MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells.

Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.

Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4+ T cell response.

Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4+ T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4+ and CD8+ tumor-specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.

Introducing palmfungi.org, an integrated fungal-host data platform.

Palm fungi are a diverse and unique group mostly found on Arecaceae hosts. They have been studied for approximately 200 years resulting in a large number of known fungal species representing over 700 genera. The timeline of palm fungal studies could be roughly divided into three phases, based on the methods and frequency of reports. They are the "Historical palm fungi era", "Classical palm fungi era" and "Molecular palm fungi era". In the first two periods, the identification of palm fungi was based on morphology, which resulted in a considerable number of morphological species scattered across the data in books, monographs and papers. With the advancement of molecular techniques, studies on palm fungi accelerated. A large number of new species were introduced in the molecular era, especially from Asia, including China and Thailand. However, there is a necessity to link these three generations of studies into a single platform combining data related to host factors, geography and utilisation. Herein, we introduce the palm fungi website: https://palmfungi.org, an integrated data platform for interactive retrieval, based on palm and fungal species. This website is not only a portal for the latest, comprehensive species information on palm fungi, but also provides a new platform for fungal researchers to explore the host-specificity of palm fungi. Additionally, this study uses palmfungi.org and related data to briefly discuss the current status of research on the distribution of palm fungi populations, showing how palmfungi.org links fungi with their palm hosts. Furthermore, the website will act as a platform for collaboration amongst taxonomists, plant pathologists, botanists, ecologists and those who are interested in palms and their relationship with ecological sustainability.

Evolutionary fingerprint in rodent PD1 confers weakened activity and enhanced tumor immunity compared to human PD1.

Mechanistic understanding of the immune checkpoint receptor PD1 is largely based on mouse models, but human and mouse PD1 orthologs exhibit only 59.6% identity in amino acid sequences. Here we show that human PD1 is more inhibitory than mouse PD1 due to stronger interactions with the ligands PDL1 and PDL2 and with the effector phosphatase Shp2. A novel motif highly conserved among PD1 orthologs in vertebrates except in rodents is primarily responsible for the differential Shp2 recruitment. Evolutionary analysis suggested that rodent PD1 orthologs uniquely underwent functional relaxation, particularly during the K-Pg boundary. Humanization of the PD1 intracellular domain disrupted the anti-tumor activity of mouse T cells while increasing the magnitude of anti-PD1 response. Together, our study uncovers species-specific features of the PD1 pathway, with implications to PD1 evolution and differential anti-PD(L)1 responses in mouse models and human patients.

Vertebral marrow fat fraction is associated with circulating RANKL in postmenopausal females.

Objective: To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. Methods: A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Results: Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (ß = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (ß = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; ß = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and ß =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (ß = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Conclusions: Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Combined application of resveratrol and a ryegrass endophyte in PAH-contaminated soil remediation and its impact on soil microbial communities.

The unique capacity of certain plant endophytes to degrade organic pollutants has garnered considerable interest in recent years. However, it remains uncertain whether endophytes can maintain high degradation activity after in vitro culture and whether they can be used directly in the remediation of contaminated soils. This study reveals that resveratrol, a plant secondary metabolite, selectively boosts the degradation of polycyclic aromatic hydrocarbons (PAHs) by endophytic Methylobacterium extorquens C1 (C1) in vitro, while exerting negligible effects on the activity of indigenous soil bacteria. For the first time, a combined application of C1 and resveratrol was employed in the remediation of polycyclic aromatic hydrocarbon (PAH)-contaminated soil. The findings indicate that the sole use of resveratrol failed to promote the removal of PAHs by indigenous soil microorganisms, whereas sole application of C1 boosted Methylobacterium-related PAH-degrading bacterial abundance, enhancing PAH removal, yet concurrently reduced overall soil microbial diversity. The combination of resveratrol and C1 not only stimulated the PAH removal but also mitigated the impact of C1 on the soil microbial community structure when C1 was applied individually. Specifically, the optimal removal efficacy was achieved with a treatment combination of 5 mg kg-1 resveratrol and 1.2 × 107 CFU kg-1 of C1, leading to a 130% and 231% increase in the removal of phenanthrene and acenaphthene, respectively, over a 15 days period. This study proposes a novel approach for the bioremediation of organic-contaminated soil by using the specific biological response of plant endophytic bacteria to secondary metabolites.

