Ultrathin zigzag-surface copper nanowire assembled hierarchical microspheres to enhance oxygen reduction catalysis.

Ultrathin catalysts predominantly expose surface active atoms to deliver promising applications in oxygen reduction reactions (ORRs). However, they are commonly synthesized at high reaction temperatures, with tedious chemical routes involved. Herein, we report a low temperature (273 K) electric field driven route to synthesize zigzag-surface ultrathin copper nanowires. Interestingly, the ultrathin copper nanowires assemble into three-dimensional microspheres, which exhibit hydrophobic-aerophilic features, eventually resulting in good ORR activities. The aerophilicity and hydrophobicity of copper nanowires are related to their Cu2O active sites and hierarchical protuberances, respectively. Our findings open a new door to grow ultrathin catalysts for new energy storage systems.

Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions.

In oxygen (O2)-controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O2 tension experienced by cells (i.e., pericellular O2). However, it is discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to cellular O2 consumption. A reaction-diffusion model is developed to predict pericellular O2 tension a priori, demonstrating that the effect of cellular O2 consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O2 tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia-inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O2 tension in cell culture incubators is insufficient to regulate O2 in cell culture, thus introducing the concept of pericellular O2-controlled cell culture.

An open auscultation dataset for machine learning-based respiratory diagnosis studies.

Machine learning enabled auscultating diagnosis can provide promising solutions especially for prescreening purposes. The bottleneck for its potential success is that high-quality datasets for training are still scarce. An open auscultation dataset that consists of samples and annotations from patients and healthy individuals is established in this work for the respiratory diagnosis studies with machine learning, which is of both scientific importance and practical potential. A machine learning approach is examined to showcase the use of this new dataset for lung sound classifications with different diseases. The open dataset is available to the public online.

Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.

Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and tumorigenesis in vivo remains unclear. We previously generated Rev1-overexpressing (Rev1-Tg) mice and reported that they exhibited a significantly increased incidence of intestinal adenoma and thymic lymphoma (TL) after N-methyl-N-nitrosourea (MNU) treatment. In this study, we investigated mutagenesis of MNU-induced TL tumorigenesis in wild-type (WT) and Rev1-Tg mice using diverse approaches, including whole-exome sequencing (WES). In Rev1-Tg TLs, the mutation frequency was higher than that in WT TL in most cases. However, no difference in the number of nonsynonymous mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) genes was observed, and mutations involved in Notch1 and MAPK signaling were similarly detected in both TLs. Mutational signature analysis of WT and Rev1-Tg TLs revealed cosine similarity with COSMIC mutational SBS5 (aging-related) and SBS11 (alkylation-related). Interestingly, the total number of mutations, but not the genotypes of WT and Rev1-Tg, was positively correlated with the relative contribution of SBS5 in individual TLs, suggesting that genetic instability could be accelerated in Rev1-Tg TLs. Finally, we demonstrated that preleukemic cells could be detected earlier in Rev1-Tg mice than in WT mice, following MNU treatment. In conclusion, Rev1 overexpression accelerates mutagenesis and increases the incidence of MNU-induced TL by shortening the latency period, which may be associated with more frequent DNA damage-induced genetic instability.

Multi-Objective Optimization for Rapid Identification of Novel Compound Metals for Interconnect Applications.

Interconnect materials play the critical role of routing energy and information in integrated circuits. However, established bulk conductors, such as copper, perform poorly when scaled down beyond 10 nm, limiting the scalability of logic devices. Here, a multi-objective search is developed, combined with first-principles calculations, to rapidly screen over 15,000 materials and discover new interconnect candidates. This approach simultaneously optimizes the bulk electronic conductivity, surface scattering time, and chemical stability using physically motivated surrogate properties accessible from materials databases. Promising local interconnects are identified that have the potential to outperform ruthenium, the current state-of-the-art post-Cu material, and also semi-global interconnects with potentially large skin depths at the GHz operation frequency. The approach is validated on one of the identified candidates, CoPt, using both ab initio and experimental transport studies, showcasing its potential to supplant Ru and Cu for future local interconnects.

The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study.

Introduction: The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods: The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results: Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions: Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration: http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.

