Ultrastrong Nanopapers with Aramid Nanofibers and Silver Nanowires Reinforced by Cellulose Nanofibril-Assisted Dispersed Graphene Nanoplates for Superior Electromagnetic Interference Shielding.

High-strength, lightweight, ultrathin, and flexible electromagnetic interference (EMI) shielding materials with a high shielding effectiveness (SE) are essential for modern integrated electronics. Herein, cellulose nanofibrils (CNFs) are employed to homogeneously disperse graphene nanoplates (GNPs) into an aramid nanofiber (ANF) network and silver nanowire (AgNW) network, respectively, producing high-performance nanopapers. These nanopapers, featuring nacre-mimetic microstructures and layered architectures, exhibited high tensile strength (601.11 MPa) and good toughness (103.56 MJ m-3) with a thickness of only 24.58 µm. Their specific tensile strength reaches 447.59 MPa·g-1·cm3, which is 1.74 times that of titanium alloys (257 MPa·g-1·cm3). The AgNW/GNP composite conductive layers exhibit an electrical conductivity of 12010.00 S cm-1, providing the nanopapers with great EMI shielding performance, achieving an EMI SE of 63.87 dB and an EMI SE/t of 25978.80 dB cm-1. The nanopapers also show reliable durability, retaining a tensile strength of 500.96 MPa and an EMI SE of 57.59 dB after 120,000 folding cycles. Additionally, they have a good electrical heating performance with a fast response time, low driving voltage, effective deicing capability, and reliable heating capacity in water. This work presents a strategy to develop a high-performance nanopaper, showing great potential for applications in electromagnetic compatibility, national defense, smart electronics, and human health.

Regulation of autophagy by ST3GAL2-mediated α2-3 sialylated glycosphingolipids in hepatic encephalopathy.

In neurological diseases, the regulation of autophagy plays a crucial role in their pathology, particularly the relationship between autophagy and hepatic encephalopathy (HE) which merits detailed investigation. Glycosphingolipids are abundant and broadly functional in the nervous system and are closely associated with autophagy. However, the specific link and mechanisms between glycosphingolipids and autophagy in HE remain unclear. This study aims to explore the impact of glycosphingolipid changes on the autophagy in HE and its potential mechanisms. Utilizing lectin microarrays, we observed elevated expression levels of α2-3 sialylated glycosphingolipid in the brain tissue of HBV transgenic mice and ammonia-induced astrocyte models, suggesting that the increase in α2-3 sialylated glycosphingolipid is related to HE. Further research revealed that the increased expression of α2-3 sialylated glycosphingolipid, mediated by ST3GAL2, affects autophagy by regulating the autophagy initiation complex Vps34-Beclin-1. In summary, our research not only comprehensively reveals the changes in brain glycosphingolipid during HBV-related HE but also elucidates the interactions and regulatory mechanisms between α2-3 sialylated glycosphingolipid and autophagy. This study provides a new perspective on understanding the pathogenesis of HE and offers novel theories and targets for future research and treatment strategies.

Studies on the Characteristics of Polycyclic Aromatic Hydrocarbons Accumulation in Lipids and the Disturbance of Lipid Metabolism of Ruditapes philippinarum.

Polycyclic aromatic hydrocarbons (PAHs) constitute a class of persistent organic pollutants with strong lipophilicity, which readily accumulate within organisms and have the effect to induce disorders in lipid metabolism. The present study aimed to investigate the accumulation localization and pattern of PAHs in Ruditapes philippinarum, and to reveal the association between PAHs and lipids metabolism. The 21-day exposure experiment was conducted using a mixture of phenanthrene, chrysene, and benzo[a]pyrene (the proportion is 1:1:1) at concentrations of 0.4 µg/L, 2 µg/L, and 10 µg/L. The tissue distribution of PAHs indicated that the digestive gland was the primary site of PAHs accumulation. Meanwhile, fluorescence colocalization suggested that PAHs primarily accumulated within the lipid droplets of digestive gland cells. This study further determined the transcriptomic and lipidomic profiles of the digestive gland to analyze the key genes involved in disrupted lipid metabolism and the major lipids affected. Lipidomic analysis identified the key differential metabolites as triglycerides (TGs). Furthermore, TGs were upregulated in the digestive gland had a total carbon atom number of 50-64 and a total number of 3-9 double bonds in the acyl side chains. Biochemical analysis experiments and oil red O stained frozen sections confirmed that the content of TGs steadily increased in various tissues during the experiment, leading to an elevated digestive gland index. Changes of lipid metabolism associated genes expression level also indicated that the synthesis of lipid in digestive gland were up-regulated while the decomposition was down-regulated. This study is the first to demonstrate the cellular localization of PAHs accumulation in bivalves and confirms the pattern of variation in TGs, providing new insights into the mechanisms of PAHs bioaccumulation and lipid metabolism disruption.