Feasibility and effectiveness of cardiac telerehabilitation for older adults with coronary heart disease: A pilot randomized controlled trial.

Background: Cardiac rehabilitation is a beneficial multidisciplinary treatment of exercise promotion, patient education, risk factor management, and psychosocial counseling for people with coronary heart disease (CHD) that is underutilized due to substantial disparities in access, referral, and participation. Empirical studies suggest that cardiac telerehabilitation (CTR) have safety and efficacy comparable to traditional in-person cardiac rehabilitation, however, older adults are under-reported with effectiveness, feasibility, and usability remains unclear. Methods: The study randomized 43 older adults (84 % males) to the 12-week CTR intervention or standard of care. Guided by Social Cognitive Theory, participants received individualized in-person assessment and e-coaching sessions, followed by CTR usage at home. Data were collected at baseline (T0), six-week (T1), and 12-week (T2). Results: Participants in the CTR intervention group showed significant improvement in daily steps (T1: ß = 4126.58, p = 0.001; T2: ß = 5285, p = 0.01) and health-promoting lifestyle profile (T1: ß = 23.26, p < 0.001; T2: ß = 12.18, p = 0.008) across study endpoints. Twenty participants completed the intervention, with 40 % used the website for data-uploading or experiential learning, 90 % used the pedometer for tele-monitoring. Improving awareness of rehabilitation and an action focus were considered key facilitators while physical discomforts and difficulties in using the technology were described as the main barriers. Conclusions: The CTR is feasible, safe and effective in improving physical activity and healthy behaviors in older adults with CHD. Considering the variation in individual cardiovascular risk factors, full-scale RCT with a larger sample is needed to determine the effect of CTR on psychological symptoms, body weight and blood pressure, and quality of life.

Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial.

INTRODUCTION: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU). METHODS: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth. RESULTS: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia. CONCLUSION: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Enlarging effects of microplastics on adsorption, desorption and bioaccessibility of chlorinated organophosphorus flame retardants in landfill soil particle-size fractions.

Chlorinated organophosphorus flame retardants (Cl-OPFRs) and microplastics (MPs) are emerging pollutants in landfills, but their synergistic behaviors and triggering risks were rarely focused on, impeding the resource utilization of landfill soils. This study systematically investigated the adsorption/desorption behaviors, bioaccessibility and human health risks of Cl-OPFRs in landfill soil particle-size fractions coexisted with MPs under simulated gastrointestinal conditions. The results showed that the adsorption capacity and bioaccessibility of Cl-OPFRs in humus soil were higher than that in subsoil. MPs promoted the adsorption of tris(1-chloro-2-methylethyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in landfill soils by up to 34.6 % and 34.1 % respectively, but inhibited the adsorption of tris(2-chloroethyl) phosphate (TCEP) by up to 43.6 %. The bioaccessibility of Cl-OPFRs in landfill soils was positively correlated with MPs addition ratio but negatively correlated with the KOW of Cl-OPFRs, soil organic matter and particle size. MPs addition increased the residual concentration of Cl-OPFRs and significantly increased the bioaccessibility of TCEP and TDCPP by up to 33.1 % in landfill soils, resulting in higher carcinogenic and noncarcinogenic risks. The study presents the first series of the combined behavior and effects of MPs and Cl-OPFRs in landfill soils, and provides a theoretical reference for landfill risk management.

Sonic hedgehog signaling facilitates pyroptosis in mouse heart following ischemia/reperfusion via enhancing the formation of CARD10-BCL10-MALT1 complex.

Pyroptosis has been found to contribute to myocardial ischemia/reperfusion (I/R) injury, but the exact mechanisms that initiate myocardial pyroptosis are not fully elucidated. Sonic hedgehog (SHH) signaling is activated in heart suffered I/R, and intervention of SHH signaling has been demonstrated to protect heart from I/R injury. Caspase recruitment domain-containing protein 10 (CARD10)-B cell lymphoma 10 (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex could transduce signals from the membrane and induce inflammatory pathways in non-hematopoietic cells, which could be a downstream effector of SHH signaling pathway. This study aims to explore the role of SHH signaling in I/R-induced myocardial pyroptosis and its relationship with the CBM complex. C57BL/6J mice were subjected to 45 min-ischemia followed by 24 h-reperfusion to establish a myocardial I/R model, and H9c2 cells underwent hypoxia/reoxygenation (H/R) to mimic myocardial I/R model in vitro. Firstly, SHH signaling was significantly activated in heart suffered I/R in an autocrine- or paracrine-dependent manner via its receptor PTCH1, and inhibition of SHH signaling decreased myocardial injury via reducing caspase-11-dependent pyroptosis, concomitant with attenuating CBM complex formation. Secondly, suppression of SHH signaling decreased protein kinase C α (PKCα) level, but inhibition of PKCα attenuated CBM complex formation without impacting the protein levels of SHH and PTCH1. Finally, disruption of the CBM complex prevented MALT1 from recruiting of TRAF6, which was believed to trigger the caspase-11-dependent pyroptosis. Based on these results, we conclude that inhibition of SHH signaling suppresses pyroptosis via attenuating PKCα-mediated CARD10-BCL10-MALT1 complex formation in mouse heart suffered I/R.

