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Bioactive peptides were prepared from Undaria pinnatifida sporophyll by bionic enzymatic hydrolysis. Response surface methodology (RSM) was used to optimize the enzymatic hydrolysis process based on single factor test with the polypeptide yield and degree of hydrolysis as the main indexes, and the scavenging ability of polypeptide on three free radicals (DPPH, ABTS, OH) was evaluated. The results showed that the optimal conditions of biomimetic enzymatic hydrolysis were as follows: Ultrasonic power 720 W, ultrasonic wall breaking time 40 min, solid-liquid ratio 1:104 g/mL, pepsin dosage 6.1%, enzymatic hydrolysis time 2.5 h, trypsin dosage 5%, enzymatic hydrolysis time 3 h. Under these conditions, the polypeptide yield was 21.17% and the degree of hydrolysis was 43.07%. Enzymatic peptide had good scavenging effects on DPPH, ABTS and OH radicals with IC50 values of 5.71, 1.31 and 1.35 mg/mL, respectively. The optimized bionic enzymatic hydrolysis process of Undaria pinnatifida sporophyll was reasonable and feasible, and the enzymatic peptide had good free radical scavenging ability, indicating that the enzymatic peptide had good antioxidant activity and could be used as ingredients in the development of functional food.

Background: Transcranial electrical stimulation (TES) is broadly investigated as a therapeutic technique for a wide range of neurological disorders. The electric fields induced by TES in the brain can be estimated by computational models. A realistic and volumetric approach to simulate TES (ROAST) has been recently released as an open-source software package and has been widely used in TES research and its clinical applications. Rigor and reproducibility of TES studies have recently become a concern, especially in the context of computational modeling. Methods: Here we reviewed 94 clinical TES studies that leveraged ROAST for computational modeling. When reviewing each study, we pay attention to details related to the rigor and reproducibility as defined by the locations of stimulation electrodes and the dose of stimulating current. Specifically, we compared across studies the electrode montages, stimulated brain areas, achieved electric field strength, and the relations between modeled electric field and clinical outcomes. Results: We found that over 1800 individual heads have been modeled by ROAST for more than 30 different clinical applications. Similar electric field intensities were found to be reproducible by ROAST across different studies at the same brain area under same or similar stimulation montages. Conclusion: This article reviews the use cases of ROAST and provides an overview of how ROAST has been leveraged to enhance the rigor and reproducibility of TES research and its applications.

In this study, Hsu et al. show that inhibition of CDK7/12/13 attenuates maladaptive transcriptional activation in cultured cardiomyocytes and a mouse model of heart failure, suggesting that targeting the transcription machinery might be a therapeutic approach to treat heart failure with reduced ejection fraction.

In this work, the inhomogeneous residual stress distribution and evolution of thick plate in single-pass full penetration laser welding are systematically investigated using phase transformation model. The material constitutive model considering solid-state phase transformation according to the actual weld microstructure is proposed to predict the inhomogeneous stress distribution of the welded joint. The inhomogeneous stress distributions along the longitudinal, transverse and thickness direction surfaces of the welded joint are systematically analyzed and deeply discussed, respectively. The results show that there is an obvious inhomogeneous distribution of the temperature field between the start-welding, middle section and end-welding position of the weld. It is obviously observed that the top and bottom surfaces of welded joint produce remarkably high stress areas and high stress gradients. The maximum longitudinal and transverse stress gradient values in the top surface are up to 1240.1 MPa and 1175.7 MPa, respectively. It is found that martensitic transformation is the main reason for the inhomogeneous stress distribution including high stress areas and high stress gradients in thick plate welded joint. The current research is beneficial to reduce the detrimental effects of welding-induced inhomogeneous residual stress on thick plate welded joints.

In this paper, a flow stress model of ultra-high-strength steel 1700MS was developed for laser welding. The model considered the material behaviors of strain hardening, temperature sensitivity, and annealing. The prediction yield strengths had good accordance with the experimental results. The effects of the three behaviors on welding stresses were studied through four calculation cases. The results showed that the behaviors should all be taken into account and there was a reasonable agreement between the predicted and measured stresses. In addition, the stress evolution process of each case was analyzed through the temperature-dependent curves of variables. The variables contained the accumulated plastic strain, deviatoric stress tensor, plastic strain, trial stress, and actual stress used in the stress updating process. It was found the behaviors could change the yield strength used in each case. The temperature sensitivity and annealing increased the possibility of plastic deformation, while the strain hardening decreased and thus gave rise to different stress updating rules.

A356-SiCp/A356 cladding composite materials were prepared by vacuum solid–liquid casting. The interfacial bonding, microstructure, and mechanical properties of this cladding composite material were investigated. The microstructures indicated that there was a good metallurgical combination interface between A356 and SiCp/A356 of the cladding composite material. The tensile tests showed that the bonding strength of the interface was lower than that of the two materials, but fracture occurred on the A356 side as the macrointerface perpendicular to load, while the tensile strength of A356 was higher than that of the cladding composite material. This fracture phenomenon could be explained by the remelt mechanism and grain coarsing mechanism. As a result of the topmost layer of the A356 alloy in contact with the SiCp/A356 composite slurry being remelted when the SiCp/A356 composite slurry was poured, an inseparable metallurgical combination interface was formed, and α-Al grains and eutectic Si on the A356 side near the interface were coarser than those on the interface. The results of this research can provide a reference for manufacturing automotive brake discs with cladding composite materials.

Abstract Background Vanishing bile duct syndrome (VBDS) is a rare but potentially severe acquired chronic cholestatic liver disease. Bile duct deficiency is a reduction of bile ducts in the liver, which can eventually lead to cholestatic liver disease and progress to biliary cirrhosis. Primary biliary cholangitis (PBC) is one of the causes of bile duct deficiency. In addition, 75% of PBC patients may have dyslipidemia, and in case of secondary dyslipidemia, cutaneous xanthomas may occur. Case summary A 49-year-old woman was admitted with jaundice and multiple subcutaneous nodules. She received diagnosis of autoimmune liver disease 2 years before. Although she was treated with liver-protecting drugs, such as Essentiale and ursodeoxycholic acid, jaundice occurred repeatedly, and the color of her skin was becoming darker and more yellow. Conclusion This case highlights that the positivity of ANA that in PBC have a well diagnostic and prognostic significance and antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim-like/membranous’ pattern scan ca diagnose primary biliary cirrhosis accurately. Since the liver biopsy of PBC alone may not be sufficient to establish the diagnosis, serum antibodies should also be examined. PBC can also lead to intrahepatic cholestasis, which can cause dyslipidemia and cutaneous xanthomas.

