Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state.

JOURNAL/nrgr/04.03/01300535-202410000-00024/figure1/v/2024-02-06T055622Z/r/image-tiff Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

Sample size adaptation designs and efficiency comparison with group sequential designs.

This study is to give a systematic account of sample size adaptation designs (SSADs) and to provide direct proof of the efficiency advantage of general SSADs over group sequential designs (GSDs) from a different perspective. For this purpose, a class of sample size mapping functions to define SSADs is introduced. Under the two-stage adaptive clinical trial setting, theorems are developed to describe the properties of SSADs. Sufficient conditions are derived and used to prove analytically that SSADs based on the weighted combination test can be uniformly more efficient than GSDs in a range of likely values of the true treatment difference δ $$ \delta $$ . As shown in various scenarios, given a GSD, a fully adaptive SSAD can be obtained that has sufficient statistical power similar to that of the GSD but has a smaller average sample size for all δ $$ \delta $$ in the range. The associated sample size savings can be substantial. A practical design example and suggestions on the steps to find efficient SSADs are also provided.

The formation mechanism of primary health care team effectiveness : a qualitative comparative analysis research.

BACKGROUND: Team-based care is an essential part of primary health care (PHC), and its team service delivery process is a systematic one involving multiple and complex influences. Research on the formation mechanism can help improve the effectiveness of primary health care teams (PHCTs). METHODS: First, based on the Donabedian model, we explored the theoretical framework of a PHC team's effectiveness formation mechanism. Semi-structured interviews were conducted with 23primary health care team members in Hangzhou, Zhejiang Province, China. A total of seven factors were then included as conditional variables using the crisp set qualitative comparative analysis (csQCA) to explore the complex influences between them and the outcome variable through univariate necessity analysis and path configuration analysis. RESULTS: Univariate necessity analysis showed that only "Clear Goals" in the structural dimension were necessary for team effectiveness perception. Six pathways to good primary health care team perception of effectiveness were identified. Two of these paths were more typical. CONCLUSION: "Clear Goals" was the core variable that should be emphasized when exploring the mechanism of PHCT formation. The results suggest that human resources in the management team should be rationally allocated, goal-oriented, and given good attention. Future studies should explore complex combinations of PHCT factors to improve the effectiveness of PHCTs.

Biomimetic 3D Color-Changing Hydrogel Actuators Constructed Based on Soft Permeable Photonic Crystals.

The integration of photonic crystals and self-shaping actuators is a promising method for constructing powerful biomimetic color-changing actuators. The major barrier is that common photonic crystals generally block the transfer/orientation of monomers/fillers and hence hinder the formation of heterogeneous structures for programmed 3D deformations as well as degrade the deformation capacity and mechanical properties of actuators. Herein, we present the construction of complex and strong 3D color-changing hydrogel actuators by asymmetric photolithography based on soft, permeable photonic crystals. The soft permeable photonic crystals are assembled by hydrogel microspheres with an ultralow volume fraction. During the asymmetric photolithography, the monomers in precursor solutions can thus transfer freely to generate heterogeneous microstructures, spatially patterned internal stresses, and interpenetrating networks for programming the deformation trajectories and initial 3D configurations and enhancing mechanical properties of actuators. Various 3D color-changing hydrogel actuators (e.g., flower and scroll painting) are constructed for applications such as information encryption and display.

Combining decellularized adipose tissue with decellularized adventitia extravascular matrix or small intestinal submucosa matrix for the construction of vascularized tissue-engineered adipose.

