Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening.

In the treatment of central nervous system disease, the blood-brain barrier (BBB) is a major obstruction to drug delivery that must be overcome. In this study, we propose a brain-targeted delivery strategy based on selective opening of the BBB. This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material; however, the BBB still maintains the ability to completely block molecules from passing through. Based on the screening of BBB opening and matrix delivery materials, we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine liposomes can efficiently carry drugs into the brain immediately. At an effective dose, this delivery system is safe, especially with its effect on the BBB being reversible. This mix & act delivery system has a simple structure and rapid preparation, making it a strong potential candidate for drug delivery across the BBB.

Comparative Proteomics Elucidates the Potential Mechanism of Sperm Capacitation of Chinese Mitten Crabs (Eriocheir sinensis).

Sperm capacitation is broadly defined as a suite of biochemical and biophysical changes resulting from the acquisition of fertilization ability. To gain insights into the regulation mechanism of crustacean sperm capacitation, 4D label-free quantitative proteomics was first applied to analyze the changes of sperm in Eriocheir sinensis under three sequential physiological conditions: seminal vesicles (X2), hatched with the seminal receptacle content (X3), and incubated with egg water (X5). In total, 1536 proteins were identified, among which 880 proteins were quantified, with 82 and 224 proteins significantly altered after incubation with the seminal receptacle contents and egg water. Most differentially expressed proteins were attributed to biological processes by Gene Ontology annotation analysis. As the fundamental bioenergetic metabolism of sperm, the oxidative phosphorylation, glycolysis, and the pentose phosphate pathway presented significant changes under the treatment of seminal receptacle contents, indicating intensive regulation for sperm in the seminal receptacle. Additionally, the seminal receptacle contents also significantly increased the oxidation level of sperm, whereas the enhancement of abundance in superoxide dismutase, peroxiredoxin 1, and glutathione S-transferase after incubation with egg water significantly improved the resistance against oxidation. These results provided a new perspective for reproduction studies in crustaceans.

H*ads dynamics engineering via bimetallic Pd-Cu@MXene catalyst for enhanced electrocatalytic hydrodechlorination.

Electrocatalytic hydrodechlorination (EHDC) is a promising approach to safely remove halogenated emerging contaminants (HECs) pollutants. However, sluggish production dynamics of adsorbed atomic H (H*ads) limit the applicability of this green process. In this study, bimetallic Pd-Cu@MXene catalysts were synthesized to achieve highly efficient removal of HECs. The alloy electrode (Pd-Cu@MX/CC) exhibited better EHDC performance in comparison to Pd@MX/CC electrode, resulting in diclofenac degradation efficiency of 93.3 ± 0.1%. The characterization analysis revealed that the Pd0/PdII ratio decreased by forming bimetallic Pd-Cu alloy. Density functional theory calculations further demonstrated the electronic configuration modulation of the Pd-Cu@MXene catalysts, optimizing binging energies for H* and thereby facilitating H*ads production and tuning the reduction capability of H*ads. Noteably, the amounts and reduction potential of H*ads for Pd-Cu@MXene catalysts were 1.5 times higher and 0.37 eV lower than those observed for the mono Pd electrode. Hence, the introduction of Cu into the Pd catalyst optimized the dynamics of H*ads production, thereby conferring significant advantages to EHDC reactions. This augmentation was underscored by the successful application of the alloy catalysts supported by MXene in EHDC experiments involving other HECs, which represented a new paradigm for EHDC for efficient recalcitrant pollutant removal by H*ads.

Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing.

Hydrogels as wound dressing have attracted extensive attention in past decade because they can provide moist microenvironment to promote wound healing. Herein, this research designed a multifunctional hydrogel with antibacterial property and antioxidant activity fabricated from quaternary ammonium bearing light emitting quaternized TPE-P(DAA-co-DMAPMA) (QTPDD) and poly(aspartic hydrazide) (PAH). The protocatechuic aldehyde (PCA) grafted to the hydrogel through dynamic bond endowed the hydrogel with antioxidant activity and the tranexamic acid (TXA) was loaded to enhance the hemostatic performance. The hydrogel possesses preferable gelation time for injectable application, good antioxidant property and tissue adhesion, improved hemostatic performance fit for wound repairing. Furthermore, the hydrogel has excellent antimicrobial property to both E. coli and S. aureus based on quaternary ammonium structure. The hydrogel also showed good biocompatibility and the in vivo experiments proved this hydrogel can promote the wound repairing rate. This study suggests that TXA/hydrogel with quaternary ammonium structure and dynamic grafted PCA have great potential in wound healing applications.