Subsequent surgical treatment or maintenance immunotherapy in stage III lung cancer patients achieving a favorable response following neoadjuvant immunotherapy: A matched retrospective cohort study from the surgical perspective.

BACKGROUND: Current treatment strategies for advanced non-small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy. METHODS: We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long-term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores. RESULTS: In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1- and 3-year overall survival (OS) and progression-free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long-term prognosis of patients (PFS and OS) but could impact their perioperative experience. CONCLUSION: Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2-4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC.

Chinese olive (Canarium album Rauesch.): a critical review on its nutritional value, phytochemical composition, health benefits, and practical applications.

Chinese olive is a popular fruit with a long history of cultivation and consumption. As a fruit with edible, nutritional, and even medicinal value, the Chinese olive has attracted increased interest from both nutrition researchers and health-conscious consumers. Chinese olive is a rich nutrient source, including essential and non-essential amino acids, various fatty acids, organic acids, vitamins, microelements, and high-quality dietary fibers. It is also an important natural source of phytochemicals such as phenolic acids, flavonoids, phenylpropanoids, and other bioactive compounds. The nutritional and phytochemical compounds obtained from the Chinese olive exhibit unique and potent biological activities, explaining its various benefits to human health, including anti-Helicobacter pylori, anti-influenza, anti-diabetes, anti-inflammatory, anti-tumor effects, among others. This review focuses on recent studies on Chinese olives and aims to summarize the major advances in their nutritional value, phytochemical composition, health benefits, and practical applications. It provides a reference for further research on Chinese olives and their properties and the development of novel functional products.

Monolithic 3D integration of 2D materials-based electronics towards ultimate edge computing solutions.

Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.

Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions.

Oxygen (O2) tension plays a key role in tissue function and pathophysiology. O2-controlled cell culture, in which the O2 concentration in an incubator's gas phase is controlled, is an indispensable tool to study the role of O2 in vivo. For this technique, it is presumed that the incubator setpoint is equal to the O2 tension that cells experience (i.e., pericellular O2). We discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0.0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to anoxic exposure followed by rapid reoxygenation. To better understand the relationship between incubator gas phase and pericellular O2 tensions, we developed a reaction-diffusion model that predicts pericellular O2 tension a priori. This model revealed that the effect of cellular O2 consumption is greatest in smaller volume culture vessels (e.g., 96-well plate). By controlling pericellular O2 tension in cell culture, we discovered that MCF7 cells have stronger glycolytic and glutamine metabolism responses in anoxia vs. hypoxia. MCF7 also expressed higher levels of HIF2A, CD73, NDUFA4L2, etc. and lower levels of HIF1A, CA9, VEGFA, etc. in response to hypoxia vs. anoxia. Proteomics revealed that 4T1 cells had an upregulated epithelial-to-mesenchymal transition (EMT) response and downregulated reactive oxygen species (ROS) management, glycolysis, and fatty acid metabolism pathways in hypoxia vs. anoxia. Collectively, these results reveal that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable to model hypoxia. We demonstrate that controlling atmospheric O2 tension in cell culture incubators is insufficient to control O2 in cell culture and introduce the concept of pericellular O2-controlled cell culture.

Exploration of Perturbed Liver Fibrosis-Related Factors and Collagen Type I in Animal Model of Non-Alcoholic Fatty Liver Disease.

To determine their involvement in the onset of the disease, we investigated the changing levels of liver fibrosis-related proteins, namely, type-I collagen, α-smooth muscle actin (α-SMA), and transforming growth factor ß1 and ß3 (TGF-ß1, ß3). The four groups of Sprague-Dawley (SD) rats were involved in the study, namely, (i) normal control group, (ii) high-fat diet group (HFD), (iii) carbon tetrachloride (CCl4) group, and (iv) NAFLD group (animal model) which were chosen at random. The NAFLD model received HFD combined with subcutaneous injection of small doses of CCl4. Histopathological examination confirmed extent of liver fibrosis, while other immunological and molecular methods were used to evaluate expression and distribution of α-SMA, type I collagen TGF-ß1 and TGF-ß3, at both m-RNA and protein levels. In contrast to the normal control group, the NAFLD group showed moderately elevated expressions of TGF-ß1, α-SMA, and type I collagen, which was proportional on temporal scale of NAFLD persistence in the model (P < 0.05). In the early phage of NAFLD, enhancement in the mRNA transcripts and, henceforth, protein expression of TGF-ß3 was observed. However, these were found to be downregulated in case of liver fibrosis (P < 0.05). This NAFLD rat model shows the histopathologic changes of human NAFLD and is suitable for the study of NAFLD pathogenesis. These findings suggest that type I collagen and the liver fibrosis-related factors TGF- ß1, TGF- ß3, and α-SMA may be significant contributors to NAFLD. Although NAFLD model is previously demonstrated by other researchers, our study is novel in terms of exploration of involvement of fibrosis-related factors and in particular aforementioned proteins at the early stage of NAFLD vis-à-vis dynamics of type-I collagen distribution.

