SLAM: Structure-aware lysine ß-hydroxybutyrylation prediction with protein language model.

Post-translational modifications (PTMs) diversify protein functions by adding/removing chemical groups to certain amino acid. As a newly-reported PTM, lysine ß-hydroxybutyrylation (Kbhb) presents a new avenue to functional proteomics. Therefore, accurate and efficient prediction of Kbhb sites is imperative. However, the current experimental methods for identifying PTM sites are often expensive and time-consuming. Up to now, there is no computational method proposed for Kbhb sites detection. To this end, we present the first deep learning-based method, termed SLAM, to in silico identify lysine ß-hydroxybutyrylation sites. The performance of SLAM is evaluated on both 5-fold cross-validation and independent test, achieving 0.890, 0.899, 0.907 and 0.923 in terms of AUROC values, on the general and species-specific independent test sets, respectively. As one example, we predicted the potential Kbhb sites in human S-adenosyl-L-homocysteine hydrolase, which is in agreement with experimentally-verified Kbhb sites. In summary, our method could enable accurate and efficient characterization of novel Kbhb sites that are crucial for the function and stability of proteins and could be applied in the structure-guided identification of other important PTM sites. The SLAM online service and source code is available at https://ai4bio.online/SLAM and https://github.com/Gabriel-QIN/SLAM, respectively.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

A Membrane-Anchoring Self-Assembling Peptide Allows Bioorthogonal Coupling of Type-I AIEgens for Pyroptosis-Induced Cancer Therapy.

Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

Superior Singlet Oxygen Electrosynthesis via Neighboring Dual Molecular Oxygen Coactivation for Selective Tetracycline Detoxification.

Oxygen (O2) electroreduction offers a green approach for singlet oxygen (1O2) synthesis in wastewater contaminants detoxification. However, traditional single O2 activation on single-metal catalytic sites seriously suffers from the kinetically-unfavorable desorption of adsorbed superoxide species (•O2-*/•OOH*). Here, we demonstrate a novel dual O2 coactivation pathway on shortened Fe1-OV-Ti sites for superior 1O2 electrosynthesis through a rapid disproportionate process between surface-confined •O2-*/•OOH*. Theoretical calculations combined with in-situ electrochemical spectroscopies demonstrated that the shortened distance between Fe single atom and adjacent unsaturated Ti atom facilitates the direct recombination of surface-confined Fe-•OOH and Ti-•OO- to yield 1O2, bypassing the formidable •O2-*/•OOH* desorption process. Impressively, Fe1-OV-Ti could realize an excellent 1O2 electrosynthesis rate of 54.5 µmol L-1 min-1 with an outstanding 1O2 selectivity of 97.6% under neutral condition, surpassing that of Fe1-O-Ti (27.1 µmol L-1 min-1, 91.7%). Using tetracycline (TC) as a model pollutant, the resulting Fe1-OV-Ti electrode achieved nearly 100% degradation in 120 min at -0.6 V, meanwhile preventing the generation of toxic intermediates. This study provides a new 1O2 electrosynthesis strategy by controlling the distance of adjacent catalytic sites for the coactivation of dual molecular oxygen.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases.

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Increased opioid consumption in neoadjuvant immunotherapy plus chemotherapy for patients with non-small-cell lung cancer: A multicenter, prospective cohort study.

AIMS: PD-1 block was reported to impair opioid-induced antinociception and affect cognitive function in rodents and non-human primates. This prospective multicenter cohort study aims to investigate the possible impact of neoadjuvant immunotherapy with PD-1 antibody on perioperative analgesic effect of opioids and postoperative delirium (POD) for non-small-cell lung cancer (NSCLC) patients. METHODS: Eighty-four NSCLC patients from three medical centers with neoadjuvant chemoimmunotherapy (nCIT) or chemotherapy (nCT) were enrolled. The primary outcome is the total perioperative opioid consumption defined as the sum of intraoperative and postoperative opioid use within 3 days after surgery. Secondary outcomes compromise of incidence of POD, pain intensity, and number of analgesic pump press. Tumor prognostic parameters and perioperative change of inflammatory cytokines and soluble PD-L1 level were also recorded. RESULTS: Eighty-one patients were included in the final analysis. The total opioid consumption (sufentanil equivalent) perioperatively in the nCIT group was significantly higher than that in the nCT group, with mean difference of 60.39 µg, 95% CI (25.58-95.19), p < 0.001. Multiple linear regression analysis showed that nCIT was correlated with increased total opioid consumption (ß = 0.305; 95% CI, 0.152-0.459; p < 0.001). The incidence of moderate-to-severe pain and cumulative analgesic pump press within 72 h was significantly higher in subjects with nCIT. There is no statistical difference in incidence of POD between groups within 72 h after surgery. The pathologic complete response rate and perioperative serum IL-6 level were higher in the nCIT group than in the nCT group. CONCLUSION: Patients with NSCLC receiving nCIT warrant increased opioid consumption perioperatively and suffered from more postoperative pain. CLINICAL TRIAL REGISTRATION: NCT05273827.

