Selective adsorption of high ionization potential value organic pollutants in wastewater.

It is imperative to devise effective removal strategies for high ionization potential (IP) organic pollutants in wastewater as their reduced electron-donating capacity challenges the efficiency of advanced oxidation systems in degradation. Against this backdrop, leveraging the metal-based carbon material structure meticulously, we employed metal-pyridine-N (M-N-C, M=Fe, Co, and Ni) as the electron transfer bridge. This distinctive design facilitated the ordered transfer of electrons from the adsorbent surface to the surface of high IP value pollutants, acting as a "supplement" to compensate for their deficient electron-donating capability, thereby culminating in the selective adsorption of these pollutants. Furthermore, this adsorbent also demonstrated effective removal of trace emerging contaminants (2 mg/L), displayed robust resistance to various salts, exhibited reusability, and maintained stability. These findings carry substantial implications for future carbon-based material design, offering a pathway toward exceptional adsorption performance in treating water pollution.

Dynamic defects boost in-situ H2O2 piezocatalysis for water cleanup.

Creating efficient catalysts for simultaneous H2O2 generation and pollutant degradation is vital. Piezocatalytic H2O2 synthesis offers a promising alternative to traditional methods but faces challenges like sacrificial reagents, harsh conditions, and low activity. In this study, we introduce a cobalt-loaded ZnO (CZO) piezocatalyst that efficiently generates H2O2 from H2O and O2 under ultrasonic (US) treatment in ambient aqueous conditions. The catalyst demonstrates exceptional performance with ~50.9% TOC removal of phenol and in situ generation of 1.3 mM H2O2, significantly outperforming pure ZnO. Notably, the CZO piezocatalyst maintains its H2O2 generation capability even after multiple cycles, showing continuous improvement (from 1.3 mM to 1.8 mM). This is attributed to the piezoelectric electrons promoting the generation of dynamic defects under US conditions, which in turn promotes the adsorption and activation of oxygen, thereby facilitating efficient H2O2 production, as confirmed by EPR spectrometry, XPS analysis, and DFT calculations. Moreover, the CZO piezocatalysts maintain outstanding performance in pollutant degradation and H2O2 production even after long periods of inactivity, and the deactivated catalyst due to metal ion dissolution could be rejuvenated by pH adjustment, offering a sustainable solution for wastewater purification.

S100A9-TLR4 axis aggravates dry eye through the blockage of autophagy.

This research focused on how upregulation of S100A9 contributed to the pathogenesis of the dry eye disease (DED) and whether S100A9 served as a promising therapeutic target in DED. Public single-cell RNA sequencing (scRNA-seq) data of a lacrimal gland excision (LGE) murine DED model was analyzed. LGE model was established and expression of protein was measured through immunofluorescence and Western blot. DED-related signs were evaluated through tear secretion and fluorescent staining. TUNEL was performed to detect the level of cell death. Briefly, S100A9 was recognized as a highly variable gene in the DED group. LGE model was successfully established, and S100A9 showed a time-dependent increase in the corneal epithelia. Autophagic blockage was predicted by the scRNA-seq data in DED, and further verified by decrease of LC3B-II/LC3B-I and increase of SQSTM1 and p-mTOR/mTOR, while S100A9 inhibitor paquinimod (PAQ) reversed the changes. PAQ also downregulated TLR4, and inhibition of TLR4 also alleviated autophagic blockage in DED. Finally, signs of DED, chronic corneal inflammation and cell death got a remission after either inhibition of S100A9 or TLR4. In general, we deduced a S100A9-TLR4-Autophagic blockage pathway in the pathogenesis of DED.

The mechanical response and microscopic deformation mechanism of graphene foams tuned by long carbon nanotubes and short crosslinkers.

The mechanical response of graphene foams (GrFs) can be enhanced by both short crosslinkers (e.g. C-C bond) and long carbon nanotubes (CNTs) in experiments; however, the underlying mechanism is still unclear. Here, a coarse-grained molecular dynamics method is used to study the mechanical response and microscopic mechanism of GrF interconnected by both short crosslinkers and long CNTs (named CNT bonded GrF, CbGrF) under tension and compression, and the effect of the properties of graphene and CNTs on the mechanical properties of CbGrF is also investigated. Compared with short bonds, long CNTs play a reinforcing role at a larger tensile strain, leading to larger tensile strength and toughness. Under compression, the sliding and rotation of graphene sheets in CbGrF are prevented by long CNTs, resulting in higher compressive stiffness than that of pure GrFs. Furthermore, the tensile and compressive moduli increase by more than 300% with increasing thickness of graphene sheets from 1 to 9 layers; they increase by no more than 50% as the CNT bending stiffness increases and are almost independent of the stretching stiffness of CNTs. These results should be helpful for understanding the tunability of GrFs using both short and long crosslinkers and guiding the preparation of advanced GrF-based composites.

