Multi-omics analyses reveal interactions between the skin microbiota and skin metabolites in atopic dermatitis.

Introduction: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear. Methods: 16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC-MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples. Results: Samples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC-MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways. Discussion: We suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.

Convenient preparation of indigo from the Ieaves of Baphicacanthus cusia(Nees) Bremek by enzymatic method and its MALDI-TOF-MS and UPLC-Q-TOF/MS analysis.

The manufacturing of indigo naturalis requires prolonged leaf soaking and lime stirring; the resulting indigo purity is less than 3.00% and the yield of indigo (measured in stems and leaves weight) is less than 0.50%, making it unsuitable for use in industrial procedures like printing and dyeing. An enzymatic method of creating indigo without the requirement for lime was investigated in order to generate high purity indigo. Single factor tests were performed to optimize the enzymatic preparation conditions. The findings showed that 60 °C, pH 5.5, 200 mL of leaves extract containing 0.45 mg/mL indican, and a 4:1 ratio of the acidic cellulose (activity: 9000 U/mL, liquid) to indican were the ideal parameters for enzymatic preparation. The yield of indigo was 40.32%, and the contents of indigo and indirubin were 37.37% and 2.30%, respectively. MALDI-TOF-MS in positive ion mode and UPLC-Q-TOF-MS in both positive and negative ion modes were used to analyze indigo extracts from Baphicacanthus cusia(Nees) Bremek by enzymatic preparation. It has been discovered that 13 alkaloids, 5 organic acids, 3 terpenoids, 3 steroids, 2 flavones, and 7 other compounds are present in indigo extracts. The presence of the indigo, indirubin, isorhamnetin, tryptanthrin, indigodole B, and indigodole C determined by UPLC-Q-TOF-MS was verified by MALDI-TOF-MS analysis. The enzymatic preparation of indigo extracts kept the same chemical makeup as conventional indigo naturalis. Thermal analysis and SEM morphology were used to confirm that there was no lime in the indigo extract. During the enzymatic process, Baphicacanthus cusia (Nees) Bremek was employed more effectively, increasing the yield and purity of indigo.

Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses.

Background: The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods: Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results: IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions: These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.

A 2-order additive fuzzy measure identification method based on hesitant fuzzy linguistic interaction degree and its application in credit assessment.

To reflect both fuzziness and hesitation in the evaluation of interactivity between attributes in the identification process of 2-order additive fuzzy measure, this work uses the hesitant fuzzy linguistic term set (HFLTS) to describe and depict the interactivity between attributes. Firstly, the interactivity between attributes is defined by the supermodular game theory. According to this definition, a linguistic term set is established to characterize the interactivity between attributes. Under the linguistic term set, the experts employ linguistic expressions generated by context-free grammar to qualitatively describe the interactivity between attributes. Secondly, through the conversion function, the linguistic expressions are transformed into the hesitant fuzzy linguistic term sets (HFLTSs). The individual evaluation results of all experts were further aggregated with the defined hesitant fuzzy linguistic weighted power average operator (HFLWPA). Thirdly, based on the standard Euclidean distance formula of the hesitant fuzzy linguistic elements (HFLEs), the hesitant fuzzy linguistic interaction degree (HFLID) between attributes is defined and calculated by constructing a piecewise function. As a result, a 2-order additive fuzzy measure identification method based on HFLID is proposed. Based on the proposed method, using the Choquet fuzzy integral as nonlinear integration operator, a multi-attribute decision making (MADM) process is then presented. Taking the credit assessment of the big data listed companies in China as an application example, the analysis results of application example prove the feasibility and effectiveness of the proposed method. This work successfully reflects both the fuzziness and hesitation in evaluating the interactivity between attributes in the identification process of 2-order additive fuzzy measure, enriches the theoretical framework of 2-order additive fuzzy measure, and expands the applicability and methodology of 2-order additive fuzzy measure in multi-attribute decision making.

Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.

