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Abstract Background Prediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated. Purpose To obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians’ decision making and benefit individuals at risk. Methods According to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group). Plasma samples from patients were collected for clinical index assessment and untargeted metabolomics using liquid chromatography-mass spectrometry. Results Among patients with the syndrome of spleen deficiency with dampness encumbrance (PXSK), those with PreDM (PDMPXSK group) had elevated levels of 2-hour post-load blood glucose (2-h PG), glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (SBP) than those in the normal blood glucose group (NDMPXSK group, P

In this paper, the HSV color space model is used to collect the color characteristics of modern interior design and classify them into three types: hue (H), saturation (S), and luminance (V). At the same time, it combines with the theory of color psychology to construct a PAD emotion model for interior design. Then, it selects experimental samples and data analysis tools to carry out an example analysis of interior design from the emotional perspective. The data show that the selection of people warm and bright color interior design in the interior design of the background color across the amplitude of the largest and more concentrated in the 47.5°, the main body color across the amplitude of the smallest and most stable, the accent color value of the whole relatively high, the highest 123.6°, the background color saturation is the highest of 34.6°, and the brightness of more than 63.9°, the overall presentation of the warmth of comfort indoor environment. Error-values were 0.004, 0.0698, and 0.038 in order, with the errors all below 10%. This study integrates psychology and color into interior emotional design to better create visually appropriate, comfortable, and culturally rich interior environments for people, and also to promote the development of the interior design field.

As the mechanism of paraquat (PQ) poisoning is still not fully elucidated, and no specific treatment has been developed in medical practice, the management of PQ poisoning continues to present a medical challenge. In this study, the objective was to investigate the early metabolic changes in serum metabolism and identify the key metabolic pathways involved in patients with PQ poisoning. Quantitative analysis was conducted to determine the relevant metabolites. Additionally, experiments were carried out in both plasma and cell to elucidate the mechanisms underlying metabolic disorder and cell death in PQ poisoning. The study found that polyunsaturated fatty acids (PUFAs) and their metabolites, such as arachidonic acid (AA) and hydroxy eicosatetraenoic acids (HETEs), were significantly increased by non-enzymatic oxidative reaction. Reactive oxygen species (ROS) production increased rapidly at 2 h after PQ poisoning, followed by an increase in PUFAs at 12 h, and intracellular glutathione, cysteine (Cys), and Fe2+ at 24 h. However, at 36 h later, intracellular glutathione and Cys decreased, HETEs increased, and the expression of SLC7A11 and glutathione peroxidase 4 (GPX4) decreased. Ultrastructural examination revealed the absence of mitochondrial cristae. Deferoxamine was found to alleviate lipid oxidation, and increase the viability of PQ toxic cells in the low dose. In conclusion, unsaturated fatty acids metabolism was the key metabolic pathways in PQ poisoning. PQ caused cell death through the induction of ferroptosis. Inhibition of ferroptosis could be a novel strategy for the treatment of PQ poisoning.

In order to optimize the parameters of the powder metallurgy process of (NixSi+C)/Cu composite materials，orthogonal tests were designed to study the effects of mixing method，sintering temperature and sintering time on the microstructure and mechanical properties of(NixSi+C)/Cu composite materials.Results showed that a low mixing energy would lead to an uneven dispersion of SiC particles，and SiC particles that didn’t take part in the reaction would remain at the boundary of the powders in the composite prepared；a high mixing energy would lead to serious deformation of the powders and increase the diffusion ability of the elements in the sintering process，making the mixture of Ni3Si and C at the boundary of the powder in the composite prepared after the reaction show a complete network structure.The increase of sintering temperature and sintering time would result in an increase of the amount of Ni3Si precipitated at the boundary of powders in the composite and an increase of the density of the composite.In addition，the conductivity and hardness showed an increasing trend.The parameter combination of the metallurgical preparation process of (NixSi+C)/Cu composite materials that could obtain the best conductivity and hardness was as follows:a vibration mixing，a pellet ratio of 1 ∶5，a sintering temperature of 950 ℃and a sintering time of 120 min.Under these conditions，the density，conductivity and Vickers hardness of the samples were verified，and the verification results were all higher than those of the samples in the orthogonal tests，which would provide an important theoretical and practical reference for the subsequent preparation of(NixSi+C)/Cu composite materials with excellent properties.

