Programmable Interfacial Band Configuration in WS2/Bi2O2Se Heterojunctions.

van der Waals heterojunctions based on transition-metal dichalcogenides (TMDs) offer advanced strategies for manipulating light-emitting and light-harvesting behaviors. A crucial factor determining the light-material interaction is in the band alignment at the heterojunction interface, particularly the distinctions between type-I and type-II alignments. However, altering the band alignment from one type to another without changing the constituent materials is exceptionally difficult. Here, utilizing Bi2O2Se with a thickness-dependent band gap as a bottom layer, we present an innovative strategy for engineering interfacial band configurations in WS2/Bi2O2Se heterojunctions. In particular, we achieve tuning of the band alignment from type-I (Bi2O2Se straddling WS2) to type-II and finally to type-I (WS2 straddling Bi2O2Se) by increasing the thickness of the Bi2O2Se bottom layer from monolayer to multilayer. We verified this band architecture conversion using steady-state and transient spectroscopy as well as density functional theory calculations. Using this material combination, we further design a sophisticated band architecture incorporating both type-I (WS2 straddles Bi2O2Se, fluorescence-quenched) and type-I (Bi2SeO5 straddles WS2, fluorescence-recovered) alignments in one sample through focused laser beam (FLB). By programming the FLB trajectory, we achieve a predesigned localized fluorescence micropattern on WS2 without changing its intrinsic atomic structure. This effective band architecture design strategy represents a significant leap forward in harnessing the potential of TMD heterojunctions for multifunctional photonic applications.

Upcycling fish scales through heating for steganography and Rhodamine B adsorption application.

With increasing population and limited resources, a potential route for improving sustainability is increased reuse of waste materials. By re-looking at wastes, interesting properties and multifunctionalities can be discovered in materials previously explored. Despite years of research on bio-compatible fish scales, there is limited study on the fluorescence property of this abundant waste material. Controlled denaturation of collagen and introduction of defects can serve as a means to transform the fluorescence property of these fish scale wastes while providing more adsorption sites for pollutant removal, turning multifunctional fish scales into a natural steganographic material for transmitting text and images at both the macroscopic and microscopic levels and effectively removing Rhodamine B pollutants (91 % removal) within a short contact time (10 minutes). Our work offers a glimpse into the realm of engineering defects-induced fluorescence in natural material with potential as bio-compatible fluorescence probes while encouraging multidimensional applicability to be established in otherwise overlooked waste resources.

Brown-fat-mediated tumour suppression by cold-altered global metabolism.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stages). Univariate and multivariate Cox proportional hazard models were used to determine the impact of these markers and other clinicopathological factors on survival, recurrence, and progression. EP263, IM142, PD1, and Ki67 levels were the highest in the T2 stage, followed by the T1 and Ta stages. HER2 and IM263 expressions were higher in the T1 and T2 stages than in the Ta stage. In NMIBC, the significant prognostic factors for recurrence-free survival were adjuvant therapy, tumor grade, and HER2 positivity, whereas those for progression-free survival included age, T-stage, and IM263. Age, T-stage, EP263, PD1, CD8, and Ki67 levels were significant factors associated with overall survival. IM263 and HER2 are potential biomarkers for progression and recurrence, respectively. Therefore, we propose HER2 as a potential target antigen for intravesical therapeutics as a BCG alternative.

Dynamic Tuning of Moiré Superlattice Morphology by Laser Modification.

In artificial van der Waals (vdW) layered devices, twisting the stacking angle has emerged as an effective strategy to regulate the electronic phases and optical properties of these systems. Along with the twist registry, the lattice reconstruction arising from vdW interlayer interaction has also inspired significant research interests. The control of twist angles is significantly important because the moiré periodicity determines the electron propagation length on the lattice and the interlayer electron-electron interactions. However, the moiré periodicity is hard to be modified after the device has been fabricated. In this work, we have demonstrated that the moiré periodicity can be precisely modulated with a localized laser annealing technique. This is achieved with regulating the interlayer lattice mismatch by the mismatched lattice constant, which originates from the variable density of sulfur vacancy generated during laser modification. The existence of sulfur vacancy is further verified by excitonic emission energy and lifetime in photoluminescence measurements. Furthermore, we also discover that the mismatched lattice constant has the equivalent contribution as the twist angle for determining the lattice mismatch. Theoretical modeling elaborates the moiré-wavelength-dependent energy variations at the interface and mimics the evolution of moiré morphology.

