Purification, characterization and inactivation kinetics of polyphenol oxidase extracted from Cistanche deserticola.

MAIN CONCLUSION: PPO was purified from Cistanche deserticola, and its enzymatic characteristics were clarified. It was found that microwave treatment was an efficient way to inactivate PPO. Polyphenol oxidase (PPO) from Cistanche deserticola was obtained and purified through an acetone precipitation and anion exchange column, the enzymatic characteristics and inactivation kinetics of PPO were studied. The specific activity of PPO was 73135.15 ± 6625.7 U/mg after purification, the purification multiple was 48.91 ± 4.43 times, and the recovery was 30.96 ± 0.27%. The molecular weight of the PPO component is about 66 kDa by SDS-PAGE analysis. The optimum substrate of PPO was catechol (Vmax = 0.048 U/mL, Km = 21.70 mM) and the optimum temperature and pH were 30 °C and 7, respectively. When the temperature is above 50 °C, pH < 3 or pH > 10, the enzyme activity can be significantly inhibited. The first-order kinetic fitting shows that microwave inactivation has lesser k values, larger D values and shorter t1/2. It was found that microwave treatment is considered as an efficient and feasible way to inactive PPO by comparing the Z values and Ea values of the two thermal treatments.

Heterocyclic Ligands with Different N/O Donor Modes for Am(III)/Eu(III) Separation: A Theoretical Perspective.

Excellent "CHON" compatible ligands based on a heterocyclic skeleton for the separation of trivalent actinides [An(III)] from lanthanides [Ln(III)] have been widely explored, the aim being spent nuclear fuel reprocessing. The combination mode of a soft/hard (N/O) donor upon the coordination chemistry of An(III) and Ln(III) should play a vital role with respect to the performance of ligands. As such, in this work, two typical experimentally available phenanthroline-derived tetradentate ligands, CyMe4-BTPhen (L1) and Et-Tol-DAPhen (L4), and two theoretically designed asymmetric tetradentate heterocyclic ligands, L2 and L3, with various N/O donors were investigated using scalar relativistic density functional theory. We have evaluated the electronic structures of L1-L4 and their coordination modes, bonding properties, and extraction reactions with Am(III) and Eu(III). We found that the Am/Eu-N interactions play a more important role in the orbital interactions between the ligand and Am(III)/Eu(III) ions. Compared with those of L1, the coordinated O atoms of L2 and L4 weaken the metal-N bonds. The Am(III)/Eu(III) selectivity follows the order L1 > L2 > L4 based on the change in Gibbs free energy, reflecting the fact that the Am(III)/Eu(III) selectivity of the ligand is affected by the number of coordinated N atoms. In addition, L3 displays the strongest binding ability for Am(III)/Eu(III) ions and the smallest Am(III)/Eu(III) selectivity among the four ligands, due to its structural preorganization. This work clarifies the influence of the number of coordinated N and O atoms of ligands on Am(III)/Eu(III) selectivity, which provides valuable fundamental information for the design of efficient ligands with N and O donors for An(III)/Ln(III) separation.

A comparative investigation on the role and interaction of EsxA and EsxB in host immune response.

Staphylococcus aureus (S. aureus) is a frequent and major cause of bovine mastitis; it poses a tremendous economic burden to dairy industries of numerous countries. Early-secretion antigen-6 secretion system (ESS) has been viewed as an essential virulence and pathogenic factor of S. aureus. EsxA and EsxB are small acidic proteins secreted by ESS and identified as potential T-cell antigens of S. aureus. Unlike those of Mycobacterium tuberculosis (M. tuberculosis), the EsxA and EsxB of S. aureus do not form a dimer. Instead, EsxA dimerizes with itself or EsaC. Therefore, the interaction of EsxA and EsxB remains incompletely understood. In this study, to explore their interactions, EsxA and EsxB were expressed and used for immunization, alone or in combination, of murine infection models. Both components can interact with each other. Through the analysis of the immune response by immunological method, EsxB could significantly enhance the EsxA-specific IgG2a antibody level and increase the proliferation proportion of CD8+ T cells. These results indicate that when vaccinated with EsxA, EsxB can play a critical role in stimulating T helper 1 immunity by activating IgG2a and CD8+ T cells. We further show that vaccination with the combination of EsxA and EsxB resulted in enhanced stimulation of TLR-4 and improved protection against S. aureus. The findings may help us better understand the role of EsxB in the virulence and pathogenesis of S. aureus.

