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One grand challenge in haptic human-machine interface devices is to electromechanically stimulate sensations on the human skin wirelessly by thin and soft patches under a low driving voltage. Here, we propose a soft haptics-feedback system using highly charged, polymeric electret films with an annulus-shape bump structure to induce mechanical sensations on the fingertip of volunteers under an applied voltage range of 5–20 V. As an application demonstration, a 3 × 3 actuators array is used for transmitting patterned haptic information, such as letters of 'T', 'H', 'U' letters and numbers of '0', '1', '2'. Moreover, together with flexible lithium batteries and a flexible circuit board, an untethered stimulation patch is constructed for operations of 1 h. The analytical model, design principle, and performance characterizations can be applicable for the integration of other wearable electronics toward practical applications in the fields of AR (augmented reality), VR (virtual reality) and robotics. • Electrical and mechanical improvement for the soft actuator to reduce the driving voltage. • Demonstration of transmitting patterned haptic information with a 3 × 3 actuators array. • An untethered system with flexible batteries and circuit further towards practical applications. [ABSTRACT FROM AUTHOR]

Background: 1-Bromoacetyl-3,3-dinitroazetidine (RRx-001) has potent antitumor effects, indicating its promising therapeutic potential against various cancers. This research investigates RRx-001 activity against hepatocellular carcinoma (HCC) and elucidates its underlying mechanisms., Methods: Huh7, Hepa1-6, and MHCC97H cells were cultured and treated with varying RRx-001 concentrations for 24, 48, and 72 h. Cell viability was assessed using cell counting kit-8. The cells were divided into control and RRx-001 treatment groups at 0.5 × IC 50 , 1.0 × IC 50 , and 2.0 × IC 50 concentrations for each cell line. Migration and invasion were evaluated using scratch and Transwell assays, and apoptosis was examined by apoptosis assays. RNA sequencing was performed on the Huh7 cells treated with RRx-001 for 24 h to identify differential gene expression. CD47 and TP53 protein levels were measured by Western blot. A xenograft mouse model was utilized to evaluate the effect of RRx-001 on HCC., Results: RRx-001 inhibits HCC cell viability, migration, and invasion while inducing apoptosis, These effects are potentially mediated by the downregulation of CD47 and the upregulation of TP53, both of which modulate key signaling pathways. In vivo experiments demonstrated that RRx-001 effectively inhibits tumor growth., Conclusion: RRx-001 reduces the viability of HCC cells and induces apoptosis. This effect may be due to the downregulation of CD47 expression and the alteration of the TP53 protein regulatory pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Zhao, Chen, Mo, Huang, Liao, Lu, Liang, Wei, Han and Ye.)

Objective: Long non-coding RNAs (lncRNAs) LINC02466 is an lncRNA newly linked to the adverse outcomes in primary liver cancer patients, and its crucial involvement in the disease's escalation. Decoding the specific role of LINC02466 in HCC progression is of great significance to provide a potential therapeutic target for HCC., Methods: RT-qPCR and Western Blot techniques was used to analyze the expression levels of LINC02466 in both malignant and surrounding healthy liver tissues. CCK8 assays and colony formation experiments indicates the LINC02466's effect on the proliferation rates of liver cancer cells. Flow cytometry was pivotal in revealing its significant influence on the cell cycle of these cells. Kaplan-Meier survival analysis with log-rank tests were employed., Results: The suppression of LINC02466 markedly reduces the stemness attributes of liver cancer cells, indicating a potential therapeutic target. LINC02466 overexpression significantly increased tumor growth rates and final volumes. Further research indicated that LINC02466 significantly influences liver cancer progression through regulating the mTOR signaling pathway., Conclusion: LINC02466 regulating cell proliferation, the cell cycle, and stemness characteristics via the mTOR pathway, suggesting LINC02466 as a potential therapeutic target for primary liver cancer., (© 2024. The Author(s).)

