FOXO-regulated DEAF1 controls muscle regeneration through autophagy.

The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) - a transcriptional factor downstream of foxo signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that DEAF1 targets to Pik3c3 and Atg16l1 promoter regions and suppresses their expression. Deaf1 depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that Deaf1 depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that Deaf1 expression is altered in aging and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.

Shift work effects on incident neuropsychiatric disorders and shift work tolerance.

BACKGROUND: Shift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. METHODS: UK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. RESULTS: The analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10-1.52), anxiety (1.08, 1.01-1.15), depression (1.29, 1.22-1.36), and sleep disorders (1.18, 1.09-1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LIMITATIONS: Self-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. CONCLUSIONS: Our findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.

Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study.

RATIONALE: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. OBJECTIVES: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). METHODS: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. MEASUREMENTS AND MAIN RESULTS: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. CONCLUSIONS: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Injectable Nanoengineered Adhesive Hydrogel for Treating Enterocutaneous Fistulas.

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.

Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease.

INTRODUCTION: Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. METHODS: Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid-positive transition and clinical progression, and faster rates of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. DISCUSSION: Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD. HIGHLIGHTS: The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (Aß) positron emission tomography (PET) burden and Aß-positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid Aß42 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. Aß PET and brain atrophy mediated the link of ALPS index with cognitive decline.

Young Plasma Attenuated Chronic Kidney Disease Progression after Acute Kidney Injury by Inhibiting Inflammation in Mice.

In the aged patients suffering from acute kidney injury, the risk for progression to chronic kidney disease and mortality is high. Aging accompanied by glomerulosclerosis, interstitial inflammation, and fibrosis might be one of the underlying mechanisms for vulnerability. In addition to sustained activation of the renin-angiotensin system, persistent chronic inflammation with tertiary lymphoid tissue formation is more common and is associated with disease progression in the aged kidney after acute injury. Based on recent laboratory evidence that young blood can rejuvenate the brain, muscle, and heart, we were intrigued by the possible protective effect of young plasma on acute kidney injury in aged mice. Here, we demonstrated that young plasma from 2-month-old mice could attenuate chronic kidney disease progression in 15-month-old mice subjected to acute kidney injury induced by ischemia-reperfusion. In the aged mice after acute kidney injury, young plasma administration decreased tubulointerstitial injury, fibrosis, and tertiary lymphoid tissue formation in kidneys assessed on day 28 after acute injury despite no significant beneficial effect on injury severity and survival. Mechanistically, young plasma inhibited angiotensin II-activated chemokines in pericytes that were responsible for tertiary lymphoid tissue formation. In summary, our data provide evidence that young plasma attenuates the transition from acute kidney injury to chronic kidney disease in aged mice. The therapeutic potential of young plasma infusion or exchange in the aged patients suffering acute kidney injury needs to be addressed in clinical trials.

Socioeconomic status, lifestyle and risk of incident dementia: a prospective cohort study of 276730 participants.

Healthy lifestyle might alleviate the socioeconomic inequities in health, but the extent of the joint and interactive effects of these two factors on dementia are unclear. This study aimed to detect the joint and interactive associations of socioeconomic status (SES) and lifestyle factors with incident dementia risk, and the underlying brain imaging alterations. Cox proportional hazards analysis was performed to test the joint and interactive associations. Partial correlation analysis was performed to reflect the brain imaging alterations. A total of 276,730 participants with a mean age of 55.9 (±8.0) years old from UK biobank were included. Over 8.5 (±2.6) years of follow-up, 3013 participants were diagnosed with dementia. Participants with high SES and most healthy lifestyle had a significantly lower risk of incident dementia (HR=0.19, 95% CI=0.14 to 0.26, P<2×10-16), Alzheimer's disease (AD, HR=0.19, 95% CI=0.13 to 0.29, P=8.94×10-15), and vascular dementia (HR=0.24, 95% CI=0.12 to 0.48, P=7.57×10-05) compared with participants with low SES and an unhealthy lifestyle. Significant interactions were found between SES and lifestyle on dementia (P=0.002) and AD (P=0.001) risks; the association between lifestyle and dementia was stronger among those of high SES. The combination of high SES and healthy lifestyle was positively associated with higher volumes in brain regions vulnerable to dementia-related atrophy. These findings suggest that SES and lifestyle significantly interact and influence dementia with its related brain structure phenotypes.

HaMYBA-HabHLH1 regulatory complex and HaMYBF fine-tune red flower coloration in the corolla of sunflower (Helianthus annuus L.).