Analysis of placebo effect of acupuncture. / é’ˆåˆºå®‰æ °å‰‚æ•ˆåº”å‰–æž.

Acupuncture is a comprehensive therapy which takes the theory of traditional Chinese medicine as the core. Currently, there is much controversy surrounding the "placebo effect" of acupuncture： some people argue that acupuncture is a "super placebo", while others believe that the so-called placebo effect is just part of the therapeutic effect of acupuncture. To solve the controversy, this article clarified the definition, composition, and research purposes of "placebo acupuncture", pointed out its differences from "sham acupuncture", elucidated the relationship between the placebo effect and the intrinsic efficacy of acupuncture, distinguished the differences between the "observed placebo effect" and the "real placebo effect" in acupuncture clinical trials, and proposed the dilemmas and prospects of implementing "placebo acupuncture" and "sham acupuncture" contrasts at the current stage, in order to provide clues for optimizing randomized controlled trials of acupuncture.

Comprehensive evaluation of Chinese herbal compound prescriptions for postoperative spinal cord injury: A network meta-analysis of randomized controlled trials.

Background: Spinal cord injury (SCI) is a catastrophic condition associated with spinal nerve damage, which can lead to complete or partial loss of sensory and motor functions. Chinese herbal compound prescriptions (CHCP) have shown varying degrees of therapeutic effects on spinal cord injuries. However, there is a significant lack of clinical evidence-based research to substantiate these effects. Purpose: This study aims to thoroughly assess the viability of CHCPs in postoperative SCI through network meta-analysis. Methods: Computer searches were conducted across multiple databases, including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and CBM, from their inception until May 2024. The meta-analysis adhered to the PRISMA guidelines and was registered in the PROSPERO database (CRD42023462686). A network meta-analysis was performed using the BUGSnet software package via R. Study design: A network meta-analysis of randomized clinical trials (RCTs). Results: A total of 26 RCTs involving 1848 patients were ultimately included. The network meta-analysis revealed the effectiveness in improving ASIA motor score as follows: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". For ASIA sensory score, the effectiveness ranking was: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". Additionally, the experimental group had a higher ADL score compared to the control group, with a statistically difference [SMD = 1.08, 95 % CI = (0.88, 1.27), p < 0.05]. The experimental group had fewer adverse events compared to the control group, with a statistically difference [RR = 0.41, 95 % CI (0.22, 0.78), p < 0.05]. Conclusion: The findings suggest that CHCP can mprove postoperative ASIA motor and sensory scores, enhance ADL scores, and reduce adverse events following SCI surgery. Specifically, combining surgery with Huangqi Guizhi Wuwu Decoction or Buyang Huanwu Decoction may provide superior therapeutic effects in SCI treatment. Integrating CHCP into postoperative care for SCI patients may offer potential benefits.

Dominant Charge Density Order in TaTe_{4}.

Electronic orders such as charge density wave (CDW) and superconductivity raise exotic physics and phenomena as evidenced in recently discovered kagome superconductors and transition metal chalcogenides. In most materials, CDW induces a weak, perturbative effect, manifested as shadow bands, minigaps, resistivity kinks, etc. Here we demonstrate a unique example-transition metal tetratellurides TaTe_{4}, in which the CDW order dominates the electronic structure and transport properties. Using angle-resolved photoemission spectroscopy, we found that the band structure of CDW TaTe_{4} is characterized by small, bulk electron pockets. Density functional theory analyses reveal their CDW origin from the folding of the original, large Fermi pockets. Importantly, the CDW induced pockets result in prominent frequencies in the quantum oscillation of the magnetoresistance. Satisfactory agreements are reached between results from photoemission spectroscopy, density functional theory, and quantum oscillation, concerning the shape, size, location, and angle dependence of the CDW pockets. Our results underline transition metal tetratellurides as an outstanding example for exploring the interplay between CDW, pressure induced superconductivity, and potential topological states under strong field.

