation rate reduced from 0.64 to 0.18 mm/s, revealing that the addition of graphite films could effectively improve the ablation resistance of C/SiC composites. [Display omitted] • For the first time, high thermal conductivity (HTC) graphite film is applied to C/SiC composite material. • The plasma ablation test of C/SiC composite material was carried out at 1500 °C for 600 s. • The thermal conductivity of composites was increased from 9.78 W/(m·K) to 333.34 W/(m·K). • The mass loss rate reduced from 1.18 to 0.74 mg/s [ABSTRACT FROM AUTHOR]

Concurrent use of simvastatin (SV) and Gardenia jasminoides J. Ellis (GJ) was adopted in patients with multi-morbidity, such as stroke rehabilitation patients with NASH. Although hepatotoxicity has been reported in both of them and NASH could alter the pharmacokinetics of drugs/herbs, the interaction between SV and GJ and the related hepatotoxicity remained uninvestigated under neither healthy nor NASH condition. The current study aimed to evaluate the potential hepatotoxicity resulted from the interactions between SV and GJ in both healthy and NASH rats. Both healthy and NASH rats received two-week SV (p. o., 8.66 mg/kg, once daily) and/or GJ (p.o., 325 mg/kg, twice daily). Pharmacokinetic profiles of SV, simvastatin acid (SVA, active metabolite of SV), and geniposide (major component in GJ); hepatic Cyp2c11/Oatp1b2/P-gp expression; and biomarker levels of liver function, lipid levels, and liver histology were compared to demonstrate the interactions in rats. To explore the mechanism of the interaction-mediated hepatotoxicity, hepatic genipin-protein adduct content and iNOS/COX-1/COX-2 expressions from related groups were compared. Moreover, liver histology of healthy/NASH rats at 90 days after discontinuation of two-week GJ in the absence and presence of SV was evaluated to estimate the long-term impact of the interactions. GJ reduced the systemic exposures of SV and SVA by up-regulating the hepatic P-gp expression in healthy but not NASH rats. Meanwhile, SV increased the systemic exposure of geniposide via inhibiting the activity of P-gp in both healthy and NASH rats. Although neither SV nor GJ induced hepatotoxicity in healthy rats, their co-treatment elevated serum ALT and AST levels, which may attribute to the aggravated genipin-protein adduct formation, inflammation infiltration, and iNOS/COX-1 expressions in the liver. In NASH rats, SV and/or GJ reduced serum ALT, AST, LDL/vLDL, and TC levels via alleviating hepatic inflammation infiltration and iNOS/COX-1 expressions. Moreover, in comparison to NASH rats, more severe fibrosis was observed in the livers of healthy rats at 90 days after discontinuation of two-week SV and GJ coadministration. Although interactions between SV and GJ induced short-term and long-term liver injuries in healthy rats, NASH condition in rats could lower such risk. [ABSTRACT FROM AUTHOR]

EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure. Image 1 [ABSTRACT FROM AUTHOR]

Simple Summary: Small heat shock proteins (sHsps) play important roles in thermal adaptation of various organisms, and insect diapause. Sitodiplosis mosellana, a key pest of wheat worldwide, undergoes obligatory larval diapause in soil to survive adverse temperature extremes during hot summers and cold winters. The objectives of this study were to characterize two sHsp genes from S. mosellana (SmHsp17.4 and SmHsp20.3), and determine their expression in response to diapause, extreme high/low temperatures, or 20-hydroxyecdysone (20E) treatment. Expression of SmHsp17.4 was down-regulated upon entry into diapause, but up-regulated during the shift to post-diapause quiescence. In contrast, expression of SmHsp20.3 was not affected by entry into diapause, but was pronounced during summer and winter. Furthermore, transcripts of both SmHsps were highly responsive to heat (≥35 °C) and cold (≤−5 °C) during diapause, and topical application of 20E on diapausing larvae also induced SmHsp17.4 in a dose-dependent manner. Notably, the recombinant SmHsp17.4 and SmHsp20.3 exhibited significant molecular chaperone activity. In conclusion, SmHsp17.4 and SmHsp20.3 play essential roles in heat/cold adaptation, and 20E-mediated SmHsp17.4 was also likely involved in diapause termination. Results have improved our understanding of the molecular mechanism underlying diapause and related stress tolerance in S. mosellana. Sitodiplosis mosellana, a periodic but devastating wheat pest that escapes temperature extremes in summer and winter by undergoing obligatory diapause. To determine the roles of small heat shock proteins (sHsps) in diapause of S. mosellana, we characterized two sHsp genes, SmHsp17.4 and SmHsp20.3, from this species. Both SmHsps contained the conserved α-crystallin domain and the carboxy-terminal I/VXI/V motif of the sHsp family. SmHsp17.4 had one intron while SmHsp20.3 had none. Quantitative PCR revealed that SmHsp17.4 expression decreased after diapause initiation, but substantially increased during transition to post-diapause quiescence. In contrast, SmHsp20.3 expression was not affected by entry of diapause, but was clearly up-regulated during summer and winter. Short-term more severe heat-stress (≥35 °C) of over-summering larvae or cold-stress (≤−5 °C) of over-wintering larvae could stimulate higher expression of both genes, and SmHsp17.4 was more responsive to cold stress while SmHsp20.3 was more sensitive to heat stress. Notably, transcription of SmHsp17.4, but not SmHsp20.3, in diapausing larvae was inducible by 20-hydroxyecdysone (20E). Recombinant SmHsp17.4 and SmHsp20.3 proteins also displayed significant chaperone functionality. These findings suggest that both SmHsps play key roles in stress tolerance during diapause; and 20E-regulated SmHsp17.4 was also likely involved in diapause termination. [ABSTRACT FROM AUTHOR]

