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Recently, phubbing has led to a significant increase in neck-related diseases such as cervical disk (CVD) herniation. CVDs experience a typical pressure of approximately 200 kPa in the upright position, which increases dramatically with the degrees of flexion. Thus, there is a high probability for patients who have undergone the cervical artificial disk replacement surgery to have the revision surgery owing to inappropriate postures. Herein, a highly sensitive piezoresistive pressure sensor array with a wide sensing range of up to 1000 kPa, using polyethylene oxide (PEO) as the sensing membrane and polyaniline (PANI) as the conductive filler, is proposed to real-time monitor the pressure distribution on CVDs. The optimal PANI doping concentration in PANI:PEO composite films was determined to be 0.1%, which demonstrated excellent sensitivity of 0.279 kPa $^{-{1}}$ , a high coefficient of determination ( ${R} ^{{2}}$ ) of 0.959, and a short relaxation time of 0.72 s of the PANI:PEO piezoresistive pressure sensors. To accommodate the sensor array within the limited space of the cervical vertebrae, the electrode size of the devices was significantly reduced to less than $100~\mu $ m to realize a $2\times 3$ PANI:PEO piezoresistive pressure sensor array. The fabricated pressure sensor array effectively monitored the pressure distribution on CVDs in a cervical spine model with a full cervical spine and dual cervical vertebrae under different flexion angles, holding favorable potential to avoid further CVD herniation after the cervical artificial disk replacement surgery.

In digital integrated circuits with multiple power domains, level shifters (LSs) are essential circuit elements that can transform the voltage region from low to high. However, high-frequency gate drivers can generate hundreds of voltages per nanosecond noise (high dV/dt noise). Such high dV/dt noise can cause malfunction of a conventional pulse-triggered cross-coupled LS (CCLS) that is used to control the high-side nMOS switch. In this article, a novel LS with noise immunity is proposed and investigated. Compared with the conventional resistor load LS, the proposed circuit adopts nMOS-R cross-coupled (NRCC) LS, and realizes the selective filtering ability by exploiting the path that filters out the noise introduced by the dV/dt. The high-voltage gate drive integrated circuit (HVIC) is implemented using a 600 V silicon-on-insulator (SOI) BCD process. Analyses and experiments show that the proposed design can help the HVIC maintain a high common-mode transient immunity (CMTI) of up to 137 V/ns while allowing a negative VS swing down to -9.4 V under a 15 V supply voltage. Compared with the traditional HVIC with resistance load LS, the proposed novel HVIC with the NRCC LS improves the noise immunity of dV/dt by 182%.

NiFeCo/Cu has excellent magnetoresistive properties and is a crucial magnetic material. However, its plastic deformation and microstructural behavior under nano-cutting remain unclear. This study investigated the effects of the number of layers and surface textures on the machining characteristics of NiFeCo/Cu polycrystalline/single-crystal multilayers using molecular dynamics simulation. The results indicated that the interface between polycrystalline NiFeCo and single-crystal Cu prevents the diffusion of shear bands, von Mises stress, atomic displacement, temperature, and dislocation in substrates. Since the interface barrier effectively limited the dislocation propagation, the dislocation concentrated in the first layer above, resulting in more hardening. The interface phase transformation and merging with the grain boundary during cutting. Moreover, the NiFeCo/Cu multilayers had a lower dislocation density than the NiFeCo alloy. The surface textures decide the effect of the number of layers on cutting characteristics. Dislocation density is sensitive to the number of layers of the smooth and square surface textures, while it insignificantly changes when the number of layers increases for the rectangle surface. The cutting forces are the smallest in the square surface for all number of layers. The dislocation splitting was generated in the single-crystal Cu layer of the rectangular and square surface substrates.

Gesture sensors are essential to collect human movements for human–computer interfaces, but their application is normally hampered by the difficulties in achieving high sensitivity and an ultrawide response range simultaneously. In this article, inspired by the spider silk structure in nature, a novel gesture sensor with a core–shell structure is proposed. The sensor offers a high gauge factor of up to 340 and a wide response range of 60%. Moreover, the sensor combining with a deep learning technique creates a system for precise gesture recognition. The system demonstrated an impressive 99% accuracy in single gesture recognition tests. Meanwhile, by using the sliding window technology and large language model, a high performance of 97% accuracy is achieved in continuous sentence recognition. In summary, the proposed high-performance sensor significantly improves the sensitivity and response range of the gesture recognition sensor. Meanwhile, the neural network technology is combined to further improve the way of daily communication by sign language users.

