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Nowadays, human beings are exposed to Cu in varieties of environmental mediums, resulting in health risks needing urgent attention. Our research found that Cu shortened lifespan and induced aging-related phenotypes of Caenorhabditis elegans (C. elegans). Transcriptomics data showed differential expression genes induced by Cu were mainly involved in regulation of metabolism and longevity, especially in fatty acid metabolism. Quantitative detection of free fatty acid by GC/MS further found that Cu upregulated free fatty acids of C. elegans. A mechanism study confirmed that Cu promoted the fat accumulation in nematodes, which was owing to disorder of fatty acid desaturase and CoA synthetase, endoplasmic reticulum unfolded protein response (UPRER), mitochondrial membrane potential, and unfolded protein response (UPRmt). In addition, Cu activated oxidative stress and prevented DAF-16 translocating into nuclear with a concomitant reduction in the expression of environmental stress-related genes. Taken together, the research suggested that Cu promoted aging and induced fat deposition and oxidative damage.

Objective. This study evaluated the distribution of vaginal microbiota dysbiosis and the association with HPV viral load test in high-risk HPV-positive women before and after 50 years old. Methods. For this cross-sectional study, 388 HPV-positive women prior to referral to colposcopy in Peking University Peoples’ Hospital were included and classified as younger than 50 years ( n = 307 ) and aged 50 years or older ( n = 81 ), midvagina bacterial community composition was characterized by FlashDetect™ MAX vaginal microbe detection kit, and BMRT-HPV reported type-specific viral loads/10,000 cells. Results. The community state type (CST) IV was the most common CST occurring in 148 women (38.1%). The proportion of CST IV in those aged 50 years or older was significantly higher than those younger than 50 years (women) (66.7% vs. 30.6%); the difference was statistically significant ( p = 0.238 and 0.263). However, the women with high-grade cervical lesion presented a more complicated trend and the abundance of vaginal microbiota dysbiosis than low-grade lesion. HPV16/18 viral load was found to be significantly higher in CST III and CST IV than CST I/II/V ( p < 0.05 )in women younger than 50 years. Conclusions. In women younger than 50 years, higher HPV16/18 load was more closely associated with CST IV; however, it had no significant correlation in women aged 50 years or older.

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3β in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

Objective. To assess the clinical efficacy of oxymatrine plus antiviral therapy in the treatment of sepsis and its effects on the levels of endotoxin and inflammatory factors. Methodology. 90 patients with sepsis were selected for retrospective analysis and were assigned to receive either conventional treatment (control group) or oxymatrine plus antiviral treatment (study group). The clinical endpoint was treatment efficacy. Results. There were no significant differences in baseline patient profile between the two groups ( P > 0.05 ). The study group showed a higher efficiency versus the control group ( P < 0.05 ). Patients in the study group had a significantly shorter mechanical ventilation duration and ICU stay versus those in the control group ( P < 0.05 ). Both groups had reduced Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Marshall score, levels of endotoxin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, C-reactive protein (CRP), and procalcitonin (PCT) after treatment, with lower results in the study group versus the control group ( P < 0.05 ). Conclusion. Oxymatrine plus antiviral therapy effectively improves clinical efficacy, reduces the levels of endotoxin and inflammatory factors, protects organ function, and boosts recovery. Further clinical trials are, however, required prior to general application in clinical practice.

Quercetin, a naturally occurring flavonoid, is mainly extracted from tea, onions, and apples. It has the underlying neuroprotective effect on experimental ischemic stroke. A systematic review and meta-analysis were used to assess quercetin’s efficacy and possible mechanisms in treating focal cerebral ischemia. Compared with the control group, twelve studies reported a remarkable function of quercetin in improving the neurological function score (NFS) ( P < 0.05 ), and twelve studies reported a significant effect on reducing infarct volume ( P < 0.05 ). Moreover, two and three studies showed that quercetin could alleviate blood-brain barrier (BBB) permeability and brain water content, respectively. The mechanisms of quercetin against focal cerebral ischemia are diverse, involving antioxidation, antiapoptotic, anti-inflammation, and calcium overload reduction. On the whole, the present study suggested that quercetin can exert a protective effect on experimental ischemic stroke. Although the effect size may be overestimated because of the quality of studies and possible publication bias, these results indicated that quercetin might be a promising neuroprotective agent for human ischemic stroke. This study is registered with PROSPERO, number CRD 42021275656.

