Bile acid profiles and classification model accuracy for inflammatory bowel disease diagnosis.

To investigate the utility of serum bile acid profiling for the diagnosis of inflammatory bowel disease (IBD). We analyzed 15 specific bile acids in the serum of 269 IBD patients, 200 healthy controls (HC), and 174 patients with other intestinal diseases (OID) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum bile acid levels were compared between IBD group, HC group, and OID group. Binary logistic regression-based models were developed to model the bile acids and diagnose IBD. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of each bile acid and the model. Compared to HC group, IBD group exhibited significantly lower levels of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), lithocholic acid (LCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and an elevated primary-to-secondary bile acid ratio. DCA had an area under the curve (AUC) of 0.860 for diagnosing IBD, with a sensitivity of 80.67% and a specificity of 82.50%. A model Y0 combining DCA and CDCA to distinguish between IBD group and HC group further improved accuracy (AUC = 0.866, sensitivity = 76.28%, specificity = 89.37%). Compared to non-IBD group (which combined healthy controls and those with other intestinal diseases), IBD group had significantly lower levels of DCA, GDCA, TDCA, LCA, GLCA, and TLCA, and elevated levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). A model Y1 incorporating GCDCA, DCA and TLCA to distinguish between IBD group and non-IBD group yielded an AUC of 0.792, with a sensitivity of 77.67% and specificity of 71.91%. IBD patients exhibit decreased serum secondary bile acid levels and an elevated primary-to-secondary bile acid ratio. Serum bile acid alterations are associated with the onset of IBD. A model consisting of CDCA and DCA has potential for distinguishing between IBD group and HC group, while a model incorporating GCDCA, DCA and TLCA may be suitable for distinguishing between IBD group and non-IBD group.

Exploration of the application potential of serum multi-biomarker model in colorectal cancer screening.

Analyzing blood lipid and bile acid profile changes in colorectal cancer (CRC) patients. Evaluating the integrated model's diagnostic significance for CRC. Ninety-one individuals with colorectal cancer (CRC group) and 120 healthy volunteers (HC group) were selected for comparison. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoproteins (Apo) A1, ApoA2, ApoB, ApoC2, and ApoC3 were measured using immunoturbidimetric and colorimetric methods. Additionally, LC-MS/MS was employed to detect fifteen bile acids in the serum, along with six tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, CA19-9, CA242, CA50, and CA72-4. Group comparisons utilized independent sample t-tests and Mann-Whitney U tests. A binary logistic regression algorithm was applied to fit the indicators and establish a screening model; the diagnostic accuracy of individual Indicators and the model was analyzed using receiver operating characteristic (ROC) curves. The CRC group showed significantly lower levels in eight serum lipid indicators and eleven bile acids compared to the HC group (P < 0.05). Conversely, serum levels of TG, CA19-9, and CEA were elevated (P < 0.05). Among the measured parameters, ApoA2 stands out for its strong correlation with the presence of CRC, showcasing exceptional screening efficacy with an area under the curve (AUC) of 0.957, a sensitivity of 85.71%, and a specificity of 93.33%. The screening model, integrating ApoA1, ApoA2, lithocholic acid (LCA), and CEA, attained an impressive AUC of 0.995, surpassing the diagnostic accuracy of individual lipids, bile acids, and tumor markers. CRC patients manifest noteworthy alterations in both blood lipids and bile acid profiles. A screening model incorporating ApoA1, ApoA2, LCA, and CEA provides valuable insights for detecting CRC.

Efficient dye adsorption of mesoporous activated carbon from bamboo parenchyma cells by phosphoric acid activation.