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2(protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood–brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50–100% of mice. Our study identifies a promising multi-targetable PTP4A–ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors.

Herein, we developed a series of benzo[1,3]oxazinyloxazolidinones as potent antibacterial agents. Some of the compounds exhibited potent antibacterial activity against a range of clinical drug-resistant pathogens, including Mtb, MRSA, MRSE, VISA, and VRE. Notably, compound 16dinhibited protein synthesis and displayed potent activity against linezolid-resistant Enterococcus faecalis. Although 16dshowed cross-resistance to linezolid-resistant MRSA, the frequency of resistance development of MRSA against 16dwas lower compared to that of linezolid. Additionally, 16dexhibited excellent pharmacokinetic properties and superior in vivoefficacy compared to linezolid. Furthermore, compound 16dmodulated cytokine levels and ameliorated histopathological changes in major organs of bacterially infected mice. Hoechst-PI double staining and scanning electron microscopy analyses revealed that 16dexhibited some similarities with linezolid in its effects while also demonstrating a distinct mechanism characterized by cell membrane damage. Moreover, 16dsignificantly disrupted the MRSA biofilms. The antibacterial agent 16drepresents a promising candidate for the treatment of serious infections caused by drug-resistant bacteria.

Tuberculosis (TB) remains a major public health challenge, with research on new anti-TB drugs crucial for global TB elimination efforts. Here, we report a novel class of anti-TB agents. Especially, compounds 5band 5jexhibited the highest activity [minimum inhibitory concentration (MIC) H37Rv: 0.16 and 0.12 μg/mL]. Chiral resolution was performed on compounds 5band 5j; the isomers were evaluated for their activity and safety, confirming that the R-isomer 5bband 5jbdisplayed significant anti-TB activity (MIC H37Rv: 0.03–0.06 μg/mL; MDR-Mtb: 0.125–0.06 μg/mL) and low hERG toxicity. Further evaluations on 5bband 5jbdemonstrated good metabolic stability, favorable kinetic parameters and oral bioavailability (F: 56.7 and 63.8%, respectively). The results of in vivoactivity assessment indicate that 5bband 5jbexhibit protective and therapeutic effects on zebrafish larvae and adult zebrafish infected with Mycobacterium marinum. Based on these results, compounds 5bband 5jbare considered promising candidates for further in-depth studies.

This article investigates the degradation mechanism in dV/dt noise immunity robustness of traditional resistive load level shifters (LSs) under total-ionizing-dose (TID) irradiation and proposes a novel radiation-hardened nMOS-R cross-coupled (NRCC) LS with dV/dt noise immunity. When TID irradiation induces threshold voltage drift and increases the off-state leakage current in power devices, the proposed circuit employs a differential and complementary structure to counteract the degradation of electrical performance in both branches caused by the TID irradiation, thereby achieving improved radiation-hardening performance. Measurement results demonstrate that the proposed high-voltage gate drive integrated circuit (HVIC) with the novel LS level exhibits 130-V/ns noise immunity at the irradiation dose of 100 krad(Si). A normalization method is used to process measurement results for visual comparison. The degradation of dV/dt noise immunity capability of the proposed LS is improved by 26.8%, 72.4%, and 94.9% compared with the traditional LS at the irradiation dose of 30, 50, and 100 krad(Si). The HVIC is implemented using a 600-V silicon-on-insulator (SOI) BCD process.

Promoting electric vehicles (EVs) is regarded as an effective solution for reducing carbon emissions and addressing growing environmental concerns. However, the increasing number of EVs has significantly heightened the demand for electric power charging, posing challenges to distribution systems. Studies have shown that a coordination strategy combining various compensation devices, such as energy storage systems and reactive power compensation devices, can enhance the integration capability of EVs. Furthermore, EVs can be managed as controllable loads that can be shed at low costs, contributing to the flexibility of the distribution network. This paper explores the uncertainties of EV load sizes and the coordination of active and reactive power. A multi-objective optimization model was developed to augment the flexibility of the distribution network and mitigate the risk of load shedding. The Monte Carlo method is utilized to simulate scenarios with EV load uncertainties. To simplify the power flow calculations in the proposed convex optimization model, the Distflow equation was adopted. Case study results demonstrate that managing EV loads in the distribution network can significantly reduce load shedding costs by 80 %, and the proposed EV charging strategy can effectively eliminate load shedding costs in most scenarios.