Interface damage and fracture mechanisms of a ceramic/polymer interface based on atomic-scale simulations.

The performance of ceramic/polymer composite materials is significantly affected by their internal interfaces. To reveal the intrinsic interface fracturing mechanism of ceramic/polymer interfaces, an interfacial model composed of SiO2 and polypropylene (PP) is investigated using the molecular dynamics method. The interface damage is quantified by the increase in the interface free volume and deformation of a single PP chain. As stretching speeds increase, the free volume and outflowing atoms of PP chains decrease with the same interfacial displacement, which results in the increase of the interface strength and fracture energy. At low stretching speeds, the interface damage mechanism is determined by a competition between attractions of the PP single chains from SiO2 and PP. In contrast, at higher stretching speeds, the interface fracture is more brittle and the interface strength and fracture energy are both higher owing to the smaller cavity ratio. The results of this study contribute to an in depth understanding of the fracture mechanism of ceramic/polymer interfaces in many systems.

Genetic evidence for the requirements of antroquinonol biosynthesis by Antrodia camphorata during liquid-state fermentation.

The solid-state fermentation of Antrodia camphorata could produce a variety of ubiquinone compounds, such as antroquinonol (AQ). However, AQ is hardly synthesized during liquid-state fermentation (LSF). To investigates the mechanism of AQ synthesis, three precursors (ubiquinone 0 UQ0, farnesol and farnesyl diphosphate FPP) were added in LSF. The results showed that UQ0 successfully induced AQ production; however, farnesol and FPP could not induce AQ synthesis. The precursor that restricts the synthesis of AQ is the quinone ring, not the isoprene side chain. Then, the Agrobacterium-mediated transformation system of A. camphorata was established and the genes for quinone ring modification (coq2-6) and isoprene synthesis (HMGR, fps) were overexpressed. The results showed that overexpression of genes for isoprene side chain synthesis could not increase the yield of AQ, but overexpression of coq2 and coq5 could significantly increase AQ production. This is consistent with the results of the experiment of precursors. It indicated that the A. camphorata lack the ability to modify the quinone ring of AQ during LSF. Of the modification steps, prenylation of UQ0 is the key step of AQ biosynthesis. The result will help us to understand the genetic evidence for the requirements of AQ biosynthesis in A. camphorata.

Quantitative visual pathway abnormalities predict visual field defects in patients with pituitary adenomas: a diffusion spectrum imaging study.

OBJECTIVES: This study was to investigate clinical applicability of diffusion spectrum imaging (DSI) for quantitative detection of visual pathway abnormalities to predict the degree of visual field defects (VFD) in patients with pituitary adenomas. METHODS: Sixty-five patients with pituitary adenomas and 33 healthy controls underwent conventional MRI and DSI scanning that allowed high-angular-resolution fiber tracking. Optic chiasmal compression and VFD were confirmed in all patients via radiological and neuro-ophthalmological examinations. Quantitative assessments of chiasmal lift, VFD, and DSI parameters from the optic nerve, optic tract, and optic radiation were performed. Group comparisons and correlation analyses were conducted in patients and controls. Using the 5-fold cross-validation method, the support vector machine classifiers were constructed to predict the degree of visual defects. RESULTS: The mean values of quantitative anisotropy and generalized fractional anisotropy in optic nerve and optic tract showed significant differences between patients and controls (p < 0.05). These parameters were also significantly correlated with the chiasmal lift distance and degree of visual defects (p < 0.05). All patients were divided into mild (n = 42) and severe (n = 23) VFD groups, using the mean deviation value of -8 dB as the threshold. The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe visual defects. CONCLUSIONS: Using high-angular-resolution fiber tracking, DSI may provide quantitative information to detect visual pathway abnormalities and be a potential diagnostic tool for determining the degree of visual field defects in pituitary adenomas. KEY POINTS: • Abnormal QA and GFA values of optic nerve and optic tract in adenoma patients • Close relationship between DSI parameters and VFD degree in adenoma patients • The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe VFD.

