Heparan sulfate-dependent phase separation of CCL5 and its chemotactic activity.

Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild-type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin-binding sequence) or by addition of heparin to wild-type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin-binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.

Reconstructing Helmholtz Plane Enables Robust F-Rich Interface for Long-Life and High-Safe Sodium-Ion Batteries.

Hard carbon (HC) is the most commonly used anode material in sodium-ion batteries. However, the solid-electrolyte-interface (SEI) layer formed in carbonate ester-based electrolytes has an imperceptible dissolution tendency and a sluggish Na+ diffusion kinetics, resulting in unsatisfactory performance of the HC anode. Given that electrode/electrolyte interface property is highly dependent on the configuration of Helmholtz plane, we filtrate proper solvents by PFBE (PF6- anion binding energy) and CAE (carbon absorption energy) and disclose the function of chosen TFEP to reconstruct the Helmholtz plane and regulate the SEI film on HC anode. Benefiting from the preferential adsorption tendency on HC surface and strong anion-dragging interaction of TFEP, a robust and thin anion-derived F-rich SEI film is established, which greatly enhances the mechanical stability and the Na+ ion diffusion kinetics of the electrode/electrolyte interface. The rationally designed TFEP-based electrolyte endows Na||HC half-cell and 2.8 Ah HC||Na4Fe3(PO4)2P2O7 pouch cell with excellent rate capability, long cycle life, high safety and low-temperature adaptability. It is believed that this insightful recognition of tuning interface properties will pave a new avenue on the design of compatible electrolyte for low-cost, long-life, and high-safe sodium-ion batteries.

Utilization of diverse probiotics to create human health promoting fatty acids: A review.

Many probiotics produce functional lipids with health-promoting properties, such as short-chain fatty acids, linoleic acid and omega-3 fatty acids. They have been shown to maintain gut health, strengthen the intestinal barrier, and have anti-inflammatory and antioxidant effects. In this article, we provide an up-to-date review of the various functional lipids produced by probiotics. These probiotics can be incorporated into foods, supplements, or pharmaceuticals to produce these functional lipids in the human colon, or they can be used in industrial biotechnology processes to generate functional lipids, which are then isolated and used as ingredients. We then highlight the different physiological functions for which they may be beneficial to human health, in addition to discussing some of the challenges of incorporating probiotics into commercial products and some potential solutions to address these challenges. Finally, we highlight the importance of testing the efficacy and safety of the new generation of probiotic-enhanced products, as well as the great potential for the marketization of related products.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Comparison of remimazolam tosilate and propofol during induction and maintenance of general anesthesia in patients undergoing laparoscopic cholecystectomy: a prospective, single center, randomized controlled trial.

BACKGROUND: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). METHODS: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg- 1 for induction, followed by 1.0-2.0 mg kg- 1 h- 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg- 1 and followed by 4-10 mg kg- 1 h- 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. RESULTS: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. CONCLUSIONS: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023).

Application of Delayed Repeated Enema With Sedation in Pediatric Intussusception: A Single Center Retrospective Study.

OBJECTIVE: This study aimed to evaluate the clinical application of delayed repeated air enema (DRE) with sedation in pediatric intussusception. METHOD: We retrospectively assessed cases of idiopathic intussusception treated with air enema reduction at the emergency department of Beijing Children's Hospital affiliated to Capital Medical University from January 2016 to August 2019. The included cases were assigned to the success or failure groups based on the outcomes of DRE with sedation. General patient information, clinical manifestations, test results, and surgical conditions were collected for comparative analysis. RESULTS: A total of 3052 cases were initially diagnosed with intussusception and underwent air enema reduction. Ultimately, 211 cases were included, with 162 in the success group and 49 in the failure group. The success rate of DRE with sedation was 76.8% (162/211), with an overall reduction success rate of 97.8% (2984/3052). Univariate logistic regression analysis showed that patients in the failure group had a significantly higher proportion of patients with age ≤1 year, bloody stools, and left-sided intussusception before DRE compared to the success group (OR = 2.3, 95%CI: 1.1∼4.6, P = 0.023; OR = 3.4, 95%CI: 1.6∼7.2, P = 0.002 and OR = 12.6, 95%CI: 4.6∼34.6, P < 0.001). Multiple logistic regression analysis based on these three factors revealed that the risk of DRE failure was 10.1 times higher in cases with the left-sided intussusception before DRE. CONCLUSIONS: DRE with sedation can improve the overall enema reduction success rate for intussusception and has good feasibility and safety profiles. Left-sided intussusception before DRE is an independent risk factor for enema failure.