In order to solve the environmental damage caused by the discharge of dyes as industrial wastewater, the development of efficient and sustainable adsorbents is the key, while most of the previous studies on bamboo parenchyma cells have focused on their microstructural, functional and mechanical properties, and few of the properties in adsorption have been investigated. To evaluate the role of the unique microstructure of bamboo parenchyma cells on adsorption after carbonization and activation, PC-based activated carbon (PPAC) was fabricated by the phosphoric acid activation method and tested for adsorption using methylene blue (MB). The effect of mesoporous structure on MB adsorption was investigated in detail using PPAC-30C impregnated with phosphoric acid at a concentration of 30%. The results showed that the adsorption performance was influenced by single-factor experiments (e.g., pH, activated carbon dosing). The adsorption isotherms and kinetics could conform to the Langmuir model (R2 = 0.983-0.994) and pseudo-second-order kinetic model (R2 = 0.822-0.991) respectively, and the maximum MB adsorption capacity of adsorbent was 576 mg g-1. The adsorption mechanism of MB on PPAC-30C includes physical adsorption, electrostatic attraction, hydrogen bonding, and the π-π conjugation effect, which was dominated by physical adsorption. The results of this study show that PPAC has good application prospects for cationic dye removal.

Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn's disease (CD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022. ELIGIBILITY CRITERIA: Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1). RESULTS: 11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, χ2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS. CONCLUSIONS: MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS. PROSPERO REGISTRATION NUMBER: CRD42022346340.

pH/H2 O2 Cascade-Responsive Nanoparticles of Lipid-Like Prodrugs through Dynamic-Covalent and Coordination Interactions for Chemotherapy.

Traditional lipid nanoparticles (LNPs) suffer from low drug loading capacity (DLC), weak stability, and lack of responsiveness. Conventional approaches to address these issues involve the synthesis of lipid-prodrug by incorporating responsive covalent linkers. However, such approaches often result in suboptimal sensitivity for drug release and undermine therapeutic effectiveness. Herein, the study reports a fundamentally different concept for designing lipid-like prodrugs through boron-nitrogen (B-N) coordination and dynamic covalent interaction. The 5-fluorouracil-based lipid-like prodrugs, featuring a borate ester consisting of a glycerophosphoryl choline head and a boronic acid-modified 5Fu/dodecanamine complex tail, are used to prepare pH/H2 O2 cascade-responsive LNPs (5Fu-LNPs). The 5Fu-LNPs exhibit enhanced DLC and stability in a neutral physiological environment due to the B-N coordination and enhanced hydrophobicity. In tumors, acidic pH triggers the dissociation of B-N coordination to release prodrugs, which further responds to low H2 O2 concentrations to release drugs, showcasing a potent pH/H2 O2 -cascade-responsive property. Importantly, 5Fu-LNPs demonstrate greater antitumor efficiency and lower toxicity compared to the commercial 5Fu. These results highlight 5Fu-LNPs as a safer and more effective alternative to chemotherapy. This work presents a unique LNP fabrication strategy that can overcome the limitations of conventional LNPs and broaden the range of intelligent nanomaterial preparation techniques.

Apoptotic Vesicular Metabolism Contributes to Organelle Assembly and Safeguards Liver Homeostasis and Regeneration.

BACKGROUND & AIMS: Apoptosis generates plenty of membrane-bound nanovesicles, the apoptotic vesicles (apoVs), which show promise for biomedical applications. The liver serves as a significant organ for apoptotic material removal. Whether and how the liver metabolizes apoptotic vesicular products and contributes to liver health and disease is unrecognized. METHODS: apoVs were labeled and traced after intravenous infusion. Apoptosis-deficient mice by Fas mutant (Fasmut) and Caspase-3 knockout (Casp3-/-) were used with apoV replenishment to evaluate the physiological apoV function. Combinations of morphologic, biochemical, cellular, and molecular assays were applied to assess the liver while hepatocyte analysis was performed. Partial hepatectomy and acetaminophen liver failure models were established to investigate liver regeneration and disease recovery. RESULTS: We discovered that the liver is a major metabolic organ of circulatory apoVs, in which apoVs undergo endocytosis by hepatocytes via a sugar recognition system. Moreover, apoVs play an indispensable role to counteract hepatocellular injury and liver impairment in apoptosis-deficient mice upon replenishment. Surprisingly, apoVs form a chimeric organelle complex with the hepatocyte Golgi apparatus through the soluble N-ethylmaleimide-sensitive factor attachment protein receptor machinery, which preserves Golgi integrity, promotes microtubule acetylation by regulating α-tubulin N-acetyltransferase 1, and consequently facilitates hepatocyte cytokinesis for liver recovery. The assembly of the apoV-Golgi complex is further revealed to contribute to liver homeostasis, regeneration, and protection against acute liver failure. CONCLUSIONS: These findings establish a previously unrecognized functional and mechanistic framework that apoptosis through vesicular metabolism safeguards liver homeostasis and regeneration, which holds promise for hepatic disease therapeutics.

