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To effectively obtain high-quality wheat aleurone layer flour suitable for food processing, the effects of milling speed and mesh size on the nutritional and functional components of wheat aleurone layer flour were investigated, and the optimal separation parameters were developed by grey correlation analysis (GCA). The effects of adding 0%–30% wheat aleurone layer flour (based on the weight of wheat flour) on the nutritional composition and thermodynamic characteristics of wheat flour, and the thermomechanical and dynamic rheological properties of dough were studied. The results showed that the optimal separation parameters for wheat aleurone layer flour were 4 000 r/min and 80-mesh, which provided a high yield of wheat aleurone layer flour, rich in crude protein, total dietary fiber and alkyl resorcinol. With increasing addition of wheat aleurone layer flour from 0% to 30%, the contents of moisture and starch continuously reduced, and the contents of ash, crude protein, total dietary fiber, crude fat, total polyphenol and alkyl resorcinol increased. Moreover, addition of wheat aleurone layer flour improved the gelatinization stability and viscoelasticity of flour and delayed the retrogradation of dough, consequently improving its processing properties. The findings of this study contribute to maximizing the development of the nutritional and processing properties of wheat aleurone layer flour, improving its processing performance and promoting the utilization of wheat by-products.

The surge in urbanization has correspondingly given rise to exacerbated carbon footprint and burgeoning heavy metal (HM) contamination, constituting a critical impediment to the realization of environmentally sustainable urban development pathways. Therefore, it is highly essential to investigate the impacts of urbanization process on soil carbon, heavy metals (HMs), as well as their interrelationships. Employing remote sensing and land use data within a 45 km radius in Chongqing, this study selected 31 sites to assess the variation in urban green spaces (UGSs) carbon sequestration capabilities and associated HM pollution risks across differing urbanization levels. Results showed that urbanization dynamics and land use history play a more decisive role than current anthropogenic management in shaping the distribution of soil carbon and HMs within urban environments. The average soil organic carbon (SOC) distribution of UGSs is 8.47 mg ha−1 (1.50–24.20 mg ha−1), concurrent with moderate HM pollution showing Ni: 32.03–33.50 mg kg−1, Pb: 27.93–29.65 mg kg−1, Cu: 26.97–41.20 mg kg−1, while Cd exhibits the most severe pollution range of 0.23–0.30 mg kg−1. The rate of urbanization significantly influences SOC stocks, exhibiting an increase when the urbanization rate is below 70.79 % and a decrease upon surpassing this threshold. The concentration of HMs is predominantly determined by the historical usage of the land, with a marked escalation correlating with the duration of land utilization history. These relationships were quantitatively modeled through the application of fitted linear functions. The structural equation model demonstrated that UGSs operating without anthropogenic disturbance tend towards degradation, indicating that temporary homeostasis might be sustained via the addition of N and P nutrients and pH modulation. In conclusion, we formulate an Urban Green Spaces Development Hypothesis that aims to shed light on the multifaceted challenges encountered by cities amidst varying degrees of urbanization and, concurrently, to probe potential ameliorative strategies.

Abstract Background With the continuous discovery of new borderline thyroid lesions and benign and malignant “gray areas”, coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. Methods In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. Results Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P

With the rapid development of computer technology, the application of artificial intelligence (AI) to ophthalmology has gained prominence in modern medicine. As modern optometry is closely related to ophthalmology, AI research on optometry has also increased. This review summarizes current AI research and technologies used for diagnosis in optometry, related to myopia, strabismus, amblyopia, optical glasses, contact lenses, and other aspects. The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

Abstract Background PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome (CTS). However, carpal tunnel release (CTR) was still a necessary treatment for individuals with moderate and severe CTS. Methods To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength were used to examine the patient's symptoms and function. Results CTR combined with PRP treatment improved the VAS (1.9 ± 0.5 versus 1.4 ± 0.4, P