Optical Control of Adaptive Nanoscale Domain Networks.

Adaptive networks can sense and adjust to dynamic environments to optimize their performance. Understanding their nanoscale responses to external stimuli is essential for applications in nanodevices and neuromorphic computing. However, it is challenging to image such responses on the nanoscale with crystallographic sensitivity. Here, the evolution of nanodomain networks in (PbTiO3)n/(SrTiO3)n superlattices (SLs) is directly visualized in real space as the system adapts to ultrafast repetitive optical excitations that emulate controlled neural inputs. The adaptive response allows the system to explore a wealth of metastable states that are previously inaccessible. Their reconfiguration and competition are quantitatively measured by scanning x-ray nanodiffraction as a function of the number of applied pulses, in which crystallographic characteristics are quantitatively assessed by assorted diffraction patterns using unsupervised machine-learning methods. The corresponding domain boundaries and their connectivity are drastically altered by light, holding promise for light-programable nanocircuits in analogy to neuroplasticity. Phase-field simulations elucidate that the reconfiguration of the domain networks is a result of the interplay between photocarriers and transient lattice temperature. The demonstrated optical control scheme and the uncovered nanoscopic insights open opportunities for the remote control of adaptive nanoscale domain networks.

Water transfer projects and microplastics: Analyzing changes in lake environments with a focus on Wabu Lake, China.

Microplastics are widespread in freshwaters, yet their interaction with navigational structures remains unclear. This study compared the distribution and characteristics of microplastics before and after navigation in Wabu Lake. Microplastic concentrations decreased significantly in both surface water and sediment due to navigation opened, from 13.7 ± 6.56 to 3.12 ± 1.8 p L-1 (p < 0.001) and from 568 ± 286 to 174 ± 60.2 p kg-1 (p < 0.001), respectively. Acrylates copolymer was frequently detected in surface water and sediment before navigation, whereas the dominant polymer after navigation was chlorinated polyisoprene in surface water and chlorinated polyethylene in sediment. The results showed that three-years dredging induced relatively severe microplastic pollution before navigation, however, these microplastics were apparently eliminated after navigation, as the distribution and characteristics of microplastics thoroughly varied. This study provides a valuable finding that microplastic transport process can be facilitated by water transfer project, which should be considered for preventing microplastic pollution.

Social media use and mental health among older adults with multimorbidity: the role of self-care efficacy.

OBJECTIVES: To describe the prevalence and trends in the use of social media over time and explore whether social media use is related to better self-care efficacy and thus related to better mental health among United States older adults with multimorbidity. MATERIALS AND METHODS: Respondents aged 65 years+ and having 2 or more chronic conditions from the 2017-2020 Health Information National Trends Survey were analyzed (N = 3341) using weighted descriptive and logistic regression analyses. RESULTS: Overall, 48% (n = 1674) of older adults with multimorbidity used social media and there was a linear trend in use over time, increasing from 41.1% in 2017 to 46.5% in 2018, and then further up to 51.7% in 2019, and 54.0% in 2020. Users were often younger, married/partnered, and non-Hispanic White with high education and income. Social media use was associated with better self-care efficacy that was further related to better mental health, indicating a significant mediation effect of self-care efficacy in the relationship between social media use and mental health. DISCUSSION: Although older adults with multimorbidity are a fast-growing population using social media for health, significant demographic disparities exist. While social media use is promising in improving self-care efficacy and thus mental health, relying on social media for the management of multimorbidity might be potentially harmful to those who are not only affected by multimorbidity but also socially disadvantaged (eg, non-White with lower education). CONCLUSION: Great effort is needed to address the demographic disparity and ensure health equity when using social media for patient care.