Comparative long-term outcomes of unicompartmental and total knee arthroplasty in knee osteoarthritis patients: a systematic review and meta-analysis.

Background: Long-term outcomes for knee osteoarthritis patients undergoing unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) remain inconclusive. Objectives: This study aims to evaluate the long-term outcomes over five years, including Knee Society Pain Scores (KSPS), Knee Society Scores (KSS), Knee Society Function Scores (KSFS), range of motion (ROM), and survival rates-of UKA vs. TKA in knee osteoarthritis patients. Design: Systematic review using data from randomized controlled and cohort trials, and world databases. Data sources: Researchers searched Medline, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov from January 1990 to March 2024. Eligibility criteria for selecting studies: The researchers selected studies based on adult participants with knee osteoarthritis. Eligible studies compare UKA and TKA reports on clinical or surgical outcomes, including KSPS, KSS, KSFS, ROM and survival rates, over 5 years. The researchers excluded the studies fewer than five years, or if English text was unavailable. Results: Researchers categorized twenty-nine eligible studies into three groups: five randomized controlled trials, 11 registries and database studies, and 13 cohort studies. The analysis revealed that neither TKA nor UKA definitively outperformed the other in terms of pain (SMD (95% CI): -0.06 [-0.41, 0.28], I 2 = 90%) and KSS scores (SMD (95% CI): -0.07 [-0.23, 0.008], I 2 = 81%) over a period of five years. However, KSFS (SMD (95% CI): -0.30 [-0.43, -0.17], I 2 = 74%) and ROM (SMD (95% CI): -0.78 [-1.11, -0.46], I 2 = 92%) tended to favor UKA, and survival rate favor TKA at 5 or over 5-year follow-up periods. Conclusions: UKA shows a trend towards better outcomes in KSFS and ROM, alongside a more favorable survival rate in TKA at the five-year and beyond follow-up periods. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=517835, PROSPERO (CRD42024517835).

Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

Nickel-Catalyzed Secondary Benzylic C-O Bond Borylation.

A remote steric hindrance ligand (m-tBu)2C6H3PCy2 (L1) was synthesized to promote Ni-catalyzed C-O bond activation. The reaction achieved high yields for secondary benzylic C(sp3)-O borylation in non-π-extended systems under mild conditions. Mechanistic studies indicate that the nickel complex containing 1 equiv of L1 serves as the active catalyst, while increased loading of L1 gives the inactive bisligated Ni species. Acetanilide is crucial for the cross-coupling reaction, which facilitates generation of the monoligated nickel species.

Lower regional urbanicity and socioeconomic status attenuate associations of green spaces with hypertension and diabetes mellitus: a national representative cross-sectional study in China.

BACKGROUND: High blood pressure (HBP) and diabetes mellitus (DM) are two of the most prevalent cardiometabolic disorders globally, especially among individuals with lower socio-economic status (SES). Studies have linked residential greenness to decreased risks of HBP and DM. However, there has been limited evidence on whether SES may modify the associations of residential greenness with HBP and DM. METHODS: Based on a national representative cross-sectional study among 44,876 adults, we generated the normalized difference vegetation index (NDVI) at 1 km spatial resolution to characterize individuals' residential greenness level. Administrative classification (urban/rural), nighttime light index (NLI), individual income, and educational levels were used to characterize regional urbanicity and individual SES levels. RESULTS: We observed weaker inverse associations of NDVI with HBP and DM in rural regions compared to urban regions. For instance, along with per interquartile range (IQR, 0.26) increment in residential NDVI at 0∼5 year moving averages, the ORs of HBP were 1.04 (95%CI: 0.94, 1.15) in rural regions and 0.85 (95%CI: 0.79, 0.93) in urban regions (P = 0.003). Along with the decrease in NLI levels, there were continuously decreasing inverse associations of NDVI with DM prevalence (P for interaction <0.001). In addition, weaker inverse associations of residential NDVI with HBP and DM prevalence were found among individuals with lower income and lower education levels compared to their counterparts. CONCLUSIONS: Lower regional urbanicity and individual SES could attenuate the associations of residential greenness with odds of HBP and DM prevalence.

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Accurate assessment of material and energy exchange between land and atmosphere is essential for water resources management and sustainable development of agriculture. To understand the characteristics of energy distribution and the dynamic change process of water and heat fluxes within the maize farmland ecosystem in the old course of Yellow River and their response to meteorological factors, we utilized the eddy covariance measurements and the full-element automatic weather station to continuously observe energy fluxes and conventional meteorological elements of summer maize farmland in the old course of Yellow River during 2019-2020. We analyzed the variation of energy fluxes and the effects of environmental factors, such as temperature, precipitation, and wind speed. Additionally, we calculated the energy closure rate and the proportion of energy distribution during the growth stage. The results showed that the peaks of net radiation, sensible heat flux, and latent heat flux occurred between 11:00 and 14:00, and the peak of soil heat flux occurred between 14:00 and 15:00. In terms of energy distribution, energy consumption of summer maize farmland during the whole growth period was dominated by latent heat flux and sensible heat flux. Energy was mainly consumed by sensible heat flux at sowing-emergence stage, accounting for 37.1% of net radiation, respectively. Energy in the rest of growth stages was dominated by latent heat flux. The energy closure rate during the whole growth period was better, with a coefficient of determination of 0.83, and the closure rate was higher in day and lower at night. Precipitation affected latent heat flux and sensible heat flux, and latent heat flux was more sensitive to precipitation. The increase of latent heat flux after rainfall was lower in late growth stage than in early growth stage. During the whole growth period of summer maize, solar radiation was the most significant meteorological factor affecting both sensible heat flux and latent heat flux, followed by vapor pressure deficit. The contribution of temperature and vapor pressure deficit to latent heat flux was significantly higher than sensible heat flux, while the relative contribution of wind speed, relative humidity, and solar radiation to latent heat flux was lower than sensible heat flux. Leaf area index and fractional vegetation cover had a significant positive correlation with latent heat flux and a significant negative correlation with sensible heat flux. Our results could deepen the understanding of water and heat transfer law of summer maize farmland in the old course of Yellow River, providing a theoretical basis for efficient water use of crops.

A ribonuclease T2 protein FocRnt2 contributes to the virulence of Fusarium oxysporum f. sp. cubense tropical race 4.

Banana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), is a major disease of banana plants worldwide. Effector proteins play critical roles in banana-Foc TR4 interaction. Our previous studies highlighted a ribonuclease protein belonging to the T2 family (named as FocRnt2) in the Foc TR4 secretome, which was predicted to be an effector. However, its biological function in Foc TR4 infection is still unclear. Herein, we observed significant expression of FocRnt2 during the early stage of fungal infection in planta. A yeast signal sequence trap assay showed that FocRnt2 contained a functional signal peptide for secretion. FocRnt2 possessed ribonuclease activity that could degrade the banana total RNA in vitro. Subcellular localization showed that FocRnt2 was localized in the nucleus and cytoplasm of Nicotiana benthamiana leaves. Transient expression of FocRnt2 suppressed the expression of salicylic acid- and jasmonic acid-signalling marker genes, reactive oxygen species accumulation, and BAX-mediated cell death in N. benthamiana. FocRnt2 deletion limited fungal penetration, reduced fusaric acid biosynthesis in Foc TR4, and attenuated fungal virulence against banana plants, but had little effect on Foc TR4 growth and sensitivity to various stresses. Furthermore, FocRnt2 deletion mutants induced higher expression of the defence-related genes in banana plants. These results suggest that FocRnt2 plays an important role in full virulence of Foc TR4, further improving our understanding of effector-mediated Foc TR4 pathogenesis.

Nanomedicines Targeting Ferroptosis to Treat Stress-Related Diseases.

Ferroptosis, a unique form of regulated cell death driven by iron-dependent lethal lipid peroxidation, is implicated in various stress-related diseases like neurodegeneration, vasculopathy, and metabolic disturbance. Stress-related diseases encompass widespread medical disorders that are influenced or exacerbated by stress. These stressors can manifest in various organ or tissue systems and have significant implications for human overall health. Understanding ferroptosis in these diseases offers insights for therapeutic strategies targeting relevant pathways. This review explores ferroptosis mechanisms, its role in pathophysiology, its connection to stress-related diseases, and the potential of ferroptosis-targeted nanomedicines in treating conditions. This monograph also delves into the engineering of ferroptosis-targeted nanomedicines for tackling stress-related diseases, including cancer, cardia-cerebrovascular, neurodegenerative, metabolic and inflammatory diseases. Anyhow, nanotherapy targeting ferroptosis holds promise by both promoting and suppressing ferroptosis for managing stress-related diseases.

Six-Membered Ring Directed Assembly of a Zirconium Zeolitic Metal-Organic Framework for Efficient Separation of Hexane Isomers.

The synthesis of zirconium MOFs with zeolite net is quite challenging due to the high connectivity of Zr6 clusters, which is far from tetrahedral connection, a requisite for zeolite net. In this work, we demonstrate a six-membered ring (6MR) strategy through mimicking of mineral zeolites with mixed ditopic and tritopic carboxylate linkers. With this strategy, the ditopic linker cross-links Zr6 clusters to form 4-connected zeolite-like nets, while the tritopic one is used to direct the formation of 6MR and simultaneously consumes extra coordination sites on the cluster. The feasibility of this strategy is shown by one zeolitic metal-organic framework (NNM-5) and this strategy has also led to the synthesis of the other dia-type zirconium MOF (NNM-6). Interestingly, as the tritopic linker not only directs the formation of 6-MR but also partitions 6-MR into small segments, NNM-5 with SOD topology shows a structural feature of small aperture and big cage, which has led to efficient separation of hexane isomers. With both exceptionally high n-hexane uptake (65.9 cm3·g-1) and size-exclusion selectivity, an exceptional separation capability is verified by breakthrough experiments. Calculation results demonstrate that the large difference of diffusion energy barrier due to the small aperture accounts for the underlying separation mechanism.

Mouse hepatitis virus JHMV I protein is required for maximal virulence.

Betacoronaviruses encode a conserved accessory gene within the +1 open reading frame (ORF) of nucleocapsid called the internal N gene. This gene is referred to as "I" for mouse hepatitis virus (MHV), ORF9b for severe acute respiratory CoV (SARS-CoV) and SARS-CoV-2, and ORF8b for Middle East respiratory syndrome CoV (MERS-CoV). Previous studies have shown ORF8b and ORF9b have immunoevasive properties, while the only known information for MHV I is its localization within the virion of the hepatotropic/neurotropic A59 strain of MHV. Whether MHV I is an innate immune antagonist or has other functions has not been evaluated. In this report, we show that the I protein of the neurotropic JHM strain of MHV (JHMV) lacks a N terminal domain present in other MHV strains, has immunoevasive properties, and is a component of the virion. Genetic deletion of JHMV I (rJHMVIΔ57-137) resulted in a highly attenuated virus both in vitro and in vivo that displayed a post RNA replication/transcription defect that ultimately resulted in fewer infectious virions packaged compared with wild-type virus. This phenotype was only seen for rJHMVIΔ57-137, suggesting the structural changes predicted for A59 I altered its function, as genetic deletion of A59 I did not change viral replication or pathogenicity. Together, these data show that JHMV I both acts as a mild innate immune antagonist and aids in viral assembly and infectious virus production, and suggest that the internal N proteins from different betacoronaviruses have both common and virus strain-specific properties.IMPORTANCECoV accessory genes are largely studied in overexpression assays and have been identified as innate immune antagonists. However, functions identified after overexpression are often not confirmed in the infected animal host. Furthermore, some accessory proteins are components of the CoV virion, but their role in viral replication and release remains unclear. Here, we utilized reverse genetics to abrogate expression of a conserved CoV accessory gene, the internal N ("I") gene, of the neurotropic JHMV strain of MHV and found that loss of the I gene resulted in a post replication defect that reduced virion assembly and ultimately infectious virus production, while also increasing some inflammatory molecule expression. Thus, the JHMV I protein has roles in virion assembly that were previously underappreciated and in immunoevasion.

Release of ions enhanced the antibacterial performance of laser-generated, uncoated Ag nanoparticles.

Identifying the antibacterial mechanisms of elemental silver at the nanoscale remains a significant challenge due to the intertwining behaviors between the particles and their released ions. The open question is which of the above factor dominate the antibacterial behaviors when silver nanoparticles (Ag NPs) with different sizes. Considering the high reactivity of Ag NPs, prior research has primarily concentrated on coated particles, which inevitably hinder the release of Ag+ ions due to additional chemical agents. In this study, we synthesized various Ag NPs, both coated and uncoated, using the laser ablation in liquids (LAL) technique. By analyzing both the changes in particle size and Ag+ ions release, the impacts of various Ag NPs on the cellular activity and morphological changes of gram-negative (E. coil) and gram-positive (S. aureus) bacteria were evaluated. Our findings revealed that for uncoated Ag NPs, smaller particles exhibited greater ions release efficiency and enhanced antibacterial efficacy. Specifically, particles approximately 1.5 nm in size released up to 55 % of their Ag+ ions within 4 h, significantly inhibiting bacterial growth. Additionally, larger particles tended to aggregate on the bacterial cell membrane surface, whereas smaller particles were more likely to be internalized by the bacteria. Notably, treatment with smaller Ag NPs led to more pronounced bacterial morphological changes and elevated levels of intracellular reactive oxygen species (ROS). We proposed that the bactericidal activity of Ag NPs stems from the synergistic effect between particle-cell interaction and the ionic silver, which is dependent on the crucial parameter of particle size.

Fluorene-9-bisphenol impaired male fertility through disrupting the testicular function and local microenvironment.

Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage.

Broad-Scope (3 + 2) Cycloaddition of Cyclopropanes and Alkynes Enabled by Boronyl Radical Catalysis.

Cyclopentene skeletons are ubiquitous in natural products and small molecule drugs. The (3 + 2) cycloaddition of cyclopropanes and alkynes represents an efficient and atom-economic strategy for synthesizing these structures. However, the types of substituents on cyclopropane and alkyne used in previous works show evident limitations, restricting the application of this type of reaction to some extent. Herein, we report a broad-scope (3 + 2) cycloaddition of cyclopropanes and alkynes catalyzed by boronyl radicals. In this method, various substrates, such as mono-, di-, tri-, and tetrasubstituted cyclopropanes, as well as mono- and disubstituted alkynes, were compatible with up to 98% isolated yield.

IL-1ß mediates Candida tropicalis-induced immunosuppressive function of MDSCs to foster colorectal cancer.

BACKGROUND: There is increasing evidence that gut fungi dysbiosis plays a crucial role in the development and progression of colorectal cancer (CRC). It has been reported that gut fungi exacerbate the severity of CRC by regulating tumor immunity. Our previous studies have shown that the opportunistic pathogenic fungal pathogen, Candida tropicalis (C. tropicalis) promotes CRC progression by enhancing the immunosuppressive function of MDSCs and activating the NLRP3 inflammasome of MDSCs. However, the relationship between IL-1ß produced by NLRP3 inflammasome activation and the immunosuppressive function of MDSCs enhanced by C. tropicalis in CRC remains unclear. METHODS: The TCGA database was used to analyze the relationship between IL-1ß and genes related to immunosuppressive function of MDSCs in human CRC. The expression of IL-1ß in human CRC tissues was detected by immunofluorescence staining. The proteomic analysis was performed on the culture supernatant of C. tropicalis-stimulated MDSCs. The experiments of supplementing and blocking IL-1ß as well as inhibiting the NLRP3 inflammasome activation were conducted. A mouse colon cancer xenograft model was established by using MC38 colon cancer cell line. RESULTS: Analysis of CRC clinical samples showed that the high expression of IL-1ß was closely related to the immunosuppressive function of tumor-infiltrated MDSCs. The results of in vitro experiments revealed that IL-1ß was the most secreted cytokine of MDSCs stimulated by C. tropicalis. In vitro supplementation of IL-1ß further enhanced the immunosuppressive function of C. tropicalis-stimulated MDSCs and NLRP3-IL-1ß axis mediated the immunosuppressive function of MDSCs enhanced by C. tropicalis. Finally, blockade of IL-1ß secreted by MDSCs augmented antitumor immunity and mitigated C. tropicalis-associated colon cancer. CONCLUSIONS: C. tropicalis promotes excessive secretion of IL-1ß from MDSCs via the NLRP3 inflammasome. IL-1ß further enhances the immunosuppressive function of MDSCs to inhibit antitumor immunity, thus promoting the progression of CRC. Therefore, targeting IL-1ß secreted by MDSCs may be a potential immunotherapeutic strategy for the treatment of CRC.