Osteoarthritis (OA) is recognized as a highly friction-related joint disease primarily associated with increased joint friction and inflammation due to pro-inflammatory M1-type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core-brush nanoplatform composed of a ROS-scavenging polydopamine-coated SiO 2 core and lubrication-enhancing zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti-inflammatory drug curcumin by a reactive oxygen species (ROS)-liable conjugation (named as SiO 2 @PP-Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono-iodoacetic acid-induced arthritis (MIA) rat model, intra-articular injection of SiO 2 @PP-Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro-inflammatory M1 to anti-inflammatory M2 state by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro-regenerative microenvironment. As a result, SiO 2 @PP-Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core-brush nanoplatform for enhanced OA therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Ubiquitination, a prevalent and highly dynamic reversible post-translational modification, is tightly regulated by the deubiquitinating enzymes (DUBs) superfamily. Among them, OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 1 (OTUB1) stands out as a critical member of the OTU deubiquitinating family, playing a pivotal role as a tumor regulator across various cancers. However, its specific involvement in BLCA (BLCA) and its clinical significance have remained ambiguous. This study aimed to elucidate the biofunctions of OTUB1 in BLCA and its implications for clinical prognosis. Our investigation revealed heightened OTUB1 expression in BLCA, correlating with unfavorable clinical outcomes. Through in vivo and in vitro experiments, we demonstrated that increased OTUB1 levels promote BLCA tumorigenesis and progression, along with conferring resistance to cisplatin treatment. Notably, we established a comprehensive network involving OTUB1, β-catenin, necroptosis, and BLCA, delineating their regulatory interplay. Mechanistically, we uncovered that OTUB1 exerts its influence by deubiquitinating and stabilizing β-catenin, leading to its nuclear translocation. Subsequently, nuclear β-catenin enhances the transcriptional activity of c-myc and cyclin D1 while suppressing the expression of RIPK3 and MLKL, thereby fostering BLCA progression and cisplatin resistance. Importantly, our clinical data suggest that the OTUB1/β-catenin/RIPK3/MLKL axis holds promise as a potential biomarker for BLCA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Wet-chemically recovering phosphorus (P) from sewage sludge incineration ash (SSIA) has already become a global initiative to address P deficit, but effectively isolating P from these accompanying metals (AMs) through adsorption in a SSIA-derived extract remains elusive. Here, we devised a hydrothermal stimulus-motivated thermodynamic and kinetic enhancement to gain anionic ethylenediaminetetraacetic acid (EDTA) molecular interfaces for AM enclosure to resolve this conundrum. A new dosage rule based on the EDTA coordination ratio with AMs was established for the first time. Upon hydrothermal extraction at 140 °C for 1 h, the P extraction efficiency reached 96.7% or higher for these obtained SSIA samples, and then exceptional P sequestration from these EDTA-chelated AMs was realized by the peculiar lanthanum (La)-based nanoadsorbent (having 188.86 mg P/g adsorbent at pH ∼ 3.0). Relevant theoretical calculations unraveled that these delocalized electrons of tetravalent EDTA molecules boosted the enclosure of liberated AMs, thereby entailing a substantially increased negative adsorption energy (-408.7 kcal/mol) of P in the form of H 2 PO 4 - through intruding lattice-edged carbonates to coordinate La with monodentate mononuclear over LaCO 5 (1 0 1). This work highlights the prospect of molecular adaptation of these common extractants in wet-chemical P recovery from various P-included wastes, further sustaining global P circularity.

The projection of fringes plays an essential role in many applications, such as fringe projection profilometry and structured illumination microscopy. However, these capabilities are significantly constrained in environments affected by optical scattering. Although recent developments in wavefront shaping have effectively generated high-fidelity focal points and relatively simple structured images amidst scattering, the ability to project fringes that cover half of the projection area has not yet been achieved. To address this limitation, this study presents a fringe projector enabled by a neural network, capable of projecting fringes with variable periodicities and orientation angles through scattering media. We tested this projector on two types of scattering media: ground glass diffusers and multimode fibers. For these scattering media, the average Pearson's correlation coefficients between the projected fringes and their designed configurations are 86.9% and 79.7%, respectively. These results demonstrate the effectiveness of the proposed neural network enabled fringe projector. This advancement is expected to broaden the scope of fringe-based imaging techniques, making it feasible to employ them in conditions previously hindered by scattering effects.