Experimental study of the effects of the void located at the pile tip on the load capacity of rock-socketed piles.

To address the design challenge of the rock-socketed piles posed by the void located below the pile tip, the physical laboratory model tests were designed and performed to simulate rock socketed piles using similar materials. The study investigates the behavior of the single pile under axial loading with the void located at varying distances from the pile tip. Through multi-level load tests, the variations of unit pile side friction, pile tip resistance, pile axial force and pile settlement are obtained for different positions of the void from the pile tip, as well as after grouting. Its comparison to the rock-socketed pile without void is performed as a reference to quantify the reduction in its bearing capacity. The results are presented in the form of graphs for different void positions and its grouting shows the influence on pile bearing capacity and emphasizes the importance of its detailed cautious investigation and introduction in the analysis. The 2D finite element modeling of the model pile-the void based on ABAQUS is performed to further investigate the influence of the void below pile tip on the bearing capacity of model pile, applying the Mohr Coulomb model as the constitutive model of rock mass behavior. The critical distance of the void below the pile tip is determined.

Metal-ligand dual-site single-atom nanozyme mimicking urate oxidase with high substrates specificity.

In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.

Regulating Reactive Oxygen Intermediates of Fe-N-C SAzyme via Second-Shell Coordination for Selective Aerobic Oxidation Reactions.

Reactive oxygen species (ROS) regulation for single-atom nanozymes (SAzymes), e.g., Fe-N-C, is a key scientific issue that determines the activity, selectivity, and stability of aerobic reaction. However, the poor understanding of ROS formation mechanism on SAzymes greatly hampers their wider deployment. Herein, inspired by cytochromes P450 affording bound ROS intermediates in O2 activation, we report Fe-N-C containing the same FeN4 but with tunable second-shell coordination can effectively regulate ROS production pathways. Remarkably, compared to the control Fe-N-C sample, the second-shell sulfur functionalized Fe-N-C delivered a 2.4-fold increase of oxidase-like activity via the bound Fe=O intermediate. Conversely, free ROS (⋅O2 -) release was significantly reduced after functionalization, down to only 17 % of that observed for Fe-N-C. The detailed characterizations and theoretical calculations revealed that the second-shell sulfur functionalization significantly altered the electronic structure of FeN4 sites, leading to an increase of electron density at Fermi level. It enhanced the electron transfer from active sites to the key intermediate *OOH, thereby ultimately determining the type of ROS in aerobic oxidation process. The proposed Fe-N-Cs with different second-shell anion were further applied to three aerobic oxidation reactions with enhanced activity, selectivity, and stability.

Tumour-microenvironment-responsive Na2S2O8 nanocrystals encapsulated in hollow organosilica-metal-phenolic networks for cycling persistent tumour-dynamic therapy.

Traditional tumour-dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)-generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono-catalytic reaction. To fight against these issues, we skilfully develop a tumour-microenvironment-driven yolk-shell nanoreactor to realize the high-efficiency persistent dynamic therapy via cascade-responsive dual cycling amplification of •SO4 -/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na2S2O8 nanocrystals into hollow tetra-sulphide-introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)-Fe(II) cross-linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra-sulphide cleavage of nanoreactors to explosively release Na+/S2O8 2 - /Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4 - (Fe2+-catalyzed S2O8 2 - oxidation), proton (•SO4 --catalyzed H2O decomposition), and •OH (proton-intensified Fenton oxidation). Synchronously, the oxidation-generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify •SO4 -/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na+ overload and weaken the ROS-scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk-shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.

