E-M349E and NS2A/2B-P1(T) are compensatory mutations of rDTMUV-NS2AB-P1P1'(AA), which regain virus proliferation by enhancing the virus package and restoring NS2A/2B cleavage.

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. The genome of DTMUV is translated into a polyprotein, which is further cleaved into several protein by viral NS2B3 protease and host proteases. Crucially, the cleavage of the NS2A/2B precursor during this process is essential for the formation of replication complexes and viral packaging. Previous research has demonstrated that alanine mutations in NS2A/2B (P1P1' (AA)) result in an attenuated strain (rDTMUV-NS2A/2B-P1P1' (AA)) by disrupting NS2A/2B cleavage. In this study, we investigate the effects of the P1P1' (AA) mutation on the viral life cycle and explore compensatory mutations in rDTMUV-NS2A/2B-P1P1' (AA). Infected ducklings exhibit similar body weight gain and viral tissue loads to DTMUV-WT. Compensatory mutations E-M349E and P1(T) emerge, restoring proliferation levels to those of rDTMUV-WT. Specifically, E-M349E enhances viral packaging, while P1(T) reinstates NS2A/2B proteolysis in vitro. Thus, our findings reveal novel compensatory sites capable of restoring the attenuated DTMUV during polyprotein cleavage and packaging.

Raman spectrum combined with deep learning for precise recognition of Carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) is a major pathogen that poses a serious threat to human health. Unfortunately, currently, there are no effective measures to curb its rapid development. To address this, an in-depth study on the surface-enhanced Raman spectroscopy (SERS) of 22 strains of 7 categories of CRE using a gold silver composite SERS substrate was conducted. The residual networks with an attention mechanism to classify the SERS spectrum from three perspectives (pathogenic bacteria type, enzyme-producing subtype, and sensitive antibiotic type) were performed. The results show that the SERS spectrum measured by the composite SERS substrate was repeatable and consistent. The SERS spectrum of CRE showed varying degrees of species differences, and the strain difference in the SERS spectrum of CRE was closely related to the type of enzyme-producing subtype. The introduced attention mechanism improved the classification accuracy of the residual network (ResNet) model. The accuracy of CRE classification for different strains and enzyme-producing subtypes reached 94.0% and 96.13%, respectively. The accuracy of CRE classification by pathogen sensitive antibiotic combination reached 93.9%. This study is significant for guiding antibiotic use in CRE infection, as the sensitive antibiotic used in treatment can be predicted directly by measuring CRE spectra. Our study demonstrates the potential of combining SERS with deep learning algorithms to identify CRE without culture labels and classify its sensitive antibiotics. This approach provides a new idea for rapid and accurate clinical detection of CRE and has important significance for alleviating the rapid development of resistance to CRE.

The dimensionality of perceptual anomalies and their relationships with bullying victimization among Chinese adolescents: From a network perspective.

Anomalous perceptual experiences in adolescents are common and may predict future psychotic disorders and other psychopathologies. However, the underlying structure and their specific relationships with bullying victimizations, a typical stressor for adolescents, remain unclear. Therefore, the current study aimed to clarify the structure of perceptual anomalies as assessed by the Cardiff Anomalous Perceptions Scale (CAPS) using exploratory graph analysis (EGA), a new factor retention method based on network psychometrics. The second aim was to explore whether specific dimensions of perceptual anomalies are particularly associated with certain forms of bullying victimization. Data from a validated sample of 1199 Chinese adolescents (56.0 % females, age range: 14-20) on perceptual anomalies and bullying victimizations were analyzed using network approaches, including EGA and mixed graphical modeling (mgm). Results showed that each anomalous perception was experienced by 13.8-50.3 % of the participants. EGA identified four dimensions: aberrant bodily perceptions, altered daily experiences, chemosensation (i.e., abnormal gustatory and olfactory experiences), and clinical psychosis (i.e., visual and auditory hallucinatory experiences). Among them, the altered daily experiences dimension possessed the highest centrality. Physical bullying and cyberbullying were directly and positively linked to two of the aberrant bodily experiences. Bootstrap analyses suggest that the results are reliable. The current findings support the existence of multiple contributive factors to perceptual anomalies and underscore the importance of bullying prevention in reducing mental health risks for adolescents, particularly the risk of psychosis.

