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Abstract The leaves of Cyclocarya paliurus (Batalin) Iljinskaja, an endemic tree with a scattered distribution in subtropical China, are rich in flavonoids with beneficial, health-promoting properties. To understand the impact of environment and genetic similarity on the variation pattern of flavonoids in this species, we analyzed C. paliurus germplasm resources from 26 different populations previously sampled from the main distribution area. Environmental, genetic and biochemical data was associated by genetic structure analysis, non-parametric tests, correlation analysis and principal component analysis. We found that populations with higher flavonoid contents were distributed at higher elevations and latitudes and fell into two groups with similar genetic diversities. Significant accumulations of isoquercitrin and kaempferol 3-O-glucoside were detected in the higher flavonoid-content resources. In addition, the genetic clusters with higher flavonoid contents exhibited broader environmental-adaptive capacities. Even in the presence of environmental factors promoting C. paliurus flavonoid accumulation, only those populations having a specific level of genetic similarity were able to exploit such environments.

To investigate the evolution of coal permeability during the process of gas pressure change, four different forms of permeability models were derived based on the correlation between mesoscale parameters of coal representative elementary volume (REV) and strain-related characteristics. The reliability of the models was verified using experimental data, and the variation law of strain caused by effective stress and adsorption strain was analyzed and compared with classical permeability models (P-M model, S-D model, Connell model). The sensitivity of model parameters was discussed, the relationship between REV mesoscale parameters and fracture porosity and permeability was clarified, and the influence mechanism of adsorption strain coefficient was analyzed. Furthermore, the extreme values of permeability of major coal mines in China were studied. Results show that for the four permeability models derived in this paper, the REV volume strain satisfies a linear relationship with its fracture volume strain, and the correlation coefficient is the initial fracture porosity. The bulk modulus and adsorption strain coefficient control the influence of effective stress and adsorption strain on permeability, respectively. Under three different experimental conditions of constant confining pressure, constant pore pressure, and constant differential pressure, the four permeability models have shown a better matching effect on the experimental data compared with the classical permeability models. However, compared with single-parameter fitting, the parameter error in the double-parameter fitting (bulk modulus and adsorption strain coefficient) is larger. From the sensitivity analysis of parameters, it is observed that when the parameters change within 10%, the predicted permeability deviates significantly from the true value. Therefore, for the double or multiple-parameter fitting of permeability models, the parameter fitting errors could lead to serious distortion of the predicted permeability results. Taking the experimental data of coal samples from the Qinshui Basin as an example, the mesoscopic scale parameters a0 and b0 of REV were calculated to range from 1.73 to 46.31 μm and from 0.06 to 0.49 μm, respectively. Under constant confining pressure and constant differential pressure conditions, the adsorption strain coefficient was related to differential pressure, gas types, and initial fracture porosity. Furthermore, the extreme values of CO2 gas and CH4 gas in major coal mines in China are within the ranges of 0.94−5.33 MPa and 1.06−6.94 MPa, respectively.

Lipopolysaccharides (LPS) are commonly used to construct inflammation models. However, poultry have a certain degree of tolerance to LPS due to the lack of thrombin XI and XII in their bodies. Thrombin activation produces clotting factors that can cleave prothrombin to form thrombin. The purpose of this study was to construct a chick oxidative stress model used different concentrations of LPS combined with thrombin in order to screen for the optimal concentration for constructing the oxidative stress model, and to explore the effects of this stimulus on various indicators of chicks. Eighty-one young chicks (4-days-old) were randomly divided into three groups with 27 chicks per group where each group contained 3 replicates with 9 birds each: a control group (physiological saline), a low-dose group (LPS 5 mg/kg thrombin 150 U/kg), and a high-dose group (LPS 10 mg/kg thrombin 300 U/kg). The results indicated that compared with the control group, the low-dose group and the high-dose group significantly increased the content of Malondialdehyde (MDA) in serum and reduced the content of T-AOC, GSH-PX and SOD, respectively. Meanwhile, the levels of NO and inflammatory factors IL-1β, IL-6 and TNF-α TNF-α in the liver were significantly increased in the low-dose and high-dose groups compared with the control group, respectively. Liver and thymus tissue sections from the low- and high-dose groups showed hemorrhage, hemolysis, and a small amount of exudation. In terms of inflammatory effect, the serum MDA content and the levels of NO, IL-1β, IL-6 and TNF-α factors in the liver were significantly increased in the low-dose group compared with the high-dose group. On histopathological observation, tissue damage was more pronounced in the low-dose group than in the high-dose group. In conclusion, LPS combined with thrombin could induce oxidative stress in chicks and the pathological changes of the low-dose effect are more pronounced.

Abstract Sialin, a member of the solute carrier 17 (SLC17) transporter family, is unique in its ability to transport not only sialic acid using a pH-driven mechanism, but also transport mono and diacidic neurotransmitters, such as glutamate and N-acetylaspartylglutamate (NAAG), into synaptic vesicles via a membrane potential-driven mechanism. While most transporters utilize one of these mechanisms, the structural basis of how Sialin transports substrates using both remains unclear. Here, we present the cryogenic electron-microscopy structures of human Sialin: apo cytosol-open, apo lumen-open, NAAG–bound, and inhibitor–bound. Our structures show that a positively charged cytosol-open vestibule accommodates either NAAG or the Sialin inhibitor Fmoc-Leu-OH, while its luminal cavity potentially binds sialic acid. Moreover, functional analyses along with molecular dynamics simulations identify key residues in binding sialic acid and NAAG. Thus, our findings uncover the essential conformational states in NAAG and sialic acid transport, demonstrating a working model of SLC17 transporters.

Abstract Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.

