Evidence for unconventional superconductivity in twisted bilayer graphene.

The emergence of superconductivity and correlated insulators in magic-angle twisted bilayer graphene (MATBG) has raised the intriguing possibility that its pairing mechanism is distinct from that of conventional superconductors1-4, as described by the Bardeen-Cooper-Schrieffer (BCS) theory. However, recent studies have shown that superconductivity persists even when Coulomb interactions are partially screened5,6. This suggests that pairing in MATBG might be conventional in nature and a consequence of the large density of states of its flat bands. Here we combine tunnelling and Andreev reflection spectroscopy with a scanning tunnelling microscope to observe several key experimental signatures of unconventional superconductivity in MATBG. We show that the tunnelling spectra below the transition temperature Tc are inconsistent with those of a conventional s-wave superconductor, but rather resemble those of a nodal superconductor with an anisotropic pairing mechanism. We observe a large discrepancy between the tunnelling gap ΔT, which far exceeds the mean-field BCS ratio (with 2ΔT/kBTc ~ 25), and the gap ΔAR extracted from Andreev reflection spectroscopy (2ΔAR/kBTc ~ 6). The tunnelling gap persists even when superconductivity is suppressed, indicating its emergence from a pseudogap phase. Moreover, the pseudogap and superconductivity are both absent when MATBG is aligned with hexagonal boron nitride. These findings and other observations reported here provide a preponderance of evidence for a non-BCS mechanism for superconductivity in MATBG.

Tunable spin-polarized correlated states in twisted double bilayer graphene.

Reducing the energy bandwidth of electrons in a lattice below the long-range Coulomb interaction energy promotes correlation effects. Moiré superlattices-which are created by stacking van der Waals heterostructures with a controlled twist angle1-3-enable the engineering of electron band structure. Exotic quantum phases can emerge in an engineered moiré flat band. The recent discovery of correlated insulator states, superconductivity and the quantum anomalous Hall effect in the flat band of magic-angle twisted bilayer graphene4-8 has sparked the exploration of correlated electron states in other moiré systems9-11. The electronic properties of van der Waals moiré superlattices can further be tuned by adjusting the interlayer coupling6 or the band structure of constituent layers9. Here, using van der Waals heterostructures of twisted double bilayer graphene (TDBG), we demonstrate a flat electron band that is tunable by perpendicular electric fields in a range of twist angles. Similarly to magic-angle twisted bilayer graphene, TDBG shows energy gaps at the half- and quarter-filled flat bands, indicating the emergence of correlated insulator states. We find that the gaps of these insulator states increase with in-plane magnetic field, suggesting a ferromagnetic order. On doping the half-filled insulator, a sudden drop in resistivity is observed with decreasing temperature. This critical behaviour is confined to a small area in the density-electric-field plane, and is attributed to a phase transition from a normal metal to a spin-polarized correlated state. The discovery of spin-polarized correlated states in electric-field-tunable TDBG provides a new route to engineering interaction-driven quantum phases.

Power generation from ambient humidity using protein nanowires.

Harvesting energy from the environment offers the promise of clean power for self-sustained systems1,2. Known technologies-such as solar cells, thermoelectric devices and mechanical generators-have specific environmental requirements that restrict where they can be deployed and limit their potential for continuous energy production3-5. The ubiquity of atmospheric moisture offers an alternative. However, existing moisture-based energy-harvesting technologies can produce only intermittent, brief (shorter than 50 seconds) bursts of power in the ambient environment, owing to the lack of a sustained conversion mechanism6-12. Here we show that thin-film devices made from nanometre-scale protein wires harvested from the microbe Geobacter sulfurreducens can generate continuous electric power in the ambient environment. The devices produce a sustained voltage of around 0.5 volts across a 7-micrometre-thick film, with a current density of around 17 microamperes per square centimetre. We find the driving force behind this energy generation to be a self-maintained moisture gradient that forms within the film when the film is exposed to the humidity that is naturally present in air. Connecting several devices linearly scales up the voltage and current to power electronics. Our results demonstrate the feasibility of a continuous energy-harvesting strategy that is less restricted by location or environmental conditions than other sustainable approaches.