Preferential association of polycyclic aromatic hydrocarbons (PAHs) with soil colloids at an e-waste recycling site: Implications for risk of PAH migration to subsurface environment.

Polycyclic aromatic hydrocarbon (PAH) contamination at e-waste recycling sites poses high ecological and human-health risks. Of note, PAHs in surface soils can be mobilized through colloid-facilitated transport, and may migrate into the subsurface and pollute groundwater. Here, we show that the colloids released from the soil samples at an e-waste recycling site in Tianjin, China contain high concentrations of PAHs, with total concentrations of 16 PAHs as high as 1520 ng/g dw. Preferential association of the PAHs with the colloids is observed, with the distribution coefficients of PAHs between colloids and bulk soil often above 10. Source diagnostic ratios show that soot-like particles are the main source of PAHs at the site, due to the incomplete combustion of fossil fuels, biomass, and electronic wastes during the e-waste dismantling practices. Due to their small sizes, a large fraction of these soot-like particles can be remobilized as colloids, and this explains the preferential association of PAHs with colloids. Moreover, the colloids-soil distribution coefficients are higher for the low-molecular-weight PAHs than for the high-molecular-weight ones, possibly attributable to the different binding routes/modes of these two groups of PAHs to the particles during combustion. Notably, the preferential association of PAHs with colloids is even more pronounced for the subsurface soils, corroborating that the presence of PAHs in the deeper soils is primarily the results of downward migration of PAH-bearing colloids. The findings highlight the important role of colloids as a vector for the subsurface transport of PAHs at e-waste recycling sites, and call for further understanding of colloid-facilitated transport of PAHs at e-waste recycling sites.

Visceral fat correlates with insulin secretion and sensitivity independent of BMI and subcutaneous fat in Chinese with type 2 diabetes.

Aim: Clinical heterogeneity exists in overall obesity and abdominal obesity in terms of insulin secretion and sensitivity. Further, the impact of visceral fat (VF) on the first- and second-phase insulin secretion (FPIS and SPIS) is controversial. We aim to investigate insulin secretion and sensitivity in Chinese patients with T2DM according to different BMI and VF levels. Methods: This study enrolled 300 participants. A dual bioelectrical impedance analyzer was used to assess the visceral and subcutaneous fat area (VFA and SFA). VF levels were categorized as normal or high, with the cutoff value of 100 cm2. FPIS and SPIS were evaluated by arginine stimulation test and standardized steamed bread meal tolerance test, respectively. ß-cell function (HOMA2-ß), insulin resistance (HOMA2-IR), and Gutt's insulin sensitivity index (Gutt-ISI) were also calculated. Spearman's correlation analysis and multivariate linear regression analysis were adopted for statistical analysis. Results: Participants were categorized into four groups: normal weight-normal VF, normal weight-high VF, overweight/obese-normal VF and overweight/obese-high VF. Multivariate linear regression showed that both VFA and SFA were correlated with FPIS, HOMA2-IR and Gutt-ISI after controlling for gender and diabetes duration. After further adjustment for BMI and VFA, some associations of SFA with insulin secretion and sensitivity disappeared. After adjustment for gender, diabetes duration, BMI and SFA, VFA was positively correlated with FPIS, SPIS and HOMA2-IR. Subjects with overweight/obese-high VF were more likely to have higher FPIS, HOMA2-IR and lower Gutt-ISI (all p < 0.05). Conclusion: VF affects both FPIS and SPIS, and worsens insulin sensitivity independent of BMI and subcutaneous fat in Chinese patients with T2DM. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2200062884.

Optimization of Sputtering Process for Medium Entropy Alloy Nanotwinned CoCrFeNi Thin Films by Taguchi Method.