Recently, there has been fast-growing interest among researchers in discovering bioactive peptides from insects and evaluating their potential applications in livestock production. The present study aimed to assess the antioxidant properties and stability of fly maggot peptide (FMP) and its effects on Arbor Acres (AA) broilers’ oxidative stress induced by lipopolysaccharide (LPS) and hemocoagulase (HC). A total of 108 one-day-old AA broilers were randomly divided into six groups: CG (normal saline, basal diet), DG (LPS + HC, basal diet), VG (DG + vitamin C 50 ug/kg), LPG (DG + FMP 5 mg/kg), MPG (DG + FMP 15 mg/kg), and HPG (DG + FMP 25 mg/kg). The results showed that the addition of FMP to the diet promoted LPS+ HC-induced increases in average daily gain (ADG), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC). Meanwhile, FMP regulated the intestinal morphology. Additionally, FMP decreased the increase in the contents of malondialdehyde (MDA), the relative weight of immune organs, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In conclusion, this research suggested that the addition of FMP can relieve the LPS+ HC-induced oxidative stress of AA broilers and the recommended dose of FMP is 25 mg/kg. This study presents a theoretical foundation for the addition of an FMP supplement for the purpose of protecting broilers’ growth.

In this study, cassava starch cross-linked using sodium trimetaphosphate was used as basic material to prepare the preservation coating agent. The addition levels of β-cyclodextrin, phytic acid and glycerol were optimized by response surface methodology with the comprehensive index of oil permeability (OP) and the water vapor permeability (WVP) of starch-based coating. The optimal formulation of the cross-linked cassava starch-based coating was as follows: 3 g/100 g cassava cross-linked starch, 0.7 g/100 g β-cyclodextrin, 0.5 g/100 g phytic acid, and 0.5 g/100 g glycerol. The preservation coating solution prepared by the optimized formula was applied to the postharvest storage of ‘Shatangju’ mandarins. The coating treatment effectively slowed down the decline of firmness during storage for 20 days at room temperature, reduced the decay rate (by 111.73%) and weight loss rate (by 43.40%), and inhibited the postharvest respiration (by 42.06%) of fruit. The soluble solid content, titratable acidity and ascorbic acid content of the coated ‘Shatangju’ mandarins were higher 1.32 times, 1.55 times, and 1.52 times, respectively, compared with the corresponding indexes of the control fruits. All these results indicate that the coating treatment could effectively reduce the loss of nutrients, delay the wilting and decay, prolong the shelf life after harvest, and improve the commercial value of ‘Shatangju’ mandarins.

The in vitro models of lysophosphatidylcholine 18:1 (LPC(18:1)), lysophosphatidy- lethanolamine 18:1 (LPE(18:1)) and oleic acid were constructed by simulating the pH, LPC(18:1) and LPE(18:1) contents and steaming conditions of Chinese water chestnut (CWC). The content of nonanal, decanal and oleic acid, and peroxide value (POV) produced by the in vitro models were used as indicators to investigate the formation mechanism of nonanal and decanal from LPC(18:1) and LPE(18:1) during the steaming of CWC. The results showed that the possible mechanism of the oxidation of LPC(18:1) and LPE(18:1) to form nonanal and decanal was as follows. First of all, the C8 and C11 positions close to the double bond on the unsaturated acyl chain of LPC(18:1) and LPE(18:1) lost H respectively, and then formed R·. In the second step, the R· directly reacted with O2 and H to form 8-hydroperoxide (8-ROOH), or reacted with O2 and H to form 9-hydroperoxide (9-ROOH) and 10-hydroperoxide (10-ROOH) after electron rearrangement. Finally, 8-ROOH split homogeneously to form decanal, 9-ROOH and 10-ROOH split homogeneously to form nonanal. The results can provide scientific reference for the formation mechanism of flavor substances and the regulation of flavor quality of fruits and vegetables.

High-temperature resistant material is becoming increasingly significant in numerous industrial applications, including aerospace and automotive use, to increase fuel efficiency and decrease CO2 emissions. Metals with nanoparticles to form metal matrix nanocomposite (MMNCs) are promising to enhance metals for structural/industrial applications at high temperatures. This review provides a comprehensive insight into the nanoparticle effect on the creep behavior of metals and alloys. Firstly, it discusses the different creep mechanisms that are activated in response to the creep strain according to the deformation parameters (temperature, load, and microstructure). The most significant creep mechanisms vary according to the grain shape accommodation mechanism required to facilitate the grain boundary sliding into accommodation by diffusion and accommodation by intragranular dislocation activity. Secondly, it reviews the threshold stress contribution in metal matrix composites as well as the load transfer phenomenon, which enhances creep resistance of metals with nanoparticles. Thirdly, the nanoparticles' influences on the creep behavior of metals, especially Al, Mg, Ti, Zn, and solder alloys, are reviewed in detail. Finally, a summary of this review and the future aspects associated with the behavior of metals with nanoparticles at high temperatures are provided.

Humidity sensors deeply influence human manufacturing production and daily life, while researchers generally focus on developing humidity sensors with higher stability, higher linearity, rapid response time, etc. Yet, few people discuss measuring humidity in the microenvironment by miniaturizing sensor size into a microscale, in which the existing humidity sensors are difficult to reach. Accordingly, this study proposes a methodology for measuring relative humidity in the microscale by utilizing the distinctive morphologies of Equisetum spores across a range of relative humidities between 50% and 90%. Equisetum spores are responsive to changes in ambient relative humidity and remain in their original activities even after iron sputtering, which aims to endow the sensor with magnetic properties. The test performed in this study demonstrated a response time of 3.3 s and a recovery time of 3.6 s. In the first application, we employed such microscale sensors to work in the channel of the microfluidic chip or the cell migration microchip, as an example of working in the microenvironment. COMSOL Multiphysics 6.2 software was also used to simulate the change in relative humidity in such microchannels. Secondly, such microscale sensors are combined with smartphone-based microscopy to measure the humidity of the skin. These microscale sensors pave the new way to sensing humidity in microenvironments.

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions.

CO2 geological utilization and storage (CGUS) is an important technology to achieve a deep cut of global CO2 emissions. CO2 leakage from the subsurface may impair the performance of CGUS projects, and the CO2 leakage through wellbores is the most common leakage pathway. This paper proposes a workflow for wellbore CO2 leakage risk management, and the workflow consists of the following steps: i) leakage risk identification; ii) leakage risk evaluation; iii) leakage risk monitoring; iv) leakage handling. Representative approaches in each step of the workflow are systematically reviewed. Key challenges of wellbore CO2 leakage risk management include: lack of effective detection and evaluation approaches to tackle the CO2 leakage risk induced by cement failure; lack of low-cost acid resistance alloys and CO2-resistant cement; lack of automated monitoring systems that could enable automated shutdowns of the wellbore whenever certain warning criteria are met.

Abstract Background To explore the efficacy and safety of laser peripheral iridoplasty (LPIp) with different energy levels and locations in the treatment of primary angle closure disease (PACD) assessed by swept-source anterior segment optical coherence tomography (AS-OCT). Methods We enrolled patients with PACD following best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber gonioscopy, ultrasound biomicroscopy(UBM), optic disc OCT, and visual field examinations. After Pentacam and AS-OCT measurements, the patients were randomly divided into four treatment groups for LPIp with two different energy levels (high vs. low energy) and two locations (far from the periphery vs. near the periphery) and combined with laser peripheral iridotomy. BCVA, IOP, pupil diameter, central anterior chamber depth, anterior chamber volume, anterior opening distance (AOD)500, AOD750, trabecular iris angle (TIA)500, and TIA750 in four quadrants before and after laser treatment were compared. Results We followed up 32 patients (64 eyes; average age, 61.80 ± 9.79 years; 8 patients/16 eyes per group) for up to 2 years. The IOP of all enrolled patients was decreased after surgery compared to that before (t = 3.297, P = 0.002), the volume of the anterior chamber was increased (t=-2.047, P = 0.047), and AOD500, AOD750, TIA500, and TIA750 were increased (all P

Abstract Background Excessive oxidative stress plays a critical role in the progression of various diseases, including intervertebral disk degeneration (IVDD). Recent studies have found that anemonin (ANE) possesses antioxidant and anti-inflammatory effects. However, the role of ANE in IVDD is still unclear. Therefore, this study investigated the effect and mechanism of ANE on H2O2 induced degeneration of nucleus pulposus cells (NPCs). Methods NPCs were pretreated with ANE, and then treated with H2O2. NOX4 was upregulated by transfection of pcDNA-NOX4 into NPCs. Cytotoxicity was detected by MTT, oxidative stress-related indicators and inflammatory factors were measured by ELISA, mRNA expression was assessed by RT-PCR, and protein expression was tested by western blot. Results ANE attenuated H2O2-induced inhibition of NPCs activity. H2O2 enhanced oxidative stress, namely, increased ROS and MDA levels and decreased SOD level. However, these were suppressed and pretreated by ANE. ANE treatment repressed the expression of inflammatory factors (IL-6, IL-1β and TNF-α) in H2O2-induced NPCs. ANE treatment also prevented the degradation of extracellular matrix induced by H2O2, showing the downregulation of MMP-3, 13 and ADAMTS-4, 5 and the upregulation of collagen II. NOX4 is a key factor regulating oxidative stress. Our study confirmed that ANE could restrain NOX4 and p-NF-κB. In addition, overexpression of NOX4 counteracted the antioxidant and anti-inflammatory activities of ANE in H2O2-induced NPCs, and the inhibition of the degradation of extracellular matrix induced by ANE was also reversed by overexpression of NOX4. Conclusion ANE repressed oxidative stress, inflammation and extracellular matrix degradation in H2O2-induced NPCs by inhibiting NOX4/NF-κB pathway. Our study indicated that ANE might be a candidate drug for the treatment of IVDD.

Abstract Background β-glucosidase is an important biomass-degrading enzyme and plays a vital role in generating renewable biofuels through enzymatic saccharification. In this study, we analyzed the transcriptome of Trichoderma harzianum HTASA derived from Hainan mangrove and identified a new gene encoding β-glucosidase Bgl3HB. And the biochemically characterization of β-glucosidase activity was performed. Results Bgl3HB showed substantial catalytic activity in the pH range of 3.0–5.0 and at temperatures of 40 ℃-60 ℃. The enzyme was found quite stable at 50 ℃ with a loss of only 33.4% relative activity after 240 min of heat exposure. In addition, all tested metal ions were found to promote the enzyme activity. The β-glucosidase activity of Bgl3HB was enhanced by 2.12-fold of its original activity in the presence of 5 M NaCl. Surprisingly, Bgl3HB also showed a remarkable ability to hydrolyze laminarin compared to other measured substrates. Enzyme efficiency was examined in the sugarcane bagasse saccharification processes, in which Bgl3HB with 5 M NaCl worked better supplementing Celluclast 1.5L than the commercial Novozyme 188 ascertained it as an admirably suited biocatalyst for the utilization of agricultural waste. In this work, this is the first report of a halophilic β-glucosidase from Trichoderma harzianum, and represents the β-glucosidase with the highest known NaCl activation concentration. And adding 5 M NaCl could enhance saccharification performance even better than commercial cellulase. Conclusions These results show that Bgl3HB has great promise as a highly stable and highly efficient cellulase with important future applications in the industrial production of biofuels.

HMG-CoA reductase (HMGCR) is regulated by UBIAD1 and Insigs and initializes cholesterol synthesis. Here authors show that the sterol sensing domain of HMGCR undergoes conformational changes to regulate its degradation via binding its protein modulators.

Structural basis of V-ATPase regulation by endogenous proteins is unclear. Here, the authors find mEAK7 as an endogenous V-ATPase modulator and determine its structure with V-ATPase, suggesting the potential role of mEAK7 in V-ATPase regulation.