Long-term changes in the daytime growing season carbon dioxide exchange following increased temperature and snow cover in arctic tundra.

Increasing temperatures and winter precipitation can influence the carbon (C) exchange rates in arctic ecosystems. Feedbacks can be both positive and negative, but the net effects are unclear and expected to vary strongly across the Arctic. There is a lack of understanding of the combined effects of increased summer warming and winter precipitation on the C balance in these ecosystems. Here we assess the short-term (1-3 years) and long-term (5-8 years) effects of increased snow depth (snow fences) (on average + 70 cm) and warming (open top chambers; 1-3°C increase) and the combination in a factorial design on all key components of the daytime carbon dioxide (CO2 ) fluxes in a wide-spread heath tundra ecosystem in West Greenland. The warming treatment increased ecosystem respiration (ER) on a short- and long-term basis, while gross ecosystem photosynthesis (GEP) was only increased in the long term. Despite the difference in the timing of responses of ER and GEP to the warming treatment, the net ecosystem exchange (NEE) of CO2 was unaffected in the short term and in the long term. Although the structural equation model (SEM) indicates a direct relationship between seasonal accumulated snow depth and ER and GEP, there were no significant effects of the snow addition treatment on ER or GEP measured over the summer period. The combination of warming and snow addition turned the plots into net daytime CO2 sources during the growing season. Interestingly, despite no significant changes in air temperature during the snow-free time during the experiment, control plots as well as warming plots revealed significantly higher ER and GEP in the long term compared to the short term. This was in line with the satellite-derived time-integrated normalized difference vegetation index of the study area, suggesting that more factors than air temperature are drivers for changes in arctic tundra ecosystems.

Drivers of contemporary and future changes in Arctic seasonal transition dates for a tundra site in coastal Greenland.

Climate change has had a significant impact on the seasonal transition dates of Arctic tundra ecosystems, causing diverse variations between distinct land surface classes. However, the combined effect of multiple controls as well as their individual effects on these dates remains unclear at various scales and across diverse land surface classes. Here we quantified spatiotemporal variations of three seasonal transition dates (start of spring, maximum normalized difference vegetation index (NDVImax ) day, end of fall) for five dominating land surface classes in the ice-free Greenland. Using a distributed snow model, structural equation modeling, and a random forest model, based on ground observations and remote sensing data, we assessed the indirect and direct effects of climate, snow, and terrain on seasonal transition dates. We then presented new projections of likely changes in seasonal transition dates under six future climate scenarios. The coupled climate, snow cover, and terrain conditions explained up to 61% of seasonal transition dates across different land surface classes. Snow ending day played a crucial role in the start of spring and timing of NDVImax . A warmer June and a decline in wind could advance the NDVImax day. Increased precipitation and temperature during July-August are the most important for delaying the end of fall. We projected that a 1-4.5°C increase in temperature and a 5%-20% increase in precipitation would lengthen the spring-to-fall period for all five land surface classes by 2050, thus the current order of spring-to-fall lengths for the five land surface classes could undergo notable changes. Tall shrubs and fens would have a longer spring-to-fall period under the warmest and wettest scenario, suggesting a competitive advantage for these vegetation communities. This study's results illustrate controls on seasonal transition dates and portend potential changes in vegetation composition in the Arctic under climate change.

