Trivalent Disulfide Unit-Masked System Efficiently Delivers Large Oligonucleotide.

Oligonucleotide drugs are shining in clinical therapeutics, but efficient and safe delivery systems severely limit their widespread use. A disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the disulfide unit CSSC dihedral angle induced by different substituents directly affects the effectiveness of this technology and its stability. Previously, we constructed a trivalent low dihedral angle disulfide unit that can effectively promote the cellular uptake of small molecules. Here, we constructed a novel disulfide unit-masked oligonucleotide hybrid based on a low dihedral angle disulfide unit, motivated by prodrug design. Cellular imaging results showed that such a system exhibited superior cellular delivery efficiency than the commercial Lipo2000 without cytotoxicity. The thiol reagents significantly reduced its cellular uptake (57-74%), which proved to be endocytosis-independent. In addition, in vivo distribution experiments in mice showed that such systems can be rapidly distributed in liver tissues with a duration of action of more than 24 h, representing a potential means of silencing genes involved in the pathogenesis of liver-like diseases. In conclusion, this trivalent disulfide unit-masked system we constructed can effectively deliver large oligonucleotide drugs.

Intraoperative hypotension and postoperative delirium in elderly male patients undergoing laryngectomy: a single-center retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common, transient postoperative cognitive dysfunction in elderly patients. The relationship between POD and intraoperative hypotension remains unclear. This study aims to determine if intraoperative hypotension predicts POD in elderly male patients undergoing laryngectomy. METHODS: This study included male patients over 65 years old who underwent laryngectomy between April 2018 and January 2022. The Confusion Assessment Method (CAM) was used to diagnose delirium. Intraoperative hypotension was defined as a Mean Arterial Pressure (MAP) during surgery that was less than 30% of the preoperative level for at least 30 minutes. The relationship between intraoperative hypotension and POD incidence was adjusted for patient demographics and surgery-related factors. RESULTS: Out of 428 male patients, 77 (18.0%) developed POD, and 166 (38.8%) experienced intraoperative hypotension. Surgery duration ≥ 300 minutes (OR = 1.873, 95% CI 1.041-3.241, p = 0.036), intraoperative hypotension (OR = 1.739, 95% CI 1.039-2.912, p = 0.035), and schooling (OR = 2.655, 95% CI 1.338-5.268) were independent risk factors for POD. The association between intraoperative hypotension and POD was significantly influenced by surgery duration (p for interaction = 0.008), with a stronger association in prolonged surgeries (adjusted OR = 4.902; 95% CI 1.816-13.230). CONCLUSIONS: Intraoperative hypotension and low education level are associated with an increased risk of POD in elderly male patients undergoing laryngectomy, especially with prolonged surgery duration.

Serum tsncRNAs reveals novel potential therapeutic targets of Salvianolic Acid B on atherosclerosis.

BACKGROUND: Salvianolic Acid B (SalB) has been proven to delay the progression of atherosclerosis. The therapeutic mechanisms of this compound are unclear. A novel class of short non-coding RNAs, pre-transfer RNA and mature transfer RNA (tsncRNAs) may regulate gene expression. TsncRNAs-sequencing revealed novel therapeutic targets for SalB. This is the first study focusing on tsncRNAs to treat atherosclerosis using SalB. PURPOSE: To explore the potential mechanism of SalB treating atherosclerosis through tsncRNAs. METHODS: Five groups of mice were created at random: control group (CON), atherosclerosis model group (MOD), SalB with high dose-treated group (SABH), SalB with low dose-treated group (SABL), and Simvastatin-treated group (ST). Aortic sinus plaque, body weight and inflammatory cytokines were evaluated. The Illumina NextSeq equipment was used to do expression profiling of tsncRNAs from serum. The targets of tsncRNAs were then predicted using tRNAscan and TargetScan. The KEGG pathway and GO analysis were utilized to forecast the bioinformatics analysis. Potential tsncRNAs and associated mRNAs were validated using quantitative real-time PCR. RESULTS: tRF-Glu-CTC-014 and tRF-Gly-GCC-074 were markedly increased by SalB with high dose treatment and validated with quantitative real-time PCR. Two mRNAs SRF and Arrb related to tRF-Glu-CTC-014 changed consistently. GO analysis revealed that the altered target genes of the selected tsncRNAs were most enriched in protein binding and cellular process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tsncRNAs were most enriched in MAPK signaling pathway. CONCLUSION: SalB can promote the expression of tRF-Glu-CTC-014 to treat atherosclerosis.