The Ginkgo biloba microRNA160-ERF4 module participates in terpene trilactone biosynthesis.

Terpene trilactones (TTLs) are important secondary metabolites in ginkgo (Ginkgo biloba); however, their biosynthesis gene regulatory network remains unclear. Here, we isolated a G. biloba ethylene response factor 4 (GbERF4) involved in TTL synthesis. Overexpression of GbERF4 in tobacco (Nicotiana tabacum) significantly increased terpenoid content and upregulated the expression of key enzyme genes (3-hydroxy-3-methylglutaryl-CoA reductase [HMGR], 3-hydroxy-3-methylglutaryl-CoA synthase [HMGS], 1-deoxy-D-xylulose-5-phosphate reductoisomerase [DXR], 1-deoxy-D-xylulose-5-phosphate synthase [DXS], acetyl-CoA C-acetyltransferase [AACT], and geranylgeranyl diphosphate synthase [GGPPS]) in the terpenoid pathway in tobacco, suggesting that GbERF4 functions in regulating the synthesis of terpenoids. The expression pattern analysis and previous microRNA (miRNA) sequencing showed that gb-miR160 negatively regulates the biosynthesis of TTLs. Transgenic experiments showed that overexpression of gb-miR160 could significantly inhibit the accumulation of terpenoids in tobacco. Targeted inhibition and dual-luciferase reporter assays confirmed that gb-miR160 targets and negatively regulates GbERF4. Transient overexpression of GbERF4 increased TTL content in G. biloba, and further transcriptome analysis revealed that DXS, HMGS, CYPs, and transcription factor genes were upregulated. In addition, yeast 1-hybrid and dual-luciferase reporter assays showed that GbERF4 could bind to the promoters of the HMGS1, AACT1, DXS1, levopimaradiene synthase (LPS2), and GGPPS2 genes in the TTL biosynthesis pathway and activate their expression. In summary, this study investigated the molecular mechanism of the gb-miR160-GbERF4 regulatory module in regulating the biosynthesis of TTLs. It provides information for enriching the understanding of the regulatory network of TTL biosynthesis and offers important gene resources for the genetic improvement of G. biloba with high contents of TTLs.

Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme.

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O2), necessitating unfeasibly large doses in a therapeutic setting. Here, we report a genetic selection strategy that directly links CycN-independent activity of NicA2 to growth of Pseudomonas putida S16. This selection enabled us to evolve NicA2 variants with substantial improvement in their rate of oxidation by O2. The encoded mutations cluster around a putative O2 tunnel, increasing flexibility and accessibility to O2 in this region. These mutations further confer desirable clinical properties. A variant form of NicA2 is tenfold more effective than the wild type at degrading nicotine in the bloodstream of rats.

Spectroscopic signatures of many-body correlations in magic-angle twisted bilayer graphene.

The discovery of superconducting and insulating states in magic-angle twisted bilayer graphene (MATBG)1,2 has ignited considerable interest in understanding the nature of electronic interactions in this chemically pristine material. The transport properties of MATBG as a function of doping are similar to those of high-transition-temperature copper oxides and other unconventional superconductors1-3, which suggests that MATBG may be a highly interacting system. However, to our knowledge, there is no direct experimental evidence of strong many-body correlations in MATBG. Here we present high-resolution spectroscopic measurements, obtained using a scanning tunnelling microscope, that provide such evidence as a function of carrier density. MATBG displays unusual spectroscopic characteristics that can be attributed to electron-electron interactions over a wide range of doping levels, including those at which superconductivity emerges in this system. We show that our measurements cannot be explained with a mean-field approach for modelling electron-electron interactions in MATBG. The breakdown of a mean-field approach when applied to other correlated superconductors, such as copper oxides, has long inspired the study of the highly correlated Hubbard model3. We show that a phenomenological extended-Hubbard-model cluster calculation, which is motivated by the nearly localized nature of the relevant electronic states of MATBG, produces spectroscopic features that are similar to those that we observed experimentally. Our findings demonstrate the critical role of many-body correlations in understanding the properties of MATBG.