IntroductionDuck circovirus (DuCV) infection is currently recognized as an important immunosuppressive disease in commercial duck flocks in China. Specific antibodies against DuCV viral proteins are required to improve diagnostic assays and understand the pathogenesis of DuCV infection.Methods and resultsTo generate DuCV-specific monoclonal antibodies (mAbs), a recombinant DuCV capsid protein without the first 36 N-terminal amino acids was produced in Escherichia coli. Using the recombinant protein as an immunogen, a mAb was developed that reacted specifically with the DuCV capsid protein, expressed in E. coli and baculovirus systems. Using homology modeling and recombinant truncated capsid proteins, the antibody-binding epitope was mapped within the region of 144IDKDGQIV151, which is exposed to solvent in the virion capsid model structure. To assess the applicability of the mAb to probe the native virus antigen, the murine macrophage cell line RAW267.4 was tested for DuCV replicative permissiveness. Immunofluorescence and Western blot analysis revealed that the mAb recognized the virus in infected cells and the viral antigen in tissue samples collected from clinically infected ducks.DiscussionThis mAb, combined with the in vitro culturing method, would have widespread applications in diagnosing and investigating DuCV pathogenesis.

Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, plays a critical role in the host antiviral response. However, the mechanism and antiviral spectrum of TRIM21 in influenza A virus (IAV) remain unclear. Here, we report that TRIM21 inhibits the replication of various IAV subtypes by targeting matrix protein 1 (M1) from H3/H5/H9, but not H1 and H7 M1. Mechanistically, TRIM21 binds to the residue R95 of M1 and facilitates K48 ubiquitination of M1 K242 for proteasome-dependent degradation, leading to the inhibition of H3, H5, and H9 IAV replication. Interestingly, the recombinant viruses with M1 R95K or K242R mutations were resistance to TRIM21 and exhibited more robust replication and severe pathogenicity. Moreover, the amino acid sequence M1 proteins, mainly from avian influenza such as H5N1, H7N9, H9N2, ranging from 1918 to 2022, reveals a gradual dominant accumulation of the TRIM21-driven R95K mutation when the virus jumps into mammals. Thus, TRIM21 in mammals' functions as a host restriction factor and drives a host adaptive mutation of influenza A virus.

BackgroundThe coexistence of Crohn's disease (CD) and acute appendicitis (AA) is rare. In this situation, therapeutic experience is lacking and the strategy is paradoxical and intractable. Appendectomy is the gold standard for the treatment of AA whereas a nonsurgical approach is recommended for CD.Case summaryA 17-year-old boy was hospitalized for right lower abdominal pain with fever of 3 days. He had the CD for 8 years. Two years ago, he underwent surgery for anal fistula with the complication of CD. His temperature was elevated at 38.3°C at admission. On physical examination, there was McBurney tenderness with mild rebound tenderness. Abdominal ultrasonography showed that the appendix was notably enlarged and dilated at 6.34 cm long and 2.76 cm wide. These findings were suggestive of uncomplicated AA in this patient with active CD. Endoscopic retrograde appendicitis therapy (ERAT) was performed. The patient had complete pain relief immediately after the procedure without tenderness in the right lower abdomen. During 18 mo follow-up, he had no more attacks in his right lower abdomen.ConclusionERAT was effective and safe in a CD patient with coexisting AA. Such cases can avoid surgery and its-related complications.

Perivascular adipose tissue (PVAT) refers to the aggregate of adipose tissue surrounding the vasculature, exhibiting the phenotypes of white, beige and brown adipocytes. PVAT has emerged as an active modulator of vascular homeostasis and pathogenesis of cardiovascular diseases in addition to its structural role to provide mechanical support to blood vessels. More specifically, PVAT is closely involved in the regulation of reactive oxygen species (ROS) homeostasis and inflammation along the vascular tree, through the tight interaction between PVAT and cellular components of the vascular wall. Furthermore, the phenotype-genotype of PVAT at different regions of vasculature varies corresponding to different cardiovascular risks. During ageing and obesity, the cellular proportions and signaling pathways of PVAT vary in favor of cardiovascular pathogenesis by promoting ROS generation and inflammation. Physiological means and drugs that alter PVAT mass, components and signaling may provide new therapeutic insights in the treatment of cardiovascular diseases. In this review, we aim to provide an updated understanding towards PVAT in the context of redox regulation, and to highlight the therapeutic potential of targeting PVAT against cardiovascular complications.

BackgroundA series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.MethodsWe incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.ResultsTotal 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m2).ConclusionIn all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

BackgroundThe field of view (FOV) considered in MRI-guided forward models of electroconvulsive therapy (ECT) are, as expected, limited to the MRI volume collected. Therefore, there is variation in model extent considered across simulation efforts. This study examines the impact of FOV on the induced electric field (E-field) due to two common electrode placements: right unilateral (RUL) and bilateral (BL).MethodsA full-body dataset was obtained and processed for modeling relevant to ECT physics. Multiple extents were derived by truncating from the head down to four levels: upper head (whole-brain), full head, neck, and torso. All relevant stimulation and focality metrics were determined. The differences in the 99th percentile peak of stimulation strength in the brain between each extent to the full-body (reference) model were considered as the relative error (RE). We also determine the FOV beyond which the difference to a full-body model would be negligible.ResultsThe 2D and 3D spatial plots revealed anticipated results in line with prior efforts. The RE for BL upper head was ~50% reducing to ~2% for the neck FOV. The RE for RUL upper head was ~5% reducing to subpercentage (0.28%) for the full-head FOV. As shown previously, BL was found to stimulate a larger brain volume—but restricted to the upper head and for amplitude up to ~480 mA. To some extent, RUL stimulated a larger volume. The RUL-induced volume was larger even when considering the neural activation threshold corresponding to brief pulse BL if ECT amplitude was >270 mA. This finding is explained by the BL-induced current loss through the inferior regions as more FOV is considered. Our result is a departure from prior efforts and raises questions about the focality metric as defined and/or inter-individual differences.ConclusionOur findings highlight that BL is impacted more than RUL with respect to FOV. It is imperative to collect full-head data at a minimum for any BL simulation and possibly more. Clinical practice resorts to using BL ECT when RUL is unsuccessful. However, the notion that BL is more efficacious on the premise of stimulating more brain volume needs to be revisited.