Efficacy of High-Flow Nasal Cannula Oxygen Therapy in Patients with Mild Hypercapnia.

OBJECTIVES: To investigate the indications of high-flow nasal cannula (HFNC) oxygen therapy among patients with mild hypercapnia and to explore the predictors of intubation when HFNC fails. METHODS: This retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients with mild hypercapnia (45 < PaCO2 ≤ 60 mmHg) received either HFNC or non-invasive ventilation (NIV) oxygen therapy. Propensity score matching (PSM) was implemented to increase between-group comparability. The Kaplan-Meier method was used to estimate overall survival and cumulative intubation rates, while 28-day mortality and 48-h and 28-day intubation rates were compared using the Chi-squared test. The predictive performances of HR/SpO2 and the ROX index (the ratio of SpO2/FiO2 to respiratory rate) at 4 h were assessed regarding HFNC failure, which was determined if intubation was given within 48 h after the initiation of oxygen therapy. The area under the receiver operating characteristic curve (AUC) for HR/SpO2 and the ROX index were calculated and compared. RESULTS: A total of 524,520 inpatient hospitalization records were screened, 106 patients in HFNC group and 106 patients in NIV group were successfully matched. No significant difference in 48-h intubation rate between the HFNC group (the treatment group) and the NIV group (the control group) (14.2% vs. 8.5%, p = 0.278); patients receiving HFNC had higher 28-day intubation rate (26.4% vs. 14.2%, p = 0.029), higher 28-day mortality (17.9% vs. 8.5%, p = 0.043), and longer ICU length of stay (4.4 vs. 3.3 days, p = 0.019), compared to those of NIV group. The AUC of HR/SpO2 at 4 h after the initiation of HFNC yielded around 0.660 for predicting 48-h intubation, greater than that of the ROX index with an AUC of 0.589 (p < 0.01). CONCLUSION: Patients with impending respiratory failure had lower intubation rate, shorter ICU length of stay, and lower mortality when treated mild hypercapnia with NIV over HFNC. As opposed to the ROX index, a modest, yet improved predictive performance is demonstrated using HR/SpO2 in predicting the failure of HFNC among these patients.

Geographic Ecological Momentary Assessment (GEMA) of environmental noise annoyance: the influence of activity context and the daily acoustic environment.

BACKGROUND: Noise annoyance is considered to be the most widespread and recognized health effect of environmental noise. Previous research is mostly based on the static study of residential environmental noise, but few studies have focused on the effects of noise exposure in different activity contexts on real-time annoyance. The two deficiency are that they neglect the influence of activity context besides residence and fail to reflect the difference of time-scale effect of noise influence. METHODS: Using portable noise and air sensors, GPS-equipped mobile phones, questionnaire survey, and geographic ecological momentary assessment (GEMA), this paper measured the environmental noise and real-time noise annoyance of participants at different activity places. Hierarchical logistic regression models were used to examine the effects of environmental noise on people's real-time annoyance. The paper further considered the influence of the geographic context of the activity places and daily acoustic environment on participants' real-time annoyance. Further, a nonlinear regression model was constructed using Random Forest to further examine the nonlinear relationship between environmental noise and real-time annoyance. RESULTS: The results showed that: (1) the average cumulative equivalent sound level during was 55 dB (A) when the participants responded to the EMA surveys; (2) Only the temperature of activity places had an influence on momentary annoyance and the higher the temperature, the more likely participants were annoyed; (3) Participants with higher perception of noise pollution in residential communities were more likely to be annoyed. However, participants with higher daily exposure to noise were less likely to feel annoyed; (4) The threshold value of the effect of noise on real-time annoyance was 58 dB (A) to 78 dB (A). CONCLUSIONS: These findings can guide the development of urban planning and environmental noise standards and also provide a reference for noise barrier requirements for different activity places.