Peroxidase 3 (Prx‐3) is an important antioxidant protein that protects the body from the toxic effects of reactive oxygen species. In this study, the full‐length Prx3 cDNA sequence (PmPrx3) was isolated from Penaeus monodon. The PmPrx3 cDNA was 942 base pairs long and encoded a 227 amino acid polypeptide. The PmPrx3 protein showed high similarity (74%–83%) with the Prx3 protein from other species and contained the conserved Prx domain and peroxidase catalytic center. The results of reverse transcription polymerase chain reaction showed that PmPrx3 mRNA was universally expressed in all tested tissues. The level of PmPrx3 mRNA expression in the gills and hepatopancreas significantly changed after heavy metal exposure. Recombinant PmPrx3 protein (rPmPrx3) was obtained using a prokaryotic expression system and purified using affinity chromatography. Antioxidant activity assays showed that rPmPrx3 reduced insulin in the presence of dithiothreitol, suggesting that the anti‐oxidant function of rPmPrx3 was thiol‐dependent. In addition, Escherichia coli transferred with pET‐28a‐PmPrx3 was significantly protected in response to metal toxicity and H₂O₂ oxidative stress. In summary, our findings provided important insights into the mechanism of action of the Prx3 gene in environmental stress in P. monodon.

The interface between anchor plate and anchorage nut can be considered as a coupling spring whose stiffness is essentially the contact stiffness related to normal force at the contact surface, thus removing the usual assumption of fixed connection. The nut threads and steel bar are also connected with a coupling spring with the stiffness determined based on the threads treated as cantilever components. An analytical model was developed to assess the axial vibration of an anchorage system consisting of prestressing fine-rolled screw-threaded steel bars (P/S FSSBs). Both laboratory model and field tests show that the contact stiffness between anchor plate and anchorage nut has good a linear relationship with the effective tension of prestressed tendons. The vibration model was used to obtain the natural frequency and tensile force of a P/S FSSB. It is shown to be feasible and practical. According to the analytical model and test method presented in this paper, the proposed tension tester for P/S FSSBs possesses the features of repeated use, rapid testing, and minimized impact on the construction and is thus suggested for wider practical applications.

To investigate the seismic performance of buckling-restrained braces under the earthquake action, the shaking table test with a two-story 1/4 scale model is carried out for the ordinary pure steel frame and the buckling-restrained bracing steel frame with low-yield-point steel as the core plate. The failure modes, dynamic characteristics, acceleration response, interstory drift ratio, strain, shear force, and other mechanical properties of those two comparative structures subjected to different levels of seismic waves are mainly evaluated by the experiment. The test results show that under the action of seismic waves with different intensities, the apparent observations of damage occur in the pure frame structure, while no obvious or serious damage in the steel members of BRB structure is observed. With the increase in loading peak acceleration for the earthquake waves, the natural frequency of both structures gradually decreases and the damping ratio gradually increases. At the end of the test, the stiffness degradation rate of the pure frame structure is 11.2%, while that of the buckling-restrained bracing steel frame structure is only 5.4%. The acceleration response of the buckling-restrained bracing steel frame is smaller than that of the pure steel frame, and the acceleration amplification factor at the second story is larger than that at the first story for both structures. The average interstory drift ratios are, respectively, 1/847 and 1/238 for the pure steel frame under the frequent earthquake and rare earthquake and are 1/3000 and 1/314 for the buckling-restrained bracing steel frame, which reveals that the reduction rate of lateral displacement reaches a maximum of 71.71% after the installation of buckling-restrained brace in the pure steel frame. The strain values at each measuring point of the structural beam and column gradually increase with the increase of the peak seismic acceleration, but the strain values of the pure steel frame are significantly larger than those of the buckling-restrained bracing steel frame, which indicates that the buckling-restrained brace as the first seismic line of defense in the structure can dramatically protect the significant structural members. The maximum shear force at each floor of the structure decreases with the increase in height, and the shear response of the pure frame is apparently higher than that of the buckling-restrained bracing structure.