Tumor immune microenvironment-based clusters in predicting prognosis and guiding immunotherapy in breast cancer.

The development and progression of breast cancer (BC) depend heavily on the tumor microenvironment (TME), especially tumor infiltration leukocytes (TILs). TME-based classifications in BC remain largely unknown and need to be clarified. Using the bioinformatic analysis, we attempted to construct a prognostic nomogram based on clinical features and TME-related differentially expressed genes (DEGs). We also tried to investigate the association between the prognostic nomogram and clinical characteristics, TILs, possible signaling pathways, and response to immunotherapy in BC patients. DEGs for BC patients were identified from The Cancer Genome Atlas Breast Invasive Carcinoma database. TME-related genes were downloaded from the Immunology Database and Analysis Portal. After intersecting DEGs and TME-related genes, 3985 overlapping TME-related DEGs were selected for non-negative matrix factorization clustering, microenvironment cell populations-counter (MCP-counter), LASSO Cox regression, tumor immune dysfunction, and exclusion (TIDE) algorithm analyses. BC patients were divided into three clusters based on the TME-related DEGs and survival data, in which cluster 3 had the best overall survival (OS). Of note, cluster 3 exhibited the highest infiltration or lowest infiltration of CD3+ T-cells, CD8+ T-cells, cytotoxic lymphocytes, B-lymphocytes, monocytic lineage, and myeloid dendritic cells (MDCs). A total of 33 TME-related DEGs were identified as a prognostic gene signature by the LASSO regression analysis. The prognostic gene signature separated BC patients into low- and high-risk groups with significant differences in OS (p<0.01) and demonstrated powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.773, 3-year AUC = 0.770, 5-year AUC = 0.792). By integrating demographic features, tumor-node metastasis (TNM) stages, and prognostic gene signature, we constructed a nomogram with better predictive value than other clinical features alone. TMErelated DEGs in the low-risk BC patients (with better OS) were enriched in chemokine, cytokine-cytokine receptor interaction, and JAK-STAT and Toll-like receptor signaling pathways. BC patients in the low-risk group exhibited higher TIDE scores associated with worse immune checkpoint blockade response. A prognostic nomogram based on TME-related DEGs and clinical characteristics could predict prognosis and guide immunotherapy in BC patients.

No effect of snow on shrub xylem traits: Insights from a snow-manipulation experiment on Disko Island, Greenland.

Widespread shrubification across the Arctic has been generally attributed to increasing air temperatures, but responses vary across species and sites. Wood structures related to the plant hydraulic architecture may respond to local environmental conditions and potentially impact shrub growth, but these relationships remain understudied. Using methods of dendroanatomy, we analysed shrub ring width (RW) and xylem anatomical traits of 80 individuals of Salix glauca L. and Betula nana L. at a snow manipulation experiment in Western Greenland. We assessed how their responses differed between treatments (increased versus ambient snow depth) and soil moisture regimes (wet and dry). Despite an increase in snow depth due to snow fences (28-39 %), neither RW nor anatomical traits in either species showed significant responses to this increase. In contrast, irrespective of the snow treatment, the xylem specific hydraulic conductivity (Ks) and earlywood vessel size (LA95) for the study period were larger in S. glauca (p < 0.1, p < 0.01) and B. nana (p < 0.01, p < 0.001) at the wet than the dry site, while both species had larger vessel groups at the dry than the wet site (p < 0.01). RW of B. nana was higher at the wet site (p < 0.01), but no differences were observed for S. glauca. Additionally, B. nana Ks and LA95 showed different trends over the study period, with decreases observed at the dry site (p < 0.001), while for other responses no difference was observed. Our results indicate that, taking into account ontogenetic and allometric trends, hydraulic related xylem traits of both species, along with B. nana growth, were influenced by soil moisture. These findings suggest that soil moisture regime, but not snow cover, may determine xylem responses to future climate change and thus add to the heterogeneity of Arctic shrub dynamics, though more long-term species- and site- specific studies are needed.