Rosmarinic Acid Alleviates Radiation-Induced Pulmonary Fibrosis by Downregulating the tRNA N7-Methylguanosine Modification-Regulated Fibroblast-to-Myofibroblast Transition Through the Exosome Pathway.

Background: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved. Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation. Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF. Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.

LncRNA HOTAIRM1 promotes radioresistance in nasopharyngeal carcinoma by modulating FTO acetylation-dependent alternative splicing of CD44.

BACKGROUND: Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC); however, almost 20% of patients experience treatment failure due to radioresistance. Therefore, understanding the mechanisms of radioresistance is imperative. HOTAIRM1 is deregulated in various human cancers, yet its role in NPC radioresistance are largely unclear. METHODS: This study investigated the association between HOTAIRM1 and radioresistance using CCK8, flow cytometry, and comet assays. Additionally, xenograft mice and patient-derived xenografts (PDX) models were employed to elucidate the biological functions of HOTAIRM1, and transcriptomic RNA sequencing was utilized to identify its target genes. RESULTS: Our study revealed an upregulation of HOTAIRM1 levels in radioresistant NPC cell lines and tissues. Furthermore, a positive correlation was noted between high HOTAIRM1 expression and increased NPC cell proliferation, reduced apoptosis, G2/M cell cycle arrest, and diminished cellular DNA damage following radiotherapy. HOTAIRM1 modulates the acetylation and stability of the FTO protein, and inhibiting FTO elevates the m6A methylation level of CD44 precursor transcripts in NPC cells. Additionally, silencing the m6A reading protein YTHDC1 was found to increase the expression of CD44V. HOTAIRM1 enhances NPC cell resistance to ferroptosis and irradiation through the HOTAIRM1-FTO-YTHDC1-CD44 axis. Mechanistically, HOTAIRM1 interacts with the FTO protein and induces m6A demethylation of the CD44 transcript. The absence of m6A modification in the CD44 transcript prevents its recognition by YTHDC1, resulting in the transition from CD44S to CD44V. An abundance of CD44V suppresses ferroptosis induced by irradiation and contributes to NPC radioresistance. CONCLUSIONS: In conclusion, the results in this study support the idea that HOTAIRM1 stimulates CD44 alternative splicing via FTO-mediated demethylation, thereby attenuating ferroptosis induced by irradiation and promoting NPC radioresistance.

Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis.

Adverse intrauterine conditions may cause fetal growth restriction (FGR), a pregnancy complication frequently linked to perinatal morbidity and mortality. Although many studies have focused on FGR, the pathophysiological processes underlying this disorder are complex and incompletely understood. We have recently determined that galectin-3 (gal-3), a ß-galactoside-binding protein, regulates pregnancy-associated processes, including uterine receptibility, maternal vascular adaptation and placentation. Because gal-3 is expressed at both sides of the maternal-fetal interface, we unraveled the contribution of maternal- and paternal-derived gal-3 on fetal-placental development in the prenatal window and its effects on the post-natal period. Deficiency of maternal gal-3 induced maternal gut microbiome dysbiosis, resulting in a sex-specific fetal growth restriction mainly observed in female fetuses and offspring. In addition, poor placental metabolic adaptions (characterized by decreased trophoblast glycogen content and insulin-like growth factor 2 (Igf2) gene hypomethylation) were only associated with a lack of maternal-derived gal-3. Paternal gal-3 deficiency caused compromised vascularization in the placental labyrinth without affecting fetal growth trajectory. Thus, maternal-derived gal-3 may play a key role in fetal-placental development through the gut-placenta axis.

LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis.

Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1+ NK cells) and drives NK cell exhaustion in TB. Mechanistically, Mtb-infected macrophages display high expression of human leukocyte antigen-G (HLA-G), which upregulates and activates LILRB1 on NK cells to impair their functions by inhibiting mitogen-activated protein kinase (MAPK) signaling via tyrosine phosphatases SHP1/2. Furthermore, LILRB1 blockade restores NK cell-dependent anti-Mtb immunity in immuno-humanized mice. Thus, LILRB1-HLA-G axis constitutes a NK cell immune checkpoint in TB and serves as a promising immunotherapy target.