Nanopath-Beacons for Directed Silver Dendrites' Migration across Graphene Oxide Terrain.

With their special hierarchical fractal and highly symmetric formation, silver dendrites have a large surface area and plentiful active sites at edges, which have allowed them to exhibit unique properties ranging from superhydrophobic surfaces to biosensors. Yet, many suggested synthesis processes either require a long reaction time or risk contamination from sacrificial elements. Limited research in directing while enhancing the growth of these silver dendrites also hinders the application of these unique microstructures as site-selective hydrophobicity of surfaces and location-dependent SERS (surface-enhanced Raman spectroscopy). A possible solution to this is to utilize WO3 nanocubes as beacons to accelerate and conduct the growth of these silver dendrites through the electrochemical migration process. These nanocubes effortlessly altered the applied electric field distributed between the electrodes, depending on their orientations and positions. As the silver dendrites branched from the nanocubes, the dendrites themselves further concentrated the electric field to encourage the growth of more loose fractal silver dendrites. The combinatory effect successfully directs the growth of silver dendrites along the concentrated electric field paths. Both changes to the electric field and directed growth of silver dendrites are underscored using Multiphysics COMSOL simulations and time-lapse microscopy. This work provided insight into the possibility of designing microstructures to direct and accelerate the growth of silver dendrites.

Cosmetic preservative labeling in Philippine products in accordance with Philippine regulations.

BACKGROUND: Preservatives are usually added to a wide array of consumer products to prevent growth of microbes and to prevent product destabilization and degradation. However, many of these preservatives are common skin sensitizers and may cause allergic contact dermatitis. The amount of preservatives may vary per country or region according to their respective legislation and may be reported in differences in prevalence rates of contact dermatitis. OBJECTIVE: To examine and identify preservatives in consumer products in accordance with Philippine legislation. To verify the accuracy of the list of ingredients of Philippine cosmetic products as legislated by the Philippine Bureau of Food and Drug Administration. METHODS: A total of 65 commonly used Philippine consumer products ranging from liquid facial and body washes, bar soaps, laundry detergents, feminine hygiene washes and wipes, shampoos and conditioners, sunblock, and moisturizers were selected. Ingredients noted on labels were documented. Products were subsequently investigated chemically for the presence of methylchloroisothiazolinone, methylisothiazolinone, or formaldehyde. RESULTS: The preservatives most commonly used in cosmetic products in the Philippine market are methylchloroisothiazolinone (MCI), methylisothiazolinone (MI), and/or formaldehyde. In accordance with Philippine legislation, almost all products provided a detailed ingredient list as printed on the packaging. Measurements of MCI/MI ranged from less than 1 ppm to 16 ppm, and MI ranged from only less than 1 ppm to 66 ppm, whereas formaldehyde was noted to range from less than 2.5 ppm to greater than 40 ppm in the products tested. Most products are manufactured by international brands, with a few products being manufactured locally. CONCLUSIONS: The preservatives found in cosmetic products were MCI, MI, and formaldehyde. Discrepancies were found in the preservatives and labeling of these products, with a majority of investigated Philippine products labeled inaccurately with varying concentrations of preservatives.

Obesity-Associated GNAS Mutations and the Melanocortin Pathway.

BACKGROUND: GNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism). METHODS: We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. RESULTS: Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P = 0.004). CONCLUSIONS: Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).

2D Electrolytes: Theory, Modeling, Synthesis, and Characterization.