3.05 kW, 13.7 GHz linewidth fiber amplifier based on PRBS phase modulation for SBS suppression.

In this paper, we establish a multi-stage fiber amplifier with pseudo-random binary sequence (PRBS) phase modulation. The stimulated Brillouin gain spectra of the main amplifier with both the unmodulated and pseudo-random binary sequence phase modulated configuration are measured (with corresponding output power), and the stimulated Brillouin scattering (SBS) threshold is investigated experimentally and theoretically. The pseudo-random binary sequence phase modulation parameters are optimized by theoretical simulation. With a two-stage preamplifier chain and a counter-pumping main amplifier stage, a maximum 3.05 kW output power with a slope efficiency of 85.9% is obtained experimentally. The central wavelength of the fiber amplifier is 1050 nm, associated with a full-width at half-maximum linewidth of 13.7 GHz. The stimulated Brillouin scattering reflectivity is below 0.01% at 3.05 kW at 13.7 GHz, which indicates that stimulated Brillouin scattering can be suppressed efficiently at this power and linewidth level.

Engineering the Coordination Environment of Ir Single Atoms with Surface Titanium Oxide Amorphization for Superior Chlorine Evolution Reaction.

The chlorine evolution reaction (CER) is essential for industrial Cl2 production but strongly relies on the use of dimensionally stable anode (DSA) with high-amount precious Ru/Ir oxide on a Ti substrate. For the purpose of sustainable development, precious metal decrement and performance improvement are highly desirable for the development of CER anodes. Herein, we demonstrate that surface titanium oxide amorphization is crucial to regulate the coordination environment of stabilized Ir single atoms for efficient and durable chlorine evolution of Ti monolithic anodes. Experimental and theoretical results revealed the formation of four-coordinated Ir1O4 and six-coordinated Ir1O6 sites on amorphous and crystalline titanium oxides, respectively. Interestingly, the Ir1O4 sites exhibited a superior CER performance, with a mass activity about 10 and 500 times those of the Ir1O6 counterpart and DSA, respectively. Moreover, the Ir1O4 anode displayed excellent durability for 200 h, far longer than that of its Ir1O6 counterpart (2 h). Mechanism studies showed that the unsaturated Ir in Ir1O4 was the active center for chlorine evolution, which was changed to the top-coordinated O in Ir1O6. This change of active sites greatly affected the adsorption energy of Cl species, thus accounting for their different CER activity. More importantly, the amorphous structure and restrained water dissociation of Ir1O4 synergistically prevent oxygen permeation across the Ti substrate, contributing to its long-term CER stability. This study sheds light on the importance of single-atom coordination structures in the reactivity of catalysts and offers a facile strategy to prepare highly active single-atom CER anodes via surface titanium oxide amorphization.

Sex differences in the relationships between macronutrients and all-cause mortality in individuals with metabolically unhealthy overweight/obesity.

This study investigates sex differences in the effects of macronutrient quantity, quality, and timing on mortality in metabolically unhealthy overweight/obesity (MUO) populations. The study included 18,345 participants, including 9204 men and 9141 women. The Cox proportional risk model and isocaloric substitution effects were used to examine the association of macronutrient intake and subtype with all-cause mortality in the MUO populations. After adjusting for the potential covariates, The risk of all-cause mortality was elevated in men in the highest 25% percentile of poor-quality carbohydrates compared with men in the lowest quartile (odds ratio [OR]: 2.04; 95% confidence interval [CI], 1.40-2.98). Compared with women in the lowest quartile, the risk of all-cause mortality for women in the highest 25% percentile for high-quality carbohydrates (OR: 0.74; 95% CI, 0.55-0.99) and unsaturated fatty acids (OR: 0.54; 95% CI, 0.32-0.93) were decreased. In women, replacing low-quality carbohydrates with high-quality carbohydrates on an isocaloric basis reduces the risk of all-cause mortality by approximately 9%. We find that different macronutrient consumption subtypes are associated with all-cause mortality in MUO populations, with differential effects between men and women, and that the risk of all-cause mortality is influenced by macronutrient quality and meal timing.

Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron-Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer.

Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth of tissue penetration and nontoxicity due to the unique anatomical location of the bladder near the abdominal surface. However, low electron-hole separation efficiency and wide bandgap of sonosensitizers limit the effectiveness of SDT. This study aims to develop a TiO2-Ru-PEG Schottky heterojunction sonosensitizer with high electron-hole separation and narrow bandgap for SDT in BC. Density functional theory (DFT) calculations and experiments collectively demonstrate that the bandgap of TiO2-Ru-PEG is reduced due to the Schottky heterojunction with the characteristic of crystalline-amorphous interface formed by the deposition of ruthenium (Ru) within the shell layer of TiO2. Thanks to the enhancement of oxygen adsorption and the efficient separation of electron-hole pairs, TiO2-Ru-PEG promotes the generation of reactive oxygen species (ROS) under ultrasound (US) irradiation, resulting in cell cycle arrest and apoptosis of bladder tumor cells. The in vivo results prove that TiO2-Ru-PEG boosted the subcutaneous and orthotopic bladder tumor models while exhibiting good safety. This study adopts the ruthenium complex for optimizing sonosensitizers, contributing to the progress of SDT improvement strategies and presenting a paradigm for BC therapy.

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic ß-cell Dysfunction.

OBJECTIVE: While the reduction of transient receptor potential channel subfamily M member 5 (TRPM5) has been reported in islet cells from type 2 diabetic (T2D) mouse models, its role in lipotoxicity-induced pancreatic ß-cell dysfunction remains unclear. This study aims to study its role. METHODS: Pancreas slices were prepared from mice subjected to a high-fat-diet (HFD) at different time points, and TRPM5 expression in the pancreatic ß cells was examined using immunofluorescence staining. Glucose-stimulated insulin secretion (GSIS) defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate (Palm). Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm, and the TRPM5 expression was detected using qRT-PCR and Western blotting. Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown. The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5 (Ad-Trpm5). RESULTS: HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets. Palm reduced TRPM5 protein expression in a time- and dose-dependent manner in MIN6 cells. Palm also inhibited TRPM5 expression in primary mouse islets. Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis. Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique to ß cells. CONCLUSION: Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreatic ß cells both in vivo and in vitro and, in turn, drives ß-cell dysfunction.

Cobalt Single-Atom Reverse Hydrogen Spillover for Efficient Electrochemical Water Dissociation and Dechlorination.

Efficient water dissociation to atomic hydrogen (H*) with restrained recombination of H* is crucial for improving the H* utilization for electrochemical dechlorination, but is currently limited by the lack of feasible electrodes. Herein, we developed a monolithic single-atom electrode with Co single atoms anchored on the inherent oxide layer of titanium foam (Co1-TiOx/Ti), which can efficiently dissociate water into H* and simultaneously inhibit the recombination of H*, by taking advantage of the single-atom reverse hydrogen spillover effect. Experimental and theoretical calculations demonstrated that H* could be rapidly generated on the oxide layer of titanium foam, and then overflowed to the adjacent Co single atom for the reductive dechlorination. Using chloramphenicol as a proof-of-concept verification, the resulting Co1-TiOx/Ti monolithic electrode exhibited an unprecedented performance with almost 100 % dechlorination at -1.0 V, far superior to that of traditional indirect reduction-driven commercial Pd/C (52 %) and direct reduction-driven Co1-N-C (44 %). Moreover, its dechlorination rate constant of 1.64 h-1 was 4.3 and 8.6 times more active than those of Pd/C (0.38 h-1) and Co1-N-C (0.19 h-1), respectively. Our research sheds light on the rational design of hydrogen spillover-related electrocatalysts to simultaneously improve the H* generation, transfer, and utilization for environmental and energy applications.

Flexible Polyolefin Elastomer/Paraffin Wax/Alumina/Graphene Nanoplatelets Phase Change Materials with Enhanced Thermal Conductivity and Mechanical Performance for Solar Conversion and Thermal Energy Storage Applications.