Abstract Background There is no consensus on whether triplet regimen is better than doublet regimen in the first‐line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. Methods This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non‐inferiority in progression‐free survival (PFS) for XELOX as compared with EOX on an intention‐to‐treat basis. Results Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5‐6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0‐6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812‐1.203; Pnon‐inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health‐related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. Conclusions This non‐inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first‐line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients.BackgroundDocetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients.MethodsIn this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment.ResultsTotal 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%).ConclusionTX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

Regenerated silk fibroin has been widely used in tissue engineering due to its tunable mechanical properties, biocompatibility and degradability, especially in biological scaffolds. In this paper, for the first time, a robust silk fibroin (SF) scaffold with a reinforced concrete structure constructed with silk nanofibers as the skeleton was prepared by combining a CaCl2-formic acid (FA-CaCl2) dissolving system with a freeze-drying method. This method consumes less time and greatly reduces the rate of silk loss, while formic acid can be collected and reused as a solvent during the lyophilization process. Moreover, the SF scaffolds prepared by this method retained the nanofibers of silk, thus preserving the mechanical toughness of the silk nanofibers. On this basis, a reinforced concrete structure with silk nanofibers as the skeleton and amorphous silk as the filler was constructed, which exhibited increased strength and toughness. Effects of preparation conditions (dissolution system, degumming time, silk content) on the mechanical properties and the relationship between structure and mechanical properties of the scaffolds were also studied. Among them, the strength of SF scaffold with degumming time of 10 min, silk content of 20 wt% and directional pores was the best, and its Young's modulus could reach 3.56 MPa. In addition, the scaffolds prepared by this method had good biocompatibility and biodegradability. This study provides a new strategy for manufacturing SF scaffolds and an alternative for the preparation of related silk fibroin materials, which have excellent potential in the field of tissue engineering.

In view of the problem that time delay always existing in wide area power system can cause severe effects on the operation performance of the whole system, this paper studies the stability of the wide area power system with interval time-varying delays. Firstly, the model of wide area power system with interval time-varying delay is established, based on that, a new augmented vector and new Lyapunov-Krasoskii functional (LKF) are constructed. Then, the delay-partitioning approach, Wirtinger integral inequality, free-matrix-based inequality and convex combination approach are used to estimate the derivative of the functional, and as a result, a less conservative stability criterion for the delayed power system is obtained. Finally, numerical simulations of the typical second-order system, the single machine system and two-area four-generator power system are given to illustrate that the proposed method in this paper expands the stability margin of the system effectively.

Abstract The aim of this study was to explore the independent prognostic factors related to postoperative recurrence‐free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low‐risk group, while borderline and malignant PTBs were classified as a high‐risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence‐free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty‐five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low‐risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high‐risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence‐free survival at 1, 3, and 5 years. For high‐risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain.

Hybrid FRP-concrete-steel double-skin tubular columns (hybrid DSTCs) are a novel form of hollow columns consisting of an outer FRP tube, an inner steel tube, and an annular layer of concrete between the two tubes. Due to the effective confinement of the two tubes, the concrete in hybrid DSTCs is well confined, leading to excellent ductility and strength enhancement. Hybrid DSTCs also have excellent corrosion resistence due to the effective protection of the outer FRP tube. However, existing studies mainly focused on hybrid DSTCs with a circular cross-section. When subjecting to different loads in the two horizontal directions, elliptical columns are preferred as they can provide different bending stiffness and moment capacity around two axes of symmetry without significantly reducing the confining effect of the FRP tube. This paper extends the existing work on circular DSTCs to elliptical DSTCs with a particular focus on four issues: the effect of elliptical aspect ratio (i.e., the ratio of the major axis to the minor axis of the outer elliptical cross-section), the effect of the FRP tube thickness, the effect of void area ratio (i.e., the ratio of the area of concrete void to the area of the outer elliptical section), and the effect of the cross-section of the inner steel tube (i.e., both rectangular and elliptical steel tubes were used). Experimental results show that, the averaged peak stress of the confined concrete in elliptical DSTCs increases with the increase in the elliptical aspect ratio, whereas the elliptical aspect ratio has no obvious effect on the ultimate axial strain; the cross-section shape of the inner steel tube has significant effect on the axial stress-strain behavior of the confined concrete in elliptical DSTCs; elliptical DSTCs with an elliptical steel tube exhibit much better ductility and strength enhancement than those specimens with a rectangular steel tube. A simple stress-strain model of confined concrete was proposed for elliptical DSTCs to account for the effects of the elliptical aspect ratio, the inner void, and the shape of the inner steel tube, which can provide reasonably accurate but conservative predictions.

Cytochrome P450 3A4 (CYP3A4) enzyme activity is known to show considerable ethnic heterogeneity and inter-individual differences, affecting the outcome of drug treatment. CYP3A4 genetic polymorphisms are believed to be one of the important causes, leading to inter-individual variability in drug metabolism. Quinine is an antipyretic drug with antimalarial properties that is metabolized primarily by CYP3A4. Quinine 3-hydroxylation has been proven as a biomarker reaction for evaluating CYP3A4 ability. Quinine has frequent adverse effects and there are distinct inter-individual differences in quinine sensitivity. The open reading frame for 30 CYP3A4 allelic variants were constructed from wild-type CYP3A4*1A by an overlap extension polymerase chain reaction. Recombinant CYP3A4 variants were expressed using baculovirus-insect cell expression system, and their catalytic activities towards quinine hydroxylation were determined and evaluated. Of the 30 CYP3A4 allelic variants, 23 variants exhibited significantly reduced intrinsic clearance towards quinine, 2 variants showed increased intrinsic clearance for quinine, 2 variants possessed no significant differences towards quinine, compared with CYP3A4*1A, and 3 variants had no detected expression and enzyme activity. Our assessment on the enzymatic activities of CYP3A4 variants towards quinine may contribute to laying an experimental foundation for further clinical studies so as to accelerate the process of determining the associations between genetic variations and clinical phenotypes.

The tight oil formation develops with microfractures and matrix pores, it is important to study the influence of matrix physical properties on flow characteristics. At first, the representative fracture and matrix samples are selected respectively in the dual media, the fracture and matrix digital rocks are constructed with micro-CT scanning at different resolutions, and the corresponding fracture and matrix pore networks are extracted, respectively. Then, the modified integration method is proposed to build the dual network model containing both fracture and matrix pore-throat elements, while the geometrictopological structure equivalent matrix pores are generated to fill in the skeleton domain of fracture network, the constructed dual network could describe the geometric-topological structure characteristics of fracture and matrix pore-throat simultaneously. At last, by adjusting the matrix pore density and the matrix filling domain factor, a series of dual network models are obtained to analyze the influence of matrix physical properties on flow characteristics in dual-media. It can be seen that the matrix system contributes more to the porosity of the dual media and less to the permeability. With the decrease in matrix pore density, the porosity/permeability contributions of matrix system to dual media keep decreasing, but the decrease is not significant, the oilewater co-flow zone decreases and the irreducible water saturation increases, and the saturation interval dominated by the fluid flow in the fracture keeps increasing. With the decrease in matrix filling domain factor, the porosity/permeability contributions of matrix system to dual media decreases, the oilewater co-flow zone increases and the irreducible water saturation decreases, and the saturation interval dominated by the fluid flow in the fracture keeps increasing. The results can be used to explain the dual-media flow pattern under different matrix types and different fracture control volumes during tight oil production. [ABSTRACT FROM AUTHOR]

Background Previous studies have demonstrated that chemokine CXCL12 and its receptor CXCR4 are critical for pain sensitization, but the mechanisms involved are not clear. In this study, we investigated the specific cellular mechanisms of CXCL12/CXCR4 chemokine signaling in the development and maintenance of bone cancer pain after tumor cell implantation (TCI). Methods TCI in the tibial cavity of rats was used to establish a bone cancer pain model. Mechanical allodynia and thermal hyperalgesia were determined by measuring the paw withdrawal threshold and latency, respectively. The protein expression and cellular localization of CXCL12 and CXCR4 were detected by western blot and immunofluorescence staining. The sensitization of neurons, activation of astrocytes and microglia were examined by observing the immunofluorescence intensity of c-Fos, GFAP and IBA1. Results Our results demonstrated that CXCL12 was upregulated in a time-related manner, both in the dorsal root ganglia and spinal cord after TCI. Spinal CXCL12 was predominately expressed in astrocytes, and an intrathecal injection of astrocyte metabolic inhibitor fluorocitrate or selective JNK inhibitor SP600125 abolished TCI-induced CXCL12 production. A single intrathecal injection of a CXCL12 neutralizing antibody (10 µg/10 µl) at day 10 after TCI transiently reversed bone cancer pain in a dose-dependent manner. Whereas repetitive intrathecal administration of a CXCL12 neutralizing antibody (10 µg/10 µl, once a day from day 3 to 5 after TCI) significantly delayed the onset of TCI-induced pain behaviors for nearly five days. Spinal CXCR4 was also upregulated after TCI and colocalized with neurons, astrocytes and microglia. Blocking CXCR4 suppressed TCI-induced activation of neurons, astrocytes and microglia in the spinal cord at day 14. Repeated intrathecal administration of AMD3100 (5 µg/10 µl, once a day for three days) significantly delayed and suppressed the initiation and persistence of bone cancer pain in the early phase (at day 5, 6 and 7 after TCI) and in the late phase (at day 12, 13 and 14 after TCI) of bone cancer, respectively. Conclusions Taken together, these results demonstrate that CXCL12/CXCR4 signaling contributed to the development and maintenance of bone cancer pain via sensitizing neurons and activating astrocytes and microglia. Additionally, this chemokine signaling may be a potential target for treating bone cancer pain. [ABSTRACT FROM AUTHOR]

A novel angucycline metabolite, 2,3-dehydro-UWM6, was identified in ajadH mutant of Streptomyces venezuelae ISP5230. Both UWM6 and 2,3-dehydro-UWM6 could be converted to jadomycin A or B by a ketosynthase α (jadA) mutant of S. venezuelae. These angucycline intermediates were also converted to jadomycin A by transformant of the heterologous host Streptomyces lividans expressing the jadFGH oxygenases in vivo and by its cell-free extracts in vitro; thus the three gene products JadFGH are implicated in catalysis of the post-polyketide synthase biosynthetic reactions converting UWM6 to jadomycin aglycone. Genetic and biochemical analyses indicate that JadH possesses dehydrase activity, not previously associated with polyketide-modifying oxygenase. Since the formation of aromatic polyketides often requires multiple dehydration steps, bifunctionality of oxygenases modifying aromatic polyketides may be a general phenomenon. [ABSTRACT FROM AUTHOR]

The magnetic-tunnel-junction (MTJ) structure is the core of many important devices, such as magnetic recording head and STT-RAM. CoFeB/MgO/CoFeB tri-layer thin-film stack is a widely researched MTJ structure. In this tri-layer, the functional property of the MTJ, i.e. its TMR ratio, is critically dependent on the crystal orientation of the CoFe grains. In order for the desired (1 0 0) out of plane texture to develop in the CoFeB layers, B needs to be engineered to be expelled out of these CoFeB layers, and diffuse or migrate into the adjacent layers. Ta is usually used as a seed layer adjacent to the MTJ structure. In this work, we investigated the important B-migration mechanisms within this MTJ structure through a combined XPS/TOF-SIMS study. Specifically, we tried to elucidate the possible physical/chemical interactions between the B and Ta that could happen with different film stack designs. Previous works have shown that there might be two possible B-migration mechanisms. One mechanism is direct B diffusion into the adjacent Ta layer during annealing. The other B-migration mechanism is through the formation of TaBOx species, in which B could be carried out by the Ta diffusion. In particular, through studying a series of film stacks, we discussed the circumstances under which one of these B-migration mechanisms becomes dominant. Furthermore, we discussed how these B-migration mechanisms facilitated the B expulsion in a common MTJ structure. [ABSTRACT FROM AUTHOR]