Adipose tissue is an endocrine organ. It serves many important functions, such as energy storage, hormones secretion, and providing insulation, cushioning and aesthetics to the body etc. Adipose tissue engineering offers a promising treatment for soft tissue defects. Early adipose tissue production and long-term survival are closely associated with angiogenesis. Decellularized matrix has a natural ECM (extracellular matrix) component, good biocompatibility, and low immunogenicity. Therefore, in this study, the injectable composite hydrogels were developed to construct vascularized tissue-engineered adipose by using the pro-angiogenic effects of aortic adventitia extravascular matrix (Adv) or small intestinal submucosa (SIS), and the pro-adipogenic effects of decellularized adipose tissue (DAT). The composite hydrogels were cross-linked by genipin. The adipogenic and angiogenic abilities of composite hydrogels were investigated in vitro, and in a rat dorsal subcutaneous implant model. The results showed that DAT and SIS or Adv 1:1 composite hydrogel promoted the migration and tube formation of endothelial cells. Furthermore, DAT and SIS or Adv 1:1 composite hydrogel enhanced adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs) through activation of PPARγ and C/EBPα. The in vivo studies further demonstrated that DAT with SIS or Adv in a 1:1 ratio also significantly promoted adipogenesis and angiogenesis. In addition, DAT with SIS or Adv in a 1:1 ratio hydrogel recruited macrophage population with enhanced M2-type macrophage polarization, suggesting a positive effect of inflammatory response on angiogenesis. In conclusion, these data suggest that the composite hydrogels of DAT with SIS or Adv in 1:1 ratio have apparent pro-adiogenic and angiogenic abilities, thus providing a promising cell-free tissue engineering biomaterial with broad clinical applications. STATEMENT OF SIGNIFICANCE: Decellularized adipose tissue (DAT) has emerged as an important biomaterial in adipose tissue regeneration. Early adipose tissue production and long-term survival is tightly related to the angiogenesis. The revascularization of the DAT is a key issue that needs to be solved in adipose regeneration. In this study, the injectable composite hydrogels were developed by using DAT with Adv (aortic adventitia extravascular matrix) or SIS (small intestinal submucosa) in different ratio. We demonstrated that the combination of DAT with SIS or Adv in 1:1 ratio effectively improved the proliferation of adipose stem cells and endothelial cells, and promoted greater adipose regeneration and tissue vascularization as compared to the DAT scaffold. This study provides the potential biomaterial for clinical soft tissue regeneration.

Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication.

Treatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impact of p53 and Fos on ILTV replication has 'not been fully understood yet. Using the sole ILTV-permissive chicken cell line LMH as a model, we examined the effects of hosts p53 and Fos on all phases of ILTV replication, including viral gene transcription, viral genome replication, and infectious virion generation. We achieved this by manipulating the expression of p53 and Fos in LMH cells. Our results demonstrate that the overexpression of either p53 or Fos can promote viral gene transcription at all stages of the temporal cascade of ILTV gene expression, viral genome replication, and infectious virion production, as assessed through absolute quantitative real-time PCR, ILTV-specific RT-qPCR assays, and TCID50 assays. These findings are consistent with our previous analyses of the effects of Fos and p53 knockdowns on virus production and also suggest that both p53 and Fos may be dispensable for ILTV replication. Based on the synergistic effect of regulating ILTV, we further found that there is an interaction between p53 and Fos. Interestingly, we found that p53 also has targeted sites upstream of ICP4, and these sites are very close to the Fos sites. In conclusion, our research offers an in-depth understanding of how hosts p53 and Fos affect ILTV replication. Understanding the processes by which p53 and Fos regulate ILTV infection will be improved by this knowledge, potentially paving the way for the development of novel therapeutics targeting virus-host interactions as a means of treating herpesvirus infections.

Cognitive Activities, Lifestyle Factors, and Risk of Cognitive Impairment, with an Analysis of the Apolipoprotein Epsilon 4 Genotype.

INTRODUCTION: Cognitive stimulating activities and a healthy lifestyle are associated with less cognitive impairment. However, whether the association is varied by Apolipoprotein epsilon 4 (APOE ε4) allele carrier status remains inconclusive. We aimed to investigate whether the association of cognitively stimulating activities and a healthy lifestyle with the risk of cognitive impairment varied by APOE ε4 allele carrier status. METHODS: A case-control study was conducted for adults aged 60 years and above. Six province administrative units (Beijing, Shanghai, Hubei, Sichuan, Guangxi, and Yunnan) were included using stratified multistage cluster sampling. A total of 1,300 individuals were identified with cognitive impairment (cases) at enrollment and were matched 1:2 on sex, age (±2 years), and residential district with controls who were cognitively normal at the time of the evaluation. We used a standardized questionnaire to collect information on cognitive stimulating activities, lifestyle factors, demographics, and comorbidity. Cognitive stimulating activities included reading books or newspapers, playing cards or mahjong, using the Internet, socializing with neighbors, and community activities. Lifestyle factors included smoking, alcohol drinking, daily tea drinking, and regular exercise. We used logistic regression to assess the interaction between cognitive stimulating activities, lifestyle factors, and APOE ε4 allele carrier status (yes/no) on the risk of cognitive impairment. We tested for additive interaction by estimating relative excess risk (RERI) due to interaction and multiplicative interaction employing the p value of the interaction term of each lifestyle factor and APOE ε4 into the model. RESULTS: Four cognitive stimulating activities were associated with less cognitive impairment regardless of APOE ε4 status. Using the Internet (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.30-0.95), daily tea drinking (OR: 0.79; 95% CI: 0.63-0.98), and regular exercise (OR: 0.78; 95% CI: 0.65-0.94) were associated with less cognitive impairment only in noncarriers. Multiplicative and additive interactions were found between community activities and APOE ε4 carrier status (multiplicative p value = 0.03; RERI 0.738, 95% CI: 0.201-1.275). CONCLUSION: The associations between cognitive activities and cognitive impairment were robust regardless of the APOE ε4 carrier status, while the associations between lifestyle factors and cognitive impairment varied by APOE ε4 carrier status.

Distribution, risk assessment of heavy metals in sediments, and their potential risk on water supply safety of a drinking water reservoir, middle China.

Heavy metals in reservoir sediments were analyzed to assess the pollution level and to understand the potential risk on water supply safety. Heavy metals in sediments will enter the biological chain through bio-enrichment and bio-amplification in water and eventually pose a threat to the safety of drinking water supply. Analysis of eight sampling sites in JG (Jian gang) drinking water reservoir of the sediments showed that from Feb 2018 to Aug 2019 heavy metals including Pb, Ni, Cu, Zn, Mo, and Cr increased by 1.09-17.2%. Vertical distributions of heavy metals indicated that the concentrations increased gradually by 9.6-35.8%. Risk assessment code analysis indicated that Pb, Zn, and Mo were of high risk in the main reservoir area. What is more, enrichment factors of Ni and Mo were 2.76-3.81 and 5.86-9.41, respectively, showing the characteristics of exogenous input. The continuous monitoring results of the bottom water showed that the concentration of heavy metals in the bottom water exceeded the environmental quality standard value of surface water in China, and exceeded the standard by 1.76 times (Pb), 1.43 times (Zn), and 2.04 times (Mo), respectively. Heavy metals in the sediments of JG Reservoir, especially in the main reservoir area, have a potential risk of release from the sediment to the overlying water. Water supply reservoir as a source of drinking water, its quality is directly related to human health and production activities. Therefore, this first study on JG Reservoir is of great significance for the protection of drinking water safety and human health.

Levocetirizine-Loaded Electrospun Fibers from Water-Soluble Polymers: Encapsulation and Drug Release.

Electrospun fibers containing levocetirizine, a BCS III drug, were prepared from three water-soluble polymers, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). Fiber-spinning technology was optimized for each polymer separately. The polymers contained 10 wt% of the active component. An amorphous drug was homogeneously distributed within the fibers. The solubility of the drug in the polymers used was limited, with a maximum of 2.0 wt%, but it was very large in most of the solvents used for fiber spinning and in the dissolution media. The thickness of the fibers was uniform and the presence of the drug basically did not influence it at all. The fiber diameters were in the same range, although somewhat thinner fibers could be prepared from PVA than from the other two polymers. The results showed that the drug was amorphous in the fibers. Most of the drug was located within the fibers, probably as a separate phase; the encapsulation efficiency proved to be 80-90%. The kinetics of the drug release were evaluated quantitatively by the Noyes-Whitney model. The released drug was approximately the same for all the polymers under all conditions (pH), and it changed somewhere between 80 and 100%. The release rate depended both on the type of polymer and pH and varied between 0.1 and 0.9 min-1. Consequently, the selection of the carrier polymer allowed for the adjustment of the release rate according to the requirements, thus justifying the use of electrospun fibers as carrier materials for levocetirizine.

Electro-reduction induced fast metal redox cycle on Co3O4-CuO@CNTs/Copper foam cathode for enhanced Fenton-like reaction.

In this study, free-standing Co3O4-CuO/CF electrodes are synthesized via an electrodeposition-annealing process and then protected by dip-coated carbon nanotubes (CNTs). The obtained Co3O4-CuO@CNTs/CF is employed as cathode to activate peroxymonosulfate (PMS) for the degradation of Bisphenol A (BPA) in an electrochemical system. The electrochemical assistant (EA) plays a critical role to accelerate metal redox by donating electrons sustainably, and the fast regeneration of Co2+/Cu+ could be achieved to promote chemical-catalysis for PMS activation, which is proved via the pre-electroreduction treatment. The rate constant of Co3O4-CuO@CNTs/CF/PMS system with EA is âˆ¼ 4.4 times compared to the system without EA. It also exhibits an excellent stability, which could still remove over 90% of BPA after eight cycles in 45 min. In addition, the coating of CNTs could decrease leaching of metals effectively. According to quenching tests and electron spin-resonance spectroscopy (ESR), the presence of EA could enhance the radical route by producing more SO4•- and •OH greatly, which is also proved by much faster degradation of carbamazepine (CBZ) and atrazine (ATZ) than that without EA. This work reveals activation mechanism of PMS in the electrochemical system, and provides an effective strategy to achieve the fast metal redox cycle for effective and long-term pollutant degradation.

Innate immune cell activation causes lung fibrosis in a humanized model of long COVID.

COVID-19 remains a global pandemic of an unprecedented magnitude with millions of people now developing "COVID lung fibrosis." Single-cell transcriptomics of lungs of patients with long COVID revealed a unique immune signature demonstrating the upregulation of key proinflammatory and innate immune effector genes CD47, IL-6, and JUN. We modeled the transition to lung fibrosis after COVID and profiled the immune response with single-cell mass cytometry in JUN mice. These studies revealed that COVID mediated chronic immune activation reminiscent to long COVID in humans. It was characterized by increased CD47, IL-6, and phospho-JUN (pJUN) expression which correlated with disease severity and pathogenic fibroblast populations. When we subsequently treated a humanized COVID lung fibrosis model by combined blockade of inflammation and fibrosis, we not only ameliorated fibrosis but also restored innate immune equilibrium indicating possible implications for clinical management of COVID lung fibrosis in patients.

Association of early-life famine exposure with low bone mass in adulthood.

Famine exposure in early life has been found to have a long-term effect on metabolic diseases, but its effect on bone health was not clear. In this study, we found women, who suffered from famine exposure during their childhood or adolescence period, had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. The risk of clinical fracture was also elevated in adolescence-exposed women. PURPOSE: To investigate the correlation between famine exposure at certain stages and bone mass in adulthood. METHODS: We enrolled participants born in 1943-1962 from the China Osteoporosis Prevalence Study (COPS), which were classified into three famine exposure groups according to their birth year: fetal-famine exposure (1959-1962, n = 1693), childhood-famine exposure (1949-1958, n = 5557), and adolescence-famine exposure (1943-1948, n = 1530). We also selected age-balanced non-exposed participants as the control groups for men and women separately. Bone mineral density (BMD) and vertebral fractures (VFs) were measured by dual X-ray absorptiometry (DXA) and X-ray, respectively. The associations of famine exposure in early life with BMD were assessed via multiple linear regression. Logistic regression was performed to examine the association of famine exposure in early life with fracture risk with adjustments for covariates. RESULTS: In women, the childhood-exposed and adolescence-exposed groups had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. No significant decreased BMD was found in the fetal-exposed groups compared to the non-exposed groups in both sexes. Multiple linear regression analysis showed that famine exposure during childhood and adolescence was negatively associated with BMD at the femoral neck after adjusting for covariates in women. The risk of clinical fracture was also elevated in adolescence-exposed women. CONCLUSION: Famine exposure during early life especially childhood and adolescence is associated with decreased bone mass in adulthood in women but did not affect bone mass in men.

Excessive dietary L-tryptophan regulated amino acids metabolism and serotonin signaling in the colon of weaning piglets with acetate-induced gut inflammation.