Integrating machine learning and genome editing for crop improvement.

Genome editing is a promising technique that has been broadly utilized for basic gene function studies and trait improvements. Simultaneously, the exponential growth of computational power and big data now promote the application of machine learning for biological research. In this regard, machine learning shows great potential in the refinement of genome editing systems and crop improvement. Here, we review the advances of machine learning to genome editing optimization, with emphasis placed on editing efficiency and specificity enhancement. Additionally, we demonstrate how machine learning bridges genome editing and crop breeding, by accurate key site detection and guide RNA design. Finally, we discuss the current challenges and prospects of these two techniques in crop improvement. By integrating advanced genome editing techniques with machine learning, progress in crop breeding will be further accelerated in the future.

Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

Phase-Field Model of Electronic Antidoping.

Charge carrier doping usually reduces the resistance of a semiconductor or insulator, but was recently found to dramatically enhance the resistance in certain series of materials. This remarkable antidoping effect has been leveraged to realize synaptic memory trees in nanoscale hydrogenated perovskite nickelates, opening a new direction for neuromorphic computing. To understand these phenomena, we formulate a physical phase-field model of the antidoping effect based on its microscopic mechanism and simulate the voltage-driven resistance change in the prototypical system of hydrogenated perovskite nickelates. Remarkably, the simulations using this model, containing only one adjustable parameter whose magnitude is justified by first-principles calculations, quantitatively reproduce the experimentally observed treelike resistance states, which are shown unambiguously to arise from proton redistribution-induced local band gap enhancement and carrier blockage. Our work lays the foundation for modeling the antidoping phenomenon in strongly correlated materials at the mesoscale, which can provide guidance to the design of novel antidoping-physics-based devices.

High water resistance starch based intelligent label for the freshness monitoring of beverages.

The traditional starch-based intelligent freshness labels struggle to maintain long-term structural stability when exposed to moisture. To solve this problem, we prepared composite crosslinked labels using phytic acid for double crosslinking of corn starch and soybean isolate proteins, with anthocyanin serving as the chromogenic dye. The mechanical properties, hydrophobic characteristics, and pH responsivity of these crosslinked labels were assessed in this study. The prepared double-crosslinked labels showed reduced moisture content (15.96%), diminished swelling (147.21%), decreased solubility (28.55%), and minimized water permeability, which suggested that they have enhanced hydrophobicity and densification. The crosslinked labels demonstrated the ability to maintain morphological stability when immersed in water for 12 h. Additionally, the mechanical properties of the crosslinked labels were enhanced without compromising their pH-sensing capabilities, demonstrated a color response visible to the naked eye for milk and coconut water freshness monitoring, suggesting great potential for application in beverages freshness monitoring.

What explains the operational efficiency of listed commercial banks in China? Evidence from a three-stage DEA-tobit modeling analysis.