A class of compounds sharing the properties of 2D materials and electrolytes, namely 2D electrolytes is described theoretically and demonstrated experimentally. 2D electrolytes dissociate in different solvents, such as water, and become electrically charged. The chemical and physical properties of these compounds can be controlled by external factors, such as pH, temperature, electric permittivity of the medium, and ionic concentration. 2D electrolytes, in analogy with polyelectrolytes, present reversible morphological transitions from 2D to 1D, as a function of pH, due to the interplay of the elastic and Coulomb energies. Since these materials show stimuli-responsive behavior to the environmental conditions, 2D electrolytes can be considered as a novel class of smart materials that expand the functionalities of 2D materials and are promising for applications that require stimuli-responsive demeanor, such as drug delivery, artificial muscles, and energy storage.

Performance Improvement by Ozone Treatment of 2D PdSe2.

Atomic-scale defects in two-dimensional transition metal dichalcogenides (TMDs) often dominate their physical and chemical properties. Introducing defects in a controllable manner can tailor properties of TMDs. For example, chalcogen atom defects in TMDs were reported to trigger phase transition, induce ferromagnetism, and drive superconductivity. However, reported strategies to induce chalcogen atom defects including postgrowth annealing, laser irradiation, or plasma usually require high temperature (such as 500 °C) or cause unwanted structural damage. Here, we demonstrate low-temperature (60 °C) partial surface oxidation in 2D PdSe2 with low disorder and good stability. The combination of scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory calculations provide evidence of atomic-scale partial oxidation with both atomic resolution and chemical sensitivity. We also experimentally demonstrate that this controllable oxygen incorporation effectively tailors the electronic, optoelectronic, and catalytic activity of PdSe2. This work provides a pathway toward fine-tuning the physical and chemical properties of 2D TMDs and their applications in nanoelectronics, optoelectronics, and electrocatalysis.

High-Performance, Room Temperature, Ultra-Broadband Photodetectors Based on Air-Stable PdSe2.

Photodetection over a broad spectral range is crucial for optoelectronic applications such as sensing, imaging, and communication. Herein, a high-performance ultra-broadband photodetector based on PdSe2 with unique pentagonal atomic structure is reported. The photodetector responds from visible to mid-infrared range (up to ≈4.05 µm), and operates stably in ambient and at room temperature. It promises improved applications compared to conventional mid-infrared photodetectors. The highest responsivity and external quantum efficiency achieved are 708 A W-1 and 82 700%, respectively, at the wavelength of 1064 nm. Efficient optical absorption beyond 8 µm is observed, indicating that the photodetection range can extend to longer than 4.05 µm. Owing to the low crystalline symmetry of layered PdSe2 , anisotropic properties of the photodetectors are observed. This emerging material shows potential for future infrared optoelectronics and novel devices in which anisotropic properties are desirable.

Nanosurfer flash-mobs: electric-field-choreographed silver migration on graphene oxide.

We report for the first time the ability to direct and control the migration path of silver nanoparticles across graphene oxide (GO). With the help of a focused laser beam, we demonstrated choreographed nanoparticle assembly on GO via a directed electric-field. Silver migration and the resultant dendrite formation on GO were characterized through electrical testing coupled with fluorescence microscopy. The proposed mechanism for silver migration in GO involves the interlayer water between GO sheets serving as the electrolyte for the electrochemical process. This interlayer water facilitates the disappearance of dendrites through oxidation and dissolution into the water. Furthermore, we demonstrate that the shape of the formed Ag dendrites can be controlled by a combination of an applied electric field and patterned regions of a reduced GO film created by a focused laser beam. This paves the way for an alternative low-cost silver nanoparticle assembly method requiring only a low-powered laser and low voltage.

Laser assisted blending of Ag nanoparticles in an alumina veil: a highly fluorescent hybrid.