Unique stick-slip crack dynamics of double-network hydrogels under pure-shear loading.

In this work, we have found that a prenotched double-network (DN) hydrogel, when subjected to tensile loading in a pure-shear geometry, exhibits intriguing stick-slip crack dynamics. These dynamics synchronize with the oscillation of the damage (yielding) zone at the crack tip. Through manipulation of the loading rate and the predamage level of the brittle network in DN gels, we have clarified that this phenomenon stems from the significant amount of energy dissipation required to form the damage zone at the crack tip, as well as a kinetic contrast between the rapid crack extension through the yielding zone (slip process) and the slow formation of a new yielding zone controlled by the external loading rate (stick process).

Hypoxic Memory Mediates Prolonged Tumor-Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression.

Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis that is associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIF). Identification of the long-lasting effects of hypoxia beyond the immediate HIF-induced alterations could provide a better understanding of hypoxia-driven metastasis and potential strategies to circumvent it. Here, we uncovered a hypoxia-induced mechanism that exerts a prolonged effect to promote metastasis. In breast cancer patient-derived circulating tumor cell lines and common breast cancer cell lines, hypoxia downregulated tumor-intrinsic type I IFN signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced durable IFN/AP suppression in certain cell types that was sustained after returning to normoxic conditions, presenting a "hypoxic memory" phenotype. Hypoxic memory of IFN/AP downregulation was established by specific hypoxic priming, and cells with hypoxic memory had an enhanced ability for tumorigenesis and metastasis. Overexpression of IRF3 enhanced IFN signaling and reduced tumor growth in normoxic, but not hypoxic, conditions. The histone deacetylase inhibitor entinostat upregulated IFN targets and erased the hypoxic memory. These results point to a mechanism by which hypoxia facilitates tumor progression through a long-lasting memory that provides advantages for circulating tumor cells during the metastatic cascade. Significance: Long-term cellular memory of hypoxia leads to sustained suppression of tumor-intrinsic type I IFN signaling and the antigen presentation pathway that facilitates tumorigenesis and metastasis. See related commentary by Purdy and Ford, p. 3125.

Negative Photoconductivity Transistors for Visuomorphic Computing.

Visuomorphic computing aims to simulate and potentially surpass the human retina by mimicking biological visual perception with an artificial retina. Despite significant progress, challenges persist in perceiving complex interactive environments. Negative photoconductivity transistors (NPTs) mimic synaptic behavior by achieving adjustable positive photoconductivity (PPC) and negative photoconductivity (NPC), simulating "excitation" and "inhibition" akin to sensory cell signals. In complex interactive environments, NPTs are desired for visuomorphic computing that can achieve a better sense of information, lower power consumption, and reduce hardware complexity. In this review, it is started by introducing the development process of NPTs, while placing a strong emphasis on the device structures, working mechanisms, and key performance parameters. The common material systems employed in NPTs based on their functions are then summarized. Moreover, it is proceeded to summarize the noteworthy applications of NPTs in optoelectronic devices, including advanced multibit nonvolatile memory, optoelectronic logic gates, optical encryption, and visual perception. Finally, the challenges and prospects that lie ahead in the ongoing development of NPTs are addressed, offering valuable insights into their applications in optoelectronics and a comprehensive understanding of their significance.

miR-200a-3p promotes the malignancy of endometrial carcinoma through negative regulation of epithelial-mesenchymal transition.