Histopathological heterogeneity is a hallmark of prostate cancer (PCa). Using spatial and parallel single-nucleus transcriptomics, we report an androgen receptor (AR)-positive but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small cell carcinoma. Such small cell-like PCa (SCLPC) is clinically aggressive with low AR, but high stemness and proliferation, activity. Molecular characterization prioritizes protein translation, represented by up-regulation of many ribosomal protein genes, and SP1, a transcriptional factor that drives SCLPC phenotype and overexpresses in castration-resistant PCa (CRPC), as two potential therapeutic targets in AR-indifferent CRPC. An SP1-specific inhibitor, plicamycin, effectively suppresses CRPC growth in vivo. Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.

Crosslinking-induced patterning of MOFs by direct photo- and electron-beam lithography.

Metal-organic frameworks (MOFs) with diverse chemistry, structures, and properties have emerged as appealing materials for miniaturized solid-state devices. The incorporation of MOF films in these devices, such as the integrated microelectronics and nanophotonics, requires robust patterning methods. However, existing MOF patterning methods suffer from some combinations of limited material adaptability, compromised patterning resolution and scalability, and degraded properties. Here we report a universal, crosslinking-induced patterning approach for various MOFs, termed as CLIP-MOF. Via resist-free, direct photo- and electron-beam (e-beam) lithography, the ligand crosslinking chemistry leads to drastically reduced solubility of colloidal MOFs, permitting selective removal of unexposed MOF films with developer solvents. This enables scalable, micro-/nanoscale (≈70 nm resolution), and multimaterial patterning of MOFs on large-area, rigid or flexible substrates. Patterned MOF films preserve their crystallinity, porosity, and other properties tailored for targeted applications, such as diffractive gas sensors and electrochromic pixels. The combined features of CLIP-MOF create more possibilities in the system-level integration of MOFs in various electronic, photonic, and biomedical devices.

Construction of a novel Eu-MOF material based on different detection mechanisms and its application in sensing pollutants aniline, F- and Hg2.

Aniline is an organic pollutant with carcinogenicity and teratogenicity, while F- and Hg2+ are toxic ions that are easily soluble in water. When they are released to the environment, they will pose a threat to human health. Designing a material that can simultaneously detect three types of pollutants is of great significance. In this paper, a novel rare earth metal organic framework material (Eu-MOF) with three-dimensional structure based on 1-methylimidazole-4,5-dicarboxylic acid was synthesized for the first time through solvent thermal method. It has excellent luminescent performance and can be used as a multifunctional fluorescent probe to detect aniline, F-, and Hg2+ based on photoinduced electron transfer, energy competitive absorption, and ion exchange mechanisms, with detection limits of 1.79 × 10-8, 8.13 × 10-8, and 8.83 × 10-7 M, respectively. It is worth noting that Eu-MOF can detect F- and Hg2+ in real water samples, such as lake water and green tea water, with favorable recovery rates.

Improvement of Pre-check and Triage Efficiency and Guarantee of Maternal and Infant Safety in Pandemic Situation.

Objective: The objective of this study was to enhance the efficiency of pre-check and triage procedures in gynecology and obstetrics, while ensuring the safety of maternal and infant patients during the COVID-19 pandemic. Methods: Between March 2020 and July 2022, the workflow in gynecology and obstetrics was optimized, and the management of medical staff working in outpatient, ward, and obstetric ward settings was strengthened. Special protocols were developed and implemented for pregnant women, parturients, and neonates. Detailed procedures and routes were established for patient movement from outpatient areas to wards, with strict adherence to pandemic prevention and control measures. Information-based methods were employed to track and monitor the health status of high-risk pregnant women, parturients, and their families, facilitating accurate and efficient pre-check and triage processes. Results: The implementation of these measures yielded favorable outcomes. No cases of COVID-19 infection were reported among pregnant women and parturients admitted to Liangzhou Hospital. The source of infection was effectively controlled, ensuring the safety of the patients. Conclusion: This study demonstrates the significance of improving pre-check and triage efficiency, strengthening the management of medical staff, and implementing specialized measures for pregnant women, parturients, and neonates to ensure their safety during the COVID-19 pandemic. The established protocols and procedures can serve as a valuable reference for other healthcare facilities seeking to enhance their pandemic prevention and control strategies in gynecology and obstetrics settings.