Clear cell renal cell carcinoma (ccRCC) is a very common cancer in urology. Many evidences suggest that complex changed pathways take a nonnegligible part in the occurrence and development of ccRCC. Nevertheless, the underlying mechanism is not clear. In this study, the expression data between ccRCC and normal tissue samples in TCGA database were compared to distinguish differentially expressed genes (DEGs: mRNAs, miRNAs, and lncRNAs). Afterwards, we used GO enrichment and KEGG pathway enrichment analyses to explore the functions of these DEGs. We also found the correlation between three RNAs and created a competing endogenous RNA (ceRNA) network. Moreover, we used univariate Cox regression analysis to select DEGs that are connected with overall survival (OS) of ccRCC patients. We found 1652 mRNAs, 1534 lncRNAs, and 173 miRNAs that were distinguished in ccRCC compared with normal tissues. According to GO analysis, the maladjusted mRNAs are mainly concentrated in immune cell activation and kidney development, while according to KEGG, they are mainly concentrated in pathways related to cancer. A total of 5 mRNAs, 1 miRNA, and 4 lncRNAs were connected with patients’ OS. In this article, a network of lncRNA-miRNA-mRNA was established; it is expected to be able to indicate possible molecular mechanisms for initial of ccRCC and provide a new viewpoint for diagnosis of ccRCC.

Toll‐like receptors (TLRs) play an indispensable role in fish immunity, being involved in pathogen recognition and the triggering of immune reactions. Here, a member of the TLR family, TLR1, from Lateolabrax japonicus was characterized and its expression pattern and intracellular localization were analysed. The full‐length LjTLR1 cDNA (2,755 bp) was found to encode a polypeptide of 827 amino acids. The deduced amino acid sequence contained three main structural domains: an extracellular leucine‐rich repeat domain, a transmembrane domain and a Toll/IL‐1 receptor domain. Tissue distribution analysis indicated that LjTLR1 was expressed in all of the examined tissues to varying degrees, with the highest levels being measured in the head kidney. In order to assess the antibacterial functions of LjTLR1 during infection, the pathogenic bacteria Vibrio harveyi and Streptococcus agalactiae were used. LjTLR1 was significantly upregulated in the three immune organs (the head kidney, spleen and liver) following bacterial stimulation, and its expression was detected 6 hr after initial exposure. In mRNA in situ hybridization experiments, positive signals were more numerous in the treatment group than the control group, verifying the expression patterns observed. Assessment of the intracellular localization of LjTLR1 revealed it to be present in the cytoplasm. These results indicate the potential role of LjTLR1 in immune responses to bacterial infection. This study enriches our knowledge of L. japonicus immune genes and provides a theoretical basis for further research concerning the antibacterial functions of fish TLRs during infection.

The standard boxplot is one of the most popular nonparametric tools for detecting outliers in univariate datasets. For Gaussian or symmetric distributions, the chance of data occurring outside of the standard boxplot fence is only 0.7%. However, for skewed data, such as telemetric rain observations in a real-time flood forecasting system, the probability is significantly higher. To overcome this problem, a medcouple (MC) that is robust to resisting outliers and sensitive to detecting skewness was introduced to construct a new robust skewed boxplot fence. Three types of boxplot fences related to MC were analyzed and compared, and the exponential function boxplot fence was selected. Operating on uncontaminated as well as simulated contaminated data, the results showed that the proposed method could produce a lower swamping rate and higher accuracy than the standard boxplot and semi-interquartile range boxplot. The outcomes of this study demonstrated that it is reasonable to use the new robust skewed boxplot method to detect outliers in skewed rain distributions.

To investigate drivers’ visual strategies and the distribution of fixation points, much work had been done and salient conclusions had been drawn. However, there is still no consensus on what the gaze target is and what functional significance the point might have. To improve theories on this subject, research was done to investigate drivers’ visual characteristics. On-road experiment was carried out, and drivers’ eye-movement and vehicle driving parameters were registered when driving around left- and right-hand curves. The results showed that drivers’ gaze direction fluctuates around the reference axis, and the fixation points are distributed in the region centered on the horizontal gaze position rather than a particular point that has geographical meanings. With the consideration of the traffic rules in China, we suggest here that there is no particular point on which drivers concentrate. Any point or position that could indicate the bend’s curvature could be the so-called target point. Drivers just want to operate their vehicle so as to pass through bends safely in a comfortable and labor-saving way.

Iterative regularization methods are efficient regularization tools for image restoration problems. The IDR(s) and LSMR methods are state-of-the-arts iterative methods for solving large linear systems. Recently, they have attracted considerable attention. Little is known of them as iterative regularization methods for image restoration. In this paper, we study the regularization properties of the IDR(s) and LSMR methods for image restoration problems. Comparative numerical experiments show that IDR(s) can give a satisfactory solution with much less computational cost in some situations than the classic method LSQR when the discrepancy principle is used as a stopping criterion. Compared to LSQR, LSMR usually produces a more accurate solution by using theL-curve method to choose the regularization parameter.