BACKGROUND: miR-200a-3p is involved in the progression of malignant behavior in various tumors, and its mechanism of action in endometrial cancer is speculated to be related to epithelial-mesenchymal transition (EMT). Therefore, this study explored the metastatic mechanism of miR-200a-3p and EMT in endometrial cancer, with the aim of identifying potential therapeutic targets. METHODS: qRT-PCR was used to analyze miR-200a-3p expression in HEC-1B and Ishikawa cell lines. The cell proliferation assay, transwell assay, and cell scratch test were used to assess changes in the malignant phenotypes of cells after regulating miR-200a-3p expression. Changes in EMT-related protein zinc finger E-box binding homeobox 1 (ZEB1) were detected after regulating miR-200a-3p expression. An endometrial carcinoma transplantation mouse tumor model was constructed, and multiple EMT-related proteins were examined. RESULTS: The expression of miR-200a-3p and ZEB1 in the endometrial cancer cell lines was higher than in normal endometrial epithelial cell lines (P < 0.05). After silencing miR-200a-3p, the expression of EMT-related protein ZEB1 increased, indicating a negative correlation. Simultaneously, the proliferation, invasion, and metastasis of endometrial cancer cells were significantly enhanced. After miR-200a-3p overexpression, the corresponding malignant phenotype was reversed (P < 0.05). In in vivo experiments, the degree of tumor malignancy and the expression level of EMT-related proteins were significantly reduced in the miR-200a-3p mimic group (P < 0.05). CONCLUSION: This study found that miR-200a-3p is a promising target, regulating the EMT process and promoting endometrial cancer progression.

Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom.

Venom plays a crucial role in the defense and predation of venomous animals. Spiders (Araneae) are among the most successful predators and have a fascinating venom composition. Their venom mainly contains disulfide-rich peptides and large proteins. Here, we analyzed spider venom protein families, utilizing transcriptomic and genomic data, and highlighted their similarities and differences. We show that spiders have specific combinations of toxins for better predation and defense, typically comprising a core toxin expressed alongside several auxiliary toxins. Among them, the CAP superfamily is widely distributed and highly expressed in web-building Araneoidea spiders. Our analysis of evolutionary relationships revealed four subfamilies (subA-subD) of the CAP superfamily that differ in structure and potential functions. CAP proteins are composed of a conserved CAP domain and diverse C-terminal domains. CAP subC shares similar domains with the snake ion channel regulator svCRISP proteins, while CAP subD possesses a sequence similar to that of insect venom allergen 5 (Ag5). Furthermore, we show that gene duplication and selective expression lead to increased expression of CAP subD, making it a core member of the CAP superfamily. This study sheds light on the functional diversity of CAP subfamilies and their evolutionary history, which has important implications for fully understanding the composition of spider venom proteins and the core toxin components of web-building spiders.

High Overexpression of SiAAP9 Leads to Growth Inhibition and Protein Ectopic Localization in Transgenic Arabidopsis.

Amino acid permeases (AAPs) transporters are crucial for the long-distance transport of amino acids in plants, from source to sink. While Arabidopsis and rice have been extensively studied, research on foxtail millet is limited. This study identified two transcripts of SiAAP9, both of which were induced by NO3- and showed similar expression patterns. The overexpression of SiAAP9L and SiAAP9S in Arabidopsis inhibited plant growth and seed size, although SiAAP9 was found to transport more amino acids into seeds. Furthermore, SiAAP9-OX transgenic Arabidopsis showed increased tolerance to high concentrations of glutamate (Glu) and histidine (His). The high overexpression level of SiAAP9 suggested its protein was not only located on the plasma membrane but potentially on other organelles, as well. Interestingly, sequence deletion reduced SiAAP9's sensitivity to Brefeldin A (BFA), and SiAAP9 had ectopic localization on the endoplasmic reticulum (ER). Protoplast amino acid uptake experiments indicated that SiAAP9 enhanced Glu transport into foxtail millet cells. Overall, the two transcripts of SiAAP9 have similar functions, but SiAAP9L shows a higher colocalization with BFA compartments compared to SiAAP9S. Our research identifies a potential candidate gene for enhancing the nutritional quality of foxtail millet through breeding.

A fluorescence probe with targeted mitochondria for detecting hydrogen peroxide in vitro and in diabetic mice.

We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.

Development of the near-infrared fluorescence probe for detection of ONOO- and its application in vitro and vivo.

Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO- level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO- level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO- response site, which can detect ONOO- with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO- level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO- level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO- was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO-.

Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain.