Integrated diagnostic and therapeutic dressings are desirable to relieve diabetic patients who often suffer from diabetic foot ulcers (DFUs) and peripheral vascular diseases (PVDs). However, it is highly difficult to monitor the pulse waves with fidelity under wet environments and connect the waveforms to diseases through a small strain sensor. Additionally, immobilizing MXenzyme to regulate spatially heterogeneous levels of reactive oxygen species (ROS) and applying active intervention to enhance ulcer healing on a single structure remain a complex task. To address these issues, we designed a multiscale wearable dressing comprising a knitted all-textile sensing array for quantitatively investigating the pulse wave toward PVD diagnosis. MXenzyme was loaded onto the dressing to provide multiple enzyme mimics for anti-inflammatory activities and deliver electrical stimulation to promote wound growth. In mice, we demonstrate that high and uniform expression of the vascular endothelial growth factor (VEGF) is observed only in the group undergoing dual mediation with electrical stimulation and MXenzyme. This observation indicates that the engineered wound dressing has the capability to accelerate healing in DFU. In human patient evaluations, the engineered dressing distinguishes vascular compliance and pulse period, enabling the diagnosis of arteriosclerosis and return blockage, two typical PVDs. The designed and engineered multiscale dressing achieves the purpose of integrating diagnostic peripheral vessel health monitoring and ulcer healing therapeutics for satisfying the practical clinical requirements of geriatric patients.

In order to explore the air ingestion characteristics of the open-ends squeeze film dampers (SFD), a 3D computational fluid dynamics solution model of the SFD was proposed based. The setting of opening boundary conditions was considered, which was verified experimentally by the bidirectional excitation. The results revealed that with the same precession frequency, the smaller radial clearance leads to the greater oil film damping. An increasing oil supply and oil holes led to the smaller air ingestion range at the end. The design guideline for the open-ends SFD was investigated in the present work.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5showed high affinity toward hTERT G4 (Kd= 1.1 μM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50= 1 μM). In cell-based assays, 5not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivoantitumor efficacy of 5was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.

Achieving high guest loading and multiguest-binding capacity holds crucial significance for advancement in separation, catalysis, and drug delivery with synthetic receptors; however, it remains a challenging bottleneck in characterization of high-stoichiometry guest-binding events. Herein, we describe a large-sized coordination cage (MOC-70-Zn8Pd6) possessing 12 peripheral pockets capable of accommodating multiple guests and a high-resolution electrospray ionization mass spectrometry (HR-ESI–MS)-based method to understand the solution host–guest chemistry. A diverse range of bulky guests, varying from drug molecules to rigid fullerenes as well as flexible host molecules of crown ethers and calixarenes, could be loaded into open pockets with high capacities. Notably, these hollow cage pockets provide multisites to capture different guests, showing heteroguest coloading behavior to capture binary, ternary, or even quaternary guests. Moreover, a pair of commercially applied drugs for the combination therapy of chronic lymphocytic leukemia (CLL) has been tested, highlighting its potential in multidrug delivery for combined treatment.

The rapid development of the antimissile weapon systems brings new challenges to the cooperative penetration strategy solution and the guidance law design for hypersonic vehicles (HVs). This article studies the cooperative game penetration guidance problem for multiple HVs with performance constraints. A cooperative differential game model for HVs is proposed wherein a cooperative gain is incorporated to assign maneuvering ratios in different cooperative missions and the ground target is considered as a member of the interceptor swarm to be able to attack the target after penetration. Then, an improved prescribed performance adaptive dynamic programming (ADP) algorithm is developed to seek the Nash equilibrium guidance solution quickly and accurately. In order to ensure the steady-state and transient approximation performance of neural networks strictly, a prescribed performance function is introduced into the weight updating law design. Using the developed strategies, it is proven that the desired approximation performance in ADP can be achieved. Finally, a comparative simulation with a two-on-three game is conducted to verify the effectiveness of the proposed method.

