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Abstract Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up‐regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5‐, 3‐, and 1‐year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p

Water loss is a serious issue affecting the quality of postharvest horticultural products. Aquaporins (AQPs) regulate the transport of water across biological membranes, along the gradient of water potential, and may play a role in water loss. In this study, matured orange fruits (Citrus sinensis) stored at ambinent temperature (RH 85-95%) for 105 d showed that the weight loss persistently increased, and its rate peaked at 45–60 d and 90–105 d. Both water content and potential were higher in the pulp than in the peel. Water content rose before 60 d, and peel water potential fell with an increased gradient after 60 d. Comparing with peel, osmolytes such as soluble sugar, sucrose, glucose, fructose, and organic acids showed higher accumulation, and their levels were the lowest around 60 d. In contrast, soluble protein and inorganic minerals showed low levels of accumulation in the pulp. In total, 31 CsAQP genes were expressed in the fruit, and most of them were down-regulated in the peel but up-regulated in the pulp during storage. These genes were subsequently classified into four clusters based on their expression patterns. Genes in Cluster I — including CsNIP1;1/2;1/2;2/2;3/3;1/4;1/6;1, CsTIP1;3/2;2/2;3/5;1/6;1, CsXIP1;1/1;2, CsSIP1;2, and CsPIP1;2 — were persistently up-regulated in the pulp for the 105 d of storage, especially at day 60, when some genes showed 103-fold higher expression. Pearson’s correlation and principal component analysis further revealed a significant positive correlation among weight loss rate, water content, and water potential gradient (R2 = 0.85). Indexes positively correlated with osmolyte content and Cluster I gene expression in pulp samples suggest that increased CsAQP gene expression in pulp is linked to faster water loss in oranges, particularly at 60 days postharvest.

Abstract Orbital current, defined as the orbital character of Bloch states in solids, can travel with larger coherence length through a broader range of materials than its spin counterpart, facilitating a robust, higher density and energy efficient information transmission. Hence, active control of orbital transport plays a pivotal role in the progress of the evolving field of quantum information technology. Unlike spin angular momentum, orbital angular momentum couples to phonon angular momentum efficiently via orbital-crystal momentum (L-k) coupling, allowing us to control orbital transport through crystal field potential mediated angular momentum transfer. Here, leveraging the orbital dependant efficient L-k coupling, we have experimentally demonstrated the active control of orbital current velocity in Ni/Pt heterostructure. We observe terahertz emission from Ni/Pt heterostructure via long-range ballistic orbital transport, as evidenced by the delay, and chirping in the emitted THz pulse correlating with increased Pt thickness. Additionally, we also have identified a critical energy density required to overcome collisions in orbital transport, enabling a swifter flow of orbital current. Femtosecond light driven active control of the ballistic orbital transport lays the foundation for the development of dynamic optorbitronics for transmitting information over extended distance.

Current-induced spin–orbit torque (SOT) facilitates the ultrafast electrical manipulation of magnetic tunnel junction (MTJ), which is a leading non-volatile technology for the microelectronic industry. The key bottleneck to the commercial application of SOT-MTJ is the absence of a practicable symmetry-breaking scheme to switch perpendicular magnetization without an external magnetic field. Here, we demonstrate the wafer-scale realization of internalized field-free switching in perpendicular SOT-MTJ using conventional materials and device structure. We utilize a dual-function tungsten (W) spacer, which generates sizable SOT while concomitantly breaking symmetry via interlayer exchange coupling (IEC). Tuning the W thickness enables field-free switching with two types of IEC. An optimized combination of SOT and IEC ensures competitive switching performance, with our device exhibiting excellent thermal stability, low switching current density, and fast operating speed. This work builds the long-sought bridge between SOT manipulation of magnetization and wafer-scale field-free perpendicular MTJ. It underscores the urgent need to incorporate perpendicular SOT-MTJ in integrated circuits for applications in logic, memory, and unconventional computing.

Existing explanation methods for Convolutional Neural Networks (CNNs) lack the pixel-level visualization explanations to generate the reliable fine-grained decision features. Since there are inconsistencies between the explanation and the actual behavior of the model to be interpreted, we propose a Fine-Grained Visual Explanation for CNN, namely F-GVE, which produces a fine-grained explanation with higher consistency to the decision of the original model. The exact backward class-specific gradients with respect to the input image is obtained to highlight the object-related pixels the model used to make prediction. In addition, for better visualization and less noise, F-GVE selects an appropriate threshold to filter the gradient during the calculation and the explanation map is obtained by element-wise multiplying the gradient and the input image to show fine-grained classification decision features. Experimental results demonstrate that F-GVE has good visual performances and highlights the importance of fine-grained decision features. Moreover, the faithfulness of the explanation in this paper is high and it is effective and practical on troubleshooting and debugging detection.

Chiral Weyl fermions with linear energy-momentum dispersion in the bulk accompanied by Fermi-arc states on the surfaces prompt a host of enticing optical effects. While new Weyl semimetal materials keep emerging, the available optical probes are limited. In particular, isolating bulk and surface electrodynamics in Weyl conductors remains a challenge. We devised an approach to the problem based on near-field photocurrent imaging at the nanoscale and applied this technique to a prototypical Weyl semimetal TaIrTe4 As a first step, we visualized nano-photocurrent patterns in real space and demonstrated their connection to bulk nonlinear conductivity tensors through extensive modeling augmented with density functional theory calculations. Notably, our nanoscale probe gives access to not only the in-plane but also the out-of-plane electric fields so that it is feasible to interrogate all allowed nonlinear tensors including those that remained dormant in conventional far-field optics. Surface- and bulk-related nonlinear contributions are distinguished through their "symmetry fingerprints" in the photocurrent maps. Robust photocurrents also appear at mirror-symmetry breaking edges of TaIrTe4 single crystals that we assign to nonlinear conductivity tensors forbidden in the bulk. Nano-photocurrent spectroscopy at the boundary reveals a strong resonance structure absent in the interior of the sample, providing evidence for elusive surface states.

Topological spin textures are field arrangements that cannot be continuously deformed to a fully polarized state. In particular, merons are topological textures characterized by half-integer topological charge ±1/2 and vortex-like swirling patterns at large distances. Merons have been studied previously in the context of cosmology, fluid dynamics, condensed matter physics and plasmonics. Here, we visualized optical spin angular momentum of phonon polaritons that resembles nanoscale meron spin textures. Phonon polaritons, hybrids of infrared photons and phonons in hexagonal boron nitride, were excited by circularly polarized light incident on a ring-shaped antenna and imaged using infrared near-field techniques. The polariton field reveals a half-integer topological charge determined by the handedness of the incident beam. Our phonon polaritonic platform opens up new pathways to create, control, and visualize topological textures.

Efficient control of photons is enabled by hybridizing light with matter. The resulting light-matter quasi-particles can be readily programmed by manipulating either their photonic or matter constituents. Here, we hybridized infrared photons with graphene Dirac electrons to form surface plasmon polaritons (SPPs) and uncovered a previously unexplored means to control SPPs in structures with periodically modulated carrier density. In these periodic structures, common SPPs with continuous dispersion are transformed into Bloch polaritons with attendant discrete bands separated by bandgaps. We explored directional Bloch polaritons and steered their propagation by dialing the proper gate voltage. Fourier analysis of the near-field images corroborates that this on-demand nano-optics functionality is rooted in the polaritonic band structure. Our programmable polaritonic platform paves the way for the much-sought benefits of on-the-chip photonic circuits.

Abstract Background Due to the poor specificity of D-dimer, more accurate thrombus biomarkers are clinically needed to improve the diagnostic power of VTE. Methods The plasma samples were classified into low-risk group (n = 6) and high-risk group (n = 6) according to the Caprini Thrombosis Risk Assessment Scale score. Data-independent acquisition mass spectrometry (DIA-MS) was performed to identify the proteins in the 12 plasma samples. Bioinformatics analysis including volcano plot, heatmap, KEGG pathways and chord diagram analysis were drawn to analyze the significantly differentially expressed proteins (DEPs) between the two groups. Then, another 26 plasma samples were collected to verify the key proteins as potential biomarkers of VTE in orthopedic surgery patients. Results A total of 371 proteins were identified by DIA-MS in 12 plasma samples. Volcano plotting showed that there were 30 DEPs. KEGG pathway enrichment analysis revealed that the DEPs were majorly involved in the blood coagulation pathway. The chord diagram analysis demonstrated that proteins SAA1, VWF, FLNA, ACTB, VINC, F13B, F13A and IPSP in the DEPs were significantly related to blood coagulation. VWF and F13B were selected for validation experiments. ELISA test showed that, as compared with those in the low-risk group, the level of VWF in the high-risk sera was significantly increased. Conclusions The level of VWF in the high-risk group of thrombosis after orthopedic surgery was significantly higher than that in the low-risk group of preoperative thrombosis, suggesting that VWF may be used as a potential thrombus biomarker in orthopedic surgery patients.