We demonstrate a systematic study optimizing the properties of CoCrFeNi medium entropy alloy (MEA) thin films by tuning the deposition parameters of the pulsed direct current (DC) magnetron sputtering process. The chemical composition and microstructure of thin films were studied with energy dispersive X-ray spectroscopy (EDS), an X-ray diffractometer (XRD) and a transmission electron microscope (TEM). Abundant nanotwins and the dual face-centered cubic-hexagonal close-packed (FCC-HCP) phases were formed in some specimens. The Taguchi experimental method and analysis of variance (ANOVA) were applied to find the optimized parameters. The control factors are five deposition parameters: substrate bias, substrate temperature, working pressure, rotation speed and pulsed frequency. According to the signal-to-noise ratio results, the optimized parameters for low electrical resistivity (98.2 ± 0.8 µΩ·cm), low surface roughness (0.5 ± 0.1 nm) and high hardness (9.3 ± 0.2 GPa) were achieved and verified with confirmed experiments.

Diabetic kidney disease progression is associated with decreased lower-limb muscle mass and increased visceral fat area in T2DM patients.

Aim: This study aimed to explore the relationship between lower-limb muscle mass/visceral fat area and diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 879 participants with T2DM were divided into 4 groups according to the prognosis of CKD classification from Kidney Disease: Improving Global Outcomes (KDIGO). Rectus femoris cross-sectional area (RFCSA) was measured through ultrasound, and visceral fat area (VFA) was evaluated with bioelectric impedance analysis (BIA). Results: T2DM patients with high to very high prognostic risk of DKD showed a reduced RFCSA (male P < 0.001; female P < 0.05), and an enlarged VFA (male P < 0.05; female P < 0.05). The prognostic risk of DKD was negatively correlated with RFCSA (P < 0.05), but positively correlated with VFA (P < 0.05). Receiver-operating characteristic analysis revealed that the cutoff points of T2DM duration combined with RFCSA and VFA were as follows: (male: 7 years, 6.60 cm2, and 111 cm2; AUC = 0.82; 95% CI: 0.78-0.88; sensitivity, 78.0%; specificity, 68.6%, P < 0.001) (female: 9 years, 5.05 cm2, and 91 cm2; AUC = 0.73; 95% CI: 0.66-0.81; sensitivity, 73.9%; specificity, 63.3%, P < 0.001). Conclusion: A significant association was demonstrated between reduced RFCSA/increased VFA and high- to very high-prognostic risk of DKD. T2DM duration, RFCSA, and VFA may be valuable markers of DKD progression in patients with T2DM. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2100042214.

Benzene Exposure Leads to Lipodystrophy and Alters Endocrine Activity In Vivo and In Vitro.

Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using in vivo and in vitro experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 µM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose (ptrend < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all p < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. In vitro cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level (r = 0.330, 0.344, both p < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.

Visceral fat might impact left ventricular remodeling through changes in arterial stiffness in type 2 diabetes: A cross-sectional study.

AIMS: Visceral fat (VF) influences left ventricular (LV) structure and diastolic function in type 2 diabetes (T2DM). However, there are limited data on the association among them based on different BMI levels as well as accounting for arterial stiffness. This study investigated the association of fat distribution, arterial stiffness, left ventricular (LV) structure and diastolic function in T2DM patients. MATERIALS AND METHODS: This cross-sectional study comprised 905 patients. VF area (VFA) and subcutaneous fat area (SFA) were assessed by a dual bioelectrical impedance analyzer. Brachial-ankle pulse wave velocity (baPWV) was measured by a volume-plethysmographic apparatus and LV structure and diastolic function were echocardiography. Patients were divided into three groups based on BMI levels. Linear and logistic regression analysis were used to investigate the association. RESULTS: In multivariate linear regression, relative wall thickness (RWT) was negatively correlated with E/A in obese patients (ß = -0.203, p = 0.004). LV mass/height2.7 was positively correlated with E/E' in normal weight (ß = 0.232, p = 0.002) and obese patients (ß = 0.232, p = 0.008). In multivariate logistic regression, baPWV was an independent determinant of LV remodeling (LVRM) in normal weight (OR = 1.001; 95% CI, 1.000, 1.002; P = 0.006), overweight (OR = 1.001; 95% CI, 1.000, 1.002; P = 0.008) and obese groups (OR = 1.003; 95% CI, 1.001, 1.004; P = 0.001), while VFA was correlated with arterial stiffness in normal weight (OR = 1.032; 95% CI, 1.017, 1.047; P < 0.001) and overweight groups (OR = 1.011; 95% CI, 1.002, 1.021; P = 0.015). CONCLUSIONS: VF might impact LVRM through changes in baPWV in T2DM patients, thus influencing diastolic function.

Key factors controlling colloids-bulk soil distribution of polybrominated diphenyl ethers (PBDEs) at an e-waste recycling site: Implications for PBDE mobility in subsurface environment.

Accumulation of polybrominated diphenyl ethers (PBDEs) in surface soils at elevated concentrations is common at e-waste recycling sites. Even though highly insoluble, migration of PBDEs into the vadose zone and groundwater is possible, due to their association with soil colloids. Here, we show that upon equilibration with artificial rainwater surface and subsurface soil samples collected at an e-waste recycling site release significant quantities of colloids, with the total concentrations of 14 PBDE congeners as high as 990 ng/g dw. The concentrations of different congeners vary markedly in the colloids, and that of BDE-209 is the highest in all the samples. Notably, even the colloids released from the soil collected at a depth of 95-105 cm contain high concentrations of PBDEs. Preferential binding of PBDEs to soil colloids is observed, with the colloids-soil distribution coefficients above 10 in certain cases. The extent of preferential binding displays no apparent correlation with the relative hydrophobicity of the PBDEs, nor can it be explained simply by considering the higher specific surface area, pore volume, and clay content of the soil colloids than the respective bulk soil. Principal component analysis shows that multiple soil properties are collectively responsible for the preferential distribution of PBDEs. Specifically, the differences in pore volume, soil organic carbon content, and pore size between colloids and soils are likely the major factors affecting the distribution of high-concentration PBDEs, whereas the differences in clay content, pore volume and specific surface area are the key factors affecting the distribution of low-concentration PBDEs. The findings clearly show that colloids are an important medium with which PBDEs are associated at contaminated sites, and underline the need of understanding colloid-facilitated transport of PBDEs at e-waste sites.

Risk and protective factors for anxiety during COVID-19 pandemic.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a global pandemic and an anxiety-provoking event. There are few studies to identify potential risk and protective factors related to anxiety during COVID-19 pandemic. METHODS: We collected information on demographic data and lifestyles by a web-based survey of 19,802 participants from 34 provinces in China during COVID-19 pandemic. Level of anxiety was evaluated using the Self-Rating Anxiety Scale. We used ordinal multivariable logistic regression to estimate the associations of anxiety level with potential risk and protective factors. We further developed a new score to simplify the assessment of anxiety during COVID-19 crisis. RESULTS: Among 19,802 participants, we found that those who were front-line medical personnel, suffered from chronic disease, with present symptoms of SARS-CoV-2 infection or contact history had 112, 93, 40 and 15% increased risk of higher anxiety level; while those with knowledge about personal protective measures or wore masks had 75 and 29% lower risk of higher anxiety level respectively. We developed a risk score by calculating the sum of single score of 17 factors. Each one increase of the risk score was associated with a 297% increase in anxiety index score. In categorical analysis, low risk (the risk score between 1 to 2), the moderate risk group (the risk score of 3) and high risk group (the risk score ≥ 4) had - 0.40 (95% CI: - 1.55, 0.76), 1.44 (95% CI: 0.27, 2.61) and 9.18 (95% CI: 8.04, 10.33) increase in anxiety index score, and 26% (95% CI: - 7, 72%), 172% (95% CI: 100, 270%), and 733% (95% CI: 516, 1026%) higher risk of anxiety respectively, when compared with the very low risk group (the risk score of 0). The AUC was 0.73 (95% CI, 0.72, 0.74) for the model fitted the developed risk score, with the cut-off point of 3.5. CONCLUSIONS: These findings revealed protective and risk factors associated with anxiety, and developed a simple method of identifying people who are at an increased risk of anxiety during COVID-19 pandemic.

Substoichiometric titanium oxide Ti2O3 exhibits greater efficiency in enhancing hydrolysis of 1,1,2,2-tetrachloroethane than TiO2 nanomaterials.