We report a functional hybrid made of silver nanoparticles (AgNPs) embedded in an amorphous aluminium oxide (alumina) film. This laser-initiated process allows formation of AgNPs and amorphous alumina in localized regions defined by the scanning laser beam. Due to metal enhanced fluorescence, this hybrid exhibits strong blue fluorescence emission under ultraviolet excitation. Upon irradiating with electrons at dosages of 1 to 20 mC cm-2, AgNPs become more metallic while the Al film is further oxidised. As a result, the fluorescing property is intensified. Using a hybrid irradiated with 10 mC cm-2, the electronic conductivity of the sample is improved by 11.5 times compared to that of the as-synthesized hybrid film. Excitation by UV light on the sample results in an increase in the detected current of nearly 29 times. Given that the electron beam patterned message is selectively visible only under UV or blue light irradiation, this hybrid film is thus a possible platform for steganographic transmission.

Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance.

Intrinsic and evasive antiangiogenic drug (AAD) resistance is frequently developed in cancer patients, and molecular mechanisms underlying AAD resistance remain largely unknown. Here we describe AAD-triggered, lipid-dependent metabolic reprogramming as an alternative mechanism of AAD resistance. Unexpectedly, tumor angiogenesis in adipose and non-adipose environments is equally sensitive to AAD treatment. AAD-treated tumors in adipose environment show accelerated growth rates in the presence of a minimal number of microvessels. Mechanistically, AAD-induced tumor hypoxia initiates the fatty acid oxidation metabolic reprogramming and increases uptake of free fatty acid (FFA) that stimulates cancer cell proliferation. Inhibition of carnitine palmitoyl transferase 1A (CPT1) significantly compromises the FFA-induced cell proliferation. Genetic and pharmacological loss of CPT1 function sensitizes AAD therapeutic efficacy and enhances its anti-tumor effects. Together, we propose an effective cancer therapy concept by combining drugs that target angiogenesis and lipid metabolism.

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abl1, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis. BC-CML is often associated with excessive phosphorylated eukaryotic translation initiation factor 4E (eIF4E), which renders LSCs capable of proliferating via self-renewal, oblivious to BCR-ABL1 inhibition. In vivo, eIF4E is exclusively phosphorylated on Ser209 by MNK1/2. Consequently, a selective inhibitor of MNK1/2 should reduce the level of phosphorylated eIF4E and re-sensitize LSCs to BCR-ABL1 inhibition, thus hindering the proliferation of BC LSCs. We report herein the structure-activity relationships and pharmacokinetic properties of a selective MNK1/2 inhibitor clinical candidate, ETC-206, which in combination with dasatinib prevents BC-CML LSC self-renewal in vitro and enhances dasatinib antitumor activity in vivo.

Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning.

Angiogenesis plays an instrumental role in the modulation of adipose tissue mass and metabolism. Targeting adipose vasculature provides an outstanding opportunity for treatment of obesity and metabolic disorders. Here, we report the physiological functions of VEGFR1 in the modulation of adipose angiogenesis, obesity, and global metabolism. Pharmacological inhibition and genetic deletion of endothelial VEGFR1 augmented adipose angiogenesis and browning of subcutaneous white adipose tissue, leading to elevated thermogenesis. In a diet-induced obesity model, endothelial-VEGFR1 deficiency demonstrated a potent anti-obesity effect by improving global metabolism. Along with metabolic changes, fatty liver and insulin sensitivity were also markedly improved in VEGFR1-deficient high fat diet (HFD)-fed mice. Together, our data indicate that targeting of VEGFR1 provides an exciting new opportunity for treatment of obesity and metabolic diseases, such as liver steatosis and type 2 diabetes.

A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning.

Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation. Pharmacological and physiological ß-adrenergic stimulation upregulates FGF10 levels and promotes preadipocyte differentiation into beige adipocytes. In vivo local delivery of miR-327 to WATs significantly compromises the beige phenotype and thermogenesis. Contrarily, systemic inhibition of miR-327 in mice induces browning and increases whole-body metabolic rate under thermoneutral conditions. Our data provide mechanistic insight into an autocrine regulatory signaling loop that regulates beige adipocyte formation and suggests that the miR-327-FGF10-FGFR2 signaling axis may be a therapeutic targets for treatment of obesity and metabolic diseases.