Transformer-CNN hybrid network for improving PET time of flight prediction.

Objective.In positron emission tomography (PET) reconstruction, the integration of time-of-flight (TOF) information, known as TOF-PET, has been a major research focus. Compared to traditional reconstruction methods, the introduction of TOF enhances the signal-to-noise ratio of images. Precision in TOF is measured by full width at half maximum (FWHM) and the offset from ground truth, referred to as coincidence time resolution (CTR) and bias.Approach.This study proposes a network combining transformer and convolutional neural network (CNN) to utilize TOF information from detector waveforms, using event waveform pairs as inputs. This approach integrates the global self-attention mechanism of Transformer, which focuses on temporal relationships, with the local receptive field of CNN. The combination of global and local information allows the network to assign greater weight to the rising edges of waveforms, thereby extracting valuable temporal information for precise TOF predictions. Experiments were conducted using lutetium yttrium oxyorthosilicate (LYSO) scintillators and silicon photomultiplier (SiPM) detectors. The network was trained and tested using the waveform datasets after cropping.Main results.Compared to the constant fraction discriminator (CFD), CNN, CNN with attention, long short-term memory (LSTM) and Transformer, our network achieved an average CTR of 189 ps, reducing it by 82 ps (more than 30%), 13 ps (6.4%), 12 ps (6.0%), 16 ps (7.8%) and 9 ps (4.6%), respectively. Additionally, a reduction of 10.3, 8.7, 6.7 and 4 ps in average bias was achieved compared to CNN, CNN with attention, LSTM and Transformer.Significance.This work demonstrates the potential of applying the Transformer for PET TOF estimation using real experimental data. Through the integration of both CNN and Transformer with local and global attention, it achieves optimal performance, thereby presenting a novel direction for future research in this field.

Characterization of the Tumor Microenvironment in Osteosarcoma Identifies Prognostic- and Immunotherapy-Relevant Gene Signatures.

The osteosarcoma (OS) microenvironment is composed of tumor cells, immune cells, and stromal tissue and is emerging as a pivotal player in OS development and progression. Thus, microenvironment-targeted strategies are urgently needed to improve OS treatment outcomes. Using principal component analysis (PCA), we systematically examined the tumor microenvironment (TME) and immune cell infiltration of 88 OS cases and constructed a TME scoring system based on the TMEscore high and TMEscore low phenotypes. Our analysis revealed that TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy. TMEscore low strongly correlated with immune exclusion. These observations were externally validated using a GEO dataset (GSE21257) from 53 OS patients. Our laboratory data also proved our findings. This finding enhances our understanding of the immunological landscape in OS and may uncover novel targeted therapeutic strategies.

A SOX17-PDGFB signaling axis regulates aortic root development.

Developmental etiologies causing complex congenital aortic root abnormalities are unknown. Here we show that deletion of Sox17 in aortic root endothelium in mice causes underdeveloped aortic root leading to a bicuspid aortic valve due to the absence of non-coronary leaflet and mispositioned left coronary ostium. The respective defects are associated with reduced proliferation of non-coronary leaflet mesenchyme and aortic root smooth muscle derived from the second heart field cardiomyocytes. Mechanistically, SOX17 occupies a Pdgfb transcriptional enhancer to promote its transcription and Sox17 deletion inhibits the endothelial Pdgfb transcription and PDGFB growth signaling to the non-coronary leaflet mesenchyme. Restoration of PDGFB in aortic root endothelium rescues the non-coronary leaflet and left coronary ostium defects in Sox17 nulls. These data support a SOX17-PDGFB axis underlying aortic root development that is critical for aortic valve and coronary ostium patterning, thereby informing a potential shared disease mechanism for concurrent anomalous aortic valve and coronary arteries.

DEPP Deficiency Contributes to Browning of White Adipose Tissue.

Decidual protein induced by progesterone (DEPP) was originally identified as a modulator in the process of decidualization in the endometrium. Here, we define that DEPP is involved in adipose tissue thermogenesis, which contributes to metabolic regulation. Knockdown of DEPP suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 cells, induced expression of brown adipose tissue (BAT) markers in primary brown adipocyte and induced mouse embryonic fibroblasts (MEFs) differentiation to brown adipocytes. Moreover, DEPP deficiency in mice induced white adipocyte browning and enhanced BAT activity. Cold exposure stimulated more browning of white adipose tissue (WAT) and maintained higher body temperature in DEPP knockout mice compared to that in wild-type control mice. DEPP deficiency also protected mice against high-fat-diet-induced insulin resistance. Mechanistic studies demonstrated that DEPP competitively binds SIRT1, inhibiting the interaction between peroxisome proliferator-activated receptor gamma (PPARγ) and Sirtuin 1 (SIRT1). Collectively, these findings suggest that DEPP plays a crucial role in orchestrating thermogenesis through regulating adipocyte programs and thus might be a potential target for the treatment of metabolic disorders.

