Role of Helicobacter pylori virulence factors and alteration of the Tumor Immune Microenvironment: challenges and opportunities for Cancer Immunotherapy.

Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.

B3GNT7 regulates mucin O-glycosylation to alleviate colonic inflammation.

BACKGROUND: B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological processes. This study elucidates novel insights into the potential role and underlying mechanisms of B3GNT7 in ulcerative colitis (UC). METHODS: An experimental colitis model was induced using DSS in mice to investigate B3GNT7 expression in the colon via transcriptomics and immunohistochemistry. Bioinformatics analysis was employed to delineate the biological functions of B3GNT7. Additionally, the correlation between the transcription levels of B3GNT7 in colonic tissues from patients with UC, sourced from the IBDMDB database, and the severity of colonic inflammation was analyzed to elucidate potential mechanisms. RESULTS: The DSS-induced colitis model was successfully established, and transcriptomic analysis identified a marked downregulation of B3GNT7 expression in the colonic tissues compared to the controls. Functional enrichment analysis indicated B3GNT7's predominant role in mucin O-glycosylation. Protein interaction analysis revealed that B3GNT7 predominantly interacts with members of the mucin MUC family, including MUC2, MUC3, and MUC6. In patients with UC, B3GNT7 transcription levels were significantly reduced, particularly in those with moderate to severe disease activity. The expression level of B3GNT7 exhibited a negative correlation with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further demonstrated significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis pathway. CONCLUSION: The downregulation of B3GNT7 expression in the colonic tissues of UC patients may contribute to the compromised mucin barrier function and the exacerbation of colitis.

Transplantation of olfactory mucosa mesenchymal stromal cells repairs spinal cord injury by inducing microglial polarization.

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.

Fabrication and Characterization of a High-Strength Polyimide/Thermoplastic Polyurethane Composite Aerogel with Hydrophobicity and Low Thermal Conductivity.

Polyimide (PI) aerogel has surfaced in research and development as a result of its heat resistance, flame retardancy, and low dielectric constant. However, it is still a challenge to reduce the thermal conductivity while improving its mechanical strength and retaining hydrophobicity. Herein, the PI/thermoplastic polyurethane (TPU) composite aerogel was synthesized by coupling TPU with PI via a novel method of chemical imidization combined with freeze-drying technology. With this technique, PI aerogel with excellent comprehensive performance is produced. Interestingly, the volume shrinkage of the composite aerogel decreased from 24.14 to 5.47%, which leads to low density (0.095 g/cm3) and elevated porosity (92.4%). In addition, strong mechanical strength (1.29 MPa) and high hydrophobicity (123.6°) were achieved. More importantly, PI/TPU composite aerogel demonstrated a low thermal conductivity of 29.51 mW m-1 K-1 at ambient temperature. Therefore, PI/TPU composite aerogel can be a promising material for hydrophobic and thermal insulation applications.

Changes in plant community assembly from patchy degradation of grasslands and grazing by different-sized herbivores.

Grassland degradation caused by increases in livestock grazing threatens a variety of ecosystem services. Understanding changes in plant community assembly during the process of grassland degradation in the presence of grazing is important to help restore degraded grasslands worldwide but has received little attention thus far. The grassland degradation process is typified by heterogeneous degradation, that is, gradual formation of degraded patches (hereafter "patchy degradation"). Here, we experimentally examined the effects of herbivore grazing and patchy degradation on plant community assembly using nine pairs of non-degraded (intact) and patch-degraded (fragmented) grasslands subject to grazing by different-sized herbivores (i.e., NG, no grazing; SG, sheep grazing; CG, cattle grazing) over 4 years. Using a null-model approach, we estimated the relative magnitude of deterministic processes of community assembly by comparing the observed and expected ß-diversity. We found that in the absence of herbivore grazing, deterministic processes played a greater role in community assembly, regardless of whether patchy degradation had occurred. However, the deterministic processes resulted in plant communities being more spatially similar in non-degraded grasslands while being more dissimilar in patchy degraded grasslands. Compared with non-degraded grasslands, species with strong competitive abilities (i.e., Leymus chinensis) were less dominant in patchy degraded grasslands, indicating relaxed competition and a reduced role of species interactions over plant communities. Instead, patchy degradation added the role of environmental variables over plant communities. SG consistently promoted more stochastic plant community assembly in both non-degraded and patch-degraded grasslands, while CG promoted more stochastic plant community assembly only in the non-degraded state, having no effect in the patch-degraded state. Our study offers important insights into changes in plant community assembly during ongoing patch-degradation of grasslands, indicating the role of increased environmental filtering of soil and reduced species interactions in driving plant community dynamics with increasing grassland patchy degradation. We also uncovered an herbivore species-specific effect on plant community assembly during the process of grassland degradation, which will better inform and improve future grassland restoration planning efforts.