Clinical algorithm model based on cfDNA to predict SLE disease activity.

BACKGROUND: Circulating cell-free DNA (cfDNA) has been widely used as a new liquid-biopsy marker. Dysregulation of cfDNA has been found in patients with systemic lupus erythematosus (SLE). However, the detailed association between cfDNA and SLE has not been thoroughly studied. METHODS: Plasma samples were collected from 88 patients with active SLE and 39 patients with inactive SLE. The cfDNA concentration was determined, and the length and distribution of cfDNA fragments were verified. RESULTS: cfDNA concentrations were significantly higher in patients with active SLE than in patients with inactive SLE (0.4 [0.18-0.897] ng/µL vs 0.249 [0.144-0.431] ng/µL; p = .043). cfDNA fragments were enriched in the ranges of 153-198 bp and 300-599 bp. cfDNA concentrations were associated with the reduction of the anti-double-stranded DNA (dsDNA) antibodies titer (r = -0.301, p = .034). The presence of anti-U1 ribonucleoprotein (p = .012), anti-Sjogren syndrome A (p = .024), anti-dsDNA (p = .0208), and anti-nucleosome antibodies (p = .0382) might associate to the variation of cfDNA concentration. Reduced cfDNA concentration was associated with renal damage in active SLE patients (0.31 [0.11-0.73] ng/µL vs 0.65 [0.27-1.53] ng/µL; p = .009). The Active index, a combination model including cfDNA concentration and other clinical indices, had an area of 0.886 under the receiver operating characteristics curve for distinguishing active SLE. The Active index was positively correlated with the SLE disease activity index score (r = 0.6724, p < .0001). CONCLUSIONS: Through systematic stratified analysis and clinical algorithm model, this study found that plasma cfDNA concentration is closely related to SLE disease severity, which has guiding significance for the future clinical application of cfDNA in SLE.

Size-segregated characteristics of water-soluble oxidative potential in urban Xiamen: Potential driving factors and implications for human health.

Oxidative potential (OP), defined as the ability of particulate matter (PM) to generate reactive oxygen species (ROS), has been considered as a potential health-related metric for PM. Particles with different sizes have different OP and deposition efficiencies in the respiratory tract and pose different health risks. In this study, size-segregated PM samples were collected at a coastal urban site in Xiamen, a port city in southeastern China, between August 2020 and September 2021. The water-soluble constituents, including inorganic ions, elements and organic carbon, were determined. Total volume-normalized OP based on the dithiothreitol assay was highest in spring (0.241 ± 0.033 nmol min-1 m-3) and lowest in summer (0.073 ± 0.006 nmol min-1 m-3). OP had a biomodal distribution with peaks at 0.25-0.44 µm and 1.0-1.4 µm in spring, summer, and winter and a unimodal pattern with peak at 0.25-0.44 µm in fall, which were different from the patterns of redox-active species. Variations in the seasonality of fine and coarse mode OP and their correlations with water-soluble constituents showed that the size distribution patterns of OP could be attributed to the combined effects of the size distributions of transition metals and redox-active organics and the interactions between them which varied with emissions, meteorological conditions and atmospheric processes. Respiratory tract deposition model indicated that the deposited OP and the toxic elements accounted for 47.9 % and 36.8 % of their measured concentrations, respectively. The highest OP doses and the excess lifetime carcinogenic risk (ELCR) were found in the head airway (>70 %). However, the size distributions of OP deposition and ELCR in the respiratory tract were different, with 63.9 % and 49.4 % of deposited ELCR and OP, respectively, coming from PM2.5. Therefore, attention must be paid to coarse particles from non-exhaust emissions and road dust resuspension.

Photomechaelectric Nanogenerators with Different Photoisomers and Dipole Units for Harvesting UV Light Energy.

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

Spatially Separated Active Sites Enable Selective CO Oxidation Reaction on Oxide Catalyst.