Abstract Low dielectric constant (k) polymers with excellent comprehensive properties are useful materials in the microelectronics industry as matrix resins or encapsulation layers. With the inherent low polarization, high reactivity, good processability, and low cost, poly(dicyclopentadiene) (PDCPD) has received considerable attention as low‐k materials. However, its practical application is limited by the relatively high thermal expansion and k value. Herein, three norbornene‐functionalized polyhedral oligomeric silsesquioxanes (POSSs) with T8, T10, and T12 polyhedral cores are synthesized and employed for enhancing the dielectric and comprehensive properties of PDCPD via reactive blending. The results show that these POSSs have good compatibility with PDCPD matrix and nano‐dispersed POSSs particles could be obtained. As a result, the materials’ properties can be largely enhanced by varying the POSS content and POSS size. Especially, PT12N12‐40 (40 wt% of T12N12) shows the lowest k value (2.1) and coefficient of thermal expansion (63.4 ppm°C−1), highest glass transition temperature (202.5 °C), yield strength (78.0 MPa), and elastic modulus (2.36 GPa), along with excellent hydrophobicity. This study highlights a useful strategy to fabricate high‐performance low‐k polymer nanocomposites by using larger POSS and reactive blending, which provides useful materials for the future microelectronic industry and high frequency communication.

Van-der Waals (vdW) atomically layered crystals can act as optical waveguides over a broad range of the electromagnetic spectrum ranging from Terahertz to visible. Unlike common Si-based waveguides, vdW semiconductors host strong excitonic resonances that may be controlled using non-thermal stimuli including electrostatic gating and photoexcitation. Here, we utilize waveguide modes to examine photo-induced changes of excitons in the prototypical vdW semiconductor, WSe2, prompted by femtosecond light pulses. Using time-resolved scanning near-field optical microscopy we visualize the electric field profiles of waveguide modes in real space and time and extract the temporal evolution of the optical constants following femtosecond photoexcitation. By monitoring the phase velocity of the waveguide modes, we detect incoherent A-exciton bleaching along with a coherent optical Stark shift in WSe2.

Drug resistance in tumours has seriously hindered the therapeutic effect. Tumour drug resistance is divided into primary resistance and acquired resistance, and the recent study has found that a significant proportion of cancer cells can acquire stable drug resistance from scratch. This group of cells first enters the drug tolerance state (DT state) under drug pressure, and gradually acquires stable drug resistance through adaptive mutations in this state. Although the specific mechanisms underlying the formation of drug tolerant cells (DTCs) remain unclear, various proteins and signalling pathways have been identified as being involved in the formation of DTCs. In the current review, we summarize the characteristics, molecular mechanisms and therapeutic strategies of DTCs in detail.

IntroductionDifferent studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke.MethodsWe performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsA total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15–1.40), CHD (RR = 1.25, 95% CI: 1.11–1.41), and HF (RR = 1.92, 95% CI: 1.51–2.45). The MACE risk increased by 10% (95% CI: 6%–15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%–83%) for an additional 10 μg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29–17.58) cases per 1,000 person-years.ConclusionsAdministration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

Precise synthesis of high‐quality, sophisticated heterostructures by ordered assembly of small nanomaterials is a key step to gain advanced materials that have elaborate functionalities, collective properties, and enhanced stabilities for mitigating the energy and environment crisis. Intricating in the structure, size, and shape of nanomaterials, ordered assembly of isotropic or anisotropic nanoscale building blocks to create specified heterostructures remains challenging, owing to the extraordinary challenges in design of lattice topology of distinct nanounits and in control of their crystallization, growth, and assembly mechanism/kinetics. Herein, the emerging methodologies to prepare a diversity of ordered heterostructures with strengthened particle–particle interaction are examined and synergistic properties are enhanced. It is aimed to unlock the principles to regulate the geometrical and electronic properties of these intriguing kinds of heterostructures for respective sustainable energy and environmental applications. Current challenges and opportunities in customization of ordered heterostructure at the nanoscale and atomic level are also discussed.

Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs.

Summary: There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.