Tracing microplastics in rural drinking water in Chongqing, China: Their presence and pathways from source to tap.

Despite the significant attention given to microplastics in urban areas, our understanding of microplastics in rural drinking water systems is still limited. To address this knowledge gap, we investigated the presence and pathways of microplastics in rural drinking water system, including reservoir, water treatment plant (WTP), and tap water of end-users. The results showed that the treatment processes in the WTP, including coagulation-sedimentation, sand-granular active carbon filtration, and ultrafiltration, completely removed microplastics from the influent. However, the microplastic abundance increased during pipe transport from WTP to residents' homes, resulting in the presence of 1.4 particles/L of microplastics in tap water. This microplastic increase was also observed during the transportation from the reservoir to the WTP, suggesting that the plastic pipe network is a key source of microplastics in the drinking water system. The main types of polymers were PET, PP, and PE, and plastic breakdown, atmospheric deposition, and surface runoff were considered as their potential sources. Furthermore, this study estimated that rural residents could ingest up to 1034 microplastics annually by drinking 2 L of tap water every day. Overall, these findings provide essential data and preliminary insights into the fate of microplastics in rural drinking water systems.

Immunotherapy for Recurrent Glioma-From Bench to Bedside.

Glioma is the most aggressive malignant tumor of the central nervous system, and most patients suffer from a recurrence. Unfortunately, recurrent glioma often becomes resistant to established chemotherapy and radiotherapy treatments. Immunotherapy, a rapidly developing anti-tumor therapy, has shown a potential value in treating recurrent glioma. Multiple immune strategies have been explored. The most-used ones are immune checkpoint blockade (ICB) antibodies, which are barely effective in monotherapy. However, when combined with other immunotherapy, especially with anti-angiogenesis antibodies, ICB has shown encouraging efficacy and enhanced anti-tumor immune response. Oncolytic viruses and CAR-T therapies have shown promising results in recurrent glioma through multiple mechanisms. Vaccination strategies and immune-cell-based immunotherapies are promising in some subgroups of patients, and multiple new tumor antigenic targets have been discovered. In this review, we discuss current applicable immunotherapies and related mechanisms for recurrent glioma, focusing on multiple preclinical models and clinical trials in the last 5 years. Through reviewing the current combination of immune strategies, we would like to provide substantive thoughts for further novel therapeutic regimes treating recurrent glioma.

Achieving near-perfect light absorption in atomically thin transition metal dichalcogenides through band nesting.

Near-perfect light absorbers (NPLAs), with absorbance, [Formula: see text], of at least 99%, have a wide range of applications ranging from energy and sensing devices to stealth technologies and secure communications. Previous work on NPLAs has mainly relied upon plasmonic structures or patterned metasurfaces, which require complex nanolithography, limiting their practical applications, particularly for large-area platforms. Here, we use the exceptional band nesting effect in TMDs, combined with a Salisbury screen geometry, to demonstrate NPLAs using only two or three uniform atomic layers of transition metal dichalcogenides (TMDs). The key innovation in our design, verified using theoretical calculations, is to stack monolayer TMDs in such a way as to minimize their interlayer coupling, thus preserving their strong band nesting properties. We experimentally demonstrate two feasible routes to controlling the interlayer coupling: twisted TMD bi-layers and TMD/buffer layer/TMD tri-layer heterostructures. Using these approaches, we demonstrate room-temperature values of [Formula: see text]=95% at λ=2.8 eV with theoretically predicted values as high as 99%. Moreover, the chemical variety of TMDs allows us to design NPLAs covering the entire visible range, paving the way for efficient atomically-thin optoelectronics.

HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.

The 70 kDa heat shock proteins (HSP70s) are a group of highly conserved and inducible heat shock proteins. One of the main functions of HSP70s is to act as molecular chaperones that are involved in a large variety of cellular protein folding and remodeling processes. HSP70s are found to be over-expressed and may serve as prognostic markers in many types of cancers. HSP70s are also involved in most of the molecular processes of cancer hallmarks as well as the growth and survival of cancer cells. In fact, many effects of HSP70s on cancer cells are not only related to their chaperone activities but rather to their roles in regulating cancer cell signaling. Therefore, a number of drugs directly or indirectly targeting HSP70s, and their co-chaperones have been developed aiming to treat cancer. In this review, we summarized HSP70-related cancer signaling pathways and corresponding key proteins regulated by the family of HSP70s. In addition, we also summarized various treatment approaches and progress of anti-tumor therapy based on targeting HSP70 family proteins.

Heat Shock Proteins in Non-Small-Cell Lung Cancer-Functional Mechanism.

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, which has the highest cancer-related mortality worldwide. Regardless of the therapeutic effects of chemotherapy or targeted therapy, drug resistance will occur after 1 year. Heat shock proteins (HSPs) are a class of molecular chaperones participated in protein stability and multiple intracellular signaling pathways. It has been widely reported that HSPs family is over expressed in non-small cell lung cancer, and these molecules are also associated with protein stability and multiple intracellular signaling pathways. The effect of chemotherapy drugs or targeted drugs on cancer cells is usually to induce apoptosis. It is necessary to explore the interaction between heat shock protein family and apoptosis pathway in NSCLC. Here we provide a brief review of how HSPs affect the apoptotic pathway in NSCLC.

Mechanisms of polystyrene nanoplastics adsorption onto activated carbon modified by ZnCl2.

In this study, the adsorption capacity of activated carbon was enhanced after zinc chloride activation. The effects of pore filling, n-π and π-π interaction and electrostatic interaction on the adsorption of polystyrene nanoplastics (PSNPs) by activated carbon were determined by SEM, BET, Raman spectrum, FTIR and surface Zeta potential. Pore filling, electrostatic interaction and n-π interaction and π-π interaction all played a role in the adsorption process, but n-π interaction and π-π interaction was not the decisive role. The adsorption of PSNPs on activated carbon conformed to the pseudo-second-order kinetics and Langmuir isotherm, and there was spontaneous physical adsorption process driven by entropy in the adsorption process. Further, the effects of common anions SO42-, HCO3-, and Cl- in water on the adsorption of PSNPs by activated carbon were investigated, and the results showed that the presence of these ions could increase the adsorption capacity to some extent. ZCAC has a stable adsorption capacity under tap water, but its adsorption capacity is affected under lake water. In addition, the reuse of activated carbon was investugated, and the adsorption capacity of activated carbon was fully recovered after high temperature calcination. This study provided a direction for materials modification of adsorbed nanoplastics and a feasible method for removal of nanoplastics in drinking water treatment plants.

Artificial intelligence empowers the second-observer strategy for colonoscopy: a randomized clinical trial.