Sunflowers are well-known ornamental plants, while sunflowers with red corolla are rare and the mechanisms underlying red coloration remain unclear. Here, a comprehensive analysis of metabolomics and transcriptomics on flavonoid pathway was performed to investigate the molecular mechanisms underlying the differential color formation between red sunflower Pc103 and two yellow sunflowers (Yr17 and Y35). Targeted metabolomic analysis revealed higher anthocyanin levels but lower flavonol content in Pc103 compared to the yellow cultivars. RNA-sequencing and phylogenetic analysis identified multiple genes involved in the flavonoid pathway, including series of structural genes and three MYB and bHLH genes. Specifically, HaMYBA and HabHLH1 were up-regulated in Pc103, whereas HaMYBF exhibited reduced expression. HaMYBA was found to interact with HabHLH1 in vivo and in vitro, while HaMYBF does not. Transient expression analysis further revealed that HabHLH1 and HaMYBA cooperatively regulate increased expression of dihydroflavonol 4-reductase (DFR), leading to anthocyanin accumulation. On the other hand, ectopic expression of HaMYBF independently modulates flavonol synthase (FLS) expression, but hindered anthocyanin production. Collectively, our findings suggest that the up-regulation of HaMYBA and HabHLH1, as well as the down-regulation of HaMYBF, contribute to the red coloration in Pc103. It offers a theoretical basis for improving sunflower color through genetic engineering.

Engineered organoids for biomedical applications.

As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.

2D quasi-layered material with domino structure.

Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V-1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Circulating metabolites and risk of incident dementia: A prospective cohort study.

Identifying circulating metabolites associated with dementia, cognition, and brain volume may improve the understanding of dementia pathogenesis and provide novel insights for preventive and therapeutic interventions. This cohort study included a total of 87 885 participants (median follow-up of 9.1 years, 54% female) without dementia at baseline from the UK Biobank. A total of 249 plasma metabolites were measured using nuclear magnetic resonance spectroscopy at baseline. Cox proportional regression was used to examine the associations of each metabolite with incident dementia (cases = 1134), Alzheimer's disease (AD; cases = 488), and vascular dementia (VD; cases = 257) during follow-up. Dementia-associated metabolites were further analyzed for association with cognitive deficits (N = 87 885) and brain volume (N = 7756) using logistic regression and linear regression. We identified 26 metabolites associated with incident dementia, of which 6 were associated with incident AD and 5 were associated with incident VD. These 26 dementia-related metabolites were subfractions of intermediate-density lipoprotein, large low-density lipoprotein (L-LDL), small high-density lipoprotein (S-HDL), very-low-density lipoprotein, fatty acids, ketone bodies, citrate, glucose, and valine. Among them, the cholesterol percentage in L-LDL (L-LDL-C%) was associated with lower risk of AD (HR [95% CI] = 0.92 [0.87-0.97], p = 0.002), higher brain cortical (ß = 0.047, p = 3.91 × 10-6 ), and hippocampal (ß = 0.043, p = 1.93 × 10-4 ) volume. Cholesteryl ester-to-total lipid ratio in L-LDL (L-LDL-CE%) was associated with lower risk of AD (HR [95% CI] = 0.93 [0.90-0.96], p = 1.48 × 10-4 ), cognitive deficits (odds ratio = 0.98, p = 0.009), and higher hippocampal volume (ß = 0.027, p = 0.009). Cholesteryl esters in S-HDL (S-HDL-CE) were associated with lower risk of VD (HR [95% CI] = 0.81 [0.71-0.93], p = 0.002), but not AD. Taken together, circulating levels of L-LDL-CE% and L-LDL-C% were robustly associated with risk of AD and AD phenotypes, but not with VD. S-HDL-CE was associated with lower risk of VD, but not with AD or AD phenotypes. These metabolites may play a role in the advancement of future intervention trials. Additional research is necessary to gain a complete comprehension of the molecular mechanisms behind these associations.

[Application of Light Therapy in Dementia Care].

Patients with dementia often display related sleep disturbance, depression, and behavioral and psychological symptoms, which are traditionally managed through the use of antipsychotic medications or physical restraint. However, these management interventions can have negative effects on the physical and psychological health of patients. The results of several meta-analyses suggest non-pharmacological interventions, including light therapy, should be used for the first-line management of these dementia symptoms. Light therapy uses artificial light to compensate for insufficient light exposure during the daytime and to help patients with dementia properly regulate their circadian rhythms. Sleep disturbance and depression in those with dementia may be effectively relieved through the application of light therapy. Nurses should assess the needs and symptoms of patients with dementia and consider applying light therapy as a complementary care intervention to improve quality of care.

Longitudinal associations of cardiovascular health and vascular events with incident dementia.