Physiological and histopathological effects of electroporation pulse on stomach of rats.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique with widespread potential, especially for cancer treatment. Although the safety and efficacy of IRE for gastric tissue ablation have been demonstrated, there is a gap of knowledge regarding the effect of electroporation pulse (EP) on the physiology and histopathology of the stomach. This study applied EP to the stomach of healthy rats and investigated the digestive function, serum marker levels, and gastric tissue structure of EP-treated rats. METHODS: Ninety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulse (500 V, 99 pluses, 1 Hz, 100 µs) was delivered to the stomachs of rats using a tweezer-style round electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate the digestive function. Serum marker levels were determined using ELISA. Haematoxylin-eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis. RESULTS: No  significant effect on gastric emptying or secretion was found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, serum TNF-α and IL-1ß levels temporarily changed during the acute phase but returned to baseline within 28 days. Moreover, histopathological analysis revealed that cell death occurred immediately post-EP in the ablation area, whereas the gastric wall scaffold in the ablation region remained intact post-EP. CONCLUSIONS: This study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for more comprehensive applications of this technique.

Magnetic anchoring and guidance-assisted endoscopic irreversible electroporation for gastric mucosal ablation: a preclinical study in canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility, safety, and efficacy of magnetic anchoring and guidance-assisted endoscopic irreversible electroporation (MAG-IRE) for gastric mucosal ablation. METHODS: A catheter-based, donut-like, and MAG-assisted electrode was developed. MAG-IRE for gastric mucosal ablation was performed in eight beagle canines. The parameters of one set of IRE was 500 V voltage, 100 µs pulse duration, and 99 pulses. The MAG time, operation time, success rate, and adverse events were measured. Endoscopic examination was performed from 30 min to 28 days post-IRE. Full-thickness gastric tissue was harvested by wedge biopsy for histopathological analysis. RESULTS: 30 (93.75%) of the 32 lesions were successfully ablated by MAG-IRE. The median MAG time was 300 s (IQR 120-422.5 s), and the median operation time was 491.5 s (IQR 358.3-632.5 s). No adverse events occurred. Ulceration was observed, starting from 3 days post-IRE. The mucosa healed 14 to 28 days post-IRE. Hematoxylin-Eosin (H&E) staining showed inflammatory infiltration, edema, and congestion in the ablated mucosa. Masson's Trichrome staining showed that the gastric wall and blood vessels in the ablation area were intact. TUNEL assay showed diffuse positive cells in ablated mucosa as early as 30 min post-IRE. CONCLUSIONS: MAG-IRE for gastric mucosal ablation is feasible, safe, and effective. It can be a potential therapeutic option for minimally invasive treatment of gastric neoplasm.

Constructing an Acidic Microenvironment by MoS2 in Heterogeneous Fenton Reaction for Pollutant Control.

Although Fenton or Fenton-like reactions have been widely used in the environment, biology, life science, and other fields, the sharp decrease in their activity under macroneutral conditions is still a large problem. This study reports a MoS2 cocatalytic heterogeneous Fenton (CoFe2 O4 /MoS2 ) system capable of sustainably degrading organic pollutants, such as phenol, in a macroneutral buffer solution. An acidic microenvironment in the slipping plane of CoFe2 O4 is successfully constructed by chemically bonding with MoS2 . This microenvironment is not affected by the surrounding pH, which ensures the stable circulation of Fe3+ /Fe2+ on the surface of CoFe2 O4 /MoS2 under neutral or even alkaline conditions. Additionally, CoFe2 O4 /MoS2 always exposes "fresh" active sites for the decomposition of H2 O2 and the generation of 1 O2 , effectively inhibiting the production of iron sludge and enhancing the remediation of organic pollutants, even in actual wastewater. This work not only experimentally verifies the existence of an acidic microenvironment on the surface of heterogeneous catalysts for the first time, but also eliminates the pH limitation of the Fenton reaction for pollutant remediation, thereby expanding the applicability of Fenton technology.

CT Imaging and Differential Diagnosis of COVID-19.

Since the beginning of 2020, coronavirus disease 2019 (COVID-19) has spread throughout China. This study explains the findings from lung computed tomography images of some patients with COVID-19 treated in this medical institution and discusses the difference between COVID-19 and other lung diseases.