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

Novel Therapies for ANCA-associated Vasculitis: Apilimod Ameliorated Endothelial Cells Injury through TLR4/NF-κB Pathway and NLRP3 Inflammasome.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rapidly progressive form of glomerulonephritis for which effective therapeutic drugs are currently lacking, and its underlying mechanism remains unclear. AIMS: This study aimed to investigate new treatment options for AAV through a combination of bioinformatics analysis and cell molecular experiments. METHODS: The research utilized integrated bioinformatics analysis to identify genes with differential expression, conduct enrichment analysis, and pinpoint hub genes associated with AAV. Potential therapeutic compounds for AAV were identified using Connectivity Map and molecular docking techniques. In vitro experiments were then carried out to examine the impact and mechanism of apilimod on endothelial cell injury induced by MPO-ANCA-positive IgG. RESULTS: The findings revealed a set of 374 common genes from differentially expressed genes and key modules of WGCNA, which were notably enriched in immune and inflammatory response processes. A proteinprotein interaction network was established, leading to the identification of 10 hub genes, including TYROBP, PTPRC, ITGAM, KIF20A, CD86, CCL20, GAD1, LILRB2, CD8A, and COL5A2. Analysis from Connectivity Map and molecular docking suggested that apilimod could serve as a potential therapeutic cytokine inhibitor for ANCA-GN based on the hub genes. In vitro experiments demonstrated that apilimod could mitigate tight junction disruption, endothelial cell permeability, LDH release, and endothelial activation induced by MPO-ANCA-positive IgG. Additionally, apilimod treatment led to a significant reduction in the expression of proteins involved in the TLR4/NF-κB and NLRP3 inflammasome-mediated pyroptosis pathways. CONCLUSION: This study sheds light on the potential pathogenesis of AAV and highlights the protective role of apilimod in mitigating MPO-ANCA-IgG-induced vascular endothelial cell injury by modulating the TLR4/ NF-kB and NLRP3 inflammasome-mediated pyroptosis pathway. These findings suggest that apilimod may hold promise as a treatment for AAV and warrant further investigation.

Promoting tissue repair using deferoxamine nanoparticles loaded biomimetic gelatin/HA composite hydrogel.

To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferationin vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.

Recent progress of UCNPs-MoS2 nanocomposites as a platform for biological applications.

Composite materials can take advantages of the functional benefits of multiple pure nanomaterials to a greater degree than single nanomaterials alone. The UCNPs-MoS2 composite is a nano-application platform that combines upconversion luminescence and photothermal properties. Upconversion nanoparticles (UCNPs) are inorganic nanomaterials with long-wavelength excitation and short-wavelength tunable emission capabilities, and are able to effectively convert near-infrared (NIR) light into visible light for increased photostability. However, UCNPs have a low capacity for absorbing visible light, whereas MoS2 shows better absorption in the ultraviolet and visible regions. By integrating the benefits of UCNPs and MoS2, UCNPs-MoS2 nanocomposites can convert NIR light with a higher depth of detection into visible light for application with MoS2 through fluorescence resonance energy transfer (FRET), which compensates for the issues of MoS2's low tissue penetration light-absorbing wavelengths and expands its potential biological applications. Therefore, starting from the construction of UCNPs-MoS2 nanoplatforms, herein, we review the research progress in biological applications, including biosensing, phototherapy, bioimaging, and targeted drug delivery. Additionally, the current challenges and future development trends of UCNPs-MoS2 nanocomposites for biological applications are also discussed.

The role of IFI16 in regulating PANoptosis and implication in heart diseases.

Interferon Gamma Inducible Protein 16 (IFI16) belongs to the HIN-200 protein family and is pivotal in immunological responses. Serving as a DNA sensor, IFI16 identifies viral and aberrant DNA, triggering immune and inflammatory responses. It is implicated in diverse cellular death mechanisms, such as pyroptosis, apoptosis, and necroptosis. Notably, these processes are integral to the emergent concept of PANoptosis, which encompasses cellular demise and inflammatory pathways. Current research implies a significant regulatory role for IFI16 in PANoptosis, particularly regarding cardiac pathologies. This review delves into the complex interplay between IFI16 and PANoptosis in heart diseases, including atherosclerosis, myocardial infarction, heart failure, and diabetic cardiomyopathy. It synthesizes evidence of IFI16's impact on PANoptosis, with the intention of providing novel insights for therapeutic strategies targeting heart diseases.