Background: In colonoscopy screening for colorectal cancer, human vision limitations may lead to higher miss rate of lesions; artificial intelligence (AI) assistance has been demonstrated to improve polyp detection. However, there still lacks direct evidence to demonstrate whether AI is superior to trainees or experienced nurses as a second observer to increase adenoma detection during colonoscopy. In this study, we aimed to compare the effectiveness of assistance from AI and human observer during colonoscopy. Methods: A prospective multicenter randomized study was conducted from 2 September 2019 to 29 May 2020 at four endoscopy centers in China. Eligible patients were randomized to either computer-aided detection (CADe)-assisted group or observer-assisted group. The primary outcome was adenoma per colonoscopy (APC). Secondary outcomes included polyp per colonoscopy (PPC), adenoma detection rate (ADR), and polyp detection rate (PDR). We compared continuous variables and categorical variables by using R studio (version 3.4.4). Results: A total of 1,261 (636 in the CADe-assisted group and 625 in the observer-assisted group) eligible patients were analysed. APC (0.42 vs 0.35, P = 0.034), PPC (1.13 vs 0.81, P < 0.001), PDR (47.5% vs 37.4%, P < 0.001), ADR (25.8% vs 24.0%, P = 0.464), the number of detected sessile polyps (683 vs 464, P < 0.001), and sessile adenomas (244 vs 182, P = 0.005) were significantly higher in the CADe-assisted group than in the observer-assisted group. False detections of the CADe system were lower than those of the human observer (122 vs 191, P < 0.001). Conclusions: Compared with the human observer, the CADe system may improve the clinical outcome of colonoscopy and reduce disturbance to routine practice (Chictr.org.cn No.: ChiCTR1900025235).

Superior Quality Low-Temperature Growth of Three-Dimensional Semiconductors Using Intermediate Two-Dimensional Layers.

The low-temperature growth of materials that support high-performance devices is crucial for advanced semiconductor technologies such as integrated circuits built using monolithic three-dimensional (3D) integration and flexible electronics. However, low growth temperature prohibits sufficient atomic diffusion and directly leads to poor material quality, imposing severe challenges that limit device performance. Here, we demonstrate superior quality growth of 3D semiconductors at growth temperatures reduced by >200 °C by using two-dimensional (2D) materials as intermediate layers to optimize the potential energy barrier for adatom diffusion. We reveal the benefits of maintaining, but reducing, the potential field through the 2D layer, which coupled with the inert surface of the 2D material lowers the kinetic barriers, enabling long-distance atomic diffusion and enhanced material quality at lower growth temperatures. As model systems, GaN and ZnSe, grown using WSe2 and graphene intermediate layers, exhibit larger grains, preferred orientation, reduced strain, and improved carrier mobility, all at temperatures lower by >200 °C compared to direct growth as characterized by diffraction, X-ray photoelectron spectroscopy, Raman, and Hall measurements. The realization of high-performance materials using 2D intermediate layers can enable transformative technologies under thermal budget restrictions, and the 2D/3D heterostructures could enable promising heterostructures for future device designs.

Profiling the role of microorganisms in quality improvement of the aged flue-cured tobacco.

BACKGROUND: The aging process in the tobacco production, as in other food industries, is an important process for improving the quality of raw materials. In the spontaneous aging, the complex components in flue-cured tobacco (FT) improve flavor or reduce harmful compounds through chemical reactions, microbial metabolism, and enzymatic catalysis. Some believed that tobacco-microbe played a significant part in this process. However, little information is available on how microbes mediate chemical composition to improve the quality of FT, which will lay the foundation for the time-consuming spontaneous aging to seek ways to shorten the aging cycle. RESULTS: Comparing aged and unaged FT, volatile and non-volatile differential compounds (DCs) were multi-dimensionally analyzed with the non-targeted metabolomes based on UPLC-QTOP-MS (the ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry), GC-MS (gas chromatography-mass spectrometer) assisted derivatization and HP-SPME-GC/MS (headspace solid-phase micro-extraction assisted GC-MS). Products associated with the degradation pathways of terpenoids or higher fatty acids were one of the most important factors in improving FT quality. With the microbiome, the diversity and functions of microbial flora were analyzed. The high relative abundance function categories were in coincidence with DCs-related metabolic pathways. According to the correlation analysis, Acinetobacter, Sphingomonas and Aspergillus were presumed to be the important contributor, in which Aspergillus was associated with the highest number of degradation products of terpenoids and higher fatty acids. At last, the screened Aspergillus nidulans strain F4 could promote the degradation of terpenoids and higher fatty acids to enhance tobacco flavor by secreting highly active lipoxygenase and peroxidase, which verified the effect of tobacco-microbes on FT quality. CONCLUSIONS: By integrating the microbiome and metabolome, tobacco-microbe can mediate flavor-related substances to improve the quality of FT after aging, which provided a basis for identifying functional microorganisms for reforming the traditional spontaneous aging.