Background: Primary family caregivers of older people with chronic care conditions are highly vulnerable to social isolation and psychological strains such as depression and anxiety due to their demanding responsibilities. This study examines how social isolation mediates the relationship between caregiving stress and mental health symptoms of primary family caregivers., Methods: The analytic sample included 881 primary caregivers of older adults from the 2015 and 2017 National Study of Caregiving (NSOC). Social isolation was measured using a composite structure that includes objective social disconnectedness and subjective loneliness. Two-wave mediation models were estimated to examine longitudinally if social isolation mediated the relationship between caregiving stress (subjective & objective stress) and mental health symptoms (depression & anxiety) of primary caregivers., Results: The study findings indicate that both subjective (β = 0.32, p < 0.001) and objective stress (β = 0.21, p = 0.003) have direct effects on depression among primary caregivers. Social isolation was found to only mediate the relationship between objective stress and depression (β = 0.18, p < 0.001). In contrast, no significant direct and indirect pathway was found in the anxiety model., Conclusions: The study demonstrates the internal mechanism where objective strains of caregiving make family caregivers socially isolated, which in turn leads to increased symptoms of depression. Future interventions and practices aimed at improving the psychological well-being of family caregivers should prioritize strategies aimed at increasing social engagement, particularly for those with heavy caregiver burdens., (© 2023. The Author(s).)

Inactivated suppressor of mothers against decapentaplegic homolog (SMAD) 4 significantly affects cancer development in pancreatic ductal adenocarcinoma (PDAC). However, the contribution of smad4 loss to drug resistance in PDAC is largely undetermined. In the present study, we reported that the loss of SMAD4 endows PDAC cells the ability to drug resistance through upregulating histone lysine demethylase, Lysine-Specific Demethylase 5B (KDM5B, also known as JARID1B or PLU1). Upregulated KDM5B was found in PDAC, associated with poor prognosis and recurrence of PDAC patients. Upregulated KDM5B promotes PDAC tumor malignancy, i.e. cancer cells stemness and drug resistance in vitro and in vivo, while KDM5B knockout exerts opposite effects. Mechanistically, loss of Smad4-mediated upregulation of KDM5B promotes drug resistance through inhibiting the discs-large homolog 1 (DLG1), thereby facilitating nuclear translocation of YAP to induce de novo lipogenesis. Moreover, m 6 A demethylase FTO is involved in the upregulation of KDM5B by maintaining KDM5B mRNA stability. Collectively, the present study suggested FTO-mediated KDM5B stabilization in the context of loss of Smad4 activate DLG1/YAP1 pathway to promote tumorigenesis by reprogramming lipid accumulation in PDAC. Our study confirmed that the KDM5B-DLG1-YAP1 pathway axis plays a crucial role in the genesis and progression of PDAC, and KDM5B was expected to become a target for the treatment of PDAC. The schematic diagram of KDM5B-DLG1-YAP pathway axis in regulating drug resistance of PDAC to gemcitabine (GEM). In the context of SMAD4 loss PDAC cells, FTO-mediated stabilization and upregulation of KDM5B promotes drug resistance through directly targeting DLG1 to promote YAP1 translocation to nucleus to induce de novo lipogenesis (DNL)., (© 2024. The Author(s).)

Background: The technique of spinal decompression under endoscopy has been widely applied, but reports on endoscopic cervical fixation are rare. The unilateral biportal endoscopic (UBE) technique stands out for its lesser muscle intrusion and more flexible surgical approach., Method: We applied the UBE approach for cervical fixation and laminectomy. We achieved bilateral lateral mass screw fixation by making an auxiliary UBE portal combined with the Roy-Camille and Magerl techniques., Conclusions: Our successful implementation of cervical fixation using the UBE technique at the C3/4 level suggests its efficacy. This approach is a valuable and minimally invasive option for cervical fixation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH)., Methods: From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up., Results: All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment., Conclusions: The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application., (© 2024. The Author(s).)