Nonaggregated Anions Enable the Undercooled Aqueous Electrolyte for Low-Temperature Applications.

Aqueous batteries, with the advantages of high safety and low cost, are highly promising for large-scale energy storage. However, freezing of the aqueous electrolyte limits the low-temperature operation. Here, we propose and achieve a highly dispersed solvation structure in the electrolyte by coupling nonaggregated Cl- anions, which reduces the water cluster size and prevents the solidification of the aqueous electrolyte until -136.3 °C. The low-temperature LiCl electrolyte exhibits a high ionic conductivity (1.0 mS cm-1) at -80 °C and enables a stable low-temperature Ag/AgCl reference electrode at -50 °C. Moreover, the polyaniline-based battery can work at an extremely low temperature of -100 °C and shows superior cycling performance of 4000 cycles at -40 °C with 95.7% capacity retention. This work elucidates the correlation between the anion effect and the thermodynamic transition of the electrolyte, offering a novel approach for designing low-temperature electrolytes.

Sustainable Aqueous Batteries Based on Bipolar Dissociation of Aluminum Hydroxyacetate Electrolyte.

Rechargeable aqueous batteries are potential systems for large-scale energy storage due to their high safety and low cost. However, developing aqueous batteries with high sustainability, affordability, and reversibility is urgent and challenging. Here we report an amphoteric aluminum hydroxyacetate (AlAc(OH)2) electrolyte with the ability of bipolar ionization of H+ and OH-, which facilitates the redox reactions at both the anthraquinone (AQ) anode and nickel hydroxide (Ni(OH)2) cathode. The bipolar ionization ability of the AlAc(OH)2(H2O)3 solvation structure results from the strong polarization ability of Al3+ and OH-. The H+/OH- dissociation ability with a dissociation constant of 5.0/3.0 is stronger than that of water (14.0), which boosts the simultaneous stable redox reactions of electrodes. Specifically, H+ uptake prevents the AQ anode from the formation of an ionic bond, suppressing the electrode dissolution, whereas OH- provides the local alkaline environment for the stable conversion reaction of the Ni(OH)2 cathode. The AQ anode in the designed AQ||Ni(OH)2 battery delivers a discharge capacity of 243.9 mAh g-1 and a capacity retention of 78.2% after 300 cycles with high reversibility. Moreover, a pouch cell with a discharge capacity of 0.90 Ah was assembled, exhibiting an energy density of 44.7 Wh kg-1 based on the total mass of the battery. This work significantly widens the types of aqueous batteries and represents a design philosophy of bipolar electrolytes and distinct electrochemical reactions with H+ and OH-.

Enhancing NIR-II Upconversion Monochromatic Emission for Temperature Sensing.

The upconversion luminescence (UCL) in the second near-infrared window (NIR-II) is highly attractive due to its excellent performance in high-resolution bioimaging, anticounterfeiting, and temperature sensing. However, upconvertion nanoparticles (UCNPs) are normally emitted in visible light, potentially impacting the imaging quality. Here, a monochromatic Er3+-rich (NaErF4:x%Yb@NaYF4) nanoparticles with excitation at 1532 nm and emission at 978 nm is proposed, both situated in the NIR-II region. The proper proportion of Yb3+ ions doping has a positive effect on the NIR-II emission, by enhancing the cross relaxation efficiency and accelerating the energy transfer rate. Owing to the interaction between the Er3+ and Yb3+ is inhibited at low temperatures, the UCL emission intensities at visible and NIR-II regions show opposite trend with temperature changing, which establishes a fitting formula to derive temperature from the luminous intensity ratio, promoting the potential application of UCL in NIR-II regions for the temperature sensing.

High-speed k-linear swept laser using acousto-optic deflectors with Doppler shift compensation for optical coherence tomography.

Swept laser based on the acousto-optic deflector (AOD) is a promising swept source in optical coherence tomography (OCT) applications for its high wavenumber linear sweep without mechanical motion. However, the poor coherence length and the elongated cavity of the laser imposed limitations on the acquisition of high-quality images with adequate imaging depth and high imaging speed. In this Letter, we demonstrate a compact high-speed wavenumber linear swept laser based on AOD using Doppler shift compensation, achieving a high linearity of Pearson's R of 0.999991, a duty cycle of ∼100%, an extended coherence length of 5.7 mm, an output power of 18 mW, and excellent phase stability at a sweep speed of 500 kHz. OCT structural images with a system sensitivity of 103.2 dB and OCT angiography (OCTA) of human palm in vivo have been successfully performed, serving as a compelling demonstration of the excellent performance of this swept laser. We believe that the proposed laser will be of high potential in various clinical and industrial applications in the future.

Integrated transcriptomics and epigenomics reveal chamber-specific and species-specific characteristics of human and mouse hearts.

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.

A Novel Multi-Functional Fluorescence Probe for the Detection of Al3+/Zn2+/Cd2+ and its Practical Applications.

A novel multi-functional fluorescence probe HMIC based on hydrazide Schiff base has been successfully synthesized and characterized. It can distinguish Al3+/Zn2+/Cd2+ in ethanol, in which fluorescence emission with different colors (blue for Al3+, orange for Zn2+, and green for Cd2+) were presented. The limits of detection of HMIC towards three ions were calculated from the titration curve as 7.70 × 10- 9 M, 4.64 × 10- 9 M, and 1.35 × 10- 8 M, respectively. The structures of HMIC and its complexes were investigated using UV-Vis spectra, Job's plot, infrared spectra, mass spectrometry, 1H-NMR and DFT calculations. Practical application studies have also demonstrated that HMIC can be applied to real samples with a low impact of potential interferents. Cytotoxicity and cellular imaging assays have shown that HMIC has good cellular permeability and potential antitumor effects. Interestingly, HMIC can image Al3+, Zn2+ and Cd2+ in the cells with different fluorescence signals.

Changing Trends in the Global Disease Burden of Pancreatic Cancer from 1990 to 2030.

AIM: To explore the global burden of pancreatic cancer (PC) from 1990 to 2019, evaluate independent effects of age, period, and cohort on the incidence of PC, and predict the incidence of PC in the next decade. METHODS: Data were obtained from the Global Burden of Disease Study 2019. We calculated the age-standardized disability-adjusted life years (DALY) rate, age-standardized mortality rate (ASMR), age-standardized incidence rate (ASIR), and age-standardized prevalence rate (ASPR) of PC. Joinpoint Poisson regression analysis was performed to identify the temporal trends in the incidence of PC. Then, a two-factor model was constructed using the Poisson log-linear model, and a three-factor model was constructed using the intrinsic estimator (IE) method to estimate the independent effects of age, period, and cohort on the incidence of PC. Finally, the Bayesian age-period-cohort (BAPC) model was also used to predict the age-standardized global incidence rate of PC and age-standardized new PC cases from 2020 to 2030. RESULTS: Overall, the DALY rate, ASMR, ASIR, and ASPR all increased from 1990 to 2019. The ASIR in males increased from 6 per 100,000 in 1990 to 7.5 per 100,000 in 2019 and was predicted to rise to 8.2 per 100,000 by 2030. Meanwhile, the ASIR in females rose from 4.5 per 100,000 in 1990 to 5.7 per 100,000 in 2019 and was predicted to rise to 6.3 per 100,000 by 2030. The age effect on the incidence of PC showed sharp increasing trends from 40 to 79 years. The period effect continuously increased with advancing periods, but the cohort effect showed substantial decreasing trends. CONCLUSIONS: The age and period effect on the incidence of PC presented increasing trends, while the cohort effect showed decreasing trends. All indicators of the global burden of PC are increasing in both males and females, and the ASIR is predicted to rise at an alarming rate by 2030. Thus, timely screening and intervention are recommended, especially for earlier birth cohorts at high risk.

Effects of gene polymorphisms on delayed MTX clearance, toxicity, and metabolomic changes after HD-MTX treatment in children with acute lymphoblastic leukemia.

This study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects. CONCLUSION: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ ). WHAT IS KNOWN: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear. WHAT IS NEW: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is among the most immunosuppressive tumour types. The tumour immune microenvironment (TIME) is largely driven by interactions between immune cells and heterogeneous tumour cells. Here, we aimed to investigate the mechanism of tumour cells in TIME formation and provide potential combination treatment strategies for PDAC patients based on genotypic heterogeneity. DESIGN: Highly multiplexed imaging mass cytometry, RNA sequencing, mass cytometry by time of flight and multiplex immunofluorescence staining were performed to identify the pro-oncogenic proteins associated with low immune activation in PDAC. An in vitro coculture system, an orthotopic PDAC allograft tumour model, flow cytometry and immunohistochemistry were used to explore the biological functions of cysteine-rich intestinal protein 1 (CRIP1) in tumour progression and TIME formation. RNA sequencing, mass spectrometry and chromatin immunoprecipitation were subsequently conducted to investigate the underlying mechanisms of CRIP1. RESULTS: Our results showed that CRIP1 was frequently upregulated in PDAC tissues with low immune activation. Elevated CRIP1 expression induced high levels of myeloid-derived suppressor cell (MDSC) infiltration and fostered an immunosuppressive tumour microenvironment. Mechanistically, we primarily showed that CRIP1 bound to nuclear factor kappa-B (NF-κB)/p65 and facilitated its nuclear translocation in an importin-dependent manner, leading to the transcriptional activation of CXCL1/5. PDAC-derived CXCL1/5 facilitated the chemotactic migration of MDSCs to drive immunosuppression. SX-682, an inhibitor of CXCR1/2, blocked tumour MDSC recruitment and enhanced T-cell activation. The combination of anti-PD-L1 therapy with SX-682 elicited increased CD8+T cell infiltration and potent antitumor activity in tumour-bearing mice with high CRIP1 expression. CONCLUSIONS: The CRIP1/NF-κB/CXCL axis is critical for triggering immune evasion and TIME formation in PDAC. Blockade of this signalling pathway prevents MDSC trafficking and thereby sensitises PDAC to immunotherapy.

Characterization of a Bacillus subtilis S-16 Thiazole-Synthesis-Related Gene thiS Knockout and Antimicrobial Activity Analysis.