Pollen samples from peat sediments on the south bank of the Heilongjiang River in northern Northeast China (NE China) were analyzed to reconstruct the historical response of vegetation to climate change since 7800 cal yr BP. Vegetation was found to have experienced five successions from cold-temperate mixed coniferous and broadleaved forest to forest-steppe, steppe-woodland, steppe, and finally meadow-woodland. From 7800 to 7300 cal yr BP, the study area was warmer than present, andBetula, Larix, andPicea-dominated mixed coniferous and broadleaved forests thrived. Two cooling events at 7300 cal yr BP and 4500 cal yr BP led to a decrease inBetulaand other broadleaved forests, whereas herbs of Poaceae expanded, leading to forest-steppe and then steppe-woodland environments. After 2500 cal yr BP, reduced temperatures and a decrease in evaporation rates are likely to have resulted in permafrost expansion and surface ponding, with meadow and isolated coniferous forests developing a resistance to the cold-wet environment. The Holocene warm period in NE China (7800–7300 cal yr BP) could have resulted in a strengthening of precipitation in northernmost NE China and encouraged the development of broadleaved forests.

Platinum nanoparticles were electrodeposited on graphene modified glassy carbon electrode to form a modified electrode, and the electrode was characterized with scanning electron microscopy (SEM). At the modified electrode, rutin, a natural flavonoid, shows a couple of well-defined redox peaks, which is corresponded to the reduction and reoxidation of rutin. The electrochemical behaviors of rutin at the electrode were investigated, and the results indicated that the electrode reaction is controlled by adsorption process. Under the optimal conditions, the peak currents of differential pulse voltammetry (DPV) increased linearly with the rutin concentration in the range from 2 . 0 × 1 0 − 8 to 8 . 0 × 1 0 − 5 M with a limit of detection of 6 . 7 × 1 0 − 9 M. The as-prepared electrode was successfully used for the selective determination of rutin in tablet, displaying a potential application of graphene composite modified electrode.

A new composite electrode has been prepared with doping graphene into the paste consisting graphite and ionic liquid, n-octyl-pyridinum hexafluorophosphate (OPFP). This electrode shows an excellent electrochemical activity for the redox of hydroquinone (HQ), catechol (CC), and resorcinol (RS). In comparison with bare paste electrode, the redox peaks of three isomers of dihydroxybenzene can be obviously, simultaneously observed at graphene doping paste electrode. Under the optimized condition, the simultaneous determination of HQ, CC, and RS in their ternary mixture can be carried out with a differential pulse voltammetric technique. The peak currents are linear to the concentration of HQ, CC, and RS in the range form 1 × 1 0 − 5 to 4 × 1 0 − 4 , 1 × 1 0 − 5 to 3 × 1 0 − 4 , and 1 × 1 0 − 6 to 1 . 7 × 1 0 − 4 mol L−1, respectively. The limits of detection are 1 . 8 × 1 0 − 6 mol L−1 for HQ, 7 . 4 × 1 0 − 7 mol L−1 for CC, and 3 . 6 × 1 0 − 7 M for RS, respectively.

The structural requirements for L-selectin shedding were studied in murine leukocytes. Upon activation, L-selectin on both lymphocytes and neutrophils undergoes cleavage by a membrane metalloprotease, resulting in the generation of a soluble ectodomain and a membrane- retained 6 kD fragment. Radiochemical sequencing demonstrated a cleavage site in the membrane-proximal region (MPR) between R321 and S322, which is homologous to the human site. Although intact neutrophil L-selectin is larger, it is cleaved at the same, or very close, site. Analysis of several transfectants expressing L-selectin point mutations and chimeric constructs suggest that, like human shedding, the proteolytic process has relatively loose sequence specificity for the substrate site. In addition, some constructs are susceptible to slow constitutive cleavage, but their shedding does not increase upon PMA stimulation, showing that basal and activated shedding are separable processes. Insertion of the 15 amino acid MPR into murine B7.2 conferred upon this molecule susceptibility to constitutive shedding. PMA stimulation results in little or no acceleration of down regulation of this molecule. These results suggest that recognition of both the membrane-proximal cleavage site and of a site distant from the MPR are required for maximal induction of L-selectin shedding.