The role of muscle LIM protein (MLP), encoded by CSRP3, is not well understood in humans. CSRP3 knockout mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Using CRISPR/Cas9, we generated an MLP deficient human ESC line WAe009-A-41 carrying a compound heterozygous 13 bp deletion/1 bp insertion in the CSRP3 gene. The WAe009-A-41 line exhibited a normal female karyotype (46, XX), expressed pluripotency markers and exhibited capability to differentiate into the three germ layers in vitro. MLP expression was not detectable in WAe009-A-41 line. This cell line can be a useful tool for studying the role of CSRP3 in cardiomyopathy and heart failure. [ABSTRACT FROM AUTHOR]

Although EGb 761, the standardized dry extract of Ginkgo biloba leaves, exhibited numerous pharmacological activities and widely used in Asia, European and North America, the quality control of its dosage forms such as tablet mainly relies on monitoring the contents of the active marker components, namely quercetin, kaempferol, isorhamnetin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C. So far, the in vitro dissolution profiles of EGb761 tablet were barely used to monitor its quality and how these dissolution profiles correlate with their in vivo pharmacokinetics was not known. Thus, the present study was proposed aiming to 1) develop the in vitro-in vivo correlations (IVIVCs) for the marker components in EGb 761 tablet; 2) identify the in vivo relevant dissolution media for the marker components in EGb 761 tablet based on the established IVIVCs. The content analyses of the marker components in EGb 761 tablet was first carried out. Then, the dissolution profiles were further obtained using paddle method of United States Pharmacopeia for bilobalide, ginkgolides A, and ginkgolide B, that have previously reported human plasma pharmacokinetics after EGb 761 tablet oral administrations. About seven different media including 0.1 M hydrochloric acid (HCl), acetate buffer, H 2 O, fasted state simulated gastric fluid (FaSSGF), fasted state simulated intestinal fluid version 2 (FaSSIF-V2), fed state simulated intestinal fluid version 2 (FeSSIF-V2), and sequential medium (0.1 M HCl for 2 h with pH adjusted to 7 for another 2 h) were tested in the current investigation. The obtained in vitro dissolution profiles of bilobalide, ginkgolides A and ginkgolide B from EGb 761 tablet were first fitted with four dissolution models, namely Weibull, Double Weibull, Hill and Makoid-Banakar, to obtain the best-fit model for each component in each medium. The human plasma concentration versus time profiles of the above three components were then inputted into the Phoenix WinNonlin IVIVC Toolkit to obtain their in vivo absorption profiles using numerical deconvolution. The best-fit dissolution profiles of each marker component in the seven studied media were further used to correlate with its obtained in vivo absorption profile by the linear correlation models to establish the corresponding IVIVCs in each studied medium. Finally, the best in vivo correlated medium for each investigated marker component was selected based on their adjusted correlation coefficients, Akaike Information Criterion (AIC) and Schwarz's Bayesian Criterion (SBC) values. As a result, the dissolution profiles of bilobalide, ginkgolide A, ginkgolide B from EGb 761 tablet in 0.1 M HCl, FaSSGF, FaSSIF-V2 demonstrated the best correlation with their in vivo absorption profiles, respectively. Our current studies for the first time applied the concept of IVIVC to EGb 761 tablet and successfully identified the in vivo relevant dissolution media for its three active marker components to improve its quality control. Image, graphical abstract [ABSTRACT FROM AUTHOR]