Neural Memory State Space Models for Medical Image Segmentation.

With the rapid advancement of deep learning, computer-aided diagnosis and treatment have become crucial in medicine. UNet is a widely used architecture for medical image segmentation, and various methods for improving UNet have been extensively explored. One popular approach is incorporating transformers, though their quadratic computational complexity poses challenges. Recently, State-Space Models (SSMs), exemplified by Mamba, have gained significant attention as a promising alternative due to their linear computational complexity. Another approach, neural memory Ordinary Differential Equations (nmODEs), exhibits similar principles and achieves good results. In this paper, we explore the respective strengths and weaknesses of nmODEs and SSMs and propose a novel architecture, the nmSSM decoder, which combines the advantages of both approaches. This architecture possesses powerful nonlinear representation capabilities while retaining the ability to preserve input and process global information. We construct nmSSM-UNet using the nmSSM decoder and conduct comprehensive experiments on the PH2, ISIC2018, and BU-COCO datasets to validate its effectiveness in medical image segmentation. The results demonstrate the promising application value of nmSSM-UNet. Additionally, we conducted ablation experiments to verify the effectiveness of our proposed improvements on SSMs and nmODEs.

A Competition for the Diagnosis of Myopic Maculopathy by Artificial Intelligence Algorithms.

Importance: Myopic maculopathy (MM) is a major cause of vision impairment globally. Artificial intelligence (AI) and deep learning (DL) algorithms for detecting MM from fundus images could potentially improve diagnosis and assist screening in a variety of health care settings. Objectives: To evaluate DL algorithms for MM classification and segmentation and compare their performance with that of ophthalmologists. Design, Setting, and Participants: The Myopic Maculopathy Analysis Challenge (MMAC) was an international competition to develop automated solutions for 3 tasks: (1) MM classification, (2) segmentation of MM plus lesions, and (3) spherical equivalent (SE) prediction. Participants were provided 3 subdatasets containing 2306, 294, and 2003 fundus images, respectively, with which to build algorithms. A group of 5 ophthalmologists evaluated the same test sets for tasks 1 and 2 to ascertain performance. Results from model ensembles, which combined outcomes from multiple algorithms submitted by MMAC participants, were compared with each individual submitted algorithm. This study was conducted from March 1, 2023, to March 30, 2024, and data were analyzed from January 15, 2024, to March 30, 2024. Exposure: DL algorithms submitted as part of the MMAC competition or ophthalmologist interpretation. Main Outcomes and Measures: MM classification was evaluated by quadratic-weighted κ (QWK), F1 score, sensitivity, and specificity. MM plus lesions segmentation was evaluated by dice similarity coefficient (DSC), and SE prediction was evaluated by R2 and mean absolute error (MAE). Results: The 3 tasks were completed by 7, 4, and 4 teams, respectively. MM classification algorithms achieved a QWK range of 0.866 to 0.901, an F1 score range of 0.675 to 0.781, a sensitivity range of 0.667 to 0.778, and a specificity range of 0.931 to 0.945. MM plus lesions segmentation algorithms achieved a DSC range of 0.664 to 0.687 for lacquer cracks (LC), 0.579 to 0.673 for choroidal neovascularization, and 0.768 to 0.841 for Fuchs spot (FS). SE prediction algorithms achieved an R2 range of 0.791 to 0.874 and an MAE range of 0.708 to 0.943. Model ensemble results achieved the best performance compared to each submitted algorithms, and the model ensemble outperformed ophthalmologists at MM classification in sensitivity (0.801; 95% CI, 0.764-0.840 vs 0.727; 95% CI, 0.684-0.768; P = .006) and specificity (0.946; 95% CI, 0.939-0.954 vs 0.933; 95% CI, 0.925-0.941; P = .009), LC segmentation (DSC, 0.698; 95% CI, 0.649-0.745 vs DSC, 0.570; 95% CI, 0.515-0.625; P < .001), and FS segmentation (DSC, 0.863; 95% CI, 0.831-0.888 vs DSC, 0.790; 95% CI, 0.742-0.830; P < .001). Conclusions and Relevance: In this diagnostic study, 15 AI models for MM classification and segmentation on a public dataset made available for the MMAC competition were validated and evaluated, with some models achieving better diagnostic performance than ophthalmologists.