Land use intensification alters the relative contributions of plant functional diversity and soil properties on grassland productivity.

Understanding the mechanisms of grassland productivity variation is critical for global carbon cycling and climate change mitigation. Heretofore, it is unknown how different environmental factors drive small-scale spatial variation in productivity, and whether land use intensification, one of the most important global changes, can regulate the processes that drive productivity change. Here we performed an 18-year exclosure experiment across six sites with high-intensity mowing/grazing history in northern China to examine the effects of land use intensification on plant functional diversity, soil properties, and their relative contributions to above-ground net primary productivity (ANPP). We found that plant functional diversity and soil properties contributed to the variation in ANPP both independently and equally in enclosed grasslands (plant diversity: 20.6%; soil properties: 19.5%). Intensive land use significantly decreased the Rao's quadratic entropy (RaoQ) and community-weighted mean value (CWM) of plant height, and further suppressed the contributions of plant functional diversity to ANPP. In contrast, intensive land use increased soil available N, P, pH, electrical conductivity, and homogeneity of soil available P, and strengthened their contributions to ANPP (31.5%). Our results indicate that high-intensity land use practices in grasslands decrease the role of plant functional diversity, but strengthen the effects of soil properties on productivity. We, therefore, suggest that plant functional diversity can be used effectively to boost productivity in undisturbed grasslands, while soil properties might be a more critical consideration for grassland management in an areas with increased land use.

Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.

Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.

The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that inflammatory bowel disease (IBD) and dementia share similar pathological mechanisms, but no consensus has yet emerged on the effect that IBD and dementia are associated. To explore such a possible correlation, we summarize herein the epidemiological evidence. We subject relevant studies to meta-analysis. METHODS: We comprehensively searched Pubmed and Embase for relevant articles published to Dec 2021. The pooled risk ratio (RR) with the 95% confidence interval (CI) was used to estimate the effect; we calculated the generic inverse variance using a random-effects model. RESULTS: Seven studies involving 65,454 patients with dementia were included in the meta-analysis. The overall risk of dementia in IBD patients was significantly higher than that in the general population (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.08-1.68; P = 0.008). The results of subgroup analyses were consistent with the overall results. The risk of Alzheimer's disease was higher in IBD patients (RR = 2.79, 95% CI = 1.1, 7.04; P < 0.001). CONCLUSIONS: Our results revealed that IBD may be a potential risk indicator for dementia.

Prevalence and related factors of peripheral arterial disease in diabetes mellitus inpatients: a cross-sectional study in China.

Peripheral arterialdisease (PAD) can result in diabetic foot ulcers, gangrene, and even amputation. Since most cases of PAD in diabetic patients are associated with peripheral neuropathy, the symptoms of vascular disease are easily concealed by the symptoms of neuropathy and are ignored by people, so it is critical for health care providers to screen PAD for the diabetes patients. This study was carried out to identify theprevalence and related factors of PAD in diabetes mellitus inpatients. This was a cross-sectional observational study. A total of 855 patients were enrolled in the study from December 2018 to December 2019. The patients were divided into a non-PAD group (ABI = 0.9-1.3) and a PAD group (ABI <0.9). Logistic multivariate regression analysis showed that age, LDL-C, dorsalis pedis artery pulsation (left foot), and sensory-current threshold (right foot) were related factors for peripheral arterial disease. Patients who are older and have a higher LDL-C level, abnormal dorsal foot pulse, and abnormal sensory-current threshold must be vigilant, and receive early screening for PAD diagnosis and treatment to avoid a malignant outcome. In clinical work, medical staff should actively apply PAD screening to diabetic patients, identify risk factors as early as possible, conduct early interventions, reduce the risk of PAD in patients, and avoid the occurrence of adverse outcomes.