Analysis of the Genetic Diversity in Methicillin-Resistant Staphylococcus aureus Isolates from Bovine Subclinical Mastitis Case in Xinjiang, China.

BACKGROUND: Diseases caused by livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) are an important global public health concern, and MRSA is increasingly being isolated in bovine milk. However, information on the genotype and antimicrobial resistance of MRSA in bovine milk in Xinjiang is limited. The objective of this study was to determine the antimicrobial-susceptible phenotypes and genotypes of the circulating MRSA clone isolated in bovine mastits milk samples in Xinjiang, China. METHODS: Fifty six MRSA isolates collected from milk of bovine mastitis were investigated by multilocus sequence typing (MLST), staphylococcal protein A (spa) typing, and a minimum inhibitory concentration test with 21 antimicrobial agents. RESULTS: Antibiotic resistance results showed that 47.4% of the isolates were resistant to 16 or more antibiotics. Twelve MLST types were defined in this study, and ST398 (n = 7) and ST2393 (n = 2) were found to be the most prevalent types. Seven spa types (t034, t269, t4030, t114, t35, t189, and t7589) were identified, of which t034 (n = 7), t189 (n = 3), and t4030 (n = 3) were predominant. Here, 3 MRSA ST188 is reported among human MRSA isolates in China, and this is the first time that it is reported in bovine MRSA strains. CONCLUSIONS: The antimicrobial susceptibility of MRSA in this area exhibited multidrug resistance, and clonal complexes CC398 and CC188, which have been reported among human MRSA isolates, do occur in Xinjiang dairy cows. This study provides a foundation for further MRSA monitoring.

[Expressions of MMP-7 and TIMP-1 in Chronic Stomach Disease Patients with Different Syndromes of Chinese Medicine].

Objective To observe the expressions of matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) in chronic stomach disease patients with different syn- dromes of Chinese medicine (CM) , and their relationships with Helicobacter pylori ( Hp ) infection. Meth- ods Totally 117 chronic stomach disease patients were recruited, and 11 healthy volunteers were also recruited. Chronic stomach disease patients were assigned to Pi-Wei dampness-heat syndrome (PWDHS, 57 cases) , disharmony of Gan and Wei syndrome (DGWS, 30 cases) , and Pi qi deficiency syndrome (PQDS, 30 cases) by syndrome typing. Healthy volunteers were recruited as the healthy con- trol group. Hp infection was detected using methylene blue dyeing and rapid urease test (RUT). The degree of inflammation was observed by conventional HE staining. The protein expressions of MMP-7 and TIMP-1 were detected qualitatively and positioningly using immunohistochemical method. Results Patients with PWDHS and patients with DGWS had equivalent Hp infection rate and degree. They showed a slightly increasing tendency than patients with PQDS, but with no statistical difference (P >0. 05). Com- pared with PWDHS and PQDS groups, more severe inflammation of mucosa occurred in patients with DG- WS (P <0. 05). More severe inflammation of mucosa occurred in patients with PWDHS than in those with PQDS, but with no statistical difference (P >0. 05). The severity of gastric mucosal inflammatory activity was sequenced from high to low as PWDHS, DGWS, PQDS, all with statistical difference (P <0. 05). Compared with Hp negative patients, the gastric mucosal inflammatory activity was more severe in Hp positive patients with PWDHS, DGWS, PQDS. The gastric mucosal inflammatory activity was more se- vere in Hp positive patients with PWDHS and PQDS (P <0. 05). Compared with the healthy control group, the expression level of TIMP-1 in gastric mucosa increased in patients with PWDHS, DGWS, PQDS (P <0. 05, P <0. 01) ; the expression level of MMP-7 increased in Hp negative patients with PWDHS (P < 0. 05). Compared with Hp negative patients with PWDHS, the expression level of MMP-7 decreased in Hp positive patients with PWDHS (P <0. 05). Compared with the PQDS group, the expression level of TIMP-1 decreased in the PWDHS group (P <0. 01). The severity of gastric mucosal inflammation was negatively correlated with the expression level of MMP-7, and positively correlated with the expression level of TIMP- 1 (P <0. 01). Hp infection degree was not obviously correlated with the expression level of MMP-7 in gastric mucosa (P >0. 05) , but positively correlated with the expression level of TIMP-1 in gastric mucosa (P <0. 05). Of them, the expression level of MMP-7 in gastric mucosa was positively correlated with the expression level of TIMP-1 in gastric mucosa (P <0. 01). Conclusions Comparatively lower expression of MMP-7 in gastric mucosal inflammation and imbalanced expression of TIMP-1 might be two of the pathogeneses of chronic stomach disease. Their various expressions in different CM syndromes might have certain expositions for microscopic research on "different syndromes of the same disease". Emotional fluctuation might also be one of important factors for chronic stomach disease.