Electrocatalytic upgrading of 5-hydroxymethylfurfural (HMF) provides a promising way to obtain both high-value-added biomass-derived chemicals and clean energy. However, development of efficient electrocatalysts for oxidizing HMF with depressed side reactions remains a challenge. Herein, we report a nickel-phytic acid hybrid (Ni-PA) using natural phytic acid as building block for highly efficient electrocatalytic oxidation of HMF to 2, 5-furandicarboxylic acid (FDCA). Due to the coordination of nickel ion and phosphate groups of phytic acid molecule, high selectivity and yield of FDCA were achieved at 1.6 V vs. RHE. Besides, Ni-PA has a higher electrochemical surface area and lower charge-transfer resistance than Cu/Fe-PA, which significantly promotes the oxidation of HMF to FDCA. This work demonstrates the potential of metal-phytic acid hybrids as effective electrocatalysts for biomass valorization.

Background Left ventricular mass index (LVMI) has been extensively studied for its relationship with mortality but has been typically assessed at a single time point. We, therefore, describe the trajectory of LVMI in a population with hypertension over 6 years to study the subsequent risk of mortality. Methods and Results We assessed LVMI that was collected during annual health examinations in round 1 (2010–2012), round 2 (2013–2014), and round 3 (2015–2016) with 2 allometric scalings, height2.7, and body surface area, in a cohort of participants with hypertension to identify 6‐year trajectories of LVMI by latent class trajectory modeling. We followed up with participants for mortality by latent trajectory from the last echocardiographic examination (September 17, 2014–December 8, 2016) to December 31, 2018. We calculated mortality hazard ratios by assigned trajectory using Cox proportional hazards models. We obtained data for LVMI from 2453 participants (mean age, 61.80 [SD, 12.14] years, 1428 [58.2%] female). We identified 3 trajectories of LVM/H2.7, characterized by maintained low stable (1298 [52.9%]); moderate stable (935 [38.1%]); high stable (220 [9.0%]), as well as 3 trajectories by LVM/body surface area. During a median follow‐up of 2.15 years, 167 participants developed all‐cause mortality, and 71 were cardiovascular mortality. Only the high stable trajectory was associated with a higher risk of all‐cause mortality compared with the low stable trajectory by LVM/H2.7 or LVM/body surface area (all P

Objective: Dietary intake of fruit is associated with lower incidence of hypertension and cardiovascular risk. Papaya is a kind of delicious fruit and reported has dietary therapeutic effects, such as digestive stimulation and hypotensive efficacy. However, the mechanism of pawpaw involved have not been elucidated. Here, we illustrate that the effect of pawpaw on the gut microbiota and the prevention of cardiac remodeling. Methods: Gut microbiome, cardiac structure/function, and blood pressure were examined in SHR and WKY groups. The intestinal barrier was tested with histopathologic; immunostaining and Western blot were used to measure the tight junction protein level; Gpr41 was tested by RT-PCR, and inflammatory factors were detected with ELISA. Results: We observed a significant decrease in microbial richness, diversity, and evenness is the spontaneously hypertensive rat (SHR), in addition to an increased Firmicutes/Bacteroidetes (F/B) ratio. These changes were accompanied by decreased in acetate and butyrate-producing bacteria. Compared with SHR, treatment with pawpaw at the dosage of 10 g/kg for 12 weeks significantly reduced the blood pressure, cardiac fibrosis and cardiac hypertrophy, while the ratio of F/B decreased. We also found that the concentration of short-chain fatty acids (SCFAs) was increased in SHR fed with pawpaw compared with that in control group, while the gut barrier was restored and level of proinflammatory cytokines in the serum were decreased. Conclusions: Pawpaw, rich of high fiber, led to changes in the gut microbiota that played a protective role in the development of cardiac remodeling. The potential mechanism of pawpaw may explained by the generation of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate, increasing tight junction protein level occluding to enhance the gut barrier for less releasing the inflammation cytokines, and upregulating G-protein-coupled receptor 41 (GPR41) to reduce blood pressure.

The concept of resilience has been extensively investigated for various systems to assess and reduce risk in dynamic environments. However, universal rainfall-resilient design criteria for artificially designed and naturally shaped slope systems have rarely been considered. This study proposes a novel methodology for implementing rainfall-resilient design for the slope system under rainfall. This approach incorporates the resilience design philosophy and the stability analysis of the slope system under rainfall. The stability analysis is solved by combining saturated–unsaturated seepage analysis and the Morgenstern–Price method. A design-oriented resilient criterion, including absorption and recovery measures, is proposed for the sound design of the slope system. An illustrative case of rainfall-resilient design for the slope system in the coastal area of Southeast China is presented. The spatial variability of geomaterial properties is considered to identify critical time points for recovery strategies. The resilience characteristics containing the absorption capacity, restorative capacity, and recovery time of eight restorative strategies for the resilience enhancement of the slope system were analyzed. The traditional design criteria were considered for comparison to verify the effectiveness of the proposed rainfall-resilient design method. The rainfall-resilient design can provide critical support to landslide mitigation in the coastal area of Southeast China.

An earth dam in service is a complex system that has different dynamic failure modes under different ground motion excitations with a certain correlation between the different failure modes. However, because of the nonlinear dynamic coupling effect of the randomness of the earthquake ground motion and the nonlinearity of the geotechnical parameters, traditional deterministic analyses cannot adequately consider the failure mechanisms of earth rock dams subjected to earthquake excitation, resulting in unexpected and uncontrollable local failure modes or weak failure areas; this makes the seismic dynamic performance of earth rock dams subjected to strong earthquake excitation non-optimal. Accordingly, the main dynamic failure modes and failure mechanisms of earth rock dams under seismic dynamic action are studied based on the nonlinear stochastic dynamics method and the first passage theory, combined with a time-domain nonlinear dynamic time-history analysis. Our results indicate that the seismic dynamic reliability of earth dam under ground motion excitation is far less than that under different single failure modes. Seismic reinforcement or heightening measures based on the overall seismic dynamic reliability can be used to effectively resist strong earthquake disasters encountered by earth rock dams in the future and optimize the seismic dynamic performance of earth rock dams.