Qualitative and quantitative analysis of phenolic compounds in blueberries and protective effects on hydrogen peroxide-induced cell injury.

This work was conducted to optimize an accelerated solvent extraction for ultra high performance liquid chromatography-mass spectrometry/mass spectrometry analysis of blueberry phenolic compounds. The conditions for accelerated solvent extraction were verified using response surface methodology to obtain the following optimized conditions: ethanol concentration (pH = 3), 48%; temperature, 50℃, and static cycle times, 3. Further, ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry and ultra high performance liquid chromatography with triple-quadrupole tandem mass methods for determination of the detailed phenolic composition were developed and validated. Total of 81 phenolic compounds were identified by ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry including 23 anthocyanins, 32 flavonols, 11 proanthocyanidins, 2 other flavonoids, and 13 phenolic acids. Fifty-one of these compounds have been simultaneously quantified by ultra high performance liquid chromatography with triple-quadrupole tandem mass including 31 anthocyanins, 8 flavonols, 6 proanthocyanidins, 2 other flavonoids, and 8 phenolic acids. Malvidin-dinhexoside has, for the first time, been detected in wild. Moreover, by verifying the protection on PC12 cells against oxidative damage, it was showed that the phenolic extracts (500 µg/mL) can improve significantly the viability (9.26-24.78%) of hydrogen peroxide-induced PC12 cells, activities of superoxide dismutase (34.59-37.90 U/mg) and glutathione peroxidase (6.87-14.42 mU/mg) and decrease the content of malonic dialdehyde (13.27-24.62 nmol/mg). Correlation analysis suggested that anthocyanins might contribute most to these activities.

Concentrations, distribution and risk of polycyclic aromatic hydrocarbons in sediments from seven major river basins in China over the past 20 years.

Polycyclic aromatic hydrocarbons (PAHs) in river sediments in China have been extensively investigated. However, most previous studies only reported information about specific locations. As a result, the distribution and changes of these chemicals in sediments nationwide remain unknown. Based on published data during 1997-2020, we conducted a systematic meta-analysis to understand the concentration, risk and the spatiotemporal variation of PAHs in river sediments from the seven major river systems in China. The report provides a national picture of PAHs in river sediments of China. Among the seven river systems, higher concentrations of sediment PAHs are found in the basins of Liaohe River and Haihe River. In the study sediments, high-molecular-mass (4-6-ring) PAHs were predominated, reflecting the widespread combustion of coal and fossil fuels across China. In addition, PAH source assessment also suggests that raw coal and crude oil are important contributors to PAH concentrations in the rivers in northeastern China. Over the past 20 years, there is no downward trend in the concentrations of Σ16PAHs in sediments in the seven river basins; but the contribution of high-temperature combustion to the pollution has declined. In addition, our calculated risks from sediment PAHs seem to decline between 1997-2006 and 2007-2017 periods, although the differences were not statistically significant (p > 0.05). Of note, the data collection and the risk assessment methods used in this preliminary survey may result in some uncertainty. Our results suggest that the PAHs in river sediments in China still need to be paid attention to due to the complexity of their sources and harms to aquatic organisms.