Based on the actual situation of listed commercial banks in China, this study utilizes a three-stage DEA model to eliminate external macro-environmental factors and random error factors. As a result, the study objectively measures the true efficiency values of 42 listed commercial banks in China from 2015 to 2021. On this basis, a Tobit model is constructed to analyze the micro-level factors influencing the operational efficiency of listed commercial banks in China. Empirical research shows that the operational efficiency values in the first stage are significantly lower than those in the third stage. Analyzing the proportion of banks with an efficiency value of 1, it is found that state-owned banks and joint-stock banks account for a large proportion. The proportion of city commercial banks decreases significantly, while agricultural banks and commercial banks have the lowest proportion. In addition, the Tobit regression results show that bank size, innovation level, profitability, and development capacity have a significant positive impact on the operational efficiency of listed commercial banks in China at the current stage. Based on the above empirical results and analysis, specific measures are proposed to improve the operational efficiency of listed commercial banks in China. Based on the above empirical results and analysis, the study finally suggests the following specific measures to enhance the operational efficiency of listed commercial banks in China: 1. Strengthening technological investment to achieve diversified operations and cultivate new niche markets; 2. Emphasizing intermediate business income to enhance market competitiveness; 3. Undertaking digital transformation and upgrading to improve sustainable profitability.

Thorium Cluster Synthesized by a Solvent-Free Flux Approach: The Richest Coordination Diversity and Application Exploration.

The renaissance of research interests in actinide oxo clusters in the past decade arises from both the concerns of radioactive contamination and their potential utility as nanoscale materials. Compared to the uranium cluster, the thorium (Th) cluster shows less coordination variation. Herein, we presented a unique Th cluster (ThC-1) that exhibits the most diverse coordination chemistry found within a single Th cluster via a solvent-free flux synthesis approach. The melt triazole not only offers a unique solvation environment that may be responsible for the coordination diversity in ThC-1 but also represents the first nitrogen-donor capping ligand in Th clusters. The potential utility of ThC-1 as a heterogeneous catalyst was also explored for a classical CO2 cycloaddition reaction. This work offers a novel approach in synthesizing Th clusters, broadening the realm of the structural diversity of Th.

Humoral and cellular immune responses following Omicron BA.2.2 breakthrough infection and Omicron BA.5 reinfection.

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.

An in situ exploration of how Fe/N/C oxygen reduction catalysts evolve during synthesis under pyrolytic conditions.

In pursuing cheap and effective oxygen reduction catalysts, the Fe/N/C system emerges as a promising candidate. Nevertheless, the structural transformations of starting materials into Fe- and N-doped carbon catalysts remains poorly characterized under pyrolytic conditions. Here, we explore the evolution of Fe species and track the formation of Fe-N4 site development by employing diverse in-situ diagnostic techniques. In-situ heating microscopy reveals the initial formation of FeOx nanoparticles and subsequent internal migration within the carbon matrix, which stops once FeOx is fully reduced. The migration and decomposition of nanoparticles then leads to carbon layer reconstruction. Experimental and theoretical analysis reveals size-dependent behavior of FeOx where nanoparticles below 7 nm readily release Fe atoms to form Fe-N4 while nanoparticles with sizes >10 nm tend to coalesce and impede Fe-N4 site formation. The work visualizes the pyrolysis process of Fe/N/C materials, providing theoretical guidance for the rational design of catalysts.

Learning curve and initial outcomes of a novel percutaneously endoscopic-assisted total hip arthroplasty through mini bikini direct anterior approach: an observational cohort study.

OBJECTIVE: Although the direct anterior approach can reduce muscle damage and ensure accurate prosthesis placement, the steep learning curve and increased risk of complications associated with DAA necessitate careful consideration. Therefore, we describe a technique for a novel percutaneously endoscopic-assisted total hip arthroplasty through mini bikini direct anterior approach (mDAA) and report the learning curve and initial outcomes. METHODS: The first 125 THA performed by a single surgeon between September 2020 and February 2022 using the anterior approach were included, comprising the initial 41 cases of bikini DAA (bDAA) and the subsequent 84 cases of mDAA. Outcome measures included perioperative outcomes and postoperative complications. The cumulative sum analysis (CUSUM) was used to determine the learning curve of anterior approach THA for each patient's ORT. Multivariable analysis was performed to determine risk correlation. RESULTS: A total of 125 anterior approach THA completed between 2020 and 2022 were identified. Among these, 41 were performed via bDAA and 84 via mDAA. No statistically significant differences were observed between the groups in terms of age, gender distribution, BMI or follow-up time. A significant reduction in ORT was noted, from 140 min for bDAA to 130 min for mDAA. Furthermore, there was a consistent decrease in LOI, LOS, and wound-healing problems. There was no statistically significant difference between groups with respect to Harris Hip Scores and other postoperative complications. The curve inflection points of the learning curve for the bDAA and mDAA group were located in the 22nd and 68th cases, respectively. The reduction of hemoglobin indicated a predicted increase in ORT. CONCLUSIONS: In this study, ORT, LOI, LOS, and wound-healing problems decreased overall in mDAA group. After mastering the bDAA technique, approximately 27 mDAA cases are needed to acquire proficiency in this technique. Hence, mDAA is a valuable alternative for those seeking smaller incisions, resolving wound healing problems, and aiming for enhanced recovery after surgery.