Room-Temperature, Solution-Processed, Robust, Transparent, and Conductive SiOx/AgNW Nanocomposite Coating.

AgNW networks show high promise as a conductive material due to excellent flexibility, low resistance, high transparency, and ease of large-scale preparation. However, the application of AgNW networks has been hindered by their inherent characteristics, such as easy oxidation degradation, chemical corrosion, and structural instability at high temperatures. In this study, a dense SiOx protective layer derived from perhydropolysilazane was introduced to fabricate a robust SiOx/AgNW nanocomposite coating through an all-solution process at room temperature. The achieved nanocomposite coating shows outstanding thermal stability up to 450 °C, resistance to ultraviolet radiation, and excellent mechanical performance by maintaining stability after 10,000 cycles of bending at a radius of 2.5 mm, 1000 cycles of peeling, and 1200 cycles of wearing. Meanwhile, the nanocomposite coating demonstrates exceptional chemical tolerance against HCl, Na2S, and organic solvents. A transparent heater based on the nanocomposite coating achieves a remarkable benchmark with a maximum temperature of 400 °C at 20 V. These features highlight the potential of the nanocomposite coating in flexible electronics, optoelectronics, touch screens, and high-performance heaters.

An injectable biomimetic hydrogel adapting brain tissue mechanical strength for postoperative treatment of glioblastoma without anti-tumor drugs participation.

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid­iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment.

FLI1 in PBMCs contributes to elevated inflammation in combat-related posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with significant public health implications that arise following exposure to traumatic events. Recent studies highlight the involvement of immune dysregulation in PTSD, characterized by elevated inflammatory markers. However, the precise mechanisms underlying this immune imbalance remain unclear. Previous research has implicated friend leukemia virus integration 1 (FLI1), an erythroblast transformation-specific (ETS) transcription factor, in inflammatory responses in sepsis and Alzheimer's disease. Elevated FLI1 levels in peripheral blood mononuclear cells (PBMCs) have been linked to lupus severity. Yet, FLI1's role in PTSD-related inflammation remains unexplored. In our study, PBMCs were collected from Veterans with and without PTSD. We found significantly increased FLI1 expression in PBMCs from PTSD-afflicted Veterans, particularly in CD4+ T cells, with no notable changes in CD8+ T cells. Stimulation with LPS led to heightened FLI1 expression and elevated levels of inflammatory cytokines IL-6 and IFNγ in PTSD PBMCs compared to controls. Knockdown of FLI1 using Gapmers in PTSD PBMCs resulted in a marked reduction in inflammatory cytokine levels, restoring them to control group levels. Additionally, co-culturing PBMCs from both control and PTSD Veterans with the human brain microglia cell line HMC3 revealed increased inflammatory mediator levels in HMC3. Remarkably, HMC3 cells co-cultured with PTSD PBMCs treated with FLI1 Gapmers exhibited significantly lower inflammatory mediator levels compared to control Gapmer-treated PTSD PBMCs. These findings suggest that suppressing FLI1 may rebalance immune activity in PBMCs and mitigate microglial activation in the brain. Such insights could provide novel therapeutic strategies for PTSD.