Objective and design: An experimental rat allergic rhinitis(AR) model was made to explore the effect of different concentrations of ozone exposure and evaluate the roles of nuclear factor erythroid 2-related factor 2(Nrf2) and oxidative stress in ozone exposure. Method: Sprague-Dawley rats were sensitized with ovalbumin (OVA). Three groups of AR rats were exposed respectively to different concentrations of ozone for 2 h on 6 weeks. Nasal symptoms and OVA- specific Ig E in the serum were evaluated. The pathological changes in the nasal mucosa were examined. Malondialdehyde (MDA) level and activity of superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px,GPX) in the nasal mucosa tissue were measured through a spectrophotometry-based method. Nrf2、Kelch-1ike ECH- associated protein-l (Keap1) proteins was measured by western blotting. GPX1、GPX2 mRNA were detected by quantitative real time-PCR(qRT-PCR). Results: Our results showed that ozone exposure induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum of AR model. Ozone effected oxidative stress in different concentration. The content of MDA in AREH group was significantly higher than AR groups. The activities of SOD and GSH-Px in nasal mucosa showed different trends in different concentration groups. The activities of SOD and GSH-Px in AREL and AREM groups were higher than AR group, but decreased at AREH group. The nucleoprotein level of Nrf2 in AREL and AREM groups was higher than AR groups. However, in AREH group, it was significantly decreased, compared with AREL and AREM groups. GPX1 and GPX2 mRNA levels in nasal mucosa showed the same trend in different exposure groups. Conclusions: Different concentrations of ozone inhalation causes changes of the expression of Nrf2 nuclear protein and its target genes in nasal mucosa of AR. High concentration ozone breaks the redox balance and aggravates oxidative damage in AR. This study suggests that inhibiting oxidative stress might be a solution for ozone-elicited detrimental effects on AR.

Anchored piles are an important combined supporting structure and widely used in landslide prevention and control. The calculation of the internal force of a pile-anchor is highly significant. In this paper, we propose a modified deformation coordination model to more accurately calculate the internal force of anchored piles based on a simple analysis model originally developed by (Qu et al. 2016). In the modified deformation coordination model, the pile-anchor interaction is divided into two stages: (1) prestressed anchor cable application stage; and (2) landslide thrust action stage. The anchor cable deformation is taken as the sum of the free section and anchorage section. A deformation coordination equation is established based on the unification of the horizontal pile displacement and anchor cable deformation at the junction of the pile and anchor cable. The anchor cable tensile stress calculation formula is then obtained by combining the virtual work principle and graph multiplication theory in structural mechanics. An engineering case study of a pile with double-row anchor cables is tested to compare the results obtained using the traditional model and Chinese codes, which demonstrates the capability of the proposed model to calculate the internal force of anchored piles.

Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids. In this paper, we report the discovery of 13 novel BRICHOS-related peptides, ranging from 18 to 91 amino acid residues in length, in the cosmopolitan marine worm Heteromastus filiformis with the assistance of transcriptome mining. Two characteristic peptides with a low homology in relation to known AMPs—the α-helical amphiphilic linear peptide, consisting of 28 amino acid residues and designated as HfBRI-28, and the 25-mer β-hairpin peptide, specified as HfBRI-25 and having a unique structure stabilized by two disulfide bonds—were obtained and analyzed as potential antimicrobials. Interestingly, both peptides showed the ability to kill bacteria via membrane damage, but mechanisms of their action and spectra of their activity differed significantly. Being non-cytotoxic towards mammalian cells and stable to proteolysis in the blood serum, HfBRI-25 was selected for further in vivo studies in a lethal murine model of the Escherichia coli infection, where the peptide contributed to the 100% survival rate in animals. A high activity against uropathogenic strains of E. coli (UPEC) as well as a strong ability to kill bacteria within biofilms allow us to consider the novel peptide HfBRI-25 as a promising candidate for the clinical therapy of urinary tract infections (UTI) associated with UPEC.

Microbially induced calcite precipitation (MICP) is a promising, more eco-friendly alternative method for landslide prevention and foundation reinforcement. In this study, we investigated the optimization of injection methods within the MICP process in porous media to enhance calcite mass and consolidation effect. The results demonstrated that staged injections with considerable advantages significantly improved precipitated calcite mass by 23.55% compared with continuous injection methods. However, extended retention times in staged injections reduced reinforcement effects. Moreover, setting the additional time in all injection methods can improve the consolidation area and effect without added injections. Apart from the injection methods, the changes in porosity and substance concentration also directly affected calcite masses and the reinforcement effect. Both the total calcite mass and the reinforcement effect should be taken into account when selecting appropriate injection methods. In terms of influencing factors on the total calcite mass, substance concentration ≫ average porosity ≫ additional time > retention time in staged injection. For the consolidation effect, substance concentration ≫ retention time in staged injection > average porosity ≫ additional time. The 5 h retention time in staged injections was recommended as the optimum injection method in the geotechnical conditions for average porosity from 0.25 to 0.45, with the changes in different reactant concentrations.

Cassava (Manihot esculenta Crantz) is a major tuber crop worldwide, but its mechanized harvesting is inefficient. The digging–pulling cassava harvester is the primary development direction of the cassava harvester. However, the harvester clamping–pulling mechanism cannot automatically adjust its position relative to the stalks in forward movement, which results in clamping stalks with a large off-center distance difficulty, causing large harvest losses. Thus, solving the device’s clamping location problem is the key to loss reduction in the harvester. To this end, this paper proposes a real-time detection method for field stalks based on YOLOv4. First, K-means clustering is applied to improve the consistency of cassava stalk detection boxes. Next, the improved YOLOv4 network’s backbone is replaced with MobileNetV2 + CA, resulting in the KMC-YOLO network. Then, the proposed model’s validity is demonstrated using ablation studies and comparison tests. Finally, the improved network is embedded into the NVIDIA Jetson AGX Xavier, and the model is accelerated using TensorRT, before conducting field trials. The results indicate that the KMC-YOLO achieves average precision (AP) values of 98.2%, with detection speeds of 33.6 fps. The model size is reduced by 53.08% compared with the original YOLOv4 model. The detection speed after TensorRT acceleration is 39.3 fps, which is 83.64% faster than before acceleration. Field experiments show that the embedded model detects more than 95% of the time at all three harvest illumination levels. This research contributes significantly to the development of cassava harvesters with intelligent harvesting operations.

Photocatalytic NO removal is usually accompanied by the generation of NO2, an intermediate with a higher toxicity than NO. Therefore, it is critically important to develop new photocatalysts capable of NO selective conversion. Herein, we report on the synergistic roles of cyano and hydroxyl functional groups in photocatalytic NO removal. According to the results, the NO2 production efficiencies on cyano/hydroxyl-group-modified g-C3N4 (DCN-O-R) was limited to 4.8%, which was lower than that of cyano-group-modified g-C3N4 (DCN, 38.6%) and pure g-C3N4 (CN, 50.0%). Meanwhile, the photocatalytic NO conversion efficiency over DCN-O-R was higher than that of DCN and g-C3N4. It was found that the insertion of cyano groups favorably changes the energy band of g-C3N4 towards the generation of •O2−. NO can only be oxidized to NO2 by the photogenerated holes. When NO2 is adsorbed on the surface of hydroxyl groups, it can be further oxidized to the product NO3− by •O2−. The synergistic effect of bifunctional groups regulates the conversion pathway from NO→NO2 to NO→NO2→NO3−. This work provides a strategy to abate toxic intermediates during the NO removal process, underlining the importance of surface/interface molecular engineering in regulating catalytic reaction pathways.