Oxygen-deficient substoichiometric titanium oxides, or "titanium suboxides," are produced incidentally from coal combustion and are environmentally abundant. Additionally, titanium suboxide nanomaterials are promising new materials with likely future environmental release. How these materials may affect contaminant fate differently than stoichiometric TiO2 (nano)materials is largely unknown. Here, we show that Ti2O3 (selected as a model titanium suboxide) exhibits significantly greater efficiency in enhancing the hydrolysis of 1,1,2,2-tetrachloroethane (TeCA), a common groundwater contaminant, than the stoichiometric anatase and rutile TiO2. At environmentally relevant pH (6.5-7.5), the surface area-normalized pseudo-first-order hydrolysis rate constant in the presence of Ti2O3 is approximately an order of magnitude higher than those associated with TiO2. The superior catalytic efficiency of Ti2O3 can be attributed to both its higher surface hydrophobicity, which renders higher adsorption affinity for TeCA, and its higher concentration of Lewis acid sites (mainly the Ti3+ and the five-coordinated Ti4+). Particularly, the deprotonated hydroxyl groups attached to Ti3+ (a weaker Lewis acid than Ti4+) exhibit higher basicity and thus, are more effective in catalyzing the base-promoted hydrolysis reaction. The findings call for further understanding of the environmental implications of titanium suboxide (nano)materials, which may not be readily predictable based on the knowledge acquired for TiO2.

Molecular mechanisms of Mycoredoxin-1 in resistance to oxidative stress in Corynebacterium glutamicum.

Glutaredoxins (Grxs) with Cys-Pro-Phe (Tyr)-Cys motif and a thioredoxin fold structure play an important role in the anti-oxidant system of bacteria by catalyzing a variety of thiol-disulfide exchange reactions with a 2-Cys mechanism or a 1-Cys mechanism. However, the catalytic and physiological mechanism of Corynebacterium glutamicum Mycoredoxin 1 (Mrx1) that shares a high amino acid sequence similarity to Grxs has not been fully elucidated. Here, we report that Mrx1 has a protective function against various adverse conditions, and the decrease of cell viability to various stress conditions by deletion of the Mrx1 in C. glutamicum was confirmed in the mrx1 mutant. The physiological roles of Mrx1 in defence to oxidative stress were corroborated by its induced expression under various stresses, regulated directly by the stress-responsive extracytoplasmic function-sigma (ECF-σ) factor SigH. As well as reducing mycothiol (MSH) mixed disulfide bonds via a 1-Cys mechanism, C. glutamicum Mrx1 catalytically reduced the disulfides in the Ib RNR, insulin and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) by exclusively linking the MSH/Mtr (mycothiol disulfide reductase)/NADPH electron pathway via a 2-Cys mechanism. Thus, we present the first evidence that the Mrx1 is able to protect against the damaging effects of various exogenous stresses by acting as a disulfide oxidoreductase, thereby giving a new insight in how C. glutamicum survives oxidative stressful conditions.

MsrR is a thiol-based oxidation-sensing regulator of the XRE family that modulates C. glutamicum oxidative stress resistance.

BACKGROUND: Corynebacterium glutamicum thrives under oxidative stress caused by the inevitably extreme environment during fermentation as it harbors antioxidative stress genes. Antioxidant genes are controlled by pathway-specific sensors that act in response to growth conditions. Although many families of oxidation-sensing regulators in C. glutamicum have been well described, members of the xenobiotic-response element (XRE) family, involved in oxidative stress, remain elusive. RESULTS: In this study, we report a novel redox-sensitive member of the XER family, MsrR (multiple stress resistance regulator). MsrR is encoded as part of the msrR-3-mst (3-mercaptopyruvate sulfurtransferase) operon; msrR-3-mst is divergent from multidrug efflux protein MFS. MsrR was demonstrated to bind to the intergenic region between msrR-3-mst and mfs. This binding was prevented by an MsrR oxidation-mediated increase in MsrR dimerization. MsrR was shown to use Cys62 oxidation to sense oxidative stress, resulting in its dissociation from the promoter. Elevated expression of msrR-3-mst and mfs was observed under stress. Furthermore, a ΔmsrR mutant strain displayed significantly enhanced growth, while the growth of strains lacking either 3-mst or mfs was significantly inhibited under stress. CONCLUSION: This report is the first to demonstrate the critical role of MsrR-3-MST-MFS in bacterial stress resistance.