Background and Objectives: Adopting preventive behaviors is crucial to avoiding coronavirus disease 2019 (COVID-19) infection, and perceived anxiousness may influence such behaviors among older adults and their caregivers. This study investigated the relationships between perceived anxiousness about COVID-19 and preventive behaviors in older adult-caregiver dyads., Research Design and Methods: A cross-sectional study was conducted using 1,565 older adult-caregiver dyads from the 2020 National Health and Aging Trend Study (NHATS)/National Study of Caregiving (NSOC) COVID-19 Supplements data. Actor-partner interdependence models were estimated to examine the associations between older adults' and family caregivers' perceived anxiousness about COVID-19 and their engagement in personal (e.g., wearing masks, washing hands) and social (e.g., avoiding contact with friends, limiting grocery shopping) preventive behaviors. Separate models were estimated based on older adults' dementia status., Results: We found significant actor effects of anxiousness about COVID-19 on preventive behaviors of both older adults and caregivers in nondementia dyads. The anxiousness about COVID-19 of older adults had significant partner effects on both personal and social preventive behaviors of caregivers, whereas caregivers' anxiousness about COVID-19 only had a significant partner effect on social preventive behaviors of older adults. No significant partner effect was found in dementia dyads., Discussion and Implications: Our findings highlight the critical role of caregivers in promoting older adults' health behaviors during the COVID-19 pandemic and maintaining mental well-being of older adults. The study also implies future efforts to explore the dyadic relationship of dementia care dyads in promoting health behaviors and mental health., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ocean ecological environments are seriously affected by oil spilling and plastic-debris, preventing and significantly reducing marine pollution via using biocomposite production from natural fiber reinforcement is a more friendly way to deal with marine oil pollution. Herein, we upcycled coir-coconut into lignin and coconut shell into spherical TENG by a combination of dip-dry and chemical treatment and used the SiO 2 nanoparticles together with cellulose nanofibrils to prepare serial sugar-templated, anisotropic and hybrid foams. The as-prepared lignin/SiO 2 porous sponge (LSPS) with a hierarchical porous morphology and uniformly dispersed nanoparticles structure benefits from the advantages of biomass-based additives, which presents reversible large-strain deformation (50%) and high compressive strength (11.42 kpa). Notably, the LSPS was significantly more hydrophobic (WCA ≈150°) than pure silicone-based foams, and its selective absorbability can separate oil from water under continuous pumping. Meanwhile, the coconut husk was also upcycled as a spherical TENG shell by a combination of the nanofiber-enhanced polymer spherical oscillator (CESO), which possessed high triboelectric properties ( U oc = 272 V, I sc = 14.5 μA, Q = 70 nC) and was comparable to the plastic shell TENG at low frequency (1.6 Hz). The monolithic foam structure developed using this clean synthetic strategy holds considerable promise for new applications in sustainable petroleum contamination remediation., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

Hybrid transformer-based segmentation approaches have shown great promise in medical image analysis. However, they typically require considerable computational power and resources during both training and inference stages, posing a challenge for resource-limited medical applications common in the field. To address this issue, we present an innovative framework called Slim UNETR, designed to achieve a balance between accuracy and efficiency by leveraging the advantages of both convolutional neural networks and transformers. Our method features the Slim UNETR Block as a core component, which effectively enables information exchange through self-attention mechanism decomposition and cost-effective representation aggregation. Additionally, we utilize the throughput metric as an efficiency indicator to provide feedback on model resource consumption. Our experiments demonstrate that Slim UNETR outperforms state-of-the-art models in terms of accuracy, model size, and efficiency when deployed on resource-constrained devices. Remarkably, Slim UNETR achieves 92.44% dice accuracy on BraTS2021 while being 34.6x smaller and 13.4x faster during inference compared to Swin UNETR. Code: https://github.com/aigzhusmart/Slim-UNETR.

Background: Endoscopically assisted screw fixation with lumbar interbody fusion is rarely performed. We succeeded in implanting the cortical bone trajectory (CBT) screws under the guidance of unilateral biportal endoscopy (UBE)., Method: We attempted endoscopically assisted screw fixation in a patient with degenerative spondylolisthesis. Through a third portal, ipsilateral CBT screws were implanted without complications., Conclusions: We successfully performed unilateral biportal endoscopic lumbar interbody fusion (ULIF) with CBT and reversed CBT screws. Compared with percutaneous pedicle screw (PPS) placement, this procedure is a minimally invasive, endoscopic alternative that allows precise screw placement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Tuning CO 2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO 2 /H 2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO 2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts., (© 2024. The Author(s).)

The development of castration-resistant prostate cancer (CRPC) is driven by intricate genetic and epigenetic mechanisms. Traf2- and Nck-interacting kinase (TNIK) has been reported as a serine/threonine kinase associated with tumor cell proliferation or unfavorable cancer behavior. The microarray approach revealed a substantial upregulation of TNIK expression levels, enabling us to investigate the functional behaviors of the TNIK gene in CRPC. Specifically, we discovered that AR suppresses TNIK gene transcription in LNCaP and C4-2 cells by forming a complex with H3K27me3. Following the reduction of AR levels induced by androgen deprivation therapy (ADT), TNIK is recruited to activate EGFR signaling through phosphorylation in C4-2 cells, thereby promoting CRPC progression. Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC., Competing Interests: None of the authors have any relevant conflicts of interest pertaining to the studies and data in this manuscript., (© 2023 The Authors.)

Background: As a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML., Methods: First, we extracted the mRNA expression profiles of bone marrow samples from an AML cohort from The Cancer Genome Atlas database and employed Cox regression analysis to select prognostic hub genes associated with lipid metabolism and immunity. We then constructed a prognostic signature with hub genes significantly related to survival and validated the stability and robustness of the prognostic signature using three external datasets. Gene Set Enrichment Analysis was implemented to explore the underlying biological pathways related to the risk signature. Finally, the correlation between signature, immunity, and drug sensitivity was explored., Results: Eight genes were identified from the analysis and verified in the clinical samples, including APOBEC3C , MSMO1 , ATP13A2 , SMPDL3B , PLA2G4A , TNFSF15 , IL2RA , and HGF , to develop a risk-scoring model that effectively stratified patients with AML into low- and high-risk groups, demonstrating significant differences in survival time. The risk signature was negatively related to immune cell infiltration. Samples with AML in the low-risk group, as defined by the risk signature, were more likely to be responsive to immunotherapy, whereas those at high risk responded better to specific targeted drugs., Conclusions: This study reveals the significant role of lipid metabolism- and immune-related genes in prognosis and demonstrated the utility of these signature genes as reliable bioinformatic indicators for predicting survival in patients with AML. The risk-scoring model based on these prognostic signature genes holds promise as a valuable tool for individualized treatment decision-making, providing valuable insights for improving patient prognosis and treatment outcomes in AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wu, Cheng, Liang, Liang, Li, Guo, Li, Zhang and Song.)

It is still challenging to achieve agility and trajectory control for untethered soft robots on an insect scale given their low mechanical impedance and compact structures. In this study, fast translational movements and swift turning motions are demonstrated on a power autonomous soft robot with a piezoelectric-thin-film-actuated body and electrostatic turning footpads. A high relative running speed of 2.5 body length per second compared with existing untethered robots is realized on a 24-mm-long untethered prototype integrated with power source, control, and wireless communication modules. An arc-shaped leg structure is adopted to self-regulate the frication forces on different footpads during turning by an inclination-induced redistribution of the payload gravity on legs and footpads. The trajectory maneuverability is demonstrated by navigating a 380 mg robot prototype with an 1810 mg payload to pass through a 58-cm-long S-shaped path with wireless control in 43.4 s. Due to the flexibility of the all-polymer body structure, the robustness of the untethered robot to large strain is demonstrated when compressed by 91 times the weight of the robot. A maximum travel distance of 58.6 m is achieved for the robot equipped with a 40 mA·h lithium battery, corresponding to the cost of transport of 261. This work provides a feasible solution to achieve high agility and advance the practicability of untethered soft robots on an insect scale.

Background: Transforaminal lumbar interbody fusion (TLIF) with a single cage and bilateral pedicle screw fixation results in decreased stability or increased risk of cage displacement Wang and Guo (Comput Methods Biomech Biomed Eng, 24(3):308-319, 6). We succeeded in inserting double traversing cages with unilateral pedicle screw fixation (UPSF) during far lateral TLIF using unilateral biportal endoscopy (UBE)., Method: We attempted far lateral UBE-TLIF through two small incisions for degenerative lumbar spondylolisthesis with unilateral stenosis. With the help of novel instruments, far lateral UBE-TLIF with double traversing cages and UPSF was performed under tracheal intubation anaesthesia., Conclusions: We successfully performed far lateral UBE-TLIF with double traversing cages and UPSF. This procedure may be an alternative minimally invasive method for treating lumbar instability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Dam numerical simulation is an important method to research the dam structural behavior, but it often takes a lot of time for calculation when facing problems that require many simulations, such as structural parameter back analysis. The surrogate model is widely used as a technology to reduce computational cost. Although various methods have been widely investigated, there are still problems in designing the surrogate model's optimal Design of Experiments (DoE). In addition, most of the current DoE focuses on establishing a single-output problem. Designing a reasonable DoE for high-dimensional outputs is also a problem that needs to be solved. Based on the above issues, this research proposes a sequential surrogate model based on the radial basis function model (RBFM) with multi-outputs adaptive sampling. The benchmark function demonstrates the applicability of the proposed method to single-input & multi-outputs and multi-inputs & multi-outputs problems. Then, this method is applied to establishing a surrogate model for dam numerical simulation with multi-outputs. The result demonstrates that the proposed technique can be sampled adaptively and samples can be targeted based on the function form of the surrogate model, which significantly reduces the required sampling and calculation cost., (© 2023. The Author(s).)

Even though the direct hydrogenation of CO 2 into aromatics has been realized via a methanol-mediated pathway and multifunctional catalyst, few works have been focused on the simultaneously rational design of each component in multifunctional catalyst to improve the performance. Also, the structure-function relationship between aromatics synthesis performance and the different catalytic components (reducible metal oxide and acidic zeolite) has been rarely investigated. Herein, we increase the oxygen vacancy (O v ) density in reducible Cr 2 O 3 by sequential carbonization and oxidation (SCO) treatments of Cr-based metal-organic frameworks. Thanks to the enriched O v , Cr 2 O 3 -based catalyst affords high methanol selectivity of 98.1 % (without CO) at a CO 2 conversion of 16.8 % under high reaction temperature (350 °C). Furthermore, after combining with the acidic zeolite H-ZSM-5, the multifunctional catalyst realizes the direct conversion of CO 2 into aromatics with conversion and selectivity as high as 25.4 % and 80.1 % (without CO), respectively. The property of acid site in H-ZSM-5, especially the Al species that located at the intersection of straight and sinusoidal channels, plays a vital role in enhancing the aromatics selectivity, which can be precisely controlled by varying the hydrothermal synthesis conditions. Our work provides a synergistic strategy to boost the aromatics synthesis performance from CO 2 hydrogenation., (© 2023 Wiley-VCH GmbH.)

This article proposes a piezoelectric-driven insect-scale soft robot with ring-like curved legs, enabling it to traverse complex three-dimensional (3D) terrain only by body-terrain mechanical action. Relying on the repeated deformation of the main body's n and u shapes, the robot's leg-ground mechanical action produces an "elastic gait" to move. Regarding the detailed design, first, a theoretical curve of the front leg with a fixed angle of attack of 75° is designed by finite element simulation and comparative experiments. It ensures no increase in drag and no decrease in the lift when climbing steps. Second, a ring-like leg structure with 100% closed degree is proposed to ensure a smooth pass through small-sized uneven terrain without getting stuck. Then, the design of the overall asymmetrical structure of the robot can improve the conversion ratio of vibration to forward force. The shape of curved legs is controlled by pulling the flexible leg structure with two metal wires working as spokes. The semirigid leg structure made of fully flexible materials has shape stability and structural robustness. Compared with the plane-legged robot, the curved-legged robot can smoothly traverse different rugged 3D terrains and cross the terrain covering obstacles 0.36 times body height (BH) at a speed of >4 body lengths per second. Moreover, the curved-legged robot shows 100% and 64% chances of climbing steps with 1.2- and 1.9-times BH, respectively.

The involvement of necroptosis in the immunosuppressive tumor microenvironment has been established and has been shown to contribute to the growth of pancreatic ductal adenocarcinoma, indicating its role in promoting tumor development. However, the relationship between necroptosis and bladder urothelial carcinoma (BUC) has yet to be fully understood. To shed light on this issue, our study aimed to uncover the impact of necroptosis on immune cell infiltration and immunotherapy response in BUC patients. We conducted an analysis of 67 necroptosis genes to assess their expression and genomic changes across pan-cancer and identified 12 necroptosis genes that are prognostically relevant and associated with immune subtypes and tumor stemness in BUC. Using a public database of 1841 BUC samples, we then performed Unsupervised Cluster Analysis and discovered two distinct necroptotic phenotypes in BUC. These phenotypes showed significant differences in molecular subtypes, immune infiltration patterns, and gene mutation profiles. We confirmed this discovery in BUC through qPCR and WB experiments. To evaluate the impact of necroptosis on prognosis, chemotherapy sensitivity, and immunotherapy response (such as anti-PD-L1), we developed a principal component analysis model called NecroScore. Finally, we validated the effects of RIPK3 and MLKL through a nude mouse transplantation model for BUC. Our study has uncovered that necroptosis plays a role in shaping the tumor immune microenvironment in BUC. The high necroptosis phenotype (Cluster B) was characterized by a higher abundance of tumor immunosuppressive cells and more key biological processes driving tumor progression, while the low necroptosis group (Cluster A) had higher FGFR3 mutations. We found that the infiltration levels of immune cells, including CD8+ T cells, were significantly different between FGFR3 mutated and wild-type (WT) samples. Our results confirmed the reliability of NecroScore as a comprehensive assessment tool for evaluating the immunotherapeutic effect and prognosis of BUC patients, with high NecroScore values favoring basal-like differentiation and lower FGFR3 alterations. We also observed that high expression of MLKL had a significant inhibitory effect on tumor growth and increased neutrophil infiltration in vivo. In our study, we uncovered the regulation pattern of necroptosis in the tumor immune microenvironment of BUC. Additionally, we developed a scoring tool called NecroScore that can be utilized to predict the most suitable chemotherapy and immunotherapy strategy for bladder urothelial carcinoma patients. This tool can effectively guide the chemotherapy and immunotherapy regimens for patients with advanced BUC., (© 2023. The Author(s).)