Background and Objectives Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody for the treatment of instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors in adults, including those with advanced colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The aim of this investigation was to examine the pharmacokinetic and exposure-response (E-R) profile of envafolimab in patients with solid tumors to support the approval of fixed and alternative dose regimens. Methods In this study, a population pharmacokinetic (PopPK) modeling approach will be employed to quantitatively evaluate intrinsic and extrinsic covariates. Additionally, PopPK-estimated exposure parameters were used to evaluate E-R relationship for safety and efficacy to provide a theoretical basis for recommending optimal treatment regimens. Simulations were performed on the dosing regimens of body weight-based regimen of 2.50 mg/kg QW, fixed dose 150 mg QW, and 300 mg Q2W for the selection of alternative dosing regimens. Data from 4 clinical studies (NCT02827968, NCT03101488, NCT03248843, and NCT03667170) were utilized. Results The PopPK dataset comprised 182 patients with 1810 evaluable envafolimab concentration records. Finally, a one-compartment model incorporating first-order absorption, first-order linear elimination, and time-dependent elimination according to an E max function was found to accurately describe the concentration-time data of envafolimab in patients with advanced solid tumors. Creatinine clearance and country were identified as statistically significant factors affecting clearance, but had limited clinical significance. A relative flat exposure-response relationship was observed between early measures of safety and efficacy to verify that no dose adjustment is required. Simulation results indicated that 2.50 mg/kg QW, 150 mg QW, and 300 mg Q2W regimen yield similar steady-state exposure. Conclusions No statistically significant difference was observed between weight-based and fixed dose regimens. Model-based simulation supports the adoption of a 150 mg weekly or 300 mg biweekly dosing regimen of envafolimab in the solid tumor population, as these schedules effectively balance survival benefits and safety risks. [ABSTRACT FROM AUTHOR]

In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts). In three-dimensional extracellular matrix culture, CtsH, among other cysteine cathepsins, was up-regulated and localized as puncta in the nuclear and cytoplasmic compartments in a complex with HDAC4 for its degradation. Conversely, along with HSC trans-differentiation, CtsH and CtsL were progressively down-regulated, whereas HDAC4 was concurrently stabilized. The inhibition of cysteine cathepsins by specific proteinase inhibitors or chloroquine, which raises cellular pH, restored HDAC4. Recombinant CtsH could break down HDAC4 in the transfected cells and in vitro at acidic pH. In human cirrhotic liver, activated HSCs express high levels of class IIa HDACs but little CtsH. We propose that cysteine cathepsin-mediated degradation of class IIa HDACs plays a key role in the modulation of MMP expression/suppression and HSC functions in tissue injury and fibrosis.

PurposeThis study aimed to investigate the association between serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and incident metabolic disease in a cohort of community-based older Chinese people.Patients and MethodsFive thousand healthy Gaohang residents who attended community health checks at the Shanghai East Hospital in 2013 were recruited. Biological, biochemical, and lifestyle variables were collected. The cohort was followed for new-onset metabolic disease in 2014 and 2017, with a final study population of 3,123 (63%) after follow-up. The study outcome included type-2 diabetes mellitus and metabolic syndrome.ResultsBaseline AST and ALT were associated with incident type-2 diabetes mellitus (HR 1.019, 95% CI 1.006–1.032, p = 0.003 and HR 1.016, 95% CI 1.008–1.025, p < 0.001 respectively). These associations persisted after adjusting for traditional risk factors including age, sex, income, waist circumference, systolic blood pressure, diastolic blood pressure, HbA1c, triglyceride, cholesterol, HDL and eGFR. Baseline AST and ALT were associated with incident metabolic syndrome in the crude analysis (HR 0.980, 95% CI 0.965–0.996, p = 0.012 and HR 0.992, 95% CI 0.988–0.997, p = 0.001, respectively). However, the association between AST and ALT with metabolic syndrome was non-significant after adjusting for biochemical parameters such as the lipid profile.ConclusionThis study demonstrated that serum AST and ALT are associated with new-onset type-2 diabetes mellitus, independent of traditional risk factors, in a cohort of older Chinese people. These findings may contribute to disease risk stratification and management in type-2 diabetes.