Association of depression and sleep quality with frailty: a cross-sectional study in China.

Background: With the rapid growth of global aging, frailty has become a serious public health burden, affecting the life quality of older adults. Depressive symptoms (depression hereafter) and sleep quality are associated with frailty, but the pathways in which sleep quality and depression affect frailty remain unclear. Method: This cross-sectional study included 1866 community-dwelling older adults. Demographic characteristics and health-related data of them was collected, and we also assessed frailty, depression, and sleep quality. Descriptive statistics were carried out and ordinal logistic regression analysis was used to identify the factors correlated with frailty. Spearman correlation analysis and mediation analysis were employed to assess associations between sleep quality, depression and frailty. Two-sided p < 0.05 was considered as significant. Results: The results showed that 4.1% older adults were frail and 31.0% were pre-frail. Ordinal logistic regression showed that age, consumptions of vegetables, exercise, sleep quality, depression, number of chronic diseases, chronic pain, and self-rated health were correlated with frailty. Spearman correlation analysis revealed that frailty was associated with depression and sleep quality. There was a mediation effect that sleep quality was a significant and positive predictor of frailty (total effect = 0.0545, 95% boot CI = 0.0449-0.0641), and depression was a mediator between sleep quality and frailty (mediation effect = 60.4%). Conclusion: Depression and poor sleep quality may be early indicators of frailty in older adults. Improving the sleep quality and psychological state of older adults can improve frailty, which is beneficial for healthy aging.

Evaluating the impact of automatic positive airway pressure therapy on cardiovascular risk index and vascular behavior in patients with obstructive sleep apnea: a study on heterogeneity in the therapeutic response.

STUDY OBJECTIVES: This study investigated the impact of APAP therapy on vascular behavior and its potential to lower cardiovascular risk in patients with OSA, as well as differentiating APAP therapy heterogeneity. METHODS: All participants were diagnosed with OSA by portable monitoring, and pulse wave parameters and cardiac risk composite parameter index (CRI) were obtained by photoplethysmography before and after APAP. Clustering analysis of pulse wave parameters before APAP in the high-risk population was performed using k-means clustering. Linear regression was used to assess the associations of changes in CRI and pulse wave parameters with clinical characteristics. RESULTS: Eighty-two patients with OSA underwent APAP therapy. The CRI after APAP was significantly lower than before APAP (0.38± 0.33 and 0.58 ± 0.31, respectively; p < 0.001). All pulse wave parameters (except irregular pulse) were significantly different (p < 0.001) in patients with OSA and in the high-risk responders group after versus before APAP. The differences in pulse wave parameters after versus before APAP were not significant in the high-risk non-responders group, except for RCRD and pulse rate variability. Four clusters were obtained from the clustering analysis of pulse wave parameters before APAP in the high-risk responders group. CONCLUSIONS: APAP reduces the CRI in patients with OSA by altering vascular behavior. Overnight photoplethysmography monitoring of pulse wave parameters can be used to assess whether patients with OSA will benefit from APAP.

Rapid and Complete Digestion of Refractory Geological Samples Using Ultrafine Powder for Accurate Analyses of Trace Elements.

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

Quantum phase synchronization via exciton-vibrational energy dissipation sustains long-lived coherence in photosynthetic antennas.

The lifetime of electronic coherences found in photosynthetic antennas is known to be too short to match the energy transfer time, rendering the coherent energy transfer mechanism inactive. Exciton-vibrational coherence time in excitonic dimers which consist of two chromophores coupled by excitation transfer interaction, can however be much longer. Uncovering the mechanism for sustained coherences in a noisy biological environment is challenging, requiring the use of simpler model systems as proxies. Here, via two-dimensional electronic spectroscopy experiments, we present compelling evidence for longer exciton-vibrational coherence time in the allophycocyanin trimer, containing excitonic dimers, compared to isolated pigments. This is attributed to the quantum phase synchronization of the resonant vibrational collective modes of the dimer, where the anti-symmetric modes, coupled to excitonic states with fast dephasing, are dissipated. The decoupled symmetric counterparts are subject to slower energy dissipation. The resonant modes have a predicted nearly 50% reduction in the vibrational amplitudes, and almost zero amplitude in the corresponding dynamical Stokes shift spectrum compared to the isolated pigments. Our findings provide insights into the mechanisms for protecting coherences against the noisy environment.