[Immunological characteristic comparison of different genetic polymorphism recombinant of FnBPA-A of bovine Staphylococcus aureus strain].

Objective: To understand the impact of genetic polymorphism of FnBPA-A on the immune biological characteristics of Staphylococcus aureus. Methods: Sequence of FnBPA-A of Staphylococcus aureus isolated from bovine in Xinjiang was analyzed and 8 different genetic polymorphism eukaryotic recombinants of FnBPA-A were constructed. C57BL/6 mice were immunized with these recombinant plasmids and mice sera were collected. Level of the immune protection of immunized mice was compared. Results: GS801, GS819 and GS856 were on the same branch; GW10-1, GW20-2, GY288 and GY309 belong to the same branch; GY278 was on a different branch. For the challenge experiment, GW20-2, GS801, GS819, GS856 and GY288 showed better protection. Conclusion: The genetic polymorphism of FnBPA-A could significantly affect the immune protection of immunized mice.

ChatGPT achieves comparable accuracy to specialist physicians in predicting the efficacy of high-flow oxygen therapy.

Background: The failure of high-flow nasal cannula (HFNC) oxygen therapy can necessitate endotracheal intubation in patients, making timely prediction of the intubation risk following HFNC therapy crucial for reducing mortality due to delays in intubation. Objectives: To investigate the accuracy of ChatGPT in predicting the endotracheal intubation risk within 48 h following HFNC therapy and compare it with the predictive accuracy of specialist and non-specialist physicians. Methods: We conducted a prospective multicenter cohort study based on the data of 71 adult patients who received HFNC therapy. For each patient, their baseline data and physiological parameters after 6-h HFNC therapy were recorded to create a 6-alternative-forced-choice questionnaire that asked participants to predict the 48-h endotracheal intubation risk using scale options ranging from 1 to 6, with higher scores indicating a greater risk. GPT-3.5, GPT-4.0, respiratory and critical care specialist physicians and non-specialist physicians completed the same questionnaires (N = 71) respectively. We then determined the optimal diagnostic cutoff point, using the Youden index, for each predictor and 6-h ROX index, and compared their predictive performance using receiver operating characteristic (ROC) analysis. Results: The optimal diagnostic cutoff points were determined to be ≥ 4 for both GPT-4.0 and specialist physicians. GPT-4.0 demonstrated a precision of 76.1 %, with a specificity of 78.6 % (95%CI = 52.4-92.4 %) and sensitivity of 75.4 % (95%CI = 62.9-84.8 %). In comparison, the precision of specialist physicians was 80.3 %, with a specificity of 71.4 % (95%CI = 45.4-88.3 %) and sensitivity of 82.5 % (95%CI = 70.6-90.2 %). For GPT-3.5 and non-specialist physicians, the optimal diagnostic cutoff points were ≥5, with precisions of 73.2 % and 64.8 %, respectively. The area under the curve (AUC) in ROC analysis for GPT-4.0 was 0.821 (95%CI = 0.698-0.943), which was the highest among the predictors and significantly higher than that of non-specialist physicians [0.662 (95%CI = 0.518-0.805), P = 0.011]. Conclusion: GPT-4.0 achieves an accuracy level comparable to specialist physicians in predicting the 48-h endotracheal intubation risk following HFNC therapy, based on patient baseline data and physiological parameters after 6-h HFNC therapy.