Endothelial NLRP3 inflammasome regulation in atherosclerosis.

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

The histologic features, molecular features, detection and management of serrated polyps: a review.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Contemporary spectrum, characteristics, and outcomes of adult patients with rheumatic valvular disease in China: Insights from the China-VHD study.

Background: Rheumatic valvular disease (RVD) represents a significant health concern in developing countries, yet a scarcity of detailed data exists. This study conducts a comprehensive examination of RVD patients in China, exploring aspects of the disease's spectrum, characteristics, investigation, management, and outcomes. Methods: The China Valvular Heart Disease (China-VHD) study, a nationwide, multicenter, prospective observational study, enrolled 13,917 adults with moderate-to-severe valvular heart disease from April to June 2018. Among these, 2402 patients with native RVD (19.7% of native VHD patients) were analyzed. Results: Among the RVD patients, the median age was 57 years (interquartile range 50-65), with 82.5% falling within the 40-70 age range; females were notably predominant (63.9%). Rheumatic etiology prevailed, particularly in southern regions (48.8%). Multivalvular involvement was observed in 47.4% of RVD cases, and atrial fibrillation emerged as the most common comorbidity (43.2%). Severe RVD affected 64.2% of patients. Valvular interventions were undertaken by 66.9% of RVD patients, predominantly involving surgical valve replacement (90.8%). Adverse events, encompassing all-cause mortality and heart failure hospitalization, occurred in 7.3% of patients during the 2-year follow-up. Multivariable analysis identified factors such as age, geographical region, low body mass index, renal insufficiency, left atrial diameter, and left ventricular ejection fraction <50% (all P < 0.05) associated with adverse events, with valvular intervention emerging as a protective factor (HR: 0.201; 95%CI: 0.139 to 0.291; p < 0.001). Conclusions: This study delivers a comprehensive evaluation of RVD patients in China, shedding light on the spectrum, characteristics, investigation, management, and outcomes of this prevalent condition.

Mechanical Properties of Lattice Structures with a Central Cube: Experiments and Simulations.

In this study, a new structure is proposed based on the body-centered cubic (BCC) lattice structure by adding a cubic truss in the center of the BCC structure and denoting it TLC (truss-lattice-cube). The different dimensions of the central cube can notably affect the mechanical properties of the lattice structure. With a fixed length (15 mm) of a unit cell, the optimal size for the central cube is determined to be 5 mm. Quasi-static compressive tests are performed on specimens made of polylactic acid (PLA) using additive manufacturing technology. The deformation characteristics of the new structure are analyzed in detail by experiments and numerical simulations. Compared to the BCC structure, the mechanical properties of the TLC structure were significantly improved. The initial flow stress of the TLC increased by 122% at a strain of 0.1; the specific strength enhanced by 293% at a strain of 0.5; and the specific energy absorption improved by 312% at a strain of 0.6. Printing defects in the lattice structure may remarkably damage its mechanical properties. In this work, incorporation of microcracks into the finite element model allows the simulation to capture the influence of printing defects and significantly improve the predictive accuracy of the simulation.

A pattern recognition receptor interleukin-1 receptor is involved in reproductive immunity in Macrobrachium nipponense ovary.

The family of TIR domain-containing receptors includes numerous proteins involved in innate immunity. In this study, a member of this family was characterized from the ovary of the oriental river prawn Macrobrachium nipponense and identified as interleukin-1 receptor (MnIL-1R). Meanwhile, to elucidate the conservation of IL-1R, its orthologous were identified in several crustacean species as well. In addition, the expression pattern of MnIL-1R in various adult tissues and post different pathogen-associated molecular patterns (PAMPs) challenge in ovary was analyzed with qRT-PCR technology. Finally, the roles of MnIL-1R in the ovary were analyzed by RNAi technology. The main results are as follows: (1) MnIL-1R comprises a 1785 bp ORF encoding 594 amino acids and is structurally composed of five domains: a signal peptide, two immunoglobulin (IG) domains, a transmembrane region, and a TIR-2 domain; (2) the TIR domain showed a high conservation among analyzed crustacean species; (3) MnIL-1R is widely detected in all tested tissues including ovary; (4) MnIL-1R showed a positive response to challenges with LPS, PGN, and polyI:C in the ovary; (5) its IG domain showed strong binding ability to LPS and PGN, confirming its role as a pattern recognition receptor; (6) the expression patterns of several members of the Toll signaling pathway (Myd88, TRAF-6, Dorsal, and Relish) was similar to that of MnIL-1R after challenges with LPS, PGN, and polyI:C in the ovary; (7) the silencing of MnIL-1R resulted in down-regulation of theses gene' (Myd88, TRAF-6, Dorsal, and Relish) expression level in the ovary. These results suggest that MnIL-1R can activate the Toll signaling pathway in the ovary by directly recognizing LPS and PGN through its IG domain, thereby contributing to the immune response in the ovary of M. nipponense.

Matairesinoside, a novel inhibitor of TMEM16A ion channel, loaded with functional hydrogel for lung cancer treatment.

The incidence and mortality rates of lung cancer have remained high for several decades, necessitating the discovery of new drugs and the development of effective treatment strategies. This study identified matairesinoside (MTS) as a potent inhibitor of TMEM16A, a novel drug target for lung cancer. Molecular simulation combined with site-directed mutagenesis experiments confirmed the key binding sites of MTS and TMEM16A. Cell experiments demonstrated that MTS significantly inhibited the growth, migration, and invasion of lung cancer cells, while inducing apoptosis. Gene knockdown and overexpression studies further revealed that TMEM16A is the target for MTS in regulating lung cancer cell growth. Western blot analysis elucidated the signaling transduction network involved in MTS-mediated regulation of lung cancer. Building upon these findings, a biodegradable self-healing functional hydrogel was developed to load MTS, aiming to enhance therapeutic efficacy and minimize side effects in vivo. Animal experiments demonstrated that the hydrogel/MTS formulation exhibited satisfactory inhibitory effects on lung cancer and mitigated the side effects associated with direct MTS injection. This study identified MTS as a potential candidate for anti-lung cancer therapy with well-defined pharmacological mechanisms. Moreover, the targeted drug delivery system utilizing the hydrogel/MTS platform offers a promising approach for lung cancer treatment.

MRI-Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis.

Triple negative breast cancer (TNBC) cells have a high demand for oxygen and glucose to fuel their growth and spread, shaping the tumor microenvironment (TME) that can lead to a weakened immune system by hypoxia and increased risk of metastasis. To disrupt this vicious circle and improve cancer therapeutic efficacy, a strategy is proposed with the synergy of ferroptosis, immunosuppression reversal and disulfidptosis. An intelligent nanomedicine GOx-IA@HMON@IO is successfully developed to realize this strategy. The Fe release behaviors indicate the glutathione (GSH)-responsive degradation of HMON. The results of titanium sulfate assay, electron spin resonance (ESR) spectra, 5,5'-Dithiobis-(2-nitrobenzoic acid (DTNB) assay and T1 -weighted magnetic resonance imaging (MRI) demonstrate the mechanism of the intelligent iron atom (IA)-based cascade reactions for GOx-IA@HMON@IO, generating robust reactive oxygen species (ROS). The results on cells and mice reinforce the synergistic mechanisms of ferroptosis, immunosuppression reversal and disulfidptosis triggered by the GOx-IA@HMON@IO with the following steps: 1) GSH peroxidase 4 (GPX4) depletion by disulfidptosis; 2) IA-based cascade reactions; 3) tumor hypoxia reversal; 4) immunosuppression reversal; 5) GPX4 depletion by immunotherapy. Based on the synergistic mechanisms of ferroptosis, immunosuppression reversal and disulfidptosis, the intelligent nanomedicine GOx-IA@HMON@IO can be used for MRI-guided tumor therapy with excellent biocompatibility and safety.

Interface-Compatible Gel-Polymer Electrolyte Enabled by NaF-Solubility-Regulation toward All-Climate Solid-State Sodium Batteries.

Gel-polymer electrolyte (GPE) is a pragmatic choice for high-safety sodium batteries but still plagued by interfacial compatibility with both cathode and anode simultaneously. Here, salt-in-polymer fibers with NaF salt inlaid in polylactide (PLA) fiber network was fabricated via electrospinning and subsequent in situ forming gel-polymer electrolyte in liquid electrolytes. The obtained PLA-NaF GPE achieves a high ion conductivity (2.50×10-3 S cm-1) and large Na+ transference number (0.75) at ambient temperature. Notably, the dissolution of NaF salt occupies solvents leading to concentrated-electrolyte environment, which facilitates aggregates with increased anionic coordination (anion/Na+ >1). Aggregates with higher HOMO realize the preferential oxidation on the cathode so that inorganic-rich and stable CEI covers cathode' surface, preventing particles' breakage and showing good compatibility with different cathodes (Na3V2(PO4)3, Na2+2xFe2-x(SO4)3, Na0.72Ni0.32Mn0.68O2, NaTi2(PO4)3). While, passivated Na anode induced by the lower LUMO of aggregates, and the lower surface tension between Na anode and PLA-NaF GPE interface, leading to the dendrites-free Na anode. As a result, the assembled Na || Na3V2(PO4)3 cells display excellent electrochemical performance at all-climate conditions.

Spatiotemporal-Controlled NIR-II Immune Agonist Sensitizes Cancer Immunotherapy.

The integration of nanomedicine and immunotherapy has presented a promising opportunity for the treatment of cancer and diverse diseases. However, achieving spatiotemporal controllable immunotherapy with excellent efficacy and safety performances remains a significant challenge. This study develops a biodegradable near-infrared II (NIR-II) photothermal response polymer nanoparticle (PTEQ) system. This platform exhibits intrinsic immunostimulatory properties while concurrently delivering siRNA for Programmed Death-Ligand 1 (siPD-L1), leveraging enhanced immune responses and immune checkpoint blockade for safe and effective cancer therapy. In the CT26 tumor-bearing mouse model, PTEQ, as an immune stimulant, significantly boosts the infiltration of CD4+ and CD8+ T cells within the tumor microenvironment (TME). The PTEQ/siPD-L1+laser group not only initiates NIR-II photothermal therapy but also promotes the activation and infiltration of T cells, M1 macrophage polarization, and maturation of dendritic cells in the TME, resulting in the complete elimination of tumors in 7/10 cases, achieving a 100% survival rate. In another in vivo vaccine experiment, all tumors on the right side are completely eliminated in the PTEQ/siPD-L1+laser group, reaching a 100% tumor eradication rate. These findings underscore the potential of this strategy to overcome the current immunotherapeutic limitations and achieve immune therapy normalization.

A pancancer analysis of histone deacetylase 3 in human tumors.

Background: Histone deacetylase 3 (HDAC3) is known to be an important role in various kinds of cancer, but its effect has not been examined on the pancancer level. Thus, a systematic pancancer analysis was conducted to explore its potential role in pancancer diagnosis, prognosis, and immune correlation research. Methods: We used a series of databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) Project, The University of Alabama at Birmingham Cancer data analysis portal (UALCAN), Tumor Immune Estimation Resource (TIMER), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), among others, to analyze the relationship between the expression of HDAC3 and the diagnosis and prognosis of cancer, the tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) system using various bioinformatics methods. Downstream pathways of HDAC3 were identified by gene set enrichment analysis (GSEA). Furthermore, the protein expression of HDAC3 in tumor tissues and normal tissues of 17 patients with gliomas was analyzed via western blotting. Results: The expression of HDAC3 changed in most types of tumors, which was closely related to most tumor diagnoses and negatively related to some patients' overall survival (OS) and recurrence-free survival (RFS). The pan-cancer analysis demonstrated that it was tightly correlated to DNA methylation and RNA methylation modifications and associated with TMB and MSI. The expression level of HDAC3 was positively correlated with many immune checkpoint molecules and regulators and positively associated with the infiltration levels of immune cells in the TME in most tumor types. Furthermore, enrichment analysis revealed that transcriptional misregulation in cancer and RNA splicing functions were involved in the functional mechanism of HDAC3-related genes. Experimental research showed that the protein expression of HDAC3 was elevated in tumor tissues of patients with glioma. Conclusions: Through our comprehensive bioinformatics analysis, we evaluated the role of HDAC3 in pancancer, and our findings suggest that it may be an indicator for some cancer diagnoses and influence immune balance.

Application of Blood Lymphocyte Immunophenotype and TCR Gene Rearrangement in the Diagnosis of CTCL.

BACKGROUND: The immunophenotype of peripheral blood lymphocytes and T-cell receptor (TCR) gene rearrangement of cutaneous T cell lymphoma (CTCL) patients were retrospectively analyzed to explore their value in the diagnosis of CTCL. METHODS: A total of fifty patients' results were enrolled from 2013 to 2021, including 29 malignant skin disorders and 21 benign skin disorders. The immunophenotype of peripheral blood lymphocytes were analyzed by flow cytometry and TCR gene rearrangement was detected by capillary electrophoresis. Lymphocyte subsets, CD4/CD8 ratio, the percentage of CD3+CD4+CD7- cells and CD45RA/CD45RO ratio was calculated between malignant and benign skin disorders. Peripheral blood lymphocyte immunophenotype and TCR gene rearrangement was compared with skin biopsy to evaluate their sensitivity and specificity. RESULTS: Lymphocyte subsets between malignant and benign groups have no significant difference in percentage of T cell (p > 0.05). The CD4/CD8 ratio is higher in patients with malignant lymphoma than the healthy range. The percentage of CD3+CD4+CD7- cells in malignant groups is higher than that in benign groups and CD45RA/ CD45RO ratio has significant difference between malignant and benign groups (p < 0.05). The sensitivity and specificity of TCR rearrangement for CTCL were 51.7% and 42.9%. The sensitivity and specificity of peripheral blood lymphocyte immunophenotype for CTCL were 44.8% and 33.3%. Combining the two methods, the sensitivity and specificity reached 69.0% and 38.1%, respectively. CONCLUSIONS: CD4/CD8 ratio of lymphocyte subsets, the proportion of CD4+CD7-T cells and CD45RA/CD45RO ratio can effectively distinguish benign and malignant dermatosis. TCR rearrangement method combined with lymphocyte immunophenotype can improve the sensitivity and specificity of CTCL diagnosis.

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Correction to: Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway.

[This corrects the article DOI: 10.1002/mco2.226.].

Multifunctional Sandwich-Structured Super-Hygroscopic Zinc-Based MOF-Overlayed Cooling Wearables for Special Personal Thermal Management.

Personal protective equipment pays attention exclusively to external safety protection and ignores the internal thermoregulation of physiological state in association with sweating. Herein, a super-hygroscopic calcium-doped poly(sodium 4-styrenesulfonate) and superhydrophobic metal-organic-framework-overlayed wearables (Ca-PSS/MOF) integrated cooling wearable is proposed for special personal thermal management (PTM). Compared to the pristine fabric, the superhydrophobic MOF wearables exhibit anti-fouling and antibacterial capabilities, and the antibacterial efficiency is up to 99.99% and 98.99% against E. coli and S. aureus, respectively. More importantly, Ca-PSS/MOF demonstrate significant heat index changes up to 25.5 °C by reducing relative humidity dramatically from 91.0% to 60.0% and temperature from 36.5 to 31.6 °C during the running test. The practical feasibility of the Ca-PSS/MOF cooling wearables is well proved with the protective suit of the fireman. Owing to these multifunctional merits, the sandwich-structured cooling Ca-PSS/MOF are expected to provide new insights for designing the next-generation multifunctional apparel for PTM.

Effect of different isolation sources of Lactococcus lactis subsp. lactis on volatile metabolites in fermented milk.

Lactococcus lactis subsp. lactis (L. lactis subsp. lactis) is a commonly used starter cultures in fermented dairy products, contributing distinct flavor and texture characteristics with high application value. However, the strains from different isolates have different contributions to milk fermentation. Therefore, this study aimed to investigate the influence of L. lactis subsp. lactis isolated from various sources on the volatile metabolites present in fermented milk. In this study, L. lactis subsp. lactis from different isolation sources (yogurt, koumiss and goat yogurt) was utilized as a starter culture for fermentation. The volatile metabolites of fermented milk were subsequently analyzed by headspace solid phase microextraction gas chromatography-mass spectrography (HS-SPME-GC-MS). The results indicated significant differences in the structure and abundance of volatile metabolites in fermented milk produced with different isolates (R2Y = 0.96, Q2 = 0.88). Notably, the strains isolated from goat yogurt appeared to enhance the accumulation of ketones (goat yogurt vs yogurt milk: 50 %; goat yogur vs koumiss: 27.3 %)and aldehydes (goat yogurt vs yogurt milk: 21.4 %; goat yogurt vs koumiss: 54.5 %) in fermented milk than strains isolated from koumiss and yogurt milk. It significantly promoted the production of 8 flavor substances (1 substance with OAV ≥ 1 and 6 substances with OAV > 0.1) and enhanced the biosynthesis of valine, leucine, and isoleucine. This study provides valuable insights for the application of Lactococcus lactis subsp. lactis isolated from different sources in fermented dairy production and screening of potential starter cultures.