It is important to understand the process of multiphase carbon dioxide (CO2) leakage in faults for the risk assessment of carbon capture and storage (CCS). To quantitatively characterize the CO2 leakage process in the fault, pressure sensors, fiber Bragg grating (FBG) temperature and strain sensors were simultaneously used to monitor CO2 leakage in the fault. Ten experiments were carried out, including five groups of gaseous CO2 leakage tests with initial pressures of 1–5 MPa and five groups of liquid CO2 leakage tests with initial pressures of 6–10 MPa. The results indicate that when liquid CO2 leaked with an initial pressure of 7–10 MPa, the pressure and temperature of CO2 dropped rapidly in the first few seconds and then remained unchanged. The behavior that CO2 continues to leak while maintaining temperature and pressure unchanged is defined as “temporary pseudo-sealing (TPS)” behavior, which continues for the first 1/3 of the leakage period. However, this TPS behavior did not occur in gaseous CO2 leakage. If only the pressure and temperature data were used to evaluate whether CO2 leakage occurred, we would misjudge the risk of leakage in CCS projects during the TPS period. The causes and conditions of TPS behavior were further studied experimentally. The results show that: (1) TPS behavior is caused by the phase transition energy generated when liquid CO2 leaks. (2) The condition for TPS behavior is a small leak aperture (0.2 mm). Only a small leakage rate can make the phase transition energy and pressure change from a dynamic equilibrium, and (3) The compression zone caused by the Bernoulli effect and fault “barrier” could reduce the CO2 leakage rate and further promote the occurrence of TPS behavior. This study provides technical and theoretical support for the quantitative characterization of the CO2 leakage process in faults of CCS projects.

The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple drugs that inhibit S1PR1 function are in use clinically for the treatment of autoimmune diseases. Cluster of Differentiation 69 (CD69) is an endogenous negative regulator of lymphocyte egress that interacts with S1PR1 in cis to facilitate internalization and degradation of the receptor. The mechanism by which CD69 causes S1PR1 internalization has been unclear. Moreover, although there are numerous class A GPCR structures determined with different small molecule agonists bound, it remains unknown whether a transmembrane protein per se can act as a class A GPCR agonist. Here, we present the cryo-EM structure of CD69-bound S1PR1 coupled to the heterotrimeric Gi complex. The transmembrane helix (TM) of one protomer of CD69 homodimer contacts the S1PR1-TM4. This interaction allosterically induces the movement of S1PR1-TMs 5–6, directly activating the receptor to engage the heterotrimeric Gi. Mutations in key residues at the interface affect the interactions between CD69 and S1PR1, as well as reduce the receptor internalization. Thus, our structural findings along with functional analyses demonstrate that CD69 acts in cis as a protein agonist of S1PR1, thereby promoting Gi-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress.

Objective To compare the effectiveness of the old mode of blood isolation and batch release (the old mode) and the new mode in Chengdu, so as to provide basis for optimizing working strategy. Methods 1) The blood testing report was released one by one in the old mode but released uniformly in accordance with the blood batches classified by blood storage and supply department in the new mode. 2) In the old mode, apheresis platelet samples were detected by serological testing first and nucleic acid testing(NAT) later, and whole blood samples were reasonably arranged according to blood inventory and detection workload. In the new mode, platelets samples collected within our center headquarters were detected by serological test and NAT simultaneously, while those collected outside the center complied with the old strategy. As for whole blood, the same batch samples classified by blood storage and supply department should be arranged to the detection line with the fewest samples.3) The turnaround time(TAT) in the laboratory (referred to as sample TAT) and the TAT in the blood to-detect stock (referred to as blood TAT) in two phases(year 2016 vs 2018, pre- and post- the new mode), involving 164 748 and 179 488 blood samples, were compared by SPSS25.0 software. The constituent ratio of the TATs were compared with Chi-square test, and the difference of blood TAT between old and new mode were compared with Mann-Whitney U test. Results 1) Significant difference was noticed in constituent ratio of TATs between old and new mode (P

The procoagulant effect of microparticles (MPs) contributes to hypercoagulability-induced thrombosis. We provide preliminary findings of the MPs-Activated Clotting Time (MPs-ACT) assay to determine the procoagulant activity of MPs. MPs-rich plasma was obtained and recalcified. Changes in plasma viscoelasticity were evaluated and the time to the peak viscoelastic changes was defined as the MPs-ACT. MPs concentration was measured by flow cytometry. Coagulation products produced during plasma clotting were identified by fibrin and fibrinopeptide A. MPs were prepared in vitro and added to standard plasma to simulate pathological samples. In addition, reproducibility and sensitivity were evaluated. We confirmed the linear relationship between MPs-ACT and MP concentrations. Dynamic changes in fibrin production were depicted. We simulated the correlation between MPs-ACT and standard plasma containing MPs prepared in vitro. The reproducibility of high-value and low-value samples was 6.0% and 10.8%, respectively. MPs-ACT sensitively detected hypercoagulable samples from patients with pre-eclampsia, hip fractures, and lung tumors. MPs-ACT largely reflects the procoagulant effect of MPs. MPs-ACT sensitively and rapidly detects hypercoagulability with MPs-rich plasma. It may be promising for the diagnosis of hypercoagulable states induced by MPs.

Abstract Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Purpose: To examine the differences in gene expression between ruptured and non-ruptured nucleus pulposus tissues of the intervertebral discs using gene chip technology.Methods: A total of 8 patients with nucleus pulposus from a lumbar disc herniation (LDH) undergoing discectomy in our hospital were selected, including 4 ruptured and 4 non-ruptured herniated nucleus pulposus cases. Total RNA was extracted from cells by using TRIzol reagent. Nucleus pulposus cDNA probes of the two groups were obtained by the single marker method and hybridized with a human gene expression profiling chip (Agilent). The fluorescence signal images were scanned by a laser, and the obtained genes were analyzed by bioinformatics.Results: There were 75 differentially expressed genes with more than 2-fold-changes, of which 56 were up-regulated and 19 were down-regulated. The differential expression of THSD7A, which was up-regulated 18 times, was the most significant, followed by CCL5, AQP3 and SDC4.Conclusion: THSD7A can be used as a characteristic differentially expressed gene in human ruptured nucleus pulposus. Moreover, CCL5, AQP3 and SDC4 may improve the chemotaxis of stem cell migration for self-healing of damaged disc tissue, increase water uptake by nucleus accumbens cells, and inhibit the inflammatory response, thus delaying the process of intervertebral disc degeneration.