Global distribution and trends of polybrominated diphenyl ethers in human blood and breast milk: A quantitative meta-analysis of studies published in the period 2000-2019.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardants that are found throughout the human body. However, global trends and diversity of the concentrations in human body and the potential risks remain largely unresolved. Based on published data during 2000-2019, we conducted a systematic meta-analysis to understand the burden and risks of PBDEs in humans and their spatiotemporal variations. The report provides a global picture of PBDE concentrations in human blood and breast milk. We found the levels of body PBDE burden in the North American population were higher than those from Asia and Europe. However, high concentrations of blood PBDEs in occupational population from Asia were observed, largely because of poorly controlled e-waste recycling operations. Penta- and deca-BDE were the main contributors in North America and Asia, respectively, reflecting the difference in the production and use of these chemicals. On a global scale, no substantial decreases in the concentrations of PBDEs in the blood and breast milk were observed, although most of the chemicals have been phased out. The results suggested that humans will be exposed to PBDEs with relatively high concentrations in a certain period because of the legacy in products and the environmental media. And the potential health risks necessitate careful study in the future. Our results also remind that the uses of degradation-resistant chemicals should be attached great importance to their safety.

Polybrominated diphenyl ethers in soils from Tianjin, North China: distribution, health risk, and temporal trends.

Available information is still insufficient for a comprehensive understanding of the global distribution of polybrominated diphenyl ethers (PBDEs) in the environment. In particular, little is known about the changing trend of their distribution in urban soils. We conducted a survey of 21 PBDEs in urban soils from Tianjin, China. The chemicals were widely present in the area and summed concentrations ranged from 0.65 to 108 ng/g in soil, indicating low to moderate levels of pollution relative to other areas. BDE-209 was the predominant congener, contributing 88.9% of the concentrations of total soil PBDEs. Source assessment indicated that soil PBDEs in the area were mainly derived from the release of commercial deca-BDE from local industrial production processes and consumer products. We found that the soil concentrations of PBDEs appear to have declined in recent years, compared with other previous reports in this region. However, more studies are needed on this possible change trend of PBDE pollution, especially its impact on human health, although their calculated non-carcinogenic health risks in this study were low.

Concentration profile, spatial distributions and temporal trends of polybrominated diphenyl ethers in sediments across China: Implications for risk assessment.

Polybrominated diphenyl ethers (PBDEs) in sediments of China have been extensively investigated; however, most studies conducted to date have focused on specific locations, and the pollution and risk posed by these chemicals in sediments at the national scale remain unknown. Therefore, we analyzed the concentrations and risks of PBDEs in sediments in China and their spatiotemporal variations based on available literature. Overall, the sediments across China contain moderate to high levels of PBDEs, with BDE-209 being the dominant congener, followed by BDE-47 and BDE-99. The sediment concentrations of PBDEs were highest in southern China and lowest in northeastern China. Additionally, based on their PBDE concentrations, 18.4%, 30.0%, and 11.9% of sediment samples from rivers, lakes, and coastal waters, respectively, posed low to moderate eco-toxicological risks, but 6.90% of river sediments posed high risks. Between 2001 and 2017, the concentrations and risks of PBDEs in the sediments from rivers and coastal waters tended to decrease gradually. Additionally, there were low to moderate risks from PBDEs in lake sediments, and the risks in 2012-2017 were 3.30 times higher than those in 2006-2011. However, more studies about the spatial and temporal trends in PBDEs in sediment across China and their impacts on aquatic organisms are needed because there is still a general lack of relevant information.

Novel approach for extraction of grape skin antioxidants by accelerated solvent extraction: Box-Behnken design optimization.

Grape skin can be considered as an excellent and inexpensive source of polyphenol antioxidant compounds. A high-efficiency accelerated solvent extraction (ASE) method was developed for antioxidant polyphenols from grape skin. A three-factors three-level Box-Behnken design by response surface methodology was employed for optimization of extraction parameters in terms of total phenolic content, total anthocyanins content and antioxidant activity. The optimized condition was ethanol concentration of 48.80%, temperature of 50.79 °C and extraction time of 14.82 min. Under these conditions, the highest yields of polyphenol, the total phenolic content (15.24 mg GAE/g), total anthocyanins content (346.68 mg CGE/100 g) in grape skin, were obtained with significant antioxidant properties by DPPH, ABTS and FRAP assays. Moreover, the extracts from various grape skins by ASE, possessed ten main antioxidant polyphenols with the highest concentration of p-hydroxybenzoic acid and malvidin-3-O-glucoside. Compared with conventional solvent extraction, ASE extracted more amounts of polyphenols, exhibited more extraction level with shorter time and higher reproducibility.