The semiconductor industry is one of the most technology-evolving and capital-intensive market sectors. Effective inspection and metrology are necessary to improve product yield, increase product quality and reduce costs. In recent years, many types of semiconductor manufacturing equipments have been equipped with sensors to facilitate real-time monitoring of the production processes. These production-state and equipment-state sensor data provide an opportunity to practice machine-learning technologies in various domains, such as anomaly/fault detection, maintenance scheduling, quality prediction, etc. In this work, we focus on the soft-sensing regression problem in metrology systems, which uses sensor data collected during wafer processing steps to predict impending inspection measurements that used to be measured in wafer inspection and metrology systems. We proposed a regressor based on Long Short-term Memory network and devised two distinct loss functions for the purpose of the training model. Although the assessment of our prediction errors by engineers is subjective, a novel piece-wise evaluation metric was introduced to evaluate model accuracy in a mathematical way. Our experimental results showcased that the proposed model is capable of achieving both accurate and early prediction across various types of inspections in complicated manufacturing processes.

As a common engineering practice, the buildings are usually evaluated under the Typical Meteorological Year (TMY), which represents the common weather situation. The warm and cool conditions, however, can affect the building performance considerably, yet building performances under such conditions cannot fully be given by the conventional TMY. This paper gives approaches to constructing the weather data that represents several warm and cool conditions and compares their differences by studying the cumulative cooling demands of a typical building in a hot and humid climate. Apart from the Extreme Weather Year (EWY), the Near-Extreme Weather Year (NEWY) and Common warm/cool Years (CY) data are proposed according to the occurrence distributions of the weather over the long term. It was found that the cooling demands of NEWY and EWY differ by 4.8% from the cooling needs of TMY. The difference between the cooling demands of NEWY and CY for most calendar months can be 20% and 15%, respectively. For the hot months, the cooling demands under NEWY and CY take 7.4–11.6% and 2.3–5.6% differences from those under TMY. The uncertainties of building performance due to the ever-changing weather conditions can be essential to the robustness of building performance evaluations.

Abstract Background The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion. Methods A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0. Results Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference = − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023). Conclusions The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG.

Abstract Background Little is known regarding life-course trajectories of important diseases. We aimed to identify diseases that were strongly associated with mortality and test temporal trajectories of these diseases before mortality. Methods Our analysis was based on UK Biobank. Diseases were identified using questionnaires, nurses’ interviews, or inpatient data. Mortality register data were used to identify mortality up to January 2021. The association between 60 individual diseases at baseline and in the life course and incident mortality was examined using Cox proportional regression models. Those diseases with great contribution to mortality were identified and disease trajectories in life course were then derived. Results During a median follow-up of 11.8 years, 31,373 individuals (median age at death (interquartile range): 70.7 (65.3–74.8) years, 59.4% male) died of all-cause mortality (with complete data on diagnosis date of disease), with 16,237 dying with cancer and 6702 with cardiovascular disease (CVD). We identified 37 diseases including cancers and heart diseases that were associated with an increased risk of mortality independent of other diseases (hazard ratio ranged from 1.09 to 7.77). Among those who died during follow-up, 2.2% did not have a diagnosis of any disease of interest and 90.1% were diagnosed with two or more diseases in their life course. Individuals who were diagnosed with more diseases in their life course were more likely to have longer longevity. Cancer was more likely to be diagnosed following hypertension, hypercholesterolemia, CVD, or digestive disorders and more likely to be diagnosed ahead of CVD, chronic kidney disease (CKD), or digestive disorders. CVD was more likely to be diagnosed following hypertension, hypercholesterolemia, or digestive disorders and more likely to be diagnosed ahead of cancer or CKD. Hypertension was more likely to precede other diseases, and CKD was more likely to be diagnosed as the last disease before more mortality. Conclusions There are significant interplays between cancer and CVD for mortality. Cancer and CVD were frequently clustered with hypertension, CKD, and digestive disorders with CKD highly being diagnosed as the last disease in the life course. Our findings underline the importance of health checks among middle-aged adults for the prevention of premature mortality.

Abstract Background The study carries the aim to compare the clinical efficacy and economic outcomes of using barbed suture closure versus conventional closure for wounds after posterior long-segment lumbar surgery. Methods One hundred and eighty-one patients undertaking posterior long-segment lumbar surgery participated in the prospective randomized controlled trial study to receive either barbed suture wound closure (n = 91) or conventional suture closure (n = 90). Outcome measures included operating room time (ORT), wound closure time, length of incision, length of hospital stay (LOS), 90-day readmission rates, wound complications of dehiscence and infection, and costs. Results Barbed suture group was related with significantly lower ORT (P = 0.036), wound closure time (P

Abstract Leaves and flowers of Amorphophallus konjac do not develop simultaneously thus unique features can be elucidated through study of flowering transformation in A. konjac. In this study, transcriptome libraries of A. konjac leaf buds (LB) and flower buds (FB) were constructed followed by high-throughput sequencing. A total of 68,906 unigenes with an average length of 920 bp were obtained after library assembly. Out of these genes, 24,622 unigenes had annotation information. A total of 6859 differentially expressed genes (DEGs) were identified through differential expression analysis using LB as control. Notably, 2415 DEGs were upregulated whereas 4444 DEGs were downregulated in the two transcriptomes. Go and KEGG analysis showed that the DEGs belonged to 44 functional categories and were implicated in 98 metabolic pathways and 38 DEGs involved in plant hormone signal transduction. Several genes were mined that may be involved in A. konjac flower bud differentiation and flower organ development. Eight DEGs were selected for verification of RNA-seq results using qRT-PCR analysis. Two FLOWERING LOCUS T (FT) genes named AkFT1 and AkFT2 were identified though homologous analysis may be the florigen gene implicated in modulation of A. konjac flowering. These genes were significantly upregulated in flower buds compared with the expression levels on leaf buds. Overexpression of AkFT genes though heterologous expression in Arabidopsis showed that the transgenics flowered at a very early stage relative to wild type plants. These findings indicate that AkFT1 and AkFT2 function as regulation genes in A. konjac flowering development and the two genes may present similar functions during flowering transition.