Zr-metal-organic frameworks (Zr-MOFs) were prepared by a solvothermal method and characterized by X-ray diffraction, scanning electron microscopy, and thermogravimetry. Zr-MOFs were used to remove doxycycline hydrochloride (DOC) from wastewater. According to the experimental results, the maximum adsorption capacity of DOC by Zr-MOFs within 5 h was 148.7 mg·g−1. From the pseudo-second-order kinetics model, all R 2 values were greater than 0.99, which proved that the adsorption of DOC by Zr-MOFs was consistent with practice. According to the Freundlich isotherm model, the adsorption of DOC by Zr-MOFs proceeded via multilayer adsorption. The aforementioned results show that Zr-MOFs have good application prospects for removing DOC from wastewater.

Summary: Drought‐induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked.We quantified the vulnerability to drought‐induced embolism, pressure–volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads.Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads.Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits – particularly vessels – may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads. [ABSTRACT FROM AUTHOR]

Polysubstituted acrylamides are ubiquitous in bioactive molecules and natural products. However, synthetic methods for the assembly of these important motifs remain underdeveloped. Herein, we report the expedient synthesis of structurally diverse and synthetically challenging polysubstituted acrylamides from readily available aromatic amines, cyclopropenones (CpOs), and aryl halides via the synergistic merging of nucleophilic phosphine-mediated amidation and palladium-catalyzed C–H arylation. The reaction is scalable, and some obtained acrylamides proved to be solid state luminogens with obvious aggregation-induced emission (AIE) properties, demonstrating the synthetic potential in drug discovery and material development. [ABSTRACT FROM AUTHOR]

The ultimate goal of neurosurgery is to remove the lesion to the greatest extent while retaining neurological function. The preservation of motor function, sensory function, especially language function is of great significance to patients. So preoperative and intraoperative functional mapping has important guidance for surgery. The current invasive method⁃intraoperative direct electrical stimulation (DES) is still the "gold standard" for language mapping and lateralization, while non⁃invasive method such as functional magnetic resonance (fMRI), diffusion tensor imaging (DTI), magnetoencephalography (MEG) and navigated transcranial magnetic stimulation (nTMS) are easy to operate and can be used for preoperative positioning, postoperative follow⁃up and review. Multimodal functional assessment can improve the accuracy of preoperative language mapping. This article intends to review the positioning methods of language function areas and compare the advantages and disadvantages of various methods. DOI:10.3969/j.issn.1672⁃6731.2020.11.003

TC4 titanium alloy bulk specimens were prepared by laser deposition manufacturing.The effect of annealing treatment on mechanical properties, microstructure of LDMed TC4 titanium alloy was studied by optical microstructure (OM),scanning electron microscopy (SEM) and X-ray diffraction (XRD).The experimental results show that the microstructure is basketweave structure after α+β two-phase region annealing treatment and is transformed to Widmanstatten structure after β phase region annealing treatment.The mechanical properties still show significant anisotropy after annealing:Z-direction samples exhibit low strength and high plasticity, while XY-direction samples show high strength and low plasticity.The samples have a greatly decrease in strength and plasticity after β phase region annealing treatment.The annealing temperature has obvious influence on the anisotropy of the samples. The tensile properties of XY-direction samples are evidently scattered.Both direction samples exhibit ductile fracture after α+β two-phase region annealing treatment. The strength and plasticity of the samples decrease greatly after β single phase region annealing treatment, and the XY-direction samples are brittle fracture.

Yaks have strong adaptability to extremely cold and hypoxic conditions but are susceptible to high ambient temperature when yaks are raised in low-altitude areas during the high-temperature season. Twenty-four adult male yaks with similar weights and ages were randomly divided into TN (Thermoneutral, altitude = 3464 m), LHS (Light heat stress, altitude = 1960 m), and MHS (Medium heat stress, altitude = 906 m) groups to evaluate adaptation strategies to HS. Non-targeted and targeted metabolomics were applied to investigate the effects of different extents of HS on yaks. LHS- and MHS-yaks showed higher rectal temperatures and respiratory rates than TN-yaks. MHS-yaks had higher levels of red blood cells (RBCs), hemoglobin (Hb), whole blood relative index of middle shear at a shear rate of 5 S−1 (WMS), whole blood relative index of high shear at a shear rate of 200 S−1 (WHS), Casson viscosity (CV), middle shear flow resistance at a shear rate of 5 S−1 (MSFR), and high shear flow resistance at a shear rate of 200 S−1 (HSFR) as compared to TN- and LHS-yaks. Differential metabolites and metabolic pathways, including fatty acid metabolism, lipid metabolism, glucose metabolism, and amino acid metabolism, were altered by HS. Metabolites in the glucose metabolism pathway in LHS- and MHS-yaks were lower than those in TN-yaks. However, LHS-yaks showed higher levels of metabolites in the HIF-1 signaling pathway compared to TN- and MHS-yaks. Most of the tricarboxylic acid cycle (TCA) intermediates and fatty acids were significantly decreased in MHS-yaks compared to the other two groups. As a whole, yaks raised at a low altitude (25.6 °C) suffered from severe HS, but they adapted to HS with vasodilatation for dissipating heat and the increased antioxidants and metabolite levels of energy substrates.