The search for efficient non-noble-metal catalysts able to perform selective oxidation reactions is of great importance, with relevance to many catalytic processes. However, this is often hampered because the origin of the selectivity remains controversial, particularly for reactions catalyzed by oxides. Here, combining high-pressure surface imaging techniques and theoretical calculations, we identify that spatially separated active sites for O2 activation and H2 adsorption on an ultrathin Mn3O4 surface enable selective oxidation of CO over H2. Theoretical calculations reveal that Mn-O pairs for H2 dissociation are separated from Mn-Mn pairs for the formation of adsorbed O2* so that H2 has to surmount much higher barriers for both H2 dissociation and H diffusion while CO can directly react with O2* following the Eley-Rideal process. Our study sheds light on the atomic-level understanding of the surface structure-dependent selective oxidation reaction on oxide catalysts.

Caspase-3/GSDME mediated pyroptosis: A potential pathway for sepsis.

The inflammatory response is one of the host's mechanisms to combat pathogens. Normal and controlled inflammation can accelerate the clearance of pathogens. However, in sepsis, the host often exhibits an excessive inflammatory response to infection, leading to tissue and organ damage. Therefore, studying the mechanisms underlying the occurrence and development of sepsis is of significant importance. Pyroptosis is a form of programmed cell death (PCD) executed by the gasdermins (GSDMs) family, and its pro-inflammatory characteristics are considered a crucial component of the sepsis mechanism. Previous research on pyroptosis in sepsis has mainly focused on the caspase-1/4/5/11-GSDMD pathway, which has made significant progress. However, there is a lack of research on the roles of other GSDMs family members in sepsis. New research has revealed that the caspase-3/GSDME pathway can also mediate pyroptosis, playing important roles in cancer, other inflammatory diseases, and even some sepsis-related conditions. This discovery suggests the potential value of investigating caspase-3/GSDME in sepsis research. This review provides an overview of the role of the GSDMs family in infectious diseases, summarizes current research on the caspase-1/4/5/11-GSDMD pathway, describes the role of caspase-3 in sepsis, and discusses the research findings related to pyroptosis mediated by the caspase-3/GSDME pathway in cancer, inflammatory diseases, and sepsis-related conditions. The aim of this article is to propose the concept of caspase-3/GSDME as a potential target in sepsis research. Considering the role of this pathway in other diseases, including inflammatory conditions, and given the unique nature of sepsis as an inflammatory disease, the article suggests that this pathway may also play a role in sepsis. This hypothesis provides new insights and options for future sepsis research, although direct experiments are needed to validate this hypothesis.

Regulating Size and Charge of Liposomes in Microneedles to Enhance Intracellular Drug Delivery Efficiency in Skin for Psoriasis Therapy.

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug-loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively-charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long-term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)-loaded cationic liposomes-integrated MNs show better therapeutic outcomes than dex-loaded anionic liposomes-integrated MNs in a psoriasis-like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation.

Propensity score analysis the clinical characteristics of active distal and extensive ulcerative colitis: a retrospective study.

Background and Objectives: Ulcerative Colitis (UC) subtypes defined by disease extent and shared pathophysiology are important. Analyzing the clinical characteristics of UC with different disease extent and optimizing clinical typing are conducive to the pathogenesis research, disease monitoring and precise treatment. Methods: 188 patients with active UC were divided into distal and extensive colitis. The clinical characteristics of the two groups were analyzed by propensity score. Spearman is used for correlation analysis, and receiver operating characteristic (ROC) curve was used to evaluate the ability of clinical indicators to predict Mayo endoscopic subscore (MES). Results: Compared with distal colitis, extensive colitis had more severe disease activity, younger age, higher utilization rate of corticosteroids and incidence of extra intestinal manifestations (EIMs), and clinical indicators were differentially expressed in the two groups. After using propensity score, the incidence of EIMs in the extensive colitis was still higher than that in distal colitis. Inflammation, coagulation and immune indicators like CRP, FC, IL-10, D-D and α1-MG are higher in extensive colitis, and metabolic indicators like LDL-C, HDL-C, TC, GSP and albumin are higher in distal colitis. The correlation between clinical indicators and MES is affected by disease extent. The area under curve (AUC) of CRP + D-D + α2-MG for predicting distal colitis MES3 was 0.85, and the AUC of IL-6+ GSP+ α1-MG predicted extensive colitis MES3 can reach 0.82. Conclusion: Differential clinical indicators can become potential markers for predicting disease progression and prognosis, and have significance for UC mechanism research and drug development. We can select biomarkers according to lesion site.