INTRODUCTION: Evidence supporting cardiovascular diseases could increase the risk of dementia remains fragmented. A comprehensive study to illuminate the distinctive associations across different dementia types is still lacking. This study is sought to: (1) determine the clinical validity of Framingham General Cardiovascular Risk Score (FGCRS) for dementia assessment and (2) examine the associations between cardiovascular diseases and the risk of dementia. METHODS: A total of 432 079 dementia-free individuals at baseline from UK Biobank were included. Multivariable Cox proportional hazard models were used to investigate the prospective associations for FGCRS and a series of cardiovascular diseases with all-cause dementia (ACD) and its major components, Alzheimer's disease (AD) and vascular dementia (VaD). RESULTS: During a median follow-up of 110.1 months, 4711 individuals were diagnosed with dementia. FGCRS was associated with increased risks across the dementia spectrum. In stratification analysis, high-risk groups have demonstrated the greatest dementia burdens, particularly to VaD. Over 74 traits, 9 adverse associations, such as chronic ischaemic heart disease (ACD: HR=1.354; AD: HR=1.269; VaD: HR=1.768), atrioventricular block (ACD: HR=1.562; AD: HR=1.556; VaD: HR=2.069), heart failure (ACD: HR=1.639; AD: HR=1.543; VaD: HR=2.141) and hypotension (ACD: HR=2.912; AD: HR=2.361; VaD: HR=3.315) were observed. Several distinctions were also found, with atrial fibrillation, cerebral infarction, and haemorrhage only associated with greater risks of ACD and VaD. DISCUSSION: By identifying distinctive associations between cardiovascular diseases and dementia, this study has established a comprehensive 'mapping' that may untangle the long-standing discrepancy. FGCRS has demonstrated its predictivity beyond cardiovascular diseases burdens, suggesting potential opportunities for implantation.

Association of biological age with health outcomes and its modifiable factors.

Identifying the clinical implications and modifiable and unmodifiable factors of aging requires the measurement of biological age (BA) and age gap. Leveraging the biomedical traits involved with physical measures, biochemical assays, genomic data, and cognitive functions from the healthy participants in the UK Biobank, we establish an integrative BA model consisting of multi-dimensional indicators. Accelerated aging (age gap >3.2 years) at baseline is associated incident circulatory diseases, related chronic disorders, all-cause, and cause-specific mortality. We identify 35 modifiable factors for age gap (p < 4.81 × 10-4 ), where pulmonary functions, body mass, hand grip strength, basal metabolic rate, estimated glomerular filtration rate, and C-reactive protein show the most significant associations. Genetic analyses replicate the possible associations between age gap and health-related outcomes and further identify CST3 as an essential gene for biological aging, which is highly expressed in the brain and is associated with immune and metabolic traits. Our study profiles the landscape of biological aging and provides insights into the preventive strategies and therapeutic targets for aging.

Genome-wide association mapping of rust resistance in Aegilops longissima.

The rust diseases, including leaf rust caused by Puccinia triticina (Pt), stem rust caused by P. graminis f. sp. tritici (Pgt), and stripe rust caused by P. striiformis f. sp. tritici (Pst), are major limiting factors in wheat production worldwide. Identification of novel sources of rust resistance genes is key to developing cultivars resistant to rapidly evolving pathogen populations. Aegilops longissima is a diploid wild grass native to the Levant and closely related to the modern bread wheat D subgenome. To explore resistance genes in the species, we evaluated a large panel of Ae. longissima for resistance to several races of Pt, Pgt, and Pst, and conducted a genome-wide association study (GWAS) to map rust resistance loci in the species. A panel of 404 Ae. longissima accessions, mostly collected from Israel, were screened for seedling-stage resistance to four races of Pt, four races of Pgt, and three races of Pst. Out of the 404 accessions screened, two were found that were resistant to all 11 races of the three rust pathogens screened. The percentage of all accessions screened that were resistant to a given rust pathogen race ranged from 18.5% to 99.7%. Genotyping-by-sequencing (GBS) was performed on 381 accessions of the Ae. longissima panel, wherein 125,343 single nucleotide polymorphisms (SNPs) were obtained after alignment to the Ae. longissima reference genome assembly and quality control filtering. Genetic diversity analysis revealed the presence of two distinct subpopulations, which followed a geographic pattern of a northern and a southern subpopulation. Association mapping was performed in the genotyped portion of the collection (n = 381) and in each subpopulation (n = 204 and 174) independently via a single-locus mixed-linear model, and two multi-locus models, FarmCPU, and BLINK. A large number (195) of markers were significantly associated with resistance to at least one of 10 rust pathogen races evaluated, nine of which are key candidate markers for further investigation due to their detection via multiple models and/or their association with resistance to more than one pathogen race. The novel resistance loci identified will provide additional diversity available for use in wheat breeding.

Eco-sustainable coatings based on chitosan, pectin, and lemon essential oil nanoemulsion and their effect on strawberry preservation.

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.

Palladium-Catalyzed Direct Esterification via C-H Bond Activation of Aldehydes.

A concise and highly efficient synthesis method of direct esterification of aldehydes via Pd-catalyzed C-H bond activation of aldehyde group has been developed. The strategy avoids the preoxidation step of aldehyde or use of condensing agents in ester synthesis, which is not only applicable to various alcohols but also suitable for the esterification of phenolics which are usually difficult to be esterified. The methodology has the significant advantages of broad substrate scope, mild reaction conditions, and nonrequirement of additional oxidants.

Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling.

Three-dimensional (3D)in vitrotumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5%-3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0%-2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. Reverse transcription-polymerase chain reaction (RT-qPCR) and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.