Effects of Aging Process on the Damping Performance of ZK60 Magnesium Alloys Prepared by Large Strain Rolling.

In this study, the effects of an aging treatment (T5) and a solution + aging treatment (T6) on the microstructure and damping properties of a ZK60 magnesium alloy prepared by large strain rolling (LSR) were studied by an optical microscope (OM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic thermomechanical analysis (DMA). The results showed that both the T5 and T6 processes had a great impact on the microstructure and damping properties of the ZK60 magnesium alloy. With the increase in aging time, the grain size was basically unchanged, and the amount of the second phase increased, resulting in a gradual decrease in the damping performance. However, compared with the damping performance of the un-aged ZK60 magnesium alloy, the damping performance of the 4 h-aged ZK60 magnesium alloy was enhanced. At the same aging time, the increase in the aging temperature promoted the precipitation of the second phase, thereby reducing the damping performance of the ZK60 magnesium alloy. It was found that the T6-treated ZK60 magnesium alloy had a larger grain size, which led to a better damping performance; in addition, the T6-treated ZK60 magnesium alloy exhibited a damping plateau, which was determined by the distribution and amount of the second phase.

Effect of the Strain Rate on the Damping and Mechanical Properties of a ZK60 Magnesium Alloy.

High strain rate rolling (HRSS) of a ZK60 magnesium alloy at 300 °C with a strain rate from 5 s-1 to 25 s-1 was used to research the effect of the rate on the mechanical properties and damping capacity of the ZK60 alloy. The results show that as the strain rate increases, the tensile strength decreases from 355 MPa at 25 s-1 to 310 MPa at 5 s-1. Two damping peaks (P1 and P2) are detected in the high strain rate rolled ZK60 alloys at different strain rates. The P1 peak appears at low temperatures and is caused by grain boundaries sliding. The P2 peak appears at high temperatures and is caused by recrystallization. As the strain rate increases from 5 to 20 s-1, the dynamic recrystallization (DRX) volume percent rises and the dislocation density decreases, both of which cause the P1 peak to become more and more obvious, and activation energy rises. At the same time, the dislocation density decreases and leads to a decrease in the storage energy, which reduces the recrystallization driving force and shifts the P2 peak to high temperatures. When the strain rate reaches 20 and 25 s-1, DRX occurs fully in the sheet, so the activation energy of the P1 peak and the temperature where the P2 peak appears are basically equal.

An integrated electrocoagulation - Electrocatalysis water treatment process using stainless steel cathodes coated with ultrathin TiO2 nanofilms.

Anodic electrocoagulation processes can remove broad varieties of pollutants in industrial wastewater. However, some stubborn contaminants may still remain in effluents after the treatment and cause environmental issues. To further improve the efficiency of pollutant removal, we have coupled electrocatalysis with electrocoagulation and applied an atomic layer deposition (ALD) enabled TiO2 ultrathin overcoating at a nanometer scale on a stainless steel cathode. The electrocatalytic overcoating increased the elimination efficiency of organics and microorganisms, likely due to the electro-generation of adequate reactive oxygen species (ROS). The thickness of TiO2 nanofilm was controlled by the number of ALD cycles, and it was found that nanofilms processed with 50-100 cycles led to the maximum benefit of pollutant removal. By using the novel electrocoagulation-electrocatalysis cell to treat synthetic wastewater, a remarkable removal of 99.92% of E. Coli, 92.1% of suspended solids, 98.3% of heavy metal ions, and 88.8% of methylene blue was observed. This hybrid electrochemical treatment process may have the potential to treat wastewater at a larger scale.

Photocatalytic degradation of phenol in water under simulated sunlight by an ultrathin MgO coated Ag/TiO2 nanocomposite.