Hydrogel-Forming Microneedles with Applications in Oral Diseases Management.

Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery.

Activating lattice oxygen of single-layer ZnO for the catalytic oxidation reaction.

Tuning an oxide/metal interface is of critical importance for the performance enhancement of many heterogeneous catalytic reactions. However, catalytic oxidation occurring at the interface between non-reducible oxide and metal has been challenging, since non-reducible oxides hardly lose their lattice oxygen (OL) or dissociate O2 from the gas phase. In this work, a ZnO monolayer film on Au(111) is used as an inverse catalyst to investigate CO oxidation occurring at the ZnO/Au(111) interface via high pressure scanning tunneling microscopy. Surface science experiments indicate that oxygen intercalation under the ZnO monolayer film, termed ZnO/O/Au(111), can be achieved via a surface reaction with 1 × 10-6 mbar O3. Subsequent exposure of the formed ZnO/O/Au(111) surface to mbar CO at room temperature leads to the recovery of the pristine ZnO/Au(111) surface. Theoretical calculations reveal that OL adjacent to intercalated oxygen (Oint) is activated due to the OL-Zn-Oint bonding and surface corrugation, which can be directly involved in CO oxidation. Subsequently, Oint migrates to the formed oxygen vacancy from the subsurface resuming the pristine ZnO structure. These results thus reveal that oxygen intercalation underneath single-layer ZnO will strongly boost the oxidation reaction via activating adjacent lattice oxygen atoms.

Design, Synthesis, and Antifungal Activities of Novel Pyrazole-4-carboxamide Derivatives Containing an Ether Group as Potential Succinate Dehydrogenase Inhibitors.

A series of novel pyrazole-4-carboxamides bearing an ether group were designed and synthesized on the basis of the structure of commercial succinate dehydrogenase inhibitor (SDHI) fungicide flubeneteram via scaffold hopping and evaluated for their antifungal activities against five fungi. The bioassay results showed that most of the target compounds exhibited excellent in vitro antifungal activity against Rhizoctonia solani and some compounds exerted remarkable antifungal activities against Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium graminearum, and Alternaria alternate. Particularly, compounds 7d and 12b displayed outstanding antifungal activity against R. solani, with an EC50 value of 0.046 µg/mL, far superior to that of boscalid (EC50 = 0.741 µg/mL) and fluxapyroxad (EC50 = 0.103 µg/mL). Meanwhile, compound 12b also presented a broader fungicidal spectrum than other compounds. Moreover, in vivo anti-R. solani results showed that compounds 7d and 12b could significantly inhibit the growth of R. solani in rice leaves with excellent protective and curative efficacies. In addition, the results of the succinate dehydrogenase (SDH) enzymatic inhibition assay showed that compound 7d generated significant SDH inhibition, with an IC50 value of 3.293 µM, which was about 2 times better than that of boscalid (IC50 = 7.507 µM) and fluxapyroxad (IC50 = 5.991 µM). Furthermore, scanning electron microscopy (SEM) analysis indicated that compounds 7d and 12b significantly destroyed the typical structure and morphology of R. solani hyphae. The molecular docking study revealed that compounds 7d and 12b could embed into the binding pocket of SDH and form hydrogen bond interactions with TRP173 and TRY58 at the activity site of SDH, which was in line with fluxapyroxad, indicating that they had a similar mechanism of action. These results demonstrated that compounds 7d and 12b could be promising candidates of SDHI fungicides, which deserved further investigation.