Chelatococcus albus sp. nov., a bacterium isolated from hot spring microbial mat.

A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25-50 °C (optimum, 37 °C), at pH 5.5-9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19 : 0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26 mol%. The average nucleotide identity (ANIm ≤84.85 % and ANIb ≤76.08  %) and digital DNA-DNA hybridization (≤ 21.9 %) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.

Preserved Ratio Impaired Spirometry (PRISm): A Global Epidemiological Overview, Radiographic Characteristics, Comorbid Associations, and Differentiation from Chronic Obstructive Pulmonary Disease.

Preserved Ratio Impaired Spirometry (PRISm) manifests notable epidemiological disparities across the globe, with its prevalence and influential factors showcasing pronounced diversities among various geographical territories and demographics. The prevalence of PRISm fluctuates considerably among regions such as Latin America, the United States, and Asian nations, potentially correlating with a myriad of determinants, including socioeconomic status, environmental factors, and lifestyle modalities. Concurrently, the link between PRISm and health risks and other disorders, especially its distinction and interrelation with chronic obstructive pulmonary disease (COPD), has become a pivotal subject of scientific enquiry. Radiographic anomalies, such as perturbations in the pulmonary parenchyma and structural alterations, are posited as salient characteristics of PRISm. Furthermore, PRISm unveils intricate associations with multiple comorbidities, inclusive of hypertension and type 2 diabetes, thereby amplifying the intricacy in comprehending and managing this condition. In this review, we aim to holistically elucidate the epidemiological peculiarities of PRISm, its potential aetiological contributors, its nexus with COPD, and its association with radiographic aberrations and other comorbidities. An integrative understanding of these dimensions will provide pivotal insights for the formulation of more precise and personalised preventative and therapeutic strategies.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Stomatohabitans albus gen. nov., sp. nov., an oral living facultative anaerobic actinobacteria isolated form Steller sea lion, and proposal of Stomatohabitantaceae fam. nov. and Stomatohabitantales ord. nov.

Two novel actinobacteria, designated as SYSU M7M538T and SYSU M7M531, were isolated from oral of Eumetopias jubatus in Zhuhai Chimelong Ocean Kingdom, China. The cells of these microorganisms stained Gram-positive and were rod shaped. These strains were facultative anaerobic, and catalase-positive. Optimal growth occurred at 37 °C and pH 7.0 over 7 days of cultivation. Both strains possessed diphosphatidylglycerol, phosphatidylglycerol and phosphocholine as the major polar lipids. The main menaquinone was MK-9(H4). The major fatty acids were C16:0, C17:1w8c, C17:0, C18:1w9c and C18:0. Analyses of genome sequences revealed that the genome size of SYSU M7M538T was 2.1 Mbp with G + C content of 52.5 %, while the genome size of SYSU M7M531 was 2.3 Mbp with G + C content of 52.7 %. The ANI and 16S rRNA gene analysis results showed that the pairwise similarities between the two strains and other recognized Nitriliruptoria species were less than 64.9 % and 89.0 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains SYSU M7M538T and SYSU M7M531 formed a well-separated phylogenetic branch distinct from other orders of Nitriliruptoria. Based on the data presented here, these two strains are considered to represent a novel species of a novel genus, for which the name Stomatohabitans albus gen. nov., sp. nov., with the type strain SYSU M7M538T (=KCTC 59113T = GDMCC 1.4286T), are proposed. We also propose that these organisms represent a novel family named Stomatohabitantaceae fam. nov. of a novel order Stomatohabitantales ord. nov.

Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity.

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.

Nanoparticle targeting of neutrophil glycolysis prevents lung ischemia-reperfusion injury.

Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI.