Proteogenomic characterization of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.

Proteogenomic Characterization of Endometrial Carcinoma.

We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/ß-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.

A complex metabolic network and its biomarkers regulate laccase production in white-rot fungus Cerrena unicolor 87613.

BACKGROUND: White-rot fungi are known to naturally produce high quantities of laccase, which exhibit commendable stability and catalytic efficiency. However, their laccase production does not meet the demands for industrial-scale applications. To address this limitation, it is crucial to optimize the conditions for laccase production. However, the regulatory mechanisms underlying different conditions remain unclear. This knowledge gap hinders the cost-effective application of laccases. RESULTS: In this study, we utilized transcriptomic and metabolomic data to investigate a promising laccase producer, Cerrena unicolor 87613, cultivated with fructose as the carbon source. Our comprehensive analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) aimed to identify changes in cellular processes that could affect laccase production. As a result, we discovered a complex metabolic network primarily involving carbon metabolism and amino acid metabolism, which exhibited contrasting changes between transcription and metabolic patterns. Within this network, we identified five biomarkers, including succinate, serine, methionine, glutamate and reduced glutathione, that played crucial roles in co-determining laccase production levels. CONCLUSIONS: Our study proposed a complex metabolic network and identified key biomarkers that determine the production level of laccase in the commercially promising Cerrena unicolor 87613. These findings not only shed light on the regulatory mechanisms of carbon sources in laccase production, but also provide a theoretical foundation for enhancing laccase production through strategic reprogramming of metabolic pathways, especially related to the citrate cycle and specific amino acid metabolism.

Z-scheme Al2SeTe/GaSe and Al2SeTe/InS van der Waals heterostructures for photocatalytic water splitting.

Designing Z-scheme van der Waals (vdW) heterostructured photocatalysts is a promising strategy for developing highly efficient overall water splitting. Herein, by employing density functional theory calculations, we systematically investigated the stability, electronic structures, photocatalytic and optical properties of Al2SeTe, GaSe, and InS monolayers and their corresponding vdW heterostructures. Interestingly, electronic structures show that all vdW heterostructures have direct band gaps, which is conducive to the transition of electrons from the valence band to the conduction band. Notably, Al2TeSe/GaSe and Al2TeSe/InS vdW heterostructures possess large overpotentials for Z-scheme photocatalytic water splitting, as proved by the results of band edge positions and band structure bending. Moreover, these vdW heterostructures exhibit good optical absorption in ultraviolet and visible light regions. We believe that our findings will open a new avenue for the modulation and development of Al2TeSe/GaSe and Al2TeSe/InS vdW heterostructures for photocatalytic water splitting.

Unraveling the Emerging Photocatalytic, Thermoelectric, and Topological Properties of Intercalated Architecture MZX (M = Ga and In; Z = Si, Ge and Sn; X = S, Se, and Te) Monolayers.

The continuous advancements in studying two-dimensional (2D) materials pave the way for groundbreaking innovations across various industries. In this study, by employing density functional theory calculations, we comprehensively elucidate the electronic structures of MZX (M = Ga and In; Z = Si, Ge, and Sn; X = S, Se, and Te) monolayers for their applications in photocatalytic, thermoelectric, and spintronic fields. Interestingly, GaSiS, GaSiSe, InSiS, and InSiSe monolayers are identified to be efficient photocatalysts for overall water splitting with band gaps close to 2.0 eV, suitable band edge positions, and excellent optical harvest ability. In addition, the InSiTe monolayer exhibits a ZT value of 1.87 at 700 K, making it highly appealing for applications in thermoelectric devices. It is further highlighted that GaSnTe, InSnS, and InSnSe monolayers are predicted to be 2D topological insulators (TIs) with bulk band gaps of 115, 54, and 152 meV, respectively. Current research expands the family of 2D GaGeTe materials and establishes a path toward the practical utilization of MZX monolayers in energy conversion and spintronic devices.

Computational mining of GeH-based Janus III-VI van der Waals heterostructures for solar cell applications.

The asymmetrical group III-VI monolayer Janus M2XY (M = Al, Ga, In; X ≠ Y = S, Se, Te) have attracted widespread attention due to their significant optical absorption properties, which are the potential building blocks for van der Waals (vdW) heterostructure solar cells. In this study, we unraveled an In2STe/GeH vdW heterostructure as a candidate for solar cells by screening the Janus M2XY and GeH monolayers on lattice mismatches and electronic band structures based on first-principles calculations. The results highlight that the In2STe/GeH vdW heterostructure exhibits a type-II band gap of 1.25 eV. The optical absorption curve of the In2STe/GeH vdW heterostructure indicates that it possesses significant optical absorption properties in the visible and ultraviolet light areas. In addition, we demonstrate that the In2STe/GeH vdW heterostructure shows high and directionally anisotropic carrier mobility and good stability. Furthermore, strain engineering improves the theoretical power conversion efficiency of the In2STe/GeH vdW heterostructure up to 19.71%. Our present study will provide an idea for designing Janus M2XY and GeH monolayer-based vdW heterostructures for solar cell applications.

Promising M2CO2/MoX2 (M = Hf, Zr; X = S, Se, Te) Heterostructures for Multifunctional Solar Energy Applications.

Two-dimensional van der Waals (vdW) heterostructures are potential candidates for clean energy conversion materials to address the global energy crisis and environmental issues. In this work, we have comprehensively studied the geometrical, electronic, and optical properties of M2CO2/MoX2 (M = Hf, Zr; X = S, Se, Te) vdW heterostructures, as well as their applications in the fields of photocatalytic and photovoltaic using density functional theory calculations. The lattice dynamic and thermal stabilities of designed M2CO2/MoX2 heterostructures are confirmed. Interestingly, all the M2CO2/MoX2 heterostructures exhibit intrinsic type-II band structure features, which effectively inhibit the electron-hole pair recombination and enhance the photocatalytic performance. Furthermore, the internal built-in electric field and high anisotropic carrier mobility can separate the photo-generated carriers efficiently. It is noted that M2CO2/MoX2 heterostructures exhibit suitable band gaps in comparison to the M2CO2 and MoX2 monolayers, which enhance the optical-harvesting abilities in the visible and ultraviolet light zones. Zr2CO2/MoSe2 and Hf2CO2/MoSe2 heterostructures possess suitable band edge positions to provide the competent driving force for water splitting as photocatalysts. In addition, Hf2CO2/MoS2 and Zr2CO2/MoS2 heterostructures deliver a power conversion efficiency of 19.75% and 17.13% for solar cell applications, respectively. These results pave the way for exploring efficient MXenes/TMDCs vdW heterostructures as photocatalytic and photovoltaic materials.

Neoplastic cell enrichment of tumor tissues using coring and laser microdissection for proteomic and genomic analyses of pancreatic ductal adenocarcinoma.

BACKGROUND: The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in PDAC for proteomic and genomic analyses. METHODS: Three fresh frozen PDAC tumors and their tumor-matched normal adjacent tissues (NATs) were obtained from three sampling techniques using bulk, coring, and LMD; and analyzed by TMT-based quantitative proteomics. The protein profiles and characterizations of differentially expressed proteins in three sampling groups were determined. These three PDACs and samples of five additional PDACs obtained by the same three sampling techniques were also subjected to genomic analysis to characterize KRAS mutations. RESULTS: The neoplastic cellularity of eight PDACs ranged from less than 10% to over 80% based on morphological review. Distinctive proteomic patterns and abundances of certain tumor-associated proteins were revealed when comparing the tumors and NATs by different sampling techniques. Coring and bulk tissues had comparable proteome profiles, while LMD samples had the most distinct proteome composition compared to bulk tissues. Further genomic analysis of bulk, cored, or LMD samples demonstrated that KRAS mutations were significantly enriched in LMD samples while coring was less effective in enriching for KRAS mutations when bulk tissues contained a relatively low neoplastic cellularity. CONCLUSIONS: In addition to bulk tissues, samples from LMD and coring techniques can be used for proteogenomic studies. The greatest enrichment of neoplastic cellularity is obtained with the LMD technique.

Comprehensive understanding of intrinsic mobility and sub-10 nm quantum transportation in Ga2SSe monolayer.

Two-dimensional chalcogenides could play an important role in solving the short channel effect and extending Moore's law in the post-Moore era due to their excellent performances in the spintronics and optoelectronics fields. In this paper, based on theoretical calculations combining density functional theory and non-equilibrium Green's function, we have systematically explored the intrinsic mobility in the Ga2SSe monolayer and quantum transport properties of sub-10 nm Ga2SSe field-effect transistors (FET). Interestingly, the Ga2SSe monolayer presents high intrinsic electron mobility up to 104 cm2 (V s)-1. It is highlighted that the intrinsic mobility in the Ga2SSe monolayer is significantly restrained by phonon scattering, where the out-of-plane acoustic mode and high-frequency optic phonon mode are found predominantly coupled with the electrons. As a result, the n-type doping sub-10 nm Ga2SSe FETs represent distinguished transport properties. In particular, even the gate length is shortened to 3 nm, the on-state current, delay time and power consumption of the n-type doping Ga2SSe FET along the armchair direction can reach the International Technology Roadmap for Semiconductor industry standards for high-performance requirements. Our present study paves the way for the application of Ga2SSe monolayers in ultra-small sized FETs in the post-silicon era.

Investigation of the half-metallicity, magnetism and spin transport properties of double half-Heusler alloys Mn2CoCrZ2 (Z = P, As).

A new subfamily of Heusler alloys, i.e. double half-Heusler alloys Mn2CoCrZ2 (Z = P, As), are investigated by employing density functional theory combined with the nonequilibrium Green's function. The calculations of their magnetic properties reveal that Mn2CoCrZ2 (Z = P, As) are half-metallic ferrimagnets. Mn2CoCrP2 possesses an indirect spin-down bandgap of 0.671 eV and maintains half-metallicity with the lattice constant ratio c/a ranging from 1.72 to 2.40, while Mn2CoCrAs2 owns a direct spin-down bandgap of 0.993 eV and maintains half-metallicity with c/a ranging from 1.5 to 2.5. By employing Mn2CoCrZ2 as the electrodes and GaAs as the tunnel barrier, two kinds of magnetic tunnel junctions (MTJs) are constructed. When two electrodes of MTJs are in parallel magnetic configuration, the spin-up electrons have strong transmission ability, while the transmission ability of spin-down electrons is severely suppressed. When two electrodes of MTJs are in antiparallel magnetic configuration, the transmission ability of both spin-channel electrons is suppressed. The calculated tunnel magnetoresistance ratios of Mn2CoCrP2/GaAs/Mn2CoCrP2 and Mn2CoCrAs2/GaAs/Mn2CoCrAs2 MTJs reach up to 7.96 × 108 and 1.85 × 108, respectively, indicating that they are promising candidates for high performance spintronic devices.

Continent-Wide Climatic Variation Drives Local Adaptation in North American White Clover.

Climate-associated clines in adaptive polymorphisms are commonly cited as evidence of local adaptation within species. However, the contribution of the clinally varying trait to overall fitness is often unknown. To address this question, we examined survival, vegetative growth, and reproductive output in a central US common garden experiment using 161 genotypes of white clover (Trifolium repens L.) originating from 15 locations across North America. White clover is polymorphic for cyanogenesis (hydrogen cyanide release upon tissue damage), a chemical defense against generalist herbivores, and climate-associated cyanogenesis clines have repeatedly evolved across the species range. Over a 12-month experiment, we observed striking correlations between the population of origin and plant performance in the common garden, with climatic distance from the common garden site predicting fitness more accurately than geographic distance. Assessments of herbivore leaf damage over the 2015 growing season indicated marginally lower herbivory on cyanogenic plants; however, this effect did not result in increased fitness in the common garden location. Linear mixed modeling suggested that while cyanogenesis variation had little predictive value for vegetative growth, it is as important as climatic variation for predicting reproductive output in the central United States. Together, our findings suggest that knowledge of climate similarity, as well as knowledge of locally favored adaptive traits, will help to inform transplantation strategies for restoration ecology and other conservation efforts in the face of climate change.

Magnetic-ferroelectric synergic control of multilevel conducting states in van der Waals multiferroic tunnel junctions towards in-memory computing.

van der Waals (vdW) multiferroic tunnel junctions (MFTJs) based on two-dimensional materials have gained significant interest due to their potential applications in next-generation data storage and in-memory computing devices. In this study, we construct vdW MFTJs by employing monolayer Mn2Se3 as the spin-filter tunnel barrier, TiTe2 as the electrodes and In2S3 as the tunnel barrier to investigate the spin transport properties based on first-principles quantum transport calculations. It is highlighted that apparent tunneling magnetoresistance (TMR) and tunneling electroresistance (TER) effects with a maximum TMR ratio of 6237% and TER ratio of 1771% can be realized by using bilayer In2S3 as the tunnel barrier under finite bias. Furthermore, the physical origin of the distinguished TMR and TER effects is unraveled from the k||-resolved transmission spectra and spin-dependent projected local density of states analysis. Interestingly, four distinguishable conductance states reveal the implementation of four-state nonvolatile data storage using one MFTJ unit. More importantly, in-memory logic computing and multilevel data storage can be achieved at the same time by magnetic switching and electrical control, respectively. These results shed light on vdW MFTJs in the applications of in-memory computing as well as multilevel data storage devices.

Contact engineering for 2D Janus MoSSe/metal junctions.

The flourish of two-dimensional (2D) materials provides a versatile platform for building high-performance electronic devices in the atomic thickness regime. However, the presence of the high Schottky barrier at the interface between the metal electrode and the 2D semiconductors, which dominates the injection and transport efficiency of carriers, always limits their practical applications. Herein, we show that the Schottky barrier can be controllably lifted in the heterostructure consisting of Janus MoSSe and 2D vdW metals by different means. Based on density functional theory calculations and machine learning modelings, we studied the electrical contact between semiconducting monolayer MoSSe and various metallic 2D materials, where a crossover from Schottky to Ohmic/quasi-Ohmic contact is realized. We demonstrated that the band alignment at the interface of the investigated metal-semiconductor junctions (MSJs) deviates from the ideal Schottky-Mott limit because of the Fermi-level pinning effects induced by the interface dipoles. Besides, the effect of the thickness and applied biaxial strain of MoSSe on the electronic structure of the junctions are explored and found to be powerful tuning knobs for electrical contact engineering. It is highlighted that using the sure-independence-screening-and-sparsifying-operator machine learning method, a general descriptor WM3/exp(Dint) was developed, which enables the prediction of the Schottky barrier height for different MoSSe-based MSJ. These results provide valuable theoretical guidance for realizing ideal Ohmic contacts in electronic devices based on the Janus MoSSe semiconductors.

Highly intense NIR emissive Cu4Pt2 bimetallic clusters featuring Pt(i)-Cu4-Pt(i) sandwich kernel.

Metal nanoclusters (NCs) capable of near-infrared (NIR) photoluminescence (PL) are gaining increasing interest for their potential applications in bioimaging, cell labelling, and phototherapy. However, the limited quantum yield (QY) of NIR emission in metal NCs, especially those emitting beyond 800 nm, hinders their widespread applications. Herein, we present a bright NIR luminescence (PLQY up to 36.7%, ∼830 nm) bimetallic Cu4Pt2 NC, [Cu4Pt2(MeO-C6H5-C[triple bond, length as m-dash]C)4(dppy)4]2+ (dppy = diphenyl-2-pyridylphosphine), with a high yield (up to 67%). Furthermore, by modifying the electronic effects of R in RC[triple bond, length as m-dash]C- (R = MeO-C6H5, F-C6H5, CF3-C6H5, Nap, and Biph), we can effectively modulate phosphorescence properties, including the PLQY, emission wavelength, and excited state decay lifetime. Experimental and computational studies both demonstrate that in addition to the electron effects of substituents, ligand modification enhances luminescence intensity by suppressing non-radiation transitions through intramolecular interactions. Simultaneously, it allows the adjustment of emitting wavelengths by tuning the energy gaps and first excited triplet states through intermolecular interactions of ligand substituents. This study provides a foundation for rational design of the atomic-structures of alloy metal NCs to enhance their PLQY and tailor the PL wavelength of NIR emission.

Rhabdomyolysis in a male adolescent associated with monotherapy of fluvoxamine.

Rhabdomyolysis is a syndrome resulting from striated muscular breakdown, which may occur due to drug therapy with agents such as selective serotonin reuptake inhibitors (SSRIs). Although studies have shown that fluvoxamine can rarely cause myalgia, there are no reported cases of rhabdomyolysis due to fluvoxamine monotherapy. Here we describe a case of rhabdomyolysis due to fluvoxamine monotherapy for obsessive-compulsive disorder. The young adolescent developed pain in the extremities, and an increase in serum creatine kinase (CK) and myoglobin during fluvoxamine treatment. These adverse reactions were reversed immediately after the medicine was changed to another SSRI-sertraline. This is the first reported case of fluvoxamine-associated rhabdomyolysis. It is advisable to determine serum CK levels before starting fluvoxamine treatment, and then at regular intervals, to avoid the occurrence of severe acute kidney injury with possible life-threatening complications.

Predicted superconductivity in one-dimensional A3Hf2B3-type electrides.

Inorganic electrides are considered potential superconductors due to the unique properties of their anionic electrons. However, most electrides require external high-pressure conditions to exhibit considerable superconducting transition temperatures (Tc). Therefore, searching for superconducting electrides under low or moderate external pressures is of significant research interest and importance. In this work, a series of A3Hf2B3-type compounds (A = Mg, Ca, Sr, Ba; B = Si, Ge, Sn, Pb) were constructed and systematically studied based on density functional theory calculations. According to the analysis of the electronic structures and phonon dispersion spectrums, stable one-dimensional electrides Ca3Hf2Ge3, Ca3Hf2Sn3, and Sr3Hf2Pb3, were screened out. Interestingly, the superconductivity of these electrides were predicted from electron phonon coupling calculations. It is highlighted that Sr3Hf2Pb3 showed the highest Tc, reaching 4.02 K, while the Tc values of Ca3Hf2Ge3 and Ca3Hf2Sn3 were 1.16 K and 1.04 K, respectively. Moreover, the Tc value of Ca3Hf2Ge3 can be increased to 1.96 K under 20 GPa due to the effect of phonon softening. This work enriches the types of superconducting electrides and has important guiding significance for the research on constructing electrides and related superconducting materials.

Enhanced Electrochemical Performance of a Ti-Cr-Doped LiMn1.5Ni0.5O4 Cathode Material for Lithium-Ion Batteries.

Ti, Cr dual-element-doped LiMn1.5Ni0.5O4 (LNMO) cathode materials (LTNMCO) were synthesized by a simple high-temperature solid-phase method. The obtained LTNMCO shows the standard structure of the Fd3®m space group, and the Ti and Cr doped ions may replace the Ni and Mn sites in LNMO, respectively. The effect of Ti-Cr doping and single-element doping on the structure of LNMO was studied by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) characteristics. The LTNMCO exhibited excellent electrochemical properties with a specific capacity of 135.1 mAh·g-1 for the first discharge cycle and a capacity retention rate of 88.47% at 1C after 300 cycles. The LTNMCO also has high rate performance with a discharge capacity of 125.4 mAh·g-1 at a 10C rate, 93.55% of that at 0.1C. In addition, the CIV and EIS results show that the LTNMCO showed the lowest charge transfer resistance and the highest diffusion coefficient of lithium ions. The enhanced electrochemical properties may be due to a more stable structure and an optimized Mn3+ content in LTNMCO through TiCr doping.

Ultrasensitive Detection for Lithium-Ion Battery Electrolyte Leakage by Rare-Earth Nd-Doped SnO2 Nanofibers.

The problems of lithium-ion battery (LIB) failure have attracted growing attention since flammable and explosive electrolyte leakage might lead to serious consequences. However, due to the redox-neutral and volatile nature of main electrolyte components, such as dimethyl carbonate (DMC), trace leakages are difficult to detect. Therefore, research on LIB electrolyte sensors is urgent and lacking. Herein, sensors based on rare-earth Nd-doped SnO2 nanofibers are reported for detecting DMC vapor in LIB. The excellent sensitivity (distinct response to 20 ppb DMC), high response (∼38.13-50 ppm DMC), and superior selectivity and stability of 3%Nd-SnO2 suggest that it should be a promising candidate for LIB safety monitors. Meanwhile, it also shows clear and rapid response during the LIB-leakage real-time detection experiment. The doping of Nd endows SnO2 with more oxygen vacancy defects. In addition, the highly active Nd sites greatly enhanced the adsorption energy of DMC on SnO2. All of these features contribute to the improvement of DMC-sensing performances.

Synergism of Edge Effect and Interlayer Engineering of VS2 on CNFs for Rapid and Precise NO2 Detection.

Although two-dimensional (2D) transition-metal dichalcogenides (TMDs) exhibit attractive prospects for gas-sensing applications, the rapid and precise sensing of TMDs at low loss remains challenging. Herein, a NO2 sensor based on an expanded VS2 (VS2-E)/carbon nanofibers (CNFs) composite (abbreviated as VS2-E-C) with ultrafast response/recovery at a low-loss state is reported. In particular, the impact of the CNF content on the NO2-sensing performance of VS2-E-C was thoroughly explored. Expanded VS2 nanosheets were grafted onto the surface of hollow CNFs, and the combination boosted the charge transport, exposing abundant active edges of VS2, which enhanced the adsorption of NO2 efficiently. The activity of the VS2 edge is further confirmed by stronger NO2 adsorption with a more negative adsorption energy (-3.42 eV) and greater than the basal VS2 surface (-1.26 eV). Moreover, the exposure of rich edges induced the emergence of the expanded interlayers, which promoted the adsorption/desorption of NO2 and the interaction of gas molecules within VS2-E-C. The synergism of edge effect and interlayer engineering confers the VS2-E-C3 sensor with ultrafast response/recovery speed (9/10 s) at 60 °C, high sensitivity (∼2.50 to 15 ppm NO2), good selectivity/stability, and a low detection limit of 23 ppb. The excellent "4S" functions indicate the promising prospect of the VS2-E-C3 sensor for fast and precise NO2 detection at low-loss condition.