Phenol is one of the most widespread, toxic and recalcitrant compounds in water sources. Due to its persistent nature, conventional wastewater treatment methods are not effective to remove or degrade phenol from water. In this work, novel photocatalysts were developed to effectively degrade phenol under simulated sunlight. The catalysts were composed of one-dimensional titanium dioxide (TiO2) nanorods decorated with silver (Ag) nanoparticles, coated by an ultrathin magnesium oxide (MgO) overlayer through atomic layer deposition (ALD). Material properties of prepared catalysts were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and UV-vis diffuse reflectance spectroscopy (UV-Vis DRS). The photocatalytic performance of phenol degradation under simulated sunlight was evaluated and correlated with the material properties. The Ag nanoparticles promoted light absorption and transfer of photo-induced electron-hole pairs from within TiO2 nanorods to the catalyst surface. The ultrathin MgO overlayer with a sub-nanometer thickness did not hinder charge transfer to the surface, but rather, it further increased the light absorption and inhibited surface charge recombination through a surface passivation effect, promoting phenol degradation. The photocatalytic reaction mechanism was investigated by examining hydroxyl and superoxide radical production in the photocatalytic system. The results from this work demonstrated a new strategy for fabricating efficient solar-driven photocatalysts for the degradation of persistent water contaminants.

Ultracompliant Heterogeneous Copper-Tin Nanowire Arrays Making a Supersolder.

Due to the substantial increase in power density, thermal interface resistance that can constitute more than 50% of the total thermal resistance has generally become a bottleneck for thermal management in electronics. However, conventional thermal interface materials (TIMs) such as solder, epoxy, gel, and grease cannot fulfill the requirements of electronics for high-power and long-term operation. Here, we demonstrate a high-performance TIM consisting of a heterogeneous copper-tin nanowire array, which we term "supersolder" to emulate the role of conventional solders in bonding various surfaces. The supersolder is ultracompliant with a shear modulus 2-3 orders of magnitude lower than traditional solders and can reduce the thermal resistance by two times as compared with the state-of-the-art TIMs. This supersolder also exhibits excellent long-term reliability with >1200 thermal cycles over a wide temperature range. By resolving this critical thermal bottleneck, the supersolder enables electronic systems, ranging from microelectronics and portable electronics to massive data centers, to operate at lower temperatures with higher power density and reliability.

SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression.

Acute lymphoblastic leukemia (ALL) is associated with significant morbidity and mortality, necessitating further improvements in diagnosis and therapy. Targeted therapies directed against chromatin regulators are emerging as promising approaches in preclinical studies and early clinical trials. Here, we demonstrate an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR+ ALL and required for their maintenance in vitro and in vivo. SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1 in a subset of ALL and suppresses expression of the cell-cycle inhibitor CDKN2C through histone H3K9 tri-methylation, thus establishing an oncogenic pathway subordinate to E2A-PBX1 that silences a major tumor suppressor in ALL. In contrast, SETDB2 was relatively dispensable for normal hematopoietic stem and progenitor cell proliferation. SETDB2 knockdown enhances sensitivity to kinase and chromatin inhibitors, providing a mechanistic rationale for targeting SETDB2 therapeutically in ALL.

Visible-Light-Driven Photocatalytic Degradation of Organic Water Pollutants Promoted by Sulfite Addition.

Solar-driven heterogeneous photocatalysis has been widely studied as a promising technique for degradation of organic pollutants in wastewater. Herein, we have developed a sulfite-enhanced visible-light-driven photodegradation process using BiOBr/methyl orange (MO) as the model photocatalyst/pollutant system. We found that the degradation rate of MO was greatly enhanced by sulfite, and the enhancement increased with the concentration of sulfite. The degradation rate constant was improved by 29 times in the presence of 20 mM sulfite. Studies using hole scavengers suggest that sulfite radicals generated by the reactions of sulfite (sulfite anions or bisulfite anions) with holes or hydroxyl radicals are the active species for MO photodegradation using BiOBr under visible light. In addition to the BiOBr/MO system, the sulfite-assisted photocatalysis approach has been successfully demonstrated in BiOBr/rhodamine B (RhB), BiOBr/phenol, BiOI/MO, and Bi2O3/MO systems under visible light irradiation, as well as in TiO2/MO system under simulated sunlight irradiation. The developed method implies the potential of introducing external active species to improve photodegradation of organic pollutants and the beneficial use of air pollutants for the removal of water pollutants since sulfite is a waste from flue gas desulfurization process.

Metal-Organic-Inorganic Nanocomposite Thermal Interface Materials with Ultralow Thermal Resistances.