BackgroundGlioblastoma, one of the common tumors of the central nervous system (CNS), is prone to recurrence even after standard treatment protocols. As an innovative physiotherapy method emerging in recent years, the tumor treating fields (TTFields) technique has been approved for the treatment of glioblastoma due to its non-invasive and portable features. The purpose of this study is to visualize and analyze the scientific results and research trends in TTFields therapy for glioblastoma.MethodsPublications related to TTFields therapy for glioblastoma were searched in the Web of Science Core Collection (WoSCC) database in September 2022. A bibliometric and visual analysis of publications in this field was performed mainly using CiteSpace and R software for country/region, author, journal, reference and keyword.ResultsA total of 618 publications in this field were retrieved, and 248 were finally obtained according to the search criteria, including 159 articles (64.11%) and 89 reviews (37.89%). The cumulative number of publications increased year by year, with an average growth rate (AGR) of 28.50%. The test results of Pearson correlation coefficient showed a high positive correlation between publications and citations (r=0.937, p

ObjectiveTo analyze the macular structure of age-related cataract (ARC) patients with different antibody levels after COVID-19 vaccine injection, in order to obtain the effect of COVID-19 vaccine on the macular structure, and speculate whether the COVID-19 vaccine has adverse effects on the macular structure.MethodsThis retrospective study is conducted to analysis on the status of COVID-19 vaccine and the thickness of different layers at different positions in the macular area of ARC patients. In the age, sex and eye axial length matched population, in the un-injection, no-antibody, IgM and IgG positive groups after vaccination, the choroid, ganglion cell complex, nerve fiber layer and retinal thickness at different positions of ETDRS zoning in the macular area were discussed.ResultsA total of 164 patients (164 eyes) were included in the analysis. There were 63 males and 101 females. The average age was 65.99 ± 8.43 years. There was no significant difference in age and sex among the groups (p>0.05). The average axial length of 164 eyes was 23.56 ± 1.46mm, and no significant difference between the groups (p>0.05). Non parametric test and ANOVA test for the thickness of choroid, retina, ganglion cell complex and retinal nerve fiber layer in each division of ETDRS showed no significant difference in the four groups of un-injection, no-antibody, IgM and IgG (p>0.05). There was no correlation between the antibody concentration and the thickness of macular structure (p>0.05).ConclusionThere was no significant difference in the thickness of choroid, retina, ganglion cell complex and retinal fiber layer in different macular areas after COVID-19 vaccine injection. There was no linear correlation between the thickness of choroid, retina, ganglion cell complex and retinal fiber layer and the antibody concentration produced after COVID-19 vaccine injection. It suggests that the injection of COVID-19 vaccine might have no significant effect on the macular structure of eye.

Chinese water chestnut (CWC) is one of the most popular hydrophytic vegetables in China due to its unique aroma and taste. The volatile compounds (VOCs) of CWC with different processing methods were evaluated. The results of headspace-gas chromatography–ion mobility spectrometry (HS-GC-IMS) showed that alcohols, aldehydes, aromatics, and esters were the main VOCs, and the headspace solid-phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC–MS) results indicated that esters, amines and aromatics were the main flavor components. Compared with other processes, the VOC alcohol levels in fresh cutting (FF) decreased, while esters and sulfide increased. The flavor of CWC in the cooking with peeling (PC) and steaming with peeling (PS) were similar, the FF and steaming with skin (WPC) are very different from the other samples. This study is the first to provide results regarding differences in the aroma compounds of CWC processed with different methods, and 146 aroma compounds were characterized.

BackgroundQuality patient care requires comprehensive health care data from a broad set of sources. However, missing data in medical records and matching field selection are 2 real-world challenges in patient-record linkage. ObjectiveIn this study, we aimed to evaluate the extent to which incorporating the missing at random (MAR)–assumption in the Fellegi-Sunter model and using data-driven selected fields improve patient-matching accuracy using real-world use cases. MethodsWe adapted the Fellegi-Sunter model to accommodate missing data using the MAR assumption and compared the adaptation to the common strategy of treating missing values as disagreement with matching fields specified by experts or selected by data-driven methods. We used 4 use cases, each containing a random sample of record pairs with match statuses ascertained by manual reviews. Use cases included health information exchange (HIE) record deduplication, linkage of public health registry records to HIE, linkage of Social Security Death Master File records to HIE, and deduplication of newborn screening records, which represent real-world clinical and public health scenarios. Matching performance was evaluated using the sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. ResultsIncorporating the MAR assumption in the Fellegi-Sunter model maintained or improved F1-scores, regardless of whether matching fields were expert-specified or selected by data-driven methods. Combining the MAR assumption and data-driven fields optimized the F1-scores in the 4 use cases. ConclusionsMAR is a reasonable assumption in real-world record linkage applications: it maintains or improves F1-scores regardless of whether matching fields are expert-specified or data-driven. Data-driven selection of fields coupled with MAR achieves the best overall performance, which can be especially useful in privacy-preserving record linkage.

Abstract Background Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels

Cyclocarya paliurus is mainly distributed in subtropical areas of China. Its leaves are rich in beneficial triterpenoids that have bioactivities against human diseases, including hyperlipemia, diabetes, and hypertension. In this study, data on the genetic diversity, distributing environment, and triterpenoids of C. paliurus samples were collected from a wide area in China. The data covered 316 C. paliurus germplasms collected from 26 distinct populations. Association analysis between genotype and triterpenoids was carried out to describe triterpenoids accumulation pattern. Based on our analyses, we identified the important trend that genotypes with higher triterpenoid contents belonged to a unique genotype subgroup. The results showed that pterocaryoside B and pterocaryoside A significantly vary among the genotypic subgroups. In addition, the different genotypic subgroups showed distinct geographical distributing areas. These findings provide information about the relationship between genetic and environmental factors and how this affects triterpenoids accumulation. This information will be valuable for targeted breeding and for further germplasm selection of C. paliurus resources.

Background The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross‐sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low‐frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min−1·1.73 m−2), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min−1·kg−1) compared with predialysis (22.7 [5.2] mL·min−1·kg−1; P12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min−1·kg−1) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min−1·kg−1; P=0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low‐risk New York Heart Association class I and higher‐risk New York Heart Association class II to IV heart failure.

BackgroundTo explore the correlation between visual field (VF) defect values and retinal nerve fiber layer (RNFL) thickness for intracranial tumor and glaucoma patients.MethodsRetrospective analysis is performed for the intracranial and glaucoma patients, whose VF defect values were measured with Octopus perimeter cluster analysis, RNFL thickness, ganglion cell layer (GCL) thickness, and optic disk parameters measured with swept-source OCT. The differences between VF and RNFL (including the data of optic disc) are calculated. The correlation between VF defect values and RNFL and GCL thickness are explored.ResultsIn total 43 eyes of 29 patients with intracranial tumor and 31 eyes of 19 patients with glaucoma were enrolled. The thickness of RNFL not only for the whole (360°), but also for the four quadrants was thinner in the glaucoma group than those of the intracranial tumor group (p). There is no significant difference in VF for those two groups except glaucoma having lower sLV (p

Abstract Efficient electron transport layers (ETLs) not only play a crucial role in promoting carrier separation and electron extraction in perovskite solar cells (PSCs) but also significantly affect the process of nucleation and growth of the perovskite layer. Herein, crystalline polymeric carbon nitrides (cPCN) are introduced to regulate the electronic properties of SnO2 nanocrystals, resulting in cPCN-composited SnO2 (SnO2-cPCN) ETLs with enhanced charge transport and perovskite layers with decreased grain boundaries. Firstly, SnO2-cPCN ETLs show three times higher electron mobility than pristine SnO2 while offering better energy level alignment with the perovskite layer. The SnO2-cPCN ETLs with decreased wettability endow the perovskite films with higher crystallinity by retarding the crystallization rate. In the end, the power conversion efficiency (PCE) of planar PSCs can be boosted to 23.17% with negligible hysteresis and a steady-state efficiency output of 21.98%, which is one of the highest PCEs for PSCs with modified SnO2 ETLs. SnO2-cPCN based devices also showed higher stability than pristine SnO2, maintaining 88% of the initial PCE after 2000 h of storage in the ambient environment (with controlled RH of 30% ± 5%) without encapsulation.

Tailing dams and waste dumps formed by the accumulation of mine wastes are usually at long-term unsaturated state under evaporation and consolidated drainage conditions. Soil-water retention relation is one of the key constitutive relations to analyze the seepage processes in tailing dams and waste dumps. In this study, typical coarse- and fine-grained tailings from a metallurgical mine were chosen to study the soil-water retention characteristics of the tailing samples. To begin with, the relationship between volumetric water content and suction of the tailing samples was experimentally measured, and typical soil-water characteristic curves (SWCCs) (i.e., Gardner, van Genuchten and Fredlund–Xing curves) were applied to fit the experimental data. After that, four empirical models to estimate the parameters in SWCCs (i.e., Aubertin-1998 model, Aubertin-2003 model, Vanapalli-2005 model and Chin-2010 model) were tested, and the Vanapalli-2005 model was the best-fit model for the tailing samples. Furthermore, this study proposes a generalized emergency risk assessment soil-water retention characteristics model for tailing dams and waste dumps, and a framework for the quick estimation of parameters in the SWCC is proposed as well. The recommended soil-water retention characteristics model and the related parameters can be used to predict water levels in tailing dams and waste dumps, which are very helpful for emergency risk assessment under rainstorm or flooding conditions. HIGHLIGHTS This study is the first study to prove the feasibility of using the Vanapalli-2005 model to estimate parameters in soil-water characteristic curves (SWCCSs) for mine wastes.; This study proposes a framework for the fast determination of SWCCs for mine wastes, which can be used to predict water levels in mine wastes.; The framework is helpful for the emergency risk assessment of mine wastes under rainstorm and flooding conditions.;

Although the current developed Blu-ray disc-based technology could realize digitized molecular detection, the result analysis of which depends on computer, not applicable for on-site applications. In order to overcome the above challenges, we herein report a quantitative detection system developed by the embedded technology. In particular, through the transplantation of embedded systems and disc quality diagnosis software, and the development of data processing programs, this system realizes the automatic analysis of bio-discs with this integrated device. It has been utilized for the detection of printed ink dots and the biotin-streptavidin binding reaction on BD surface, preving the reliability and feasibility for biomolecular detection.

Detection of uric acid is crucial for real-time monitoring of human health. In this work, a method of portable scanner-based quantitative detection of uric acid with a smartphone was developed, meanwhile, a filter paper chip was designed and fabricated for the detection process, which provides an on-site, fast, and accurate measurement of the uric acid in human blood serum. The limit of detection was 0.8 mg/dL, and the detection results of human serum samples showed good agreement between the spectrophotometric method and the proposed one. This method does not require complex operations or expensive instruments, which is suitable for resource-limited areas, users’ home, as well as on-site detection, with wide applications and broad market prospects.

Bafilomycin A1, a member of macrolide antibiotics and an autophagy inhibitor, serves as a specific and potent V-ATPases inhibitor. Here authors report the cryo-EM structure of bafilomycin A1-bound V-ATPase with six bafilomycin A1 molecules bound to the c-ring and reveal the molecular basis for Bafilomycin A1 inhibition of the V-ATPase.