L-Tryptophan (Trp) was shown to improve the gut barrier and growth of weaning piglets. However, whether excessive dietary Trp regulates amino acids (AAs) metabolism and gut serotonin (5-HT) homeostasis in piglets with gut inflammation is not clear yet. We hypothesize that excessive dietary Trp alleviates acetate-induced colonic inflammation and gut barrier damage in weaning piglets partially through the regulation of colonic AAs metabolism and 5-HT signaling. Fifty-four 21-day-old weaned piglets were divided into six groups: control, acetate, 0.2%Trp, 0.2%Trp + acetate, 0.4% Trp, and 0.4%Trp + acetate. Piglets were fed a basal diet supplemented with 0%, 0.2%, or 0.4% of Trp throughout the 12-day experiment. During days 0-7, all piglets had free access to diet and drinking water. On day 8, piglets were intrarectal administered with 10 mL of 10% acetate saline solution or 0.9% saline. During days 8-12, all piglets were pair-fed the same amount of feed per kg bodyweight. Results showed that excessive dietary Trp alleviated acetate-induced reductions in daily weight gain and increase in feed/gain ratio. Trp restored (P < 0.05) acetate-induced increase in concentrations of free aspartate, glutamate/glutamine, glycine, 5-HT, and 3-methylindole in the colon, downregulation of zonula occludens-1 and 5-HT reuptake transporter (SERT) expression and upregulation of IL-1ß, IL-8, TLR4, and 5-HT receptor 2A (HTR2A) expression, and the increase in ratios of p-STAT3/ STAT3 and p-p65/p65 in the colon. The above findings suggested that excessive dietary Trp in the proper amount regulated colonic AAs metabolism, 5-HT homeostasis, and signaling that may contribute as important regulators of gut inflammation during the weaning transition.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

How to Break through the Bottlenecks of in Ovo Vaccination in Poultry Farming.

Poultry farming is one of the pillar industries of global animal husbandry. In order to guarantee production, poultry are frequently vaccinated from the moment they are hatched. Even so, the initial immunity of chicks is still very poor as they are in the "window period" of immune protection. In ovo vaccination pushes the initial immunization time forward to the incubation period, thereby providing earlier immune protection for chicks. In ovo vaccination is currently a research hotspot of poultry disease prevention and control, which is in line with the intensification of poultry production. However, the vaccines currently available for in ovo vaccination are limited and cannot meet the needs of industrial development, so how to efficiently activate the adaptive immune response of chicken embryos becomes the key to restrict product development and technological progress of in ovo vaccination. Its breakthrough, to a large extent, depends on systematic illustration of the mechanism underlying the adaptive immune response post immunization. Clarification of this issue will provide us with theoretical support and potential solutions for the development of novel vaccines for in ovo vaccination, the augmentation of efficacy of current vaccines and the optimization of immune programs.

P53 maintains gallid alpha herpesvirus 1 replication by direct regulation of nucleotide metabolism and ATP synthesis through its target genes.

P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-α (PFT-α) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-α and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-α on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-α in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.

Characterization of chicken p53 transcriptional function via parallel genome-wide chromatin occupancy and gene expression analysis.

The tumor suppressor p53, which acts primarily as a transcription factor, can regulate infections from various viruses in chickens. However, the underlying mechanisms of the antiviral functions of chicken p53 (chp53) remain unclear due to the lack of detailed information on its transcriptional regulation. Here, to gain comprehensive insights into chp53 transcriptional regulatory function in a global and unbiased manner, we determined the genome-wide chromatin occupancy of chp53 by chromatin immunoprecipitation, which was followed by sequencing and chp53-mediated gene expression profile by RNA sequencing using chemically immortalized leghorn male hepatoma (LMH) cells with ectopic expression of chp53 as the model. The integrated parallel genome-wide chromatin occupancy and gene expression analysis characterized chp53 chromatin occupancy and identified 754 direct target genes of chp53. Furthermore, functional annotation and cross-species comparative biological analyses revealed the conserved key biological functions and DNA binding motifs of p53 between chickens and humans, which may be due to the consensus amino acid sequence and structure of p53 DNA-binding domains. The present study, to our knowledge, provides the first comprehensive characterization of the chp53 transcriptional regulatory network, and can possibly help to improve our understanding of p53 transcriptional regulatory mechanisms and their antiviral functions in chickens.

[Urban thermal environment effects based on visual indices: A case study in Xuzhou City, China]. / 基于视觉指数的城市热环境效应­­ä»¥å¾å·žå¸‚为例.