Glutenite (coarse-grained clastic) reservoirs of intergranular–secondary dissolution pore type are dominated by residual intergranular pores and secondary dissolution pores, and characterized by low porosity, low permeability, strong heterogeneity, and highly variable physical properties. It is difficult to conduct a quantitative quality assessment of these reservoirs while their primary control factors remain unclear. In this paper, experimental core data and drilling, logging and seismic data are used to assess the effect of sedimentary facies on reservoir quality. Favorable sedimentary facies zones are identified by analyzing the characteristics of glutenite reservoirs, which includes investigating rock components and their effects on reservoir quality. Argillaceous matrix content and rigid particle content are identified as the primary control factors for these reservoirs. Logging curves sensitive to reservoir quality are selected and examined to continuously characterize the physical parameters of the reservoirs. It establishes a calculation model of reservoir assessment parameters through multivariate regression and determines the quantitative assessment parameter Fr. The quality of the glutenite reservoirs is defined using conventional logging curves. This study also predicts the plane distribution of high-quality reservoirs through geostatistical inversion of the reservoir assessment parameters based on conventional wave impedance inversion, thus providing insight and guidance for quantitative assessment and quality prediction of glutenite reservoirs of the intergranular-secondary dissolution pore type. The application of this method to well deployment based on qualitative evaluation of the glutenite reservoirs in oilfields yielded favorable results.

The mixed infection of duck Tembusu virus (DTMUV) and goose astrovirus (GoAstV) is an important problem that endangers the goose industry. Although quantitative PCR has been widely used in monitoring these two viruses, there is no reliable method to detect them at the same time. In this study, by analyzing the published genomes of DTMUV and goose astrovirus genotype 2 (GoAstV-2) isolated in China, we found that both viruses have high conservation, showing 96.5 to 99.5% identities within different strains of DTMUV and GoAstV, respectively. Subsequently, PCR primers and TaqMan probes were designed to identify DTMUV and GoAstV-2, and different fluorescent reporters were given to two probes for differential diagnosis. Through the optimization and verification, this study finally developed a duplex TaqMan qPCR method that can simultaneously detect the above two viruses. The lower limits of detection were 100 copies/μL and 10 copies/μL for DTMUV and GoAstV-2 under optimal condition. The assay was also highly specific in detecting one or two viruses in various combinations in specimens, and provide tool for clinical diagnosis of mixed infections of viruses in goose.

BackgroundDiversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. The colonscopic score is a good tool for differentiating the severity of patients with DC. At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora.MethodsRetrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups.ResultsIn retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P

Summary: Beige adipocytes are thermogenic with high expression of uncoupling protein 1 in the white adipose tissue (WAT), accompanied by angiogenesis. Previous studies showed that Smad4 is important for angiogenesis. Here we studied whether endothelial Smad4-mediated angiogenesis is involved in WAT beiging. Inducible knockout of endothelial cell (EC) selective Smad4 (Smad4iEC-KO) was achieved by using the Smad4Floxp/floxp and Tie2CreERT2 mice. Beige fat induction achieved by cold or adrenergic agonist, and angiogenesis were attenuated in WAT of Smad4iEC-KO mice, with the less proliferation of ECs and adipogenic precursors. RNA sequencing of human ECs showed that Smad4 is involved in angiogenesis-related pathways. Knockdown of SMAD4 attenuated the upregulation of VEGFA, PDGFA, and angiogenesis in vitro. Treatment of human ECs with palmitic acid-induced Smad1/5 phosphorylation and the upregulation of core endothelial genes. Our study shows that endothelial Smad4 is involved in WAT beiging through angiogenesis and the expansion of adipose precursors into beige adipocytes.

Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome-wide methylation patterns are poorly defined. While methylation is known to alter gene expression, the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n = 39) that was subsequently replicated in a larger validation cohort (n = 296). Gene body–related regions made up more than 60% of the methylation differences and emphasized the importance of methylation sequencing. We observed differentially methylated genes associated with DN in 3 independent T1D registries originating from Denmark (n = 445), Hong Kong (n = 107), and Thailand (n = 130). Reduced DNA methylation at CTCF and Pol2B sites was tightly connected with DN pathways that include insulin signaling, lipid metabolism, and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubule cells. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding, and the activation of insulin-signaling phosphoproteins in hyperglycemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophages and vascular endothelial cells.

BackgroundColorectal cancer (CRC) is the most common gastrointestinal malignancy and is generally thought to be caused by the transformation of colorectal polyps. It has been shown that early detection and removal of colorectal polyps may reduce the mortality and morbidity of colorectal cancer.ObjectiveBased on the risk factors associated with colorectal polyps, an individualized clinical prediction model was built to predict and evaluate the possibility of developing colorectal polyp.MethodsA case-control study was conducted. Clinical data were collected from 475 patients who underwent colonoscopy at the Third Hospital of Hebei Medical University from 2020 to 2021. All clinical data were then divided into training sets and validation sets by using R software (7:3). A multivariate logistic analysis was performed to identify the factors associated with colorectal polyps according to the training set, and a predictive nomogram was created by R software based on the multivariate analysis. The results were internally validated by receiver operating characteristic (ROC) curves, calibration curves, and externally validated by validation sets.ResultsMultivariate logistic regression analysis showed that age (OR = 1.047, 95% CI = 1.029–1.065), history of cystic polyp (OR = 7.596, 95% CI = 0.976–59.129), and history of colorectal diverticulums (OR = 2.548, 95% CI = 1.209–5.366) were independent risk factors for colorectal polyps. History of constipation (OR = 0.457, 95% CI = 0.268–0.799) and fruit consumption (OR = 0.613, 95% CI 0.350–1.037) were protective factors for colorectal polyps. The nomogram demonstrated good accuracy for predicting colorectal polyps, with both C index and AUC being 0.747 (95% CI = 0.692–0.801). The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes. Both internal and external validation of the model showed good results.ConclusionIn our study, the nomogram prediction model is reliable and accurate, which can help early clinical screening of patients with high-risk colorectal polyps, improve polyp detection rate, and reduce the incidence of colorectal cancer (CRC).