The current prevailing paradigm in the renin-angiotensin system dictates that most, if not all, biological, physiological, and pathological responses to its most potent peptide, angiotensin II (Ang II), are mediated by extracellular Ang II activating its cell surface receptors. Whether intracellular (or intracrine) Ang II and its receptors are involved remains incompletely understood. The present study tested the hypothesis that extracellular Ang II is taken up by the proximal tubules of the kidney by an AT1 (AT1a) receptor-dependent mechanism and that overexpression of an intracellular Ang II fusion protein (ECFP/Ang II) in mouse proximal tubule cells (mPTC) stimulates the expression of Na+/H+ exchanger 3 (NHE3), Na+/HCO3- cotransporter, and sodium and glucose cotransporter 2 (Sglt2) by AT1a/MAPK/ERK1/2/NF-kB signaling pathways. mPCT cells derived from male wild-type and type 1a Ang II receptor-deficient mice (Agtr1a-/-) were transfected with an intracellular enhanced cyan fluorescent protein-tagged Ang II fusion protein, ECFP/Ang II, and treated without or with AT1 receptor blocker losartan, AT2 receptor blocker PD123319, MEK1/MEK2 inhibitor U0126, NF-кB inhibitor RO 106-9920, or p38 MAP kinase inhibitor SB202196, respectively. In wild-type mPCT cells, the expression of ECFP/Ang II significantly increased NHE3, Na+/HCO3-, and Sglt2 expression (p < 0.01). These responses were accompanied by >3-fold increases in the expression of phospho-ERK1/2 and the p65 subunit of NF-кB (p < 0.01). Losartan, U0126, or RO 106-9920 all significantly attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). Deletion of AT1 (AT1a) receptors in mPCT cells attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). Interestingly, the AT2 receptor blocker PD123319 also attenuated ECFP/Ang II-induced NHE3 and Na+/HCO3- expression (p < 0.01). These results suggest that, similar to extracellular Ang II, intracellular Ang II may also play an important role in Ang II receptor-mediated proximal tubule NHE3, Na+/HCO3-, and Sglt2 expression by activation of AT1a/MAPK/ERK1/2/NF-kB signaling pathways.

Patient engagement in the process of developing a diabetes treatment plan is associated with person-centered care and improved treatment outcomes. The objective of the present study was to evaluate the self-reported patient and parent-centered satisfaction and well-being outcomes associated with the three treatment strategies utilized in a comparative effectiveness trial of technology-enhanced blood glucose monitoring and family-centered goal setting. We evaluated data from 97 adolescent-parent pairs at baseline and 6-months during the randomized intervention. Measures included: Problem Areas in Diabetes (PAID) child and parent scales, pediatric diabetes-related quality of life, sleep quality, and satisfaction with diabetes management. Inclusion criteria were 1) ages 12-18 years, 2) a T1D diagnosis for at least six months and 3) parent/caregiver participation. Longitudinal changes in survey responses were measured at 6 months from baseline. Differences between and within participant groups were evaluated using ANOVA. The average age of youth participants was 14.8 ± 1.6 years with half of the participants being female (49.5%). The predominant ethnicity/race was Non-Hispanic (89.9%) and white (85.9%). We found that youth perceived 1) greater of diabetes-related communication when using a meter capable of transmitting data electronically, 2) increased engagement with diabetes self-management when using family-centered goal setting, and 3) worse sleep quality when using both strategies together (technology-enhanced meter and family-centered goal setting). Throughout the study, scores for self-reported satisfaction with diabetes management were higher in youth than parents. This suggests that patients and parents have different goals and expectations regarding their diabetes care management and care delivery. Our data suggest that youth with diabetes value communication via technology and patient-centered goal setting. Strategies to align youth and parent expectations with the goal of improving satisfaction could be utilized as a strategy to improve partnerships in diabetes care management.

PurposeAge-related macular degeneration (AMD) and retinal vein occlusion (RVO) are irreversible chorioretinal diseases, which might induce severe damage in visual function. The metabolic factor and inflammatory factors might play important roles in the pathogenesis of AMD and RVO. The levels of irisin and 14 cytokines were analyzed in aqueous humor of AMD and RVO eyes to evaluate the roles of irisin and inflammatory factors.MethodsWe collected aqueous humor samples from patients with AMD (n = 27), RVO (n = 30), and cataract (as control, n = 23) eyes. Samples were assayed using ELISA kit for irisin and a multiplex immunoassay kit for 14 cytokines. The macular thickness (MT) was measured with OCT in all included eyes.ResultsMT in the RVO group is significantly higher than that in the AMD or control group. Irisin levels in the aqueous samples of AMD and RVO eyes were both significantly lower than that in the control. Furthermore, a positive correlation was found between irisin and MT in the RVO. Compared with the controls, AMD eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-10, TNF-α, VCAM-1, IP-10, and MCP-1. Similarly, RVO eyes had significantly higher levels of BDNF, VEGF-A, VEGF-R1, VEGF-R2, IL-6, IL-8, IL-10, TNF-α, ICAM-1, VCAM-1, IP-10, and MCP-1. However, there was no significant difference between the levels of PDGF-BB or TNF-β in these three groups. A negative correlation was found between VEGF-A and MT in AMD, as well as in control. Furthermore, a positive correlation was found between IL-6 and MT in the 80 included eyes, as well as in RVO. A positive correlation was found between ICAM-1 and MT in the 80 included eyes, as well as in RVO.ConclusionsThe metabolic factor, irisin levels in the aqueous humor are decreased in AMD and RVO eyes and show a positive correlation between irisin and MT in RVO eyes, prompting researchers to explore the relationship between irisin and macular edema. We also identified the higher expression of vascular growth factors (VEGF-A, VEGF-R1, and PDGF-BB), inflammatory cytokines (IL-6, IL-8, IL-10, and TNF-α), and chemokines (ICAM-1, VCAM-1, IP-10, and MCP-1) in AMD and RVO eyes.

Thermal drawing of glass-cladded metal nanowires is limited by fluid instabilities. Hwang et al. show how admixing tungsten carbide nanoparticles to the zinc core of a borosilicate-cladded wire leads to intact fibres over lengths significantly exceeding those of metals with high melting points.

The vacuolar-type H+ -ATPases (V-ATPase) hydrolyze ATP to pump protons across the plasma or intracellular membrane. Here authors report two cryo-EM structures of the intact V-ATPase from bovine brain with all the subunits including the subunit H, which is essential for ATPase activity.

There is a link between rural-urban remittances and wage inequality. However, the existing literature sheds little light on this topic. In this study, we establish a three-sector general equilibrium model to investigate the effects of rural-urban migrants' remittances on wage inequality. Further, we use Chinese macroeconomic data to calibrate the parameters and conduct analysis with numerical simulation. We find that, when rural-urban migrants raise their remittance rate, wage inequality between skilled labour and the urban formal sector remains unchanged in the sector-specific capital case but narrows in the sector-mobile capital case. Moreover, in the sector-specific case, skilled and unskilled wage inequalities, wSY and wSZ, decrease at the same rate as the urban-rural wage inequalities, wXY and wXZ, respectively. In the mobile case, however, the former declines faster than the latter.

