Using ultrasonic washing combined with UV-LEDs as a novel chemical-free method to disinfect fresh ready-to-eat produce.

The consumption of ready-to-eat fresh produce raises the issue of food-borne pathogen infections; thus, disinfecting ready-to-eat produce for commercial use, such as in homes and restaurants, is important to ensure food safety. Chemical sanitizers are typically used for disinfection. Ultraviolet-light emitting diodes (UV-LEDs) are a novel non-thermal disinfection technology that consumes less energy and generates less heat than traditional UV lamps, making them more appealing to consumers. In this study, we combined ultrasonic (US) washing method with UV-LEDs (US-UV-LEDs) to develop a technique for disinfecting fresh produce without using chemical sanitizers and compared its efficacy with three common household sanitizers ("84" (sodium hypochlorite) disinfectant, kettle descaler (citric acid), and vinegar (acetic acid)). In addition, we investigated the efficacy of this method in controlling pathogen numbers in the water used to wash (washing water) the produce to prevent cross-contamination between water and produce. Cherry tomatoes and lettuce were selected as produce models and Salmonella Typhimurium and Escherichia coli O157:H7 were used as the bacterial models. The results showed that US-UV-LEDs reduced the numbers of S. Typhimurium and E. coli O157:H7 on produce by 2.1-2.2 log CFU/g, consistent with the results achieved by the three household sanitizers; however, kettle descaler and vinegar had a limited effect (2.6-3.5 log CFU/mL) on residual pathogens in the washing water. Furthermore, we created washing water with low (754 mg/L) and high (1425 mg/L) chemical oxygen demand (COD) levels and determined the disinfection efficacy of "84" disinfectant and US-UV-LEDs. The results showed that US-UV-LEDs reduced the number of S. Typhimurium and E. coli O157:H7 by 2.0-2.1 and 1.8-2.1 log CFU/g under low and high COD levels, respectively, which was similar a result to that of "84" disinfectant. However, the residual pathogen numbers in the washing water were reduced to 1.4-1.9 log CFU/mL after treatment with US-UV-LED under high COD, whereas the pathogens were undetected in the washing water disinfected with "84" disinfectant. These results suggest that US-UV-LEDs have better application potential than acidic household sanitizers, but chlorine sanitizer remains the most effective disinfecting method.

A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

Fluorescence sensing of water in various organic solvents based on a novel cyclic polymer.

A sensor capable of sensing of water in various organic solvents ranging from water-soluble to water-miscible solvents is still a challenging task. In this research, a cyclic polymer fluorescence chemosensor (CPFC) has been developed for sensing of water by turn-on model in 9 organic solvents and turn-off model in DMA, where the broadest concentration range and the lowest detection limit was obtained for water in DMA (10 %-90 %) and dioxane (0.011 %), respectively. The sensing mechanism is explored by theory calculation and experimental investigation. The amphiphilic nature endows the polymer probe with great potential for measuring various contaminants from aqueous and nonaqueous mediums. Furthermore, the present search highlights the potential applications of cyclic polymer as fluorescence probes in the field of sensing.

When surface-enhanced Raman spectroscopy meets complex biofluids: A new representation strategy for reliable and comprehensive characterization.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems. RESULTS: Herein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification. SIGNIFICANCE: The proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS.

Ratiometric luminescent simultaneous sensing of aristolochic acids (I-IV) by a novel metal-organic framework and its nanowire.

Aristolochic acids (AAs), which are a group of nitrophenanthrene carboxylic acids formed by Aristolochia plant, have become an increasing serious threat to humans due to their nephrotoxicity and carcinogenicity. Fast and accurate approaches capable of simultaneous sensing of aristolochic acids (I-IV) are vital to avoid intake of such compounds. In this research, the novel ratiometric fluorescence zinc metal-organic framework and its nanowire have been prepared. The two different coordination modes (tetrahedral configuration and twisted triangular bipyramidal configuration) within zinc metal-organic framework lead to the significant double emissions. The ratiometric fluorescence approach based on nanowire provides a broader concentration range (3.00 × 10-7~1.00 × 10-4 M) and lower limit of detection (3.70 × 10-8 M) than that based on zinc metal-organic framework (1.00 × 10-6~1.00 × 10-4 M, 5.91 × 10-7 M). The RSDs of the results are in the range 1.4-3.5% (nanowire). The density functional theory calculations and UV-Vis absorption verify that the sensing mechanism is due to charge transfer and energy transfer. Excellent spiked recoveries for AAs(I-IV) in soil and water support that nanowire is competent to simultaneously detect these targets in real samples, and the proposed approach has potential as a fluorescence sensing platform for the simultaneous detection of AAs (I-IV) in complex systems.

Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO-1/GPX4 pathway.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.

Co-sensitization of Copper Indium Gallium Disulfide and Indium Sulfide on Zinc Oxide Nanostructures: Effect of Morphology in Electrochemical Carbon Dioxide Reduction.

Recent advances in nanoparticle materials can facilitate the electro-reduction of carbon dioxide (CO2) to form valuable products with high selectivity. Copper (Cu)-based electrodes are promising candidates to drive efficient and selective CO2 reduction. However, the application of Cu-based chalcopyrite semiconductors in the electrocatalytic reduction of CO2 is still limited. This study demonstrated that novel zinc oxide (ZnO)/copper indium gallium sulfide (CIGS)/indium sulfide (InS) heterojunction electrodes could be used in effective CO2 reduction for formic acid production. It has been determined that Faradaic efficiencies for formic acid production using ZnO nanowire (NW) and nanoflower (NF) structures vary due to structural and morphological differences. A ZnO NW/CIGS/InS heterojunction electrode resulted in the highest efficiency of 77.2% and 0.35 mA cm-2 of current density at a -0.24 V (vs. reversible hydrogen electrode) bias potential. Adding a ZTO intermediate layer by the spray pyrolysis method decreased the yield of formic acid and increased the yield of H2. Our work offers a new heterojunction electrode for efficient formic acid production via cost-effective and scalable CO2 reduction.

Solute carrier family 16 member 1 as a potential prognostic factor for pancreatic ductal adenocarcinoma and its influence on tumor immunity.

Background: Solute carrier family 16 member 1 (SLC16A1) serves as a biomarker in numerous types of cancer. Tumor immune infiltration has drawn increasing attention in cancer progression and treatment. The objective of our study was to explore the association between SLC16A1 and the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Methods: Data were obtained from The Cancer Genome Atlas. The xCell web tool was used to calculate the proportion of immune cells according to SLC16A1 expression. To further explore the mechanism of SLC16A1, immunity-related genes were screened from differentially expressed genes through weighted gene coexpression network analysis, examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and filtrated using univariate Cox regression and least absolute shrinkage and selection operator regression model combined correlation analysis (P<0.05). Next, CIBERSORT was used to analyze the correlation between immune cells and five important genes. SLC16A1 expression and its clinical role in pancreatic cancer was clarified via immunohistochemical staining experiments. Finally, the effects of SLC16A1 on the results of cancer immunity were evaluated by in vitro experiments. Results: SLC16A1 was overexpressed in PDAC tissues and could be an independent prognostic factor. SLC16A1 was significantly negatively correlated with overall survival and suppressed the tumor immunity of PDAC. In clinic, SLC16A1 expression was significantly positively correlated with tumor progression and poor prognosis. We also found that SLC16A1 could suppress the antitumor ability of CD8+ T cells. Conclusions: SLC16A1 is a biomarker for the prognosis of PDAC and can influence the immune environment of PDAC. These findings provide new insights into the treatment of PDAC.

VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300.

Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEAD. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 and TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. We demonstrate that, in contrast to VGLL2 and TEAD1, the fusion proteins are strong activators of TEAD-dependent transcription, and their function does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase p300 to control TEAD-mediated transcriptional and epigenetic landscapes. We showed that small molecule p300 inhibition can suppress fusion proteins-induced oncogenic transformation both in vitro and in vivo. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Individualized survival prediction and surgery recommendation for patients with glioblastoma.