Whole-Genome Sequencing and Phenotypic Analysis of Streptococcus equi subsp. zooepidemicus Sequence Type 147 Isolated from China.

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is one of the important zoonotic and opportunistic pathogens. In recent years, there has been growing evidence that supports the potential role of S. zooepidemicus in severe diseases in horses and other animals, including humans. Furthermore, the clinical isolation and drug resistance rates of S. zooepidemicus have been increasing yearly, leading to interest in its in-depth genomic analysis. In order to deepen the understanding of the S. zooepidemicus characteristics and genomic features, we investigated the genomic islands, mobile genetic elements, virulence and resistance genes, and phenotype of S. zooepidemicus strain ZHZ 211 (ST147), isolated from an equine farm in China. We obtained a 2.18 Mb, high-quality chromosome and found eight genomic islands. According to a comparative genomic investigation with other reference strains, ZHZ 211 has more virulence factors, like an iron uptake system, adherence, exoenzymes, and antiphagocytosis. More interestingly, ZHZ 211 has acquired a mobile genetic element (MGE), prophage Ph01, which was found to be in the chromosome of this strain and included two hyaluronidase (hyl) genes, important virulence factors of the strain. Moreover, two transposons and two virulence (virD4) genes were found to be located in the same genome island of ZHZ 211. In vitro phenotypic results showed that ZHZ 211 grows faster and is resistant to clarithromycin, enrofloxacin, and sulfonamides. The higher biofilm-forming capabilities of ZHZ 211 may provide a competitive advantage for survival in its niche. The results expand our understanding of the genomic, pathogenicity, and resistance characterization of Streptococcus zooepidemicus and facilitate further exploration of its molecular pathogenic mechanism.

No-interfered and visual evaluation of global warming impacts on phytoplankton-based copper bioavailability and then carbon sequestration.

Global warming has an increasingly serious impact on the ecological environment. Copper bioavailability plays an important physiological role in revealing the mechanism of carbon cycle, photosynthesis, and respiration. Here we reported a multifunctional carbon quantum dots fluorescence probe for no-interfered and visual determination of phytoplankton-based intracellular Cu(II), glucose, and reactive oxygen species (ROS). Glucose and ROS were explored to reflect the change in primary biomass and carbon sequestration. H2O2 is acted as the standard material of ROS, and the fitting parameter for glucose and H2O2 concentrations was 0.42(r = 0.9972). Both glucose, ROS, and Cu2+ detection have advantages of wide linear range (24.8-3.96 × 105 µg/L, 6-9.6 × 105 ng/L and 5-15 × 103 nmol/L, respectively), high precision (1.22 %, 6.38 %, and 7.37 %, respectively), and low detection limit (86.7 ng/L, 5.32 ng/L, and 0.367 nmol/L, respectively). Cu2+ uptake was increased with the increasing of temperature, and the copper bioavailability in increasing order was Cu-PorPhyr > Cu-phthalate > Cu-EDTA. There were significant positive correlation between glucose and Cu2+(r = 0.9943). Copper bioavailability would directly affect the carbon sequestration, i.e., when the concentration of intracellular copper increases by 1 mg/L, the content of intracellular glucose increases by 412 mg/L approximately, equally to 2.47 g/L of carbon dioxide was fixed.

Preparation of pectin-coated and chitosan-coated phenylethanoside liposomes: Studies on characterization, stability, digestion and release behavior.