In this article, we propose the novel core-shell Si/InxGa $_{{1}- {x}}$ As FinFETs, where an In $_{{0}.{53}}$ Ga $_{{0}.{47}}$ As shell channel was epitaxially grown on a silicon core fin. Based on the model calibrated using conventional bulk In $_{{0}.{53}}$ Ga $_{{0}.{47}}$ As FinFET, the device characteristics, including dc and RF performance of the core-shell FinFET, were analyzed and compared with the bulk FinFET. Due to the conduction band offset between InxGa $_{{1}- {x}}$ As shell and Si fin, a quantum well is formed in the InxGa $_{{1}- {x}}$ As channel region, which is lying between the high dielectric constant (HK) gate and the Si core. The advantages of the core-shell FinFET include increasing the gate controllability, enhancing the effective bandgap, and reducing the leakage current, while the on-state performance in transconductance ( ${g}_{m}\text {)}$ and drain current ( ${I}_{\text {ON}}\text {)}$ is maintained. The effects of varying the channel thickness, length, and the indium content of the InxGa $_{{1}- {x}}$ As shell are also explored in both dc and RF aspects. The results show that the core-shell FinFET exhibits superior characteristics in terms of leakage current, subthreshold swing, and drain-induced barrier lowering, owing to its superior gate controllability, with comparable RF performance in current gain cutoff frequency ( ${f}_{t} \gt 400$ GHz for 50-nm ${L}_{\text {Ch}}\text {)}$ with the bulk FinFET. The major objective of this article is to provide the possible directions for the design of the Si/InxGa $_{{1}- {x}}$ As core-shell FinFET for future device applications.

Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell–cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed. By convection-enhanced delivery, membrane-disrupted amphiphilic polymer micelles (poly(methoxypoly(ethylene glycol)-benzoic imine-octadecane, mPEG-b-C18) with CuS nanoflakes enhances tumor permeability and resides in deep brain tumors. Under low-power NIR II irradiation (0.8 W/cm2), the intense heat generated by well-distributed CuS nanoflakes actuates the thermolytic efficacy, facilitating cell apoptosis and the subsequent antigen release. Then, the positively charged polymer after hydrolysis of the benzoic-imine bond serves as an antigen depot, detaining autologous tumor-associated antigens and presenting them to dendritic cells, ensuring sustained immune stimulation. This self-cascading penetrative immunotherapy amplifies the immune response to postoperative brain tumors but also enhances survival outcomes through effective brain immunotherapy.

AbstractObjectiveBenzene is widely recognized as a potential carcinogen. Furthermore, the deficiency of specific nutrients may render individuals more vulnerable to cancer. For instance, β-cryptoxanthin, which possesses anti-inflammatory, antioxidant, and anticancer properties, has been identified as one such nutrient. Elevated benzene levels and reduced β-cryptoxanthin levels are reportedly correlated with an augmented susceptibility to cancer. To date, whether these 2 substances are linked with one another in the above correlation is yet to be determined.MethodThis study included 1358 participants with data on the serum concentration of β-cryptoxanthin as well as benzene and its derivatives. The data were sourced from the 2003–2004 National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Headspace solid-phase microextraction with gas chromatography and mass spectrometry was used to measure serum benzene and its derivatives, while high-performance liquid chromatography using multiwavelength photodiode-array absorbance detection was employed to quantify serum β-cryptoxanthin.ResultsIn this study, male and female participants showed average β-cryptoxanthin levels of 9.10 ± 6.35 and 9.92 ± 8.95 ug/dL, respectively (p = 0.049). Styrene exhibited the strongest correlation with the change in β-cryptoxanthin concentration (β = −3.30, pfor trend <0.001) upon comparing highest-quartile participants with those in the lowest quartile, followed by benzene (β = −2.95, pfor trend <0.001), toluene (β = −2.90, pfor trend <0.001), and ethylbenzene (β = −1.43, pfor trend = 0.09). Subgroup analysis by sex displayed a statistically significant negative correlation of β-cryptoxanthin with benzene, styrene, and toluene in both the unadjusted and multivariate-adjusted models.ConclusionsThe sera of noninstitutionalized US individuals exhibit a negative association of β-cryptoxanthin levels with benzene and its derivatives. Styrene demonstrates the strongest link with a substantial decline in serum β-cryptoxanthin levels, followed by benzene, toluene, and ethylbenzene.