MicroRNA-744 Inhibits Proliferation of Bronchial Epithelial Cells by Regulating Smad3 Pathway via Targeting Transforming Growth Factor-ß1 (TGF-ß1) in Severe Asthma.

BACKGROUND Bronchial epithelial cells proliferation plays a pivotal role in airway remodeling in children with severe asthma. MicroRNAs (miRNAs) have gained great attention for many diseases, including asthma. The purpose of this study was to explore the mechanisms that underlie miR-744 modulating bronchial epithelial cells proliferation in severe asthma in children. MATERIAL AND METHODS Bronchial epithelial cells were isolated from bronchial biopsies of normal controls and asthmatic subjects. miR-744 and transforming growth factor-ß1 (TGF-ß1) expressions were measured by quantitative reverse transcription PCR (qRT-PCR). Proliferating cell nuclear antigen (PCNA), phosphorylation or total of mothers against decapentaplegic homolog3 (Smad3) and production of Smad anchor for receptor activation (SARA) were measured via Western blot analysis. A link between miR-744 and TGF-ß1 was probed by luciferase activity and RNA immunoprecipitation. Cell proliferation was evaluated using the Cell Proliferation Assay Kit. RESULTS Severe asthma showed a significantly elevated cell proliferation rate and reduced abundance of miR-744, which in turn inhibited cell proliferation of bronchial epithelial cells. In particular, TGF-ß1 might be a candidate target of miR-744, and enrichment of miR-744 lowered the expression of TGF-ß1 at mRNA and protein levels. Indeed, overexpression of miR-744 lowered the proliferation rate of bronchial epithelial cells via driving TGF-ß1. Moreover, addition of miR-744 limited phosphorylation of Smad3 but reversed SARA protein abundance by regulating TGF-ß1. CONCLUSIONS The presence of miR-744 repressed bronchial epithelial cells proliferation through mediating the Smad3 pathway by modulating TGF-ß1, providing a promising therapeutic approach for epithelial function in severe asthma.

MFG-E8/integrin ß3 signaling contributes to airway inflammation response and airway remodeling in an ovalbumin-induced murine model of asthma.

Asthma is the most common chronic childhood disease worldwide, characterized by airway remodeling and chronic inflammation, orchestrated primarily by Th2 cytokines. The aim of the current study was to explore the influences of milk fat globule epidermal growth factor 8 (MFG-E8)/integrin ß3 signaling involved in airway inflammation and remodeling in asthma. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. The levels of MFG-E8 expression were declined markedly in the OVA-induced allergy murine model. In addition, administration of MFG-E8 strongly reduced the accumulation of T-helper type 2 (Th2)-associated cytokines (such as interleukin-4, -5, and -13) as well as chemokine CCL11 (eotaxin) in bronchoalveolar lavage fluid and tissues in the OVA-sensitized mice. Moreover, MFG-E8 remarkably repressed the total immunoglobulin E and OVA-specific immunoglobulin E in serum in OVA-challenged mice. Meanwhile, treatment with recombinant murine MFG-E8 noticeably prevented inflammatory cell infiltration into the airways, as showed by a marked decrease in the numbers of total immune cells, eosinophils, neutrophils, macrophages, and lymphocytes in the bronchoalveolar lavage fluid in response to OVA challenge. Importantly, MFG-E8 apparently alleviated OVA-driven airway remodeling, which were evidenced by declined secretion of important mediators of airway remodeling, including transforming growth factor-ß1, matrix metalloproteinase 9, ADAM8, and vascular endothelial growth factor, and reduced airway collagen deposition and inhibited goblet cell hyperplasia in OVA-induced asthma in mice. Mechanistically, integrin 3 contributes to the protective effect of MFG-E8 in inhibiting airway inflammation and remodeling in OVA-driven features of allergic asthma. Overall, MFG-E8, as a candidate molecule to evaluate airway inflammation and remodeling, could be a potential target for the management and prevention of asthma exacerbations, suggesting that MFG-E8/integrin ß3 signaling may serve as a promising therapeutic agent for childhood asthma.

Long non-coding RNA (LncRNA) non-coding RNA activated by DNA damage (NORAD) knockdown alleviates airway remodeling in asthma via regulating miR-410-3p/RCC2 and inhibiting Wnt/ß-catenin pathway.

Background: Asthma is a chronic inflammatory disorder with high prevalence in childhood. Airway remodeling, an important structural change of the airways, is resulted from epithelial-mesenchymal transition. Long non-coding RNA non-coding RNA activated by DNA damage (NORAD) has been found to promote epithelial-mesenchymal transition in multiple cancers. This study aimed to analyze the role of NORAD in asthma, mainly focusing on epithelial-mesenchymal transition-mediated airway remodeling, and further explored the NORAD-miRNA-mRNA network. Methods: NORAD expression was analyzed in transforming growth factor-ß1-induced BEAS-2B human bronchial epithelial cells and ovalbumin-challenged asthmatic mice. The influences of NORAD on the epithelial-mesenchymal transition characteristics and Wnt/ß-catenin pathway activation were analyzed in vitro. The interactions between NORAD and miR-410-3p as well as miR-410-3p and regulator of chromosome condensation 2 were detected by dual-luciferase reporter assay and RNA pull-down assay. Rescue experiments using miR-410-3p antagonist and chromosome condensation 2 overexpression were used to confirm the mechanism of NORAD. Additionally, the role and mechanism of NORAD were further evaluated in asthmatic mice. Results: NORAD expression was elevated in both asthmatic models. Knockdown of NORAD impeded spindle-like morphology changes, elevated E-cadherin expression, decreased N-cadherin expression, suppressed cell migration, and inactivated the Wnt/ß-catenin pathway in transforming growth factor-ß1-stimulated BEAS-2B cells. NORAD acted as a sponge of miR-410-3p to regulate chromosome condensation 2 expression. Rescue assays demonstrated that silencing of NORAD ameliorated transforming growth factor-ß1-induced EMT via miR-410-3p/chromosome condensation 2/Wnt/ß-catenin axis. In vivo, knockdown of NORAD led to the reduction of inflammatory cell infiltration and collagen deposition, suppression of IL-4, IL-13, transforming growth factor-ß1 and immunoglobulin E production, decreasing of N-cadherin, chromosome condensation 2, ß-catenin and c-Myc expression, but increasing of E-cadherin and miR-410-3p expression. Conclusions: Silencing of NORAD alleviated epithelial-mesenchymal transition-mediated airway remodeling in asthma via mediating miR-410-3p/chromosome condensation 2/Wnt/ß-catenin pathway.

Circadian disruption reduces MUC4 expression via the clock molecule BMAL1 during dry eye development.

Circadian disruption, as a result of shiftwork, jet lag, and other lifestyle factors, is a common public health problem associated with a wide range of diseases, such as metabolic disorders, neurodegenerative diseases, and cancer. In the present study, we established a chronic jet lag model using a time shift method every 3 days and assessed the effects of circadian disruption on ocular surface homeostasis. Our results indicated that jet lag increased corneal epithelial defects, cell apoptosis, and proinflammatory cytokine expression. However, the volume of tear secretion and the number of conjunctival goblet cells did not significantly change after 30 days of jet lag. Moreover, further analysis of the pathogenic mechanism using RNA sequencing revealed that jet lag caused corneal transmembrane mucin deficiency, specifically MUC4 deficiency. The crucial role of MUC4 in pathogenic progression was demonstrated by the protection of corneal epithelial cells and the inhibition of inflammatory activation following MUC4 replenishment. Unexpectedly, genetic ablation of BMAL1 in mice caused MUC4 deficiency and dry eye disease. The underlying mechanism was revealed in cultured human corneal epithelial cells in vitro, where BMAL1 silencing reduced MUC4 expression, and BMAL1 overexpression increased MUC4 expression. Furthermore, melatonin, a circadian rhythm restorer, had a therapeutic effect on jet lag-induced dry eye by restoring the expression of BMAL1, which upregulated MUC4. Thus, we generated a novel dry eye mouse model induced by circadian disruption, elucidated the underlying mechanism, and identified a potential clinical treatment.

Design and synthesis of Thieno[3, 2-b]pyridinone derivatives exhibiting potent activities against Mycobacterium tuberculosis in vivo by targeting Enoyl-ACP reductase.

In this study, a series of novel thieno [3, 2-b]pyridinone derivatives were designed and synthesized using a scaffold hopping strategy. Six compounds showed potent anti-mycobacterial activity (minimum inhibitory concentration (MIC) ≤ 1 µg/mL) against Mycobacterium tuberculosis (Mtb) UAlRa. Compound 6c displayed good activity against Mtb UAlRv (MIC = 0.5-1 µg/mL). Compounds 6c and 6i also showed activity against Mtb UAlRa in macrophages and exhibited low cytotoxicity against LO-2 cells. The selected compounds displayed a narrow antibacterial spectrum, with no activity against representative Gram-positive, Gram-negative bacteria, as well as fungi. Furthermore, compound 6c demonstrated favorable oral pharmacokinetic properties with a T1/2 value of 47.99 h and exhibited good in vivo activity in an acute mouse model of tuberculosis (TB). The target of compound 6c was identified as a NADH-dependent enoyl-acyl carrier protein reductase (InhA) by genome sequencing of spontaneously compound 6c-resistant Mtb mutants, indicating that compound 6c may not require activation and can directly target InhA. In vitro antimicrobial assays against a recombinant M. smegmatis overexpressing the Mtb-InhA, along with InhA inhibition assays, confirmed that InhA is the target of thieno [3, 2-b]pyridinone derivatives. Overall, this study identified thieno [3, 2-b]pyridinone scaffold as a novel chemotype that is promising for the development of anti-TB agents.

Characterization and Simulation of Nanoscale Catastrophic Failure of Metal/Ceramic Interfaces.

The catastrophic failure of metal/ceramic interfaces is a complex process involving the energy transfer between accumulated elastic strain energy and many types of energy dissipation. To quantify the contribution of bulk and interface cohesive energy to the interface cleavage fracture without global plastic deformation, we characterized the quasi-static fracture process of both coherent and semi-coherent fcc-metal/MgO(001) interface systems using a spring series model and molecular static simulations. Our results show that the theoretical catastrophe point and spring-back length by the spring series model are basically consistent with the simulation results of the coherent interface systems. For defect interfaces with misfit dislocations, atomistic simulations revealed an obvious interface weakening effect in terms of reduced tensile strength and work of adhesion. As the model thickness increases, the tensile failure behaviors show significant scale effects-thick models tend to catastrophic failure with abrupt stress drop and obvious spring-back phenomenon. This work provides insight into the origin of catastrophic failure at metal/ceramic interfaces, which highlights a pathway by combining the material and structure design to improve the reliability of layered metal-ceramic composites.

Dynamic analysis of microbial communities and flavor properties in Merlot wines produced from inoculation and spontaneous fermentation.

The microbiota is of great importance in forming flavor compounds and improving sensory characteristics during wine fermentation. Understanding microbial succession is critical for controlling its contribution to wine flavor with predictable sensory quality. In this study, microbial community composition and characteristic flavor compounds were identified during the inoculation fermentation (IF) and spontaneous fermentation (SF) to provide a basis for exploring the relationship between these microorganisms and volatile components. The results demonstrated that SF had higher fungal community diversity and lower bacterial community diversity than IF. Eleven (11) fungal and 10 bacterial genera (relative abundance > 0.1 %) were considered beneficial microbiota. Saccharomyces, Hanseniaspora, and Alternaria were the leading fungal genera in SF. Massilia, Nesterenkonia, and Halomonas were the predominant bacteria in IF, while Tatumella and Ochrobactrum were mainly from SF. In addition, the microbial community composition was reshaped via correlational analysis between microbiota succession and physicochemical properties, mainly attributed to the changes in environmental factors during fermentation. The SF wines had more aromatic higher alcohols, acetate esters, and terpenes. Also, the sensory evaluation showed that the SF wines were characterized by more fruity, floral, intense, and typical aromas. The associations between the microbial community and the volatile components indicated that the dominant species largely determined the characteristic flavor compounds during fermentation.

NPC1 Deficiency Contributes to Autophagy-Dependent Ferritinophagy in HEI-OC1 Auditory Cells.

Niemann-Pick type C disease (NPCD) is a rare genetic syndrome characterized by cholesterol accumulation in multiple organelles. NPCD is mainly caused by gene deficiency of NPC intracellular cholesterol transporter 1 (NPC1). It has been reported that some of the NPCD patients exhibit clinical features of progressive hearing loss at high frequency and iron disorder, but the underlying relationship is unknown. A recent study has reported that ferroptosis contributes to the impairment of cochlear hair cells that are related to sensory hearing. In this study, we generated NPC1-deficient HEI-OC1 cells to show the effect of NPC1 deficiency on cochlear outer hair cells. We found that NPC1 deficiency enhances autophagy-dependent ferritinophagy to release Fe (II). Our work provides important insights into the effect of NPC1 deficiency in auditory cells, indicating that it induces ferroptosis and results in hearing loss.