In this paper, the effects of extrusion, ultrasound on physicochemical properties of liposomes were studied, and the liposomes were prepared by ethanol injection combined with extrusion-ultrasound. In addition, the quality of PhGs lips, pectin-coated PhGs lips (P-lips) and chitosan-coated PhGs lips (C-lips) was evaluated by the average particle size, encapsulation efficiency (EE) and other indicators, which indicated that the nanoparticles had been successfully prepared. Compared with extrusion or ultrasonic operation alone, the EEs of ethanol injection combined with extrusion-ultrasonic increased by 8 % and 18 % respectively. Subsequently, transmission electron microscopy, Fourier transform infrared spectroscopy and DSC thermal analysis showed that PhGs in PhGs lips may produce hydrogen bonding forces with phospholipids, and pectin and chitosan in P-lips and C-lips were not only coated on the surface of PhGs lips, but also might have some interaction between them. Cell experiments showed that PhGs lips, P-lips and C-lips can effectively improve the bioavailability of PhGs. In addition, the storage stability of P-lips and C-lips was not significantly improved compared to PhGs lips, but their digestive stability was significantly improved, and the final retention rate in simulated intestinal fluid was about 25 % higher than that of PhGs lips.

Inside and outside the neighborhood: Short-term and long-term subjective well-being by geographical context.

The value of linking urban environment and subjective well-being (SWB) is now well recognized. But whether the geographical context inside and outside the neighborhood has differential influence on long- and short-term SWB remains unclear. Based on the activity perspective, we used survey data from Guangzhou, China, integrating GPS data, portable environmental sensors data to analyze time-weighted and real-time geographical context inside and outside the neighborhood on long- and short-term SWB. The results show that SWB is not only influenced by the neighborhood environment, but also the geographical context outside the neighborhood. Time-weighted geographical environment inside the neighborhood has a higher impact and explanatory ability on long-term SWB, while real-time geographical environment outside the neighborhood has a higher impact and explanatory ability on short-term SWB. This study provides a new understanding for geographies of SWB through the extension of time and space, and also provides reference for more refined urban planning and governance in the future.

Application of a New Approach for Laparoscopic Resection of Bismuth IIIa Hilar Cholangiocarcinoma.

Background: Hilar cholangiocarcinoma (HCCA) has a high degree of malignancy and poor prognosis, and the best long-term prognosis can only be achieved by radical resection. However, the surgical steps are complicated, and the operating space is limited, making it hard to complete laparoscopically. So our team proposes a new surgical approach for laparoscopic left-liver-first anterior radical modular orthotopic right hemihepatectomy (Lap-Larmorh). In this way, we can simplify the operation steps and reduce the difficulty. Materials and Methods: We recorded and analyzed the clinical data of 26 patients with type IIIa HCCA, who underwent laparoscopic radical resection in our department from December 2018 to January 2023. According to the laparoscopic surgical approach, we divided the patients into the new approach (NA) group (n = 14) using the Lap-Lamorh and the traditional approach (TA) group (n = 12) not using the Lap-Lamorh. Results: All surgeries in this study were completed laparoscopically with no conversion to open surgery. The operation time in the NA group and TA group had statistically significant differences, which was 372.5 (332.8, 420.0) minutes versus 423.5 (385.8, 498.8) minutes (P = .019). The two groups showed no significant difference in other characteristics (P > .05). Only 1 patient suffered from transient liver failure due to portal vein thrombosis. Patients with pleural effusion or ascites were cured by catheter drainage and enhanced nutrition. Conclusion: Lap-Larmorh reduces the difficulty of serving the vessels at the second and third hepatic hilum by splitting the right and left livers early intraoperatively. The new approach is more suitable for the narrow space of laparoscopic surgery and reflects the no-touch principle of oncology.

[Using reporter gene to compare infection efficiency of HIV-1 pseudovirus to suspended and adherent cells].