[Transepithelial transport in vivo and in vitro and anti-inflammatory activity of cannabidiol].

This study used Caco-2 cells and normal rats to investigate the in vitro absorption characteristics and in vivo pharmacokinetic characteristics of cannabidiol(CBD) and explore the anti-inflammatory mechanism of CBD. The safe concentration range of CBD was determined by the CCK-8 assay, and then the effects of time, concentration, temperature, endocytosis inhibitors, and transport inhibitors on the transepithelial absorption and transport of CBD were assessed. The blood drug concentration was measured at different time points after oral administration in rats for pharmacokinetic profiling, and the pharmacokinetic parameters were calculated. The Caco-2 cell model of inflammation injury was established with lipopolysaccharide(LPS). The effects of CBD on lactate dehydrogenase(LDH) activity, transendothelial electrical resistance(TEER), and levels of inflammatory cytokines of the modeled cells were exami-ned, on the basis of which the anti-inflammatory mechanism of CBD was deciphered. The results showed that within the concentration range tested in this study, the CBD uptake by Caco-2 cells reached saturation at the time point of 2 h. Moreover, the CBD uptake was positively correlated with concentration and temperature and CBD could be endocytosed into the cells. CBD could penetrate Caco-2 cells through active transport pathways involving multidrug resistance-associate protein 2(MRP2) and breast cancer resistance protein(BCRP), while the addition of P-gp inhibitors had no effect on CBD transport. Rats exhibited rapid absorption of CBD, with the peak time(t_(max)) of(1.00±0.11) h, and fast elimination of CBD, with a half-life(t_(1/2)) of only(1.86±0.16) h. In addition, CBD significantly ameliorated the increased LDH activity and decreased TEER that were caused by inflammatory response. It maintained the intestinal barrier by down-regulating the expression of pro-inflammatory cytokines interleukin-8(IL-8), interleukin-1 beta(IL-1ß) and tumor necrosis factor-α(TNF-α), thus exerting anti-inflammatory effects.

Novel Helicoma and Neohelicosporium (Tubeufiaceae, Tubeufiales) species and two new host records of Helicoma on tropical palms (Arecaceae) from China.

Asexual species of Tubeufiaceae are characterised as helicosporous hyphomycetes and are abundantly discovered in tropical and subtropical regions. The present study collected helicosporous fungal samples from rotting tissues of Caryotamitis, Elaeisguineensis and E.oleifera in Xishuangbanna, Yunan Province, China. Fungal isolates were identified, based on the morphological characteristics and multi-gene phylogeny with DNA sequence data of the internal transcribed spacer (ITS), part of the large subunit nuclear rRNA gene (LSU), translation elongation factor 1-alpha gene (tef 1-α) and RNA polymerase II second largest subunit gene (rpb2). Herein, we introduce three new species viz. Helicomaoleifera, Neohelicosporiumguineensis and N.xishuangbannaensis. In addition, we introduce two new host records of Helicomaguttulatum and H.rufum on Caryotamitis. The illustrations of all identified species, detailed descriptions and in-depth phylogenetic analyses are provided. Our results add new knowledge of fungal species associated with palm hosts in southern China. Moreover, our data will contribute to the biodiversity of fungi in tropical China.

Endoplasmic reticulum-targeted biomimetic nanoparticles induce apoptosis and ferroptosis by regulating endoplasmic reticulum function in colon cancer.

Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment.

Research progress of gene therapy combined with tissue engineering to promote bone regeneration.

Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is a common clinical need. Meanwhile, many preclinical data have demonstrated that gene and cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, and molecules with stimulatory capability, provides promising alternatives to enhance bone regeneration. To deliver and localize growth factors and associated intracellular signaling components into the defect site, gene therapy strategies combined with bioengineering could achieve a uniform distribution and sustained release to ensure mesenchymal stem cell osteogenesis. In this review, we will describe the process and cell molecular changes during normal fracture healing, followed by the advantages and disadvantages of various gene therapy vectors combined with bone tissue engineering. The growth factors and other bioactive peptides in bone regeneration will be particularly discussed. Finally, gene-activated biomaterials for bone regeneration will be illustrated through a description of characteristics and synthetic methods.

Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway.

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.