Background: There is a lack of individualized evidence on surgical choices for glioblastoma (GBM) patients. Aim: This study aimed to make individualized treatment recommendations for patients with GBM and to determine the importance of demographic and tumor characteristic variables in the selection of extent of resection. Methods: We proposed Balanced Decision Ensembles (BDE) to make survival predictions and individualized treatment recommendations. We developed several DL models to counterfactually predict the individual treatment effect (ITE) of patients with GBM. We divided the patients into the recommended (Rec.) and anti-recommended groups based on whether their actual treatment was consistent with the model recommendation. Results: The BDE achieved the best recommendation effects (difference in restricted mean survival time (dRMST): 5.90; 95% confidence interval (CI), 4.40-7.39; hazard ratio (HR): 0.71; 95% CI, 0.65-0.77), followed by BITES and DeepSurv. Inverse probability treatment weighting (IPTW)-adjusted HR, IPTW-adjusted OR, natural direct effect, and control direct effect demonstrated better survival outcomes of the Rec. group. Conclusion: The ITE calculation method is crucial, as it may result in better or worse recommendations. Furthermore, the significant protective effects of machine recommendations on survival time and mortality indicate the superiority of the model for application in patients with GBM. Overall, the model identifies patients with tumors located in the right and left frontal and middle temporal lobes, as well as those with larger tumor sizes, as optimal candidates for SpTR.

Pd-Catalyzed Enantioselective Desymmetrizing 1,7-Enyne Cycloisomerization of Alkyne-Tethered Cyclopentenes.

An enantioselective Pd-catalyzed intramolecular desymmetrizing cycloisomerization of N-(cyclopent-3-en-1-yl)propiolamides has been developed by employing a new chiral phosphoramidite ligand. A series of structurally unique bridged azabicycles are achieved in moderate to excellent yields with good E/Z selectivity and high enantioselectivity. Synthetic transformations are conducted to demonstrate the practical utility of this reaction.

Research on the facile regeneration of degraded cathode materials from spent LiNi0.5Co0.2Mn0.3O2 lithium-ion batteries.

Rational reusing the waste materials in spent batteries play a key role in the sustainable development for the future lithium-ion batteries. In this work, we propose an effective and facile solid-state-calcination strategy for the recycling and regeneration of the cathode materials in spent LiNi0.5Co0.2Mn0.3O2 (NCM523) ternary lithium-ion batteries. By systemic physicochemical characterizations, the stoichiometry, phase purity and elemental composition of the regenerated material were deeply investigated. The electrochemical tests confirm that the material characteristics and performances got recovered after the regeneration process. The optimal material was proved to exhibit the excellent capacity with a discharge capacity of 147.9 mAh g-1 at 1 C and an outstanding capacity retention of 86% after 500 cycles at 1 C, which were comparable to those of commercial NCM materials.

Optimizing bioelectromethanosynthesis of CO2 and membrane fouling mitigation in MECs via in-situ biogas recirculation.

The CO2 bioelectromethanosynthesis via two-chamber microbial electrolysis cell (MEC) holds tremendous potential to solve the energy crisis and mitigate the greenhouse gas emissions. However, the membrane fouling is still a big challenge for CO2 bioelectromethanosynthesis owing to the poor proton diffusion across membrane and high inter-resistance. In this study, a new MEC bioreactor with biogas recirculation unit was designed in the cathode chamber to enhance secondary-dissolution of CO2 while mitigating the contaminant adhesion on membrane surface. Biogas recirculation improved CO2 re-dissolution, reduced concentration polarization, and facilitated the proton transmembrane diffusion. This resulted in a remarkable increase in the cathodic methane production rate from 0.4 mL/L·d to 8.5 mL/L·d. A robust syntrophic relationship between anodic organic-degrading bacteria (Firmicutes 5.29%, Bacteroidetes 25.90%, and Proteobacteria 6.08%) and cathodic methane-producing archaea (Methanobacterium 65.58%) enabled simultaneous organic degradation, high CO2 bioelectromethanosynthesis, and renewable energy storage.

Long-term prognostic value of big endothelin-1 and its combination with late gadolinium enhancement in patients with idiopathic restrictive cardiomyopathy.