BackgroundNon-high-density lipoprotein cholesterol (non-HDL-C) has been associated with atherosclerosis. However, the association between non-HDL-C and mortality in adult population remains unclear. We intended to investigate the association of non-HDL-C with cardiovascular and all-cause mortality using national representative data.MethodsThe study included 32,405 participants from the National Health and Nutrition Examination Survey (1999–2014). Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2015. Multivariable-adjusted Cox regression models were used to evaluate hazard ratio (HR) and 95% confidence interval (CI) of non-HDL-C concentrations in quintiles. Two-piecewise linear regression and restricted cubic spline analyzes were performed to test dose–response associations.ResultsAfter a median follow-up of 98.40 months, 2,859 (8.82%) all-cause and 551 (1.70%) cardiovascular deaths occurred. Compared with the highest group, the multivariable-adjusted hazard ratio (HR) of the first quintile for all-cause mortality was 1.53 (95%CI, 1.35–1.74). Higher non-HDL-C above a cutoff value of 4.9 mmol/L was related with cardiovascular mortality (HR = 1.33, 95%CI, 1.13–1.57). A U-shaped relationship between non-HDL-C and all-cause mortality was found in spline analysis with a cutoff value around 4 mmol/L. Similar results in subgroups analyzes were found among male, non-white population, participants who were not taking lipid-lowering drugs, and with body mass index (BMI)

Abstract With the development of blue laser endoscopy (BLE) technique, it's often used to diagnose early gastric cancer (EGC) by the morphological changes of blood vessels through BLE. However, EGC is still not obvious to identify, resulting in a high rate of missed diagnosis. Molecular imaging can show the changes in early tumors at molecular level, which provides a possibility for diagnosing EGC. Therefore, developing a probe that visually monitors blood vessels of EGC under BLE is particularly necessary. Herein, a bis‐pyrene (BP) based nanoprobe (BP‐FFVLK‐(PEG)‐RGD, M1) is designed, which can target angiogenesis and self‐assemble into fibers in situ, resulting in stable and long‐term retention in tumor. Moreover, M1 probe can emit yellow‐green fluorescence for imaging under BLE. M1 probe is confirmed to steadily remain in tumor for up to 96 hours in mice transplanted subcutaneously. In addition, the M1 probe is able to target angiogenesis for molecular imaging of isolated human gastric cancer tissue under BLE. Finally, M1 probe i.v. injected into primary gastric cancer model rabbits successfully highlighted the tumor site under BLE, which is confirmed by pathological analysis. It's the first time to develop a probe for diagnosing EGC by visualizing angiogenesis under BLE, showing great clinical significance.

With the concern for biodiversity conservation and ecological sustainability, the traditional method of assessing conservation management based on single elements such as timber production, stand structure, and forest area is no longer applicable. Especially for China, where the primary goal of national park conservation management is to “protect and maintain the authenticity and integrity of natural ecosystems”, it is necessary to construct a set of indicators that can comprehensively evaluate the effectiveness of natural ecosystem conservation management. Therefore, in this study, we take Jiuzhaigou and Giant Panda National Park, in Sichuan, China, as examples, and construct a set of ecological integrity evaluation indices system from the perspective of attributes of forest ecosystems. Initially, we screened the candidate indicators based on the coefficient of variation, distribution range, and redundancy analysis and identified 16 indicators as the evaluation indices of ecological integrity. Next, the model fit and the interrelationship of the components of the ecological integrity model were verified using a combination of structural equation modeling and actual data. The model validation results showed that: (1) CMIN/DF = 1.66, RMSEA = 0.058, GFI = 0.954, and other model fit metrics have reached the best reference standard, indicating that the ecological integrity model overall fit is high. (2) In the parameter estimation results of the model observed and latent variables, the ecological integrity model explained 96%, 85% and 89% of the variance in species composition, stand structure and ecological processes, respectively, indicating that the evaluation indices selected can effectively predict the ecological integrity of forests. In addition, we used the factor loadings in the structural equation model to calculate the weights of the indices and used the weighted sum to calculate the ecological integrity. A one-way ANOVA was conducted to compare the differences among the ecological integrity of forests of different origins, forest types and life forms. The relative importance and linear regression were used to elucidate the main factors affecting forest ecological integrity. The results showed that (1) except for the scrub community, the mean value of forest ecological integrity was >0.45, which was in the middle-to-upper level. (2) the ecological integrity of forests of different origins and different forest types showed a changing pattern: natural forest > plantation forest, mixed forest > pure forest. (3) Stand age and elevation strongly influenced the ecological integrity of forests, with relative contribution rates of 64.54% and 11.88%, respectively.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

Over the past few years, significant exploration breakthroughs have been made in the sandy conglomerates reservoir of the Triassic Baikouquan Formation in the Mahu Sag, Junggar Basin, China. However, the elasticity and pore characteristics of the tight sandy conglomerates reservoir in this area are still unclear. Through a systematic sonic testing program of the sandy conglomerates sample collected from the Mahu Sag, the regularity behind the variation of the elasticity and pore characteristics of the sample has been analyzed and captured. The Triassic Baikouquan Formation of the slope of Mahu Sag has been through complex burial and diagenetic history. The compaction, cementation, and dissolution are the three types of diagenesis that have the greatest impact on pore characteristics in the study area. In order to quantitatively describe the influence of this complex burial and diagenetic history, we present a rock-physics modeling approach to describe the elastic properties of sandy conglomerate sample. The overall strategy of the modeling is to combine the contact cement theory (CCT), differential effective medium (DEM) and the upper Hashin-Shtrikman bound. The CCT model can well describe the history of cementation, DEM model is suitable for the history of dissolution, and HS upper bound is used to describe the history of compaction. Then, the model is used to describe well log data from sandy conglomerates reservoirs in Mahu Sag and successfully explain the rock porosity, pore shape trends, and the elasticity in the sandy conglomerate reservoirs.

As an increasingly prevalent form of human activity, roads drive the taxonomic homogenization of mountain plant assemblages, threatening global biodiversity. However, little is known about how mountain roads impact functional and phylogenetic beta diversity and how these effects are related to taxonomic homogenization. To understand the mechanism of taxonomic homogenization triggered by mountain roads, we used species absence/presence data from 76 plots (2 m*50 m) and values for 12 traits measured on 978 species from the interior and roadside communities in the Qionglai mountain range, one of the temperate regions with the highest plant species richness in the world. We used a structural equation modeling approach (SEM) to consider several surrogates of road disturbance (changes in soil physicochemical properties and the presence or absence of roads) and the causal relationship between three facets of beta diversity (taxonomic beta diversity, TBD; functional beta diversity, FBD and phylogenetic beta diversity, PBD). The results suggest that TBD, FBD and PBD respond inconsistently to mountain roads, despite strong positive correlations between the three facets of plant beta diversity in the study area. Compared with the interior community, the βtotal.tax and βtotal.func of the roadside community decreased by 2.54% and 2.22%, respectively, which were related to the reduction of species and trait richness differences and replacements; however, we did not find the same results when assessing the changes in βtotal.phy, which represents tip-weighted PBD (twPBD). Furthermore, the largest effect of roads on beta diversity was reflected in basal-weighted PBD (bwPBD), which decreased by 9.97%, indicating that those species with fewer extant relatives and longer evolutionary histories are more sensitive to mountain roads. Therefore, it is necessary to take targeted protection measures for ancient species in roadside communities. In addition, we believe that it is still necessary to take measures to prevent the further dispersal of nonnative species, although the presence of non-native species in roadside plots has led to small changes in three facets of beta diversity. There were causal relationships between the three facets of beta diversity, but their intensity and sign different in the SEM of different components of beta diversity (i.e., richness difference and replacement). Our findings suggest that the homogenization of community species composition at the landscape scale arises by a combination of adaptive responses of the functional traits of organisms to environmental consistency (e.g., reduced the differences in soil variables) caused by roads and resorting or reassembly of community clades composition due to environmental filtering. These results contribute to our comprehensive understanding of the impact of mountain roads on plant diversity, which highlights the complex relationship between human pressure and biodiversity loss.