Urban thermal environments are closely related to habitats, citizens' health, and sustainable development. Based on green view index (GVI), we proposed two new visual indices, construction view index (CVI) and imperious surface view index (R&PVI). Mobile observation was used to obtain urban thermal environment data, images and coordinates synchronously in Xuzhou City in late summer, including urban area (U), scenic area (S), exterior of university campus (E), and university campus inside (CUMT). We analyzed the impacts of the urban composition represented by the visual index on the urban thermal environment. The results showed that, along the sampling line, mean air temperature (Ta) was highest (30.42 ℃) and mean relative humidity (RH) was lowest (40.7%) in urban area, while mean Ta was lowest (29.35 ℃) and mean RH was highest (48.4%) in scenic area. The situation of mean wind-chill temperature (TaW) was the highest (32.95 ℃) in the urban area and the lowest (31.93 ℃) in the scenic area. As for CVI, urban area, university campus inside, exterior of university campus and scenic area ranked in descending order, while GVI showed an opposite pattern. CVI was significantly positively correlated to Ta and TaW, but negatively to RH. GVI was significantly negatively correlated to Ta and TaW, but positively to RH. R&PVI was significantly positively correlated to Ta and TaW, but not correlated to RH. CVI and GVI influenced Ta significantly, with the independent effects being 10.4% and 18.9%, and joint effects being 7.8% and 11.3%, respectively. As for RH, CVI and GVI contributed significantly as well, independent effects were 37.5% and 15.7%, and joint effects were 51.4% and 30.2%, respectively. As for TaW, the three visual indices contributed significantly, but independent and joint effects were lower than those on Ta. Moreover, visual indices contributed more on RH than Ta or TaW. The results could provide ideas for optimizing urban thermal environments and mitigating urban heat island effects, and have practical implications for urban renewal and improvement of the quality of human living environment.

Retrospective analysis of Hemoporfin-mediated photodynamic therapy in the treatment of naïve port-wine stains.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) is a safe and effective treatment modality for port-wine stain (PWS). However, there is still no consensus about the influential factors for the efficacy of the treatment. This study investigated the influential factors associated with the efficacy of Hemoporfin-PDT. METHODS: We retrospectively analyzed 321 PWS patients who underwent Hemoporfin-PDT at our center from August 2017 to July 2021. The correlation between efficacy versus sex, age, location, type of PWS, treatment numbers, and the lesion size were analyzed. RESULTS: The numbers of treatment sessions undertaken were associated with the response to therapy, and compared with patients who received one session, patients who received two or more sessions showed a better response (ORadj=2.46, 95%CI, 1.49-4.07; ORadj=6.01, 95%CI, 3.38-10.70, P<0.001). The effect on central face, peripheral face, and neck was superior to the extremity and trunk, respectively (P<0.001). The lesion size smaller than and equal to 25 cm² showed a better effect than those whose lesion size was larger than 64 cm² (ORadj=1.92, 95%CI, 1.03-3.57, P=0.040). However, other variables, including sex and age, were not associated with the efficacy of the treatment. CONCLUSIONS: Hemoporfin-PDT is an effective and safe treatment for PWS. The number of treatments was a favorable factor for Hemoporfin-PDT, smaller lesion sizes showed a better effect than the larger one, and the location of extremity and trunk was a negative factor.

Pectic polysaccharides ameliorate the pathology of ulcerative colitis in mice by reducing pyroptosis.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease which seriously affects the quality of life of patients. There has been an increasing amount of research related to the therapeutic effects and mechanisms of natural plant substances in the treatment of recurrent UC. Rauwolfia verticillata var. Hainanensis is a medicinal plant that is native to Hainan Island, China. Some studies have documented that pectic polysaccharides (PPs) from Rauvolfia inhibited the progression of colon ulcers. However, their mechanisms of action have not been established. Studies have revealed that suppressing pyroptosis can attenuate the damage of experimental colitis. However, it is unclear whether PPs from Rauvolfia verticillata inhibit inflammation through pyroptosis. This study investigated the effects and potential mechanisms of PPs extracted from Rauvolfia verticillata on experimental UC in mice. Methods: Male C57 mice (6-8 weeks old) were allocated into the control group, the dextran sulfate sodium (DSS)-induced UC model group (DSS group), or the DSS with pectic polysaccharides treatment group (DSS + PP group). The body weights, rectal bleeding, and stool consistencies in the mice were observed, and the disease activity index (DAI) score was calculated. Colon tissues were collected for pathological analysis by histological hematoxylin and eosin (H&E) staining. The levels of caspase-1 and interleukin (IL)-1ß were detected by immunohistochemistry. Pyroptosis was assessed by transmission electron microscopy. Results: UC in mice induced by DSS resulted in decreased general physical activity and body weight, increased DAI score, significant histological changes, inhibited caspase-1 and IL-1ß expression, and promoted pyroptosis. These DSS-induced changes could be partially ameliorated by administration of PP. Conclusions: PPs exerted an ameliorative effect on DSS-induced UC in mice by reducing pyroptosis.