BACKGROUND AND AIMS: Idiopathic restrictive cardiomyopathy (RCM) has a low incidence. This study aimed to determine the prognostic value of big endothelin-1 (ET-1) in idiopathic RCM. MATERIALS AND METHODS: We prospectively enrolled patients with idiopathic RCM from 2009 to 2017 and followed them up. The primary outcome was a composite of all-cause mortality and cardiac transplantation, and the secondary outcome was a composite of cardiac death and cardiac transplantation. RESULTS: Ninety-one patients were divided into the high big ET-1 (>0.85 pmol/L, n = 56) and low big ET-1 (≤0.85 pmol/L, n = 35) groups, and 87 of them completed the follow-up. Big ET-1 concentrations (hazard ratio: 1.756, 95 % confidence interval [CI]: 1.117-2.760) and late gadolinium enhancement (LGE) (hazard ratio: 3.851, 95 % CI: 1.238-11.981) were independent risk factors for the primary outcome. Big ET-1 concentrations (C-statistic estimation: 0.764, 95 % CI: 0.657-0.871) and the combination of LGE and big ET-1 concentrations (C-statistic estimation: 0.870, 95 % CI: 0.769-0.970) could accurately predict the 5-year transplant-free survival rate, and 0.85 pmol/L was a suitable cutoff for big ET-1. CONCLUSION: Big ET-1 and its combination with LGE may be useful to predict an adverse prognosis in patients with idiopathic RCM.

WTAP-mediated m6A modification of lncRNA Snhg1 improves myocardial ischemia-reperfusion injury via miR-361-5p/OPA1-dependent mitochondrial fusion.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m6A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m6A methylation. METHODS: Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m6A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis. RESULTS: LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m6A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels. CONCLUSION: WTAP-mediated m6A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.

Polyphenols functionalized MOF encapsulated BPQDs for synergistic photothermal/photodynamic antibacterial properties and multifunctional food preservation.

Active antibacterial materials play an important role in solving food safety problems caused by pathogen contamination. In this study, a composite active antibacterial material with the synergistic antibacterial effectiveness of photothermal, photodynamic and the surface charge of polyphenols was developed, where the multi-porous polyphenol functionalized metal-organic frameworks (ZIF-8-TA) were used as the framework carrier, and black phosphorus quantum dots (BPQDs) were used as the photosensitive source. The resulted ZIF-8-TA/PBQDs possesses excellent photothermal conversion efficiency (27.92%), photodynamic performance and surface charge, and these factors ensure the outstanding broad-spectrum antibacterial performance (100%). Multifunctional characteristics and excellent biocompatibility endow the materials with vast potential for foodstuff packaging. The results showed that the composite antibacterial film produced by doping ZIF-8-TA/PBQDs into chitosan could effectively prolong the shelf life of foodstuff compared with commercial membrane. The successful implementation of this research provides a new idea for controlling microbial contamination and developing multifunctional antibacterial materials.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

t-BuOLi promoted regioselective N-thiolation of indoles with N-arylthio phthalimide.

The selective N-thiolation of indole substrates poses a challenge due to their diminished nucleophilicity at nitrogen. Herein, we present a novel method for the thiolation of the NH group in indole derivatives by using N-arylthio phthalimide as the sulfur source, t-BuOLi as the base and MeCN as the solvent. The process was successfully conducted under transition metal catalyst-free and room temperature conditions with a high product yield and a short reaction time. The developed protocol exhibited excellent regioselectivity and broad substrate tolerance in the preparation of N-thioindoles with diverse functional groups.

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

SERSomes for metabolic phenotyping and prostate cancer diagnosis.

Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis. Since present methods are expensive, time-consuming, and still not sensitive enough, there is an urgent need for approaches that can interrogate complex biological fluids at a system-wide level. Here, we introduce hyperspectral surface-enhanced Raman spectroscopy (SERS) to profile microliters of biofluidic metabolite extraction in 15 min with a spectral set, SERSome, that can be used to describe the structures and functions of various molecules produced in the biofluid at a specific time via SERS characteristics. The metabolite differences of various biofluids, including cell culture medium and human serum, are successfully profiled, showing a diagnosis accuracy of 80.8% on the internal test set and 73% on the external validation set for prostate cancer, discovering potential biomarkers, and predicting the tissue-level pathological aggressiveness. SERSomes offer a promising methodology for metabolic phenotyping.