Preparation and Antioxidant Activity of Ethyl-Linked Anthocyanin-Flavanol Pigments from Model Wine Solutions.

Anthocyanin-flavanol pigments, formed during red wine fermentation and storage by condensation reactions between anthocyanins and flavanols (monomers, oligomers, and polymers), are one of the major groups of polyphenols in aged red wine. However, knowledge of their biological activities is lacking. This is probably due to the structural diversity and complexity of these molecules, which makes the large-scale separation and isolation of the individual compounds very difficult, thus restricting their further study. In this study, anthocyanins (i.e., malvidin-3-glucoside, cyanidin-3-glucoside, and peonidin-3-glucoside) and (⁻)-epicatechin were first isolated at a preparative scale by high-speed counter-current chromatography. The condensation reaction between each of the isolated anthocyanins and (⁻)-epicatechin, mediated by acetaldehyde, was conducted in model wine solutions to obtain ethyl-linked anthocyanin-flavanol pigments. The effects of pH, molar ratio, and temperature on the reaction rate were investigated, and the reaction conditions of pH 1.7, molar ratio 1:6:10 (anthocyanin/(⁻)-epicatechin/acetaldehyde), and reaction temperature of 35 °C were identified as optimal for conversion of anthocyanins to ethyl-linked anthocyanin-flavanol pigments. Six ethyl-linked anthocyanin-flavanol pigments were isolated in larger quantities and collected under optimal reaction conditions, and their chemical structures were identified by HPLC-QTOF-MS and ECD analyses. Furthermore, DPPH, ABTS, and FRAP assays indicate that ethyl-linked anthocyanin-flavanol pigments show stronger antioxidant activities than their precursor anthocyanins.

In Vitro Antibacterial Activity of a Novel Acid-Activated Antimicrobial Peptide against Streptococcus mutans.

BACKGROUND: Dental caries is an oral disease associated with infection by microbial biofilm. The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm, causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque microenvironment to prevent and treat dental caries has become a hot research topic in recent years, such as the development of pH-sensitive drug delivery systems. AIMS: Design of a new acid-activated antibacterial peptide. OBJECTIVES: To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF sequence. METHODS: Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity study confirmed the phototoxicity of PPIX-P12. RESULTS: MIC and MBC testing confirmed that P12 possessed acid-activated anti-Streptococcus mutans activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments showed that P12 killed planktonic S. mutans UA159 cells leading to the leakage of nucleic acids in the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct the protoporphyrin derivative PpIX-P12. In vitro experiments revealed that PpIX-P12 displayed better antibacterial activity in pH 5.5 medium than in pH 7.2 medium. CONCLUSION: In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity at neutral pH, but had antimicrobial activity at an acidic pH.

Report on the diagnosis and treatment of 3 cases of emphysematous pyelonephritis with two different outcomes.

Background: Emphysematous pyelonephritis (EPN) is a rare acute severe necrotising infection of the kidneys in clinical practice. It is characterized by the presence of gas in the renal parenchyma, collecting system, or perirenal tissue. The prognosis is poor, with a high nephrectomy rate and a mortality rate of up to 20-40%. Methods: Retrospective analysis of 3 cases of emphysematous pyelonephritis with two different outcomes. Results: Three patients who we described were all female with diabetes mellitus, and their blood sugar was poorly controlled. One patient with the advanced age and poor general health died due to the patient's family choosing to terminate therapy. Two patients underwent surgical procedures achieved an excellent clinical recovery. Both of them underwent percutaneous nephrostomy and perinephric abscess puncture drainage before nephrectomy. Escherichia coli were the microorganisms implicated. Conclusion: EPN is a rare and severe urinary system infection. Computed tomography (CT) and microbiological culture confirmed the diagnosis. Control of diabetes, sensitive antibiotic therapy, fluid resuscitation and prompt surgical intervention are crucial.