Buffalo are mainly distributed in low-altitude (LA), medium-altitude (MA), and high-altitude (HA) regions characterised by different thermal and oxygen environments in Yunnan province, China. Due to black skin, sparse hair, and the low density of skin sweat glands, buffalo are more sensitive to heat stress. Here, we used data-independent acquisition (DIA) proteomics to reveal a broad spectrum of proteins that play roles in adaptation to the heat stress of buffalo raised at low altitude or hypoxia at high altitude. LA buffalo showed higher body temperatures than MA- and HA buffalo, and HA buffalo had higher levels of GSH and SOD and lower levels of ROS compared to LA and MA buffalo. In 33 samples, 8476 peptides corresponding to 666 high-confidence proteins were detected. The levels of circulating complement proteins in the immune pathways were lower in LA and MA buffalo than in HA buffalo. There were higher levels of alpha-1 acid glycoprotein in LA buffalo than in MA and HA buffalo. Relative to MA buffalo, levels of blood oxygen delivery proteins were higher in LA and HA buffalo. A higher abundance of apolipoproteins was detected in LA and MA buffalo than in HA buffalo. In summary, buffalo adopted similar adaptation strategies to oxidative stress induced by heat stress or hypoxia, including immunological enhancement, high efficiency of blood oxygen delivery, and the inhibition of lipid oxidation.

C19H18N4O6S, monoclinic, P21/n (no. 14), a = 8.343(4) Å, b = 7.367(3) Å, c = 31.532(14) Å, β = 97.398(8)°, V = 1921.8(14) Å3, Z = 4, Rgt(F) = 0.0420, wRref(F2) = 0.1158, T = 296.15 K.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe6− (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2‐TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti‐aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth‐doped semiconductor materials. [ABSTRACT FROM AUTHOR]

The propagation of hydraulic fractures is highly influenced by the geological structure of the reservoir in unconventional reservoirs, such as natural fractures. In this paper, a new fluid–solid coupling dynamic model was built which presents the failure mechanism of hydraulic fracture with pre-existing simple and complex natural fractures. The cohesive element method and the maximum principal stress fracture criterion were used in the new model. An analysis was conducted to investigate the impact of various factors, including encounter angle, in situ stress, elastic modulus, and Poisson's ratio, on the propagation of hydraulic fractures. The simulation results indicate that the encounter angle and the in situ stress are the main factors affecting the fracture morphology. When the encounter angle and the in situ stress difference are small, hydraulic fractures propagate along natural fractures. When the elastic modulus is small, it is advantageous for the advancement of both hydraulic and natural fractures. The Poisson's ratio has a slight effect on the fracture propagation pattern. [ABSTRACT FROM AUTHOR]

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1–7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1–7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals. [ABSTRACT FROM AUTHOR]

TC4 titanium alloy bulk specimens were prepared by laser deposition manufacturing.The effect of annealing treatment on mechanical properties, microstructure of LDMed TC4 titanium alloy was studied by optical microstructure (OM),scanning electron microscopy (SEM) and X-ray diffraction (XRD).The experimental results show that the microstructure is basketweave structure after α+β two-phase region annealing treatment and is transformed to Widmanstatten structure after β phase region annealing treatment.The mechanical properties still show significant anisotropy after annealing:Z-direction samples exhibit low strength and high plasticity, while XY-direction samples show high strength and low plasticity.The samples have a greatly decrease in strength and plasticity after β phase region annealing treatment.The annealing temperature has obvious influence on the anisotropy of the samples. The tensile properties of XY-direction samples are evidently scattered.Both direction samples exhibit ductile fracture after α+β two-phase region annealing treatment. The strength and plasticity of the samples decrease greatly after β single phase region annealing treatment, and the XY-direction samples are brittle fracture.