Bacillus subtilis S-16 isolated from sunflower-rhizosphere soil is an effective biocontrol agent for preventing soilborne diseases in plants. Previous research revealed that the volatile organic compounds (VOCs) produced by the S-16 strain have strong inhibitory effects on Sclerotinia sclerotiorum. The identification of the VOCs of S-16 using gas chromatography-tandem mass spectrometry (GC-MS/MS) revealed 35 compounds. Technical-grade formulations of four of these compounds were chosen for further study: 2-pentadecanone, 6,10,14-trimethyl-2-octanone, 2-methyl benzothiazole (2-MBTH), and heptadecane. The major constituent, 2-MBTH, plays an important role in the antifungal activity of the VOCs of S-16 against the growth of Sclerotinia sclerotiorum. The purpose of this study was to determine the impact of the thiS gene's deletion on the 2-MBTH production and to conduct an antimicrobial activity analysis of the Bacillus subtilis S-16. The thiazole-biosynthesis gene was deleted via homologous recombination, after which the contents of 2-MBTH in the wild-type and mutant S-16 strains were analyzed using GC-MS. The antifungal effects of the VOCs were determined using a dual-culture technique. The morphological characteristics of the Sclerotinia sclerotiorum mycelia were examined via scanning-electron microscopy (SEM). Additionally, the lesion areas on the sunflower leaves with and without treatment with the VOCs from the wild-type and mutant strains were measured to explore the effects of the VOCs on the virulence of the Sclerotinia sclerotiorum. Moreover, the effects of the VOCs on the sclerotial production were assessed. We showed that the mutant strain produced less 2-MBTH. The ability of the VOCs produced by the mutant strain to inhibit the growth of the mycelia was also reduced. The SEM observation showed that the VOCs released by the mutant strain also caused more flaccid and gapped hyphae in the Sclerotinia sclerotiorum. The Sclerotinia sclerotiorum treated by the VOCs produced by the mutant strains caused more damage to the leaves than that treated by the VOCs produced by the wild type and the mutant-strain-produced VOCs inhibited sclerotia formation less. The production of 2-MBTH and its antimicrobial activities were adversely affected to varying degrees by the deletion of thiS.

Multi-instance learning of graph neural networks for aqueous pKa prediction.

MOTIVATION: The acid dissociation constant (pKa) is a critical parameter to reflect the ionization ability of chemical compounds and is widely applied in a variety of industries. However, the experimental determination of pKa is intricate and time-consuming, especially for the exact determination of micro-pKa information at the atomic level. Hence, a fast and accurate prediction of pKa values of chemical compounds is of broad interest. RESULTS: Here, we compiled a large-scale pKa dataset containing 16 595 compounds with 17 489 pKa values. Based on this dataset, a novel pKa prediction model, named Graph-pKa, was established using graph neural networks. Graph-pKa performed well on the prediction of macro-pKa values, with a mean absolute error around 0.55 and a coefficient of determination around 0.92 on the test dataset. Furthermore, combining multi-instance learning, Graph-pKa was also able to automatically deconvolute the predicted macro-pKa into discrete micro-pKa values. AVAILABILITY AND IMPLEMENTATION: The Graph-pKa model is now freely accessible via a web-based interface (https://pka.simm.ac.cn/). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Event-based dual photography for transparent scene reconstruction.

Light transport contains all light information between a light source and an image sensor. As an important application of light transport, dual photography has been a popular research topic, but it is challenged by long acquisition time, low signal-to-noise ratio, and the storage or processing of a large number of measurements. In this Letter, we propose a novel hardware setup that combines a flying-spot micro-electro mechanical system (MEMS) modulated projector with an event camera to implement dual photography for 3D scanning in both line-of-sight (LoS) and non-line-of-sight (NLoS) scenes with a transparent object. In particular, we achieved depth extraction from the LoS scenes and 3D reconstruction of the object in a NLoS scene using event light transport.

Cancer stem cells and their niche in cancer progression and therapy.

High recurrence and metastasis rates and poor prognoses are the major challenges of current cancer therapy. Mounting evidence suggests that cancer stem cells (CSCs) play an important role in cancer development, chemoradiotherapy resistance, recurrence, and metastasis. Therefore, targeted CSC therapy has become a new strategy for solving the problems of cancer metastasis and recurrence. Since the properties of CSCs are regulated by the specific tumour microenvironment, the so-called CSC niche, which targets crosstalk between CSCs and their niches, is vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. In this review, we aim to highlight the factors within the CSC niche that have important roles in regulating CSC properties, including the extracellular matrix (ECM), stromal cells (e.g., associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs)), and physiological changes (e.g., inflammation, hypoxia, and angiogenesis). We also discuss recent progress regarding therapies targeting CSCs and their niche to elucidate developments of more effective therapeutic strategies to eliminate cancer.