As electronic devices get smaller and more powerful, energy density of energy storage devices increases continuously, and moving components of machinery operate at higher speeds, the need for better thermal management strategies is becoming increasingly important. The removal of heat dissipated during the operation of electronic, electrochemical, and mechanical devices is facilitated by high-performance thermal interface materials (TIMs) which are utilized to couple devices to heat sinks. Herein, we report a new class of TIMs involving the chemical integration of boron nitride nanosheets (BNNS), soft organic linkers, and a copper matrix-which are prepared by the chemisorption-coupled electrodeposition approach. These hybrid nanocomposites demonstrate bulk thermal conductivities ranging from 211 to 277 W/(m K), which are very high considering their relatively low elastic modulus values on the order of 21.2-28.5 GPa. The synergistic combination of these properties led to the ultralow total thermal resistivity values in the range of 0.38-0.56 mm2 K/W for a typical bond-line thickness of 30-50 µm, advancing the current state-of-art transformatively. Moreover, its coefficient of thermal expansion (CTE) is 11 ppm/K, forming a mediation zone with a low thermally induced axial stress due to its close proximity to the CTE of most coupling surfaces needing thermal management.

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment.

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-ß2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-ß2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.

Unveiling the adsorption mechanism of zeolitic imidazolate framework-8 with high efficiency for removal of copper ions from aqueous solutions.

Among the heavy metal ions, copper(ii) can cause eye and liver damage at high uptake. The existence of copper ions (Cu(2+)) even with an ultralow concentration of less than 0.1 µg g(-1) can be toxic to living organisms. Thus, it is highly desirable to develop efficient adsorbents to remove Cu(2+) from aqueous solutions. In this work, without any surface functionalization or pretreatment, a water-stable zeolitic imidazolate framework (ZIF-8) synthesized at room temperature is directly used as a highly efficient adsorbent for removal of copper ions from aqueous solutions. To experimentally unveil the adsorption mechanism of Cu(2+) by using ZIF-8, we explore various effects from a series of important factors, such as pH value, contact time, temperature and initial Cu(2+) concentration. As a result, ZIF-8 nanocrystals demonstrate an unexpected high adsorption capacity of Cu(2+) and high removal efficiency for both high and low concentrations of Cu(2+) from water. Moreover, ZIF-8 nanocrystals possess fast kinetics for removing Cu(2+) with the adsorption time of less than 30 min. In addition, the pH of the solution ranging from 3 to 6 shows little effect on the adsorption of Cu(2+) by ZIF-8. The adsorption mechanism is proposed for the first time and systematically verified by various characterization techniques, such as TEM, FTIR, XPS, XRD and SEM.

Kr/Xe Separation over a Chabazite Zeolite Membrane.

Herein we demonstrate that chabazite zeolite SAPO-34 membranes effectively separated Kr/Xe gas mixtures at industrially relevant compositions. Control over membrane thickness and average crystal size led to industrial range permeances and high separation selectivities. Specifically, SAPO-34 membranes can separate Kr/Xe mixtures with Kr permeances as high as 1.2 × 10 (-7) mol/m(2) s Pa and separation selectivities of 35 for molar compositions close to typical concentrations of these two gases in air. In addition, SAPO-34 membranes separated Kr/Xe mixtures with Kr permeances as high as 1.2 × 10 (-7) mol/m(2) s Pa and separation selectivities up to 45 for molar compositions as might be encountered in nuclear reprocessing technologies. Molecular sieving and differences in diffusivities were identified as the dominant separation mechanisms.

Hierarchical Sandwich-Like Structure of Ultrafine N-Rich Porous Carbon Nanospheres Grown on Graphene Sheets as Superior Lithium-Ion Battery Anodes.

A sandwich-like, graphene-based porous nitrogen-doped carbon (PNCs@Gr) has been prepared through facile pyrolysis of zeolitic imidazolate framework nanoparticles in situ grown on graphene oxide (GO) (ZIF-8@GO). Such sandwich-like nanostructure can be used as anode material in lithium ion batteries, exhibiting remarkable capacities, outstanding rate capability, and cycling performances that are some of the best results among carbonaceous electrode materials and exceed most metal oxide-based anode materials derived from metal orgainc frameworks (MOFs). Apart from a high initial capacity of 1378 mAh g(-1) at 100 mA g(-1), this PNCs@Gr electrode can be cycled at high specific currents of 500 and 1000 mA g(-1) with very stable reversible capacities of 1070 and 948 mAh g(-1) to 100 and 200 cycles, respectively. At a higher specific current of 5000 mA g(-1), the electrode still delivers a reversible capacity of over 530 mAh g(-1) after 400 cycles, showing a capacity retention of as high as 84.4%. Such an impressive electrochemical performance is ascribed to the ideal combination of hierarchically porous structure, a highly conductive graphene platform, and high-level nitrogen doping in the sandwich-like PNCs@Gr electrode obtained via in situ synthesis.