OBJECTIVE: In order to compare the infection of HIV-1 pseudovirus to suspended and adherent cells, Tzmbl cells containing beta-gal (beta-galactosidase) reporter gene were used here to do the analysis. pseudoviruses were generated by co-transfection of 293T cells with the plasmid pNL43R-E- and HIV envelope expressing plasmid. Supernatant of co-transfected 293T cells was collected and used to infect Tzmbl cells with or without trypsin treatment. Forty-eight hours after infection, beta-gal positive Tzmbl cells and virus infection were determined using X-gal staining and beta-glo (beta-galactosidase) assay. RESULTS: The efficiency of HIV pseudoviruses infection of suspended Tzmbl cell was higher than that of adherent cells and the increase of infection correlated with the pseudoviral subtype. CONCLUSION: This study may provide a useful method for HIV biological study and neutralization assays using a single-round replicative pseudovirus in the future.

Long-Term Residential Environment Exposure and Subjective Wellbeing in Later Life in Guangzhou, China: Moderated by Residential Mobility History.

With rapid global urbanization, the importance of understanding relationships between the changing environment and wellbeing is being increasingly recognized. However, there is still a lack of understanding of how long-term residential environment exposure affects subjective wellbeing under the dual changes of geographical environment and residential location. Based on a survey of the elderly (people over 60 years old) in Guangzhou, China, this study analyzes the effect of long-term residential environment exposure over 25 years on subjective wellbeing in later life in the context of residential mobility. The study found that subjective wellbeing in later life is not only related to the current residential environment but also the cumulative exposure to the long-term residential environment. The relationship between long-term residential environment exposure and subjective wellbeing in later life tends to be stable with the increase of cumulative time, especially the cumulative years over 15 years. Considering the importance of residential mobility history, the study further analyzes the moderating effects of relocation frequency and residential location. Relocation frequency can strengthen the positive effect of residential environment on subjective wellbeing and weaken the negative effect of residential environment on subjective wellbeing, which confirms the existence of residential self-selection. In addition, the direction of effect of residential environment on residents who move between living in the urban center and the periphery is consistent with that of residents who have always lived in the urban center, while the effects of the residential environment on residents who have always lived in the urban center and those who have always lived in the urban periphery are related in different directions. The conclusion of this study can provide guidance for individuals' residential choice and governance of the urban environment to improve wellbeing.

Spatial Inequalities and Influencing Factors of Self-Rated Health and Perceived Environmental Hazards in a Metropolis: A Case Study of Zhengzhou City, China.

Research on environmental pollution and public health has aroused increasing concern from international scholars; particularly, environmental hazards are among the important issues in China, focusing public attention on significant health risks. However, there are few studies concentrated on how perceived environmental hazards are characterized by spatial variation and on the impact of these risks on residents' health. Based on a large-scale survey of Zhengzhou City in 2020, we investigated how the self-rated health of residents and the environmental hazards perceived by them were spatially inequal at a fine (subdistrict) scale in Zhengzhou City, China, and examined the relationship among self-rated health, environmental hazards, and geographical context. The Getis-Ord Gi* method was applied to explore the spatially dependent contextual (neighborhood) effect on environmental health inequality, and the ordered multivariate logistic regression method was used to examine the correlative factors with environmental hazards, geographical context, and health inequality. The results reveal that self-rated health and environmental hazards were disproportionately distributed across the whole city and that these distributions showed certain spatial cluster characteristics. The hot spot clusters of self-rated health had favorable environmental quality where the hot spot clusters of environmental hazards were located and vice versa. In addition, health inequality was evident and was related to gender, income level, educational attainment, and housing area of residents, and the inequalities of environmental hazards existed with respect to income and housing area. Meanwhile, environmental risk inequalities associated with the social vulnerability of residents (the poor and those with low educational attainment) were obvious, with those residents experiencing a disproportionately high exposure to environmental hazards and reporting bad health conditions. The role of the geographical context (subdistrict location feature) also helps to explain the spatial distribution of health and environmental inequalities. Residents with better exposure to green coverage generally reported higher levels of self-rated health condition. In addition, the geographical location of the subdistrict also had a significant impact on the difference in residents' self-rated health status. The purpose of this study is to provide reference for policy makers to optimize the spatial pattern of urban public services and improve public health and environmental quality at a fine scale.