Background: Hypertension (HTN), dyslipidemia and hyperhomocysteinemia (HHcy) are risk factors for cardiovascular disease (CVD). Methods: Hypertensive Chinese subjects (n = 228) were enrolled. MTHFR C667T, MTHFR A1298C, MTR A2756G, and MTRR A66G genotypes were determined. Unconditional logistic regression was performed to determine the associations of serum Hcy status and genotypes with HTN and dyslipidemia. Results: The mean age of hypertensive adults was 65.53 ± 9.94 years, including 88 (38.6%) men and 140 (61.4%) women. Patients with MTHFR 667TT and MTRR GG carriers showed higher serum Hcy levels (P = 0.019 and 0.018, respectively), which is associated with higher serum triacylglycerols (TAG) and total cholesterol (TC) levels (P = 0.014 and 0.044, respectively) and a higher risk for hypertriglyceridemia (OR = 1.889, 95% CI: 1.105–3.229, P = 0.020). Compared with low Hcy and MTRR 66AA, those with high Hcy and 66AA or 66AG+GG showed higher odd\s of hypertriglyceridemia (MTRR 66AA+ high Hcy: OR: 2.692, 95% CI: 1.189–6.096, Pcombined = 0.018; MTRR 66AG/GG+ high Hcy: OR: 3.433, 95% CI: 1.517–7.772, Pcombined = 0.003, respectively). Patients with high Hcy and MTHFR 667CC, as well as those with low Hcy and 667CT+TT, showed lower odds of uncontrolled SBP (MTHFR 667CC+ high Hcy: OR: 0.338, 95% CI: 0.115–0.996, Pcombined = 0.049; MTHFR 667CT/TT+ low Hcy: OR: 0.421, 95% CI: 0.193–0.921, Pcombined = 0.030) compared to patients with low Hcy and MTHFR 667CC. Conclusions: Serum Hcy status and Hcy metabolism gene polymorphisms (MTHFR C667T and MTRR A66G) may have synergistic effects on the prevalence of HTN and dyslipidemia.

Bone is a unique tissue that is capable of repairing itself after damage. However, there are certain instances of fractures and defects that require clinical intervention for proper alignment and healing. As with any implant, careful consideration of the material used to create the implants to treat these problems is needed. If the incorrect material is chosen, the implants themselves can lead to bone fractures or defects, or bone healing may not take place at all. All three classes of biomaterials–metals, ceramics, and polymers–have been used in the treatment of both bone fractures and bone defects, and each has its own unique benefits and limitations for its applications. Furthermore, composites of these different materials have also been created to try to take advantage of all the different benefits offered by each different material. This review highlights different materials that have been used for the development of internal fixators and bone graft substitutes to treat fracture and bone defects as well as their limitations and needed future research.

Niemann-Pick C1 (NPC1) exports low-density-lipoprotein (LDL)-derived cholesterol from lysosomes and comporses a Sterol-Sensing Domain (SSD). Here authors report a cryo-EM structure of human NPC1 bound to itraconazole which reveals how this binding site in the center of NPC1 blocks a putative lumenal tunnel linked to the SSD.

Shaoyao-Gancao Decoction (SGD) is a well-known classic traditional Chinese medicine (TCM) with antispasmodic, anti-inflammatory, and analgesic effects. This preparation has been widely used to treat spasticity diseases in the clinic. To date, the material basis of SGD remains unclear, and the spectrum-effect correlation of its antispasmodic activity has not been reported yet. In this study, high-performance liquid chromatography (HPLC) was used to establish the fingerprint and determine the multiple components of SGD. The common peaks of fingerprints were evaluated by the similarity with the chromatographic fingerprints of the TCM. Meanwhile, the multiple components were quantified and analysed using the heatmap and box size analysis. Furthermore, data on the antispasmodic effect were extracted through in vitro smooth muscle contraction assay. Grey relational analysis combined with partial least square regression was used to study the spectrum–effect correlation of SGD. Finally, the potential antispasmolytic components were validated using an isolated tissue experiment. The HPLC fingerprint was established, and 20 common peaks were identified. The similarities of 15 batches of SGD were all above 0.965. The HPLC method for simultaneous determination of the multiple components was accurate and reliable. The contents of albiflorin, paeoniflorin, liquiritin, and glycyrrhizic acid were higher than the other components in SGD. The heatmap and box size also showed that X3 (albiflorin), X4 (paeoniflorin), X5 (liquiritin), X11 (liquirtigenin), and X16 (glycyrrhizic acid) could be used as quality indicators in the further establishment of quality standards. The spectrum–effect correlation results indicated that X4, X11, and X16 were highly correlated with antispasmolytic activity. Verification tests showed that paeoniflorin (11.7–29.25 μg/mL) and liquirtigenin (17.19–28.65 μg/mL) could significantly reduce the maximum contractile (P

In this paper, we concern with the split feasibility problem (SFP) whenever the convex sets involved are composed of level sets. By applying Gradient-projection algorithm which is used to solve constrained convex minimization problem of a real valued convex function, we construct two new algorithms for the split feasibility problem and prove that both of them are convergent weakly to a solution of the feasibility problem. In the end, as an application, we obtain a new algorithm for solving the split equality problem.

In order to study the construction effect of deep and large foundation pit excavation and its impact on the surrounding environment under complex stratum conditions, the deep and large foundation pit of the top-down construction method of shield exit shaft of S2 line of Wenzhou City railway is taken as the research object in this paper. According to the complex geological conditions of deep soft soil layer with underlying inclined rock surface in Wenzhou, the numerical simulation method is used to carry out the related research. The simulation results of the deformation characteristics of the diaphragm wall under two different working conditions which are the same length diaphragm wall and the suspended foot diaphragm wall are compared and analyzed. According to the analysis results, the suspended foot diaphragm wall is determined as the final construction scheme of the diaphragm wall, and it is verified by field measurement. The research results can provide technical support for the construction of similar projects. At the same time, it can also provide basic accumulation for the construction of major projects in Wenzhou.