Promoter Hypermethylation Downregulates MiR-125b-5p and MiR-199b-5p Targeting of ΔNp63, Resulting in PI3K/AKT/mTOR Pathway Activation and Keratinocyte Differentiation.

BACKGROUND: Normal keratinocyte differentiation is important for epidermal wound healing. ΔNp63 is a major gene regulating epidermal formation and differentiation. We identified miRNAs targeting ΔNp63 and studied the association between the miRNAs and DNA methylation in keratinocyte differentiation. AIMS: This study aimed to explore the mechanisms regulating ΔNp63 expression during keratinocyte differentiation. METHODS: Bioinformatics analysis was performed to screen the miRNAs targeting ΔNp63 and uncover potential pathway mechanisms. The differentiation model of keratinocytes was established by CaCl2 treatment. Furthermore, the effects of the miRNA transgenic technique on Δ Np63 and keratinocyte differentiation were studied. In addition, the RNA FISH experiment was conducted to detect the location of different miRNAs. A double luciferase reporter experiment was carried out to verify the potential bindings between the miRNAs and ΔNp63. A rescue experiment was also performed to assess the effects of different miRNAs targeting ΔNp63 on keratinocyte differentiation. We analyzed the methylation patterns of the promoter regions of miRNAs using keratinocytes treated with 5-Aza-2'-deoxycytidine. Finally, we designed a methylation rescue experiment to verify the effects of miRNA promoter methylation on keratinocyte differentiation. RESULTS: Bioinformatics analysis showed that the miR-125b-5p and miR-199b-5p binding to the ΔNp63 3'UTR region decreased during skin development. Moreover, such binding may downregulate the PI3K/AKT/mTOR pathway. The expression levels of CK10, Inv, TG1, ΔNp63, and PI3K/AKT/mTOR were all significantly increased during keratinocyte differentiation. Both miR- 125b-5p and miR-199b-5p were localized in the cytoplasm. Luciferase assay results showed that both miR-125b-5p and miR-199b-5p can bind to the 3'UTR region of ΔNp63. Overexpression of ΔNp63 can significantly counteract the inhibitory effect of miRNA mimics on keratinocyte differentiation. Moreover, the promoter regions of both miR-125b-5p and miR-199b-5p had methylation sites, and the methylation levels in those promoter regions were significantly increased during keratinocyte differentiation. 5-Aza-2'-Deoxycytidine treatment increased the expression of miR- 125b-5p and miR-199b-5p and inhibited the differentiation of keratinocytes. Finally, miRNA inhibitors reversed the inhibitory effects of 5-Aza-2'-deoxycytidine on keratinocyte differentiation. CONCLUSION: Promoter hypermethylation in miR-125b-5p and miR-199b-5p seem to promote keratinocyte differentiation via upregulation of ΔNp63 expression and the activation of the PI3K/AKT/mTOR pathway. The findings of this study are helpful for future research on skin development and clinical scar-free healing.

Protective effects of DcR3-SUMO on lipopolysaccharide-induced inflammatory cells and septic mice.

Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.