WD repeat domain 62 (WDR62) promotes resistance of colorectal cancer to oxaliplatin through modulating mitogen-activated protein kinase (MAPK) signaling.

WD repeat domain 62 (WDR62) is involved in embryonic brain growth through regulation of glial and neural cell populations. WDR62 is also implicated in the carcinogenesis of various cancers. The role of WDR62 in progression and chemoresistance of colorectal cancer (CRC) was investigated. Firstly, oxaliplatin-resistant CRC cells (HCT116/R and HT29/R) were sequentially exposed to an increasing concentration of oxaliplatin. The results showed that WDR62 was elevated in CRC tissues, and oxaliplatin resistance conferred up-regulation of WDR62 in CRC cells. Knockdown of WDR62 reduced cell proliferation and promoted the apoptosis of oxaliplatin-resistant CRC cells. Moreover, silencing of WDR62 increased fluorescence intensity of γH2AX, and decreased protein expression of p-DNA-PK and Rad51 in the oxaliplatin-resistant CRC cells. The protein expression of p-ERK, p-JNK, and p-p38 in oxaliplatin-resistant CRC cells were down-regulated by knockdown of WDR62. In conclusion, silencing of WDR62 suppressed oxaliplatin resistance and DNA damage repair of CRC cells through inactivation of MAPK signaling.

Enhanced immune effects and protection conferred by simultaneously targeting GAPDH, SeM, and EAG of S. equi via TLR4.

Strangles, which is caused by Streptococcus equi subspecies equi, is one of the most prevalent equine infectious diseases and poses heavy economic losses worldwide. Although various vaccines have been used for decades, they seemed to be sub-optimal to demonstrate effective protection, and the antigen component of vaccines against S. equi remains to be optimized. In the present study, three target antigens (M-like protein, α2-macroglobulin and IgG-binding protein, and glyceraldehyde-3-phosphate dehydrogenase) were selected and expressed. Mice were immunized and challenged, and their immune response and efficacy were evaluated. The results revealed that this optimized multi-antigen treatment elicited a high expression level of T-cell receptor, major histocompatibility complex I, toll-like receptor TLR-4, and increased specific antibody. In addition, the challenge experiment showed an evidently improved protection efficacy. The present work demonstrated that these three proteins might be used as a promising multicomponent subunit vaccine candidate against S. equi infection.

Optimized GAPDH-truncated immunogen of Streptococcus equi elicits an enhanced immune response and provides effective protection in a mouse model.

Strangles is an acute and frequently diagnosed infectious disease caused by Streptococcus equi subsp. equi. Infection with this pathogen can cause grave losses to the equine industry. The present work investigates glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important surface-localized virulence factor of S. equi, to determine whether it could be developed into an efficacious and suitable subunit vaccine against strangles. Two different recombinant fragments of S. equi GAPDH, namely, GAPDH-L and GAPDH-S, were constructed and expressed. Further, the antigenicity and immunogenicity of these two recombinant proteins were compared and evaluated in a mouse model. Our results revealed that immune responses were efficiently induced by the proteins in immunized mice. Remarkably, higher survival rates and significantly lower bacterial loads in the lung, liver, kidney, and spleen were observed in the GAPDH-S group compared with the GAPDH-L group after challenge with S. equi. High levels of specific antibodies, elevated antibody titers, and increased proportions of CD8 + T cells further indicated that GAPDH-S elicited better humoral and cellular immune responses than GAPDH-L. Furthermore, the induction of TCR, TLR-2, TLR-3, and TLR-4 significantly increased in the GAPDH-S group compared with those in the GAPDH-L and negative control groups. In summary, our results indicate that the optimized recombinant protein GAPDH-S is a promising candidate construct that may be further developed into a multivalent subunit vaccine for strangles.