In this study, electrically insulating polyolefin elastomer (POE)-based phase change materials (PCMs) comprising alumina (Al2O3) and graphene nanoplatelets (GNPs) are prepared using a conventional injection moulding technique, which exhibits promising applications for solar energy storage due to the reduced interfacial thermal resistance, excellent stability, and proficient photo-thermal conversion efficiency. A synergistic interplay between Al2O3 and GNPs is observed, which facilitates the establishment of thermally conductive pathways within the POE/paraffin wax (POE/PW) matrix. The in-plane thermal conductivity of POE/PW/GNPs 5 wt%/Al2O3 40 wt% composite reaches as high as 1.82 W m-1K-1, marking a remarkable increase of ≈269.5% when compared with that of its unfilled POE/PW counterpart. The composite exhibits exceptional heat dissipation capabilities, which is critical for thermal management applications in electronics. Moreover, POE/PW/GNPs/Al2O3 composites demonstrate outstanding electrical insulation, enhanced mechanical performance, and efficient solar energy conversion and transportation. Under 80 mW cm-2 NIR light irradiation, the temperature of the POE/PW/GNPs 5 wt%/Al2O3 40 wt% composite reaches approximately 65 °C, a notable 20 °C improvement when compared with the POE/PW blend. The pragmatic and uncomplicated preparation method, coupled with the stellar performance of the composites, opens a promising avenue and broader possibility for developing flexible PCMs for solar conversion and thermal storage applications.

Self-Adjuvanting Polyguanidine Nanovaccines for Cancer Immunotherapy.

Tapping into the innate immune system's power, nanovaccines can induce tumor-specific immune responses, which is a promising strategy in cancer immunotherapy. However, traditional vaccine design, requiring simultaneous loading of antigens and adjuvants, is complex and poses challenges for mass production. Here, we developed a tumor nanovaccine platform that integrates adjuvant functions into the delivery vehicle, using branched polyguanidine (PolyGu) nanovaccines. These nanovaccines were produced by modifying polyethylenimine (PEI) with various guanidine groups, transforming PEI's cytotoxicity into innate immune activation. The PolyGu nanovaccines based on poly(phenyl biguanidine ) (Poly-PBG) effectively stimulated dendritic cells, promoted their maturation via the TLR4 and NLRP3 pathways, and displayed robust in vivo immune activity. They significantly inhibited tumor growth and extended mouse survival. The PolyGu also showed promise for constructing more potent mRNA-based nanovaccines, offering a platform for personalized cancer vaccine. This work advances cancer immunotherapy toward potential clinical application by introducing a paradigm for developing self-adjuvanting nanovaccines.

Association between inflammatory biomarkers and mortality in individuals with type 2 diabetes: NHANES 2005-2018.

PURPOSE: This study aimed to examine independent association between inflammatory biomarkers and all-cause mortality as well as cardio-cerebrovascular disease (CCD) mortality among U.S. adults with diabetes. METHODS: A cohort of 6412 U.S. adults aged 20 or older was followed from the start until December 31, 2019. Statistical models such as Cox proportional hazards model (Cox) and Kaplan-Meier (K-M) survival curves were employed to investigate the associations between the inflammatory biomarkers and all-cause mortality and CCD mortality. RESULTS: After adjusting for confounding factors, the highest quartile of inflammatory biomarkers (NLR HR = 1.99; 95 % CI:1.54-2.57, MLR HR = 1.93; 95 % CI:1.46-2.54, SII HR = 1.49; 95 % CI:1.18-1.87, SIRI HR = 2.32; 95 % CI:1.81-2.96, nLPR HR = 2.05; 95 % CI:1.61-2.60, dNLR HR = 1.94; 95 % CI:1.51-2.49, AISI HR = 1.73; 95 % CI:1.4 1-2.12)) were positively associated with all-cause mortality compared to those in the lowest quartile. K-M survival curves indicated that participants with an inflammatory biomarker above a certain threshold had a higher risk of both all-cause mortality and CCD mortality (Log rank P < 0.05). CONCLUSION: Some biomarkers such as NLR, MLR, SII, AISI, SIRI, and dNLR, are significantly associated with all-cause mortality and CCD mortality among U.S. adults with diabetes. The risk of both outcomes increased when the biomarkers surpassed a specific threshold.