The interaction between irradiation defects and dislocations could lead to macroscopic hardening and embrittlement. In this study, molecular dynamics (MD) and machine learning were conducted to study three-dimensional void- and Cu-cluster-induced kinetics models under interaction with dislocations in body-centered cubic Fe-based alloys. MD Results show that dislocation climb and shear are two types of interaction mechanism based on the defect size. Combined MD results and machine learning, it was found that the dislocation length increased linearly with an increase in the size of the defects after the interaction. In addition, the number of atoms in the Cu-rich cluster and the reduced number of vacancies in the voids had a square relationship with the defect size where 0.85D2is for Cu-rich cluster and 0.50D2is for void. Furthermore, atomic-scale three-dimensional irradiation-induced defect kinetics models were developed and incorporated into the crystal plasticity finite element model (CPFEM). We also analyzed the contributions of various defects to the increase in the yield stress during CPFEM simulation. Compared with DBH model, the prediction of MD data-driven CPFEM matches better with the experimental data. Cluster contributed the most to hardening with low obstacle strength due to the higher number density compared with dislocation loops and voids. The loops also contributed to hardening; however, their contribution was smaller than that of the clusters. Although the number density and size of voids were minimized, they may have contributed because of the high obstacle strengths. This work can indeed deepen the understanding of irradiation effect in Fe-based alloys.

Gaining insight into the underlying mechanisms driving nanoindentation-induced behavior in tungsten is essential for comprehending its mechanical properties. Although the plasticity of conventional pure tungsten under nanocontact conditions is well understood, these theoretical constructs may become inadequate when applied to irradiated tungsten due to the interplay between helium bubbles and dislocations. Here, we employed an integrated approach, combining crystal defect theories, molecular dynamics simulations, and machine learning, to explore the initiation and progression of dislocations in tungsten containing helium bubbles during nanoindentation, focusing on elucidating the impact of helium bubbles. In contrast to the typical dislocation nucleation in pure tungsten, the presence of helium bubbles mitigates local shear strain, thereby hindering dislocation nucleation and propagation, leading to a reduction of indentation force. Additionally, we conducted a comparative analysis between samples with and without helium bubbles, examining factors such as atomic displacement, strain localization parameters, dislocation line length, and stress component distribution. More importantly, a significant outcome of our study is the establishment of a relationship between the consistent alteration in the shape of helium bubbles and their size during micro-scale nanoindentation, achieved through machine learning techniques. Our findings reveal that the area occupied by helium bubbles post-nanoindentation is inversely correlated with indentation depth and directly linked to helium bubble size. These discoveries represent a notable advancement in understanding the effects of irradiation to a certain degree.

To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse.

Cas12a (Cpf1), a Class 2 Type V CRISPR/Cas nuclease, has several unique attributes for genome editing and may provide a valuable alternative to Cas9. However, a low editing efficiency due to temperature sensitivity and insufficient cleavage activity of the Cas12a nuclease are major obstacles to its broad application. In this report, we generated two variants, ttAsCas12 Ultra and ttLbCas12a Ultra harboring three (E174R, M537R, and F870L) or two (D156R and E795L) mutations, respectively, by combining the mutations from the temperature-tolerant variants ttAsCas12a (E174R) and ttLbCas12a (D156R), and those from the highly active variants AsCas12a Ultra (M537R and F870L) and LbCas12a Ultra (E795L). We compared editing efficiencies of the five resulting Cas12a variants (LbCas12a, ttLbCas12a, ttLbCas12a Ultra, AsCas12a Ultra, and ttAsCas12 Ultra) at six target sites of four genes in Arabidopsis (Arabidopsis thaliana). The variant ttLbCas12a Ultra, harboring the D156R and E795L mutations, exhibited the highest editing efficiency of all variants tested in Arabidopsis and can be used to generate homozygous or biallelic mutants in a single generation in Arabidopsis plants grown at 22 °C. In addition, optimization of ttLbCas12a Ultra, by varying nuclear localization signal sequences and codon usage, further greatly improved editing efficiency. Collectively, our results indicate that ttLbCas12a Ultra is a valuable alternative to Cas9 for editing genes or promoters in Arabidopsis.