Thyroid carcinoma is the most common endocrine cancer in the world, and its incidence has been steadily increasing in recent years. Despite its relatively good prognosis, therapies have not improved greatly in recent years. Therefore, exploring new therapies for thyroid carcinoma represents an unmet need. Nitric oxide (NO) is a short-term endogenous signaling molecule that plays a vital role in various physiological and pathological processes and is synthesized by nitric oxide synthase (NOS). Many studies have been conducted over the past decades to explain its correlation to cancer. NO exerts a wide range of effects on cancer, involving angiogenesis, apoptosis, cell cycle, invasion, and metastasis. It also serves a dual function by promoting and halting tumor development simultaneously. The relationship between NO and thyroid carcinoma has been intensively studied and discussed. This paper reviews the role and molecular mechanism of NO in thyroid carcinoma and discusses potentials of prevention and treatment of thyroid carcinoma.

Pure malt wine was brewed from germinated malt by semi-solid fermentation technology, and the process optimization and physicochemical properties were determined. The single factor experiment was designed to study the effects of fermentation time, inoculation amount of koji and addition amount of glucoamylase on the alcohol content of pure malt wine, and to determine the best single factor. The experimental conditions were studied after the single factor level determination, meanwhile the orthogonal design was carried out, and the optimal combination was determined as follows: fermentation time of 4 d, inoculation amount of 2‰ koji and addition amount of 2% glucoamylase. Under these conditions, the alcohol content of pure malt wine was 10.6%vol±0.3%vol, the total phenol content was 1.159±0.066 g/L, the protein content was 209.568±19.178 mg/L, the total acid content was 6.4±0.2 g/L, reducing sugar content was 8.409±0.021 g/L, the scavenging rate of hydroxyl radical was 86.75%±1.42%, and the total reduction capacity could reach 1.842±0.004. Through the analysis of variance of orthogonal experiment, it was concluded that fermentation time and glucoamylase dosage had significant effect on the alcohol content of pure malt wine (P0.05). The results would provide a theoretical basis for the production and development of pure malt wine.

Abstract Background Gastric cancer (GC) is one of the most pernicious tumors that seriously harm human healthcare. GC metastasis is one of the prime cause of failed cancer treatment, but correlation between N6-methyladenosine (m6A) and GC metastasis was less reported. Methods Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of GC tissues was conducted. Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) were taken to determine the expression of ALKBH5 in GC tissues and cell lines. RNA-seq together with MeRIP-qRT-PCR was used to screen the target gene of ALKBH5. RNA pulldown, mass spectrometry and RNA immunoprecipitation (RIP) were used to search the “reader” protein of target gene. The mechanism was also validated via a tail vein injection method for lung metastasis model. Results Decreased expression of ALKBH5 was detected in GC samples, and it was correlated with clinical tumor distal metastasis and lymph node metastasis. ALKBH5 interference promoted metastasis of GC cells and this effect was closely related to the demethylase activity of ALKBH5. PKMYT1, as a downstream target of ALKBH5, promoted invasion and migration in GC. Caused by ALKBH5 knockdown or its demethylase activity mutation, upregulated expression of PKMYT1 indicated that ALKBH5 modulates expression of PKMYT1 in an m6A-dependent manner. IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site. Conclusions This study established an ALKBH5-PKMYT1-IGF2BP3 regulation system in metastasis, representing a new therapeutic target for GC metastasis.

Abstract Emerging evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the metastasis and recurrence of hepatocellular carcinoma (HCC). A kinds of lncRNAs were found to be involved in regulating epithelial–mesenchymal transition (EMT) or stem-like traits in human cancers, however, the molecular mechanism and signaling pathways targeting EMT and stemness remains largely unknown. Previously, we found that linc00261 was down-regulated in HCC and associated with multiple worse clinical pathological parameters and poor prognosis. Here, we show that linc00261 was down-regulated in TGF-β1 stimulated cells, and forced expression of linc00261 attenuated EMT and stem-like traits in HCC. Linc00261 also inhibited the tumor sphere forming in vitro and decreased the tumorigenicity in vivo. Furthermore, we revealed that linc00261 suppressed the expression and phosphorylation of SMAD3 (p-SMAD3), which could be core transcriptional modulator in TGF-β1 signaling mediated EMT and the acquisition of stemness traits. A negative correlation between linc00261 and p-SMAD3 was determined in HCC samples. Conclusion: Our study revealed that linc00261 suppressed EMT and stem-like traits in HCC cells by inhibiting TGF-β1/SMAD3 signaling.

Abstract Major depressive disorder (MDD) is a debilitating mental disease, but its underlying molecular mechanisms remain obscure. Our previously established model of naturally occurring depression-like (DL) behaviors in Macaca fascicularis, which is characterized by microbiota-gut–brain (MGB) axis disturbances, can be used to interrogate how a disturbed gut ecosystem may impact the molecular pathology of MDD. Here, gut metagenomics were used to characterize how gut virus and bacterial species, and associated metabolites, change in depression-like monkey model. We identified a panel of 33 gut virus and 14 bacterial species that could discriminate the depression-like from control macaques. In addition, using lipidomic analyses of central and peripheral samples obtained from these animals, we found that the DL macaque were characterized by alterations in the relative abundance, carbon-chain length, and unsaturation degree of 1,2-diacylglyceride (DG) in the prefrontal cortex (PFC), in a brain region-specific manner. In addition, lipid-reaction analysis identified more active and inactive lipid pathways in PFC than in amygdala or hippocampus, with DG being a key nodal player in these lipid pathways. Significantly, co-occurrence network analysis showed that the DG levels may be relevant to the onset of negative emotions behaviors in PFC. Together our findings suggest that altered DG levels and structure in the PFC are hallmarks of the DL macaque, thus providing a new framework for understanding the gut microbiome’s role in depression.