Background: Risk stratification is fundamental in the management of pulmonary arterial hypertension (PAH). Pulmonary artery pulsatility index (PAPi), defined as pulmonary arterial pulse pressure divided by right atrial pressure (RAP), is a hemodynamic index shown to predict acute right ventricular (RV) dysfunction in several settings. Our objective was to test the prognostic utility of PAPi in a diverse multicentre cohort of patients with PAH., Methods: A multicentre retrospective cohort study of consecutive adult patients with a new diagnosis of PAH on right heart catheterization between January 2016 and December 2020 was undertaken across 4 major centres in Canada. Hemodynamic data, clinical data, and outcomes were collected. The association of PAPi and other hemodynamic variables with mortality was assessed by receiver-operating characteristic curves and Cox proportional hazards modeling., Results: We identified 590 patients with a mean age of 61.4 ± 15.5 years, with 66.3% being female. A low PAPi (defined as < 5.3) was associated with higher mortality at 1 year: 10.2% vs 5.2% ( P  = 0.02). In a multivariable model including age, sex, body mass index, and functional class, a low PAPi was associated with mortality at 1 year (area under the curveof 0.64 (95% confidence interval 0.55-0.74). However, high RAP (> 8 mm Hg) was similarly predictive of mortality, with an area under the curve of 0.65., Conclusion: PAPi was associated with mortality in a large incident PAH cohort. However, the discriminative value of PAPi was not higher than that of RAP alone., (© 2023 The Authors.)

Prostate cancer is a major disease that threatens men's health. Its rapid progression, easy metastasis, and late castration resistance have brought obstacles to treatment. It is necessary to find new effective anticancer methods. Ferroptosis is a novel iron-dependent programmed cell death that plays a role in various cancers. Understanding how ferroptosis is regulated in prostate cancer will help us to use it as a new way to kill cancer cells. In this review, we summarize the regulation and role of ferroptosis in prostate cancer and the relationship with AR from the perspective of metabolism and molecular pathways. We also discuss the feasibility of ferroptosis in prostate cancer treatment and describe current limitations and prospects, providing a reference for future research and clinical application of ferroptosis., (© 2023. The Author(s).)

Background: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH., Methods: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy ( i.e. monotherapy versus combination therapy)., Results: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53)., Conclusions: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure., Competing Interests: Conflict of interest: J.G.E. Zelt has nothing to disclose. Conflict of interest: J. Sugarman has nothing to disclose. Conflict of interest: J. Weatherald reports grants, personal fees and nonfinancial support from Janssen Inc. and Actelion, personal fees and nonfinancial support from Bayer, personal fees from Novartis, outside the submitted work. Conflict of interest: A.C.R. Partridge has nothing to disclose. Conflict of interest: J. Liang has nothing to disclose. Conflict of interest: J. Swiston reports personal fees from Janssen J&J, outside the submitted work. Conflict of interest: N. Brunner reports personal fees from Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: G. Chandy reports personal fees for advisory board work and consultancy from Bayer Pharmaceuticals, personal fees for advisory board work, lectures and consultancy from Janssen Pharmaceuticals, personal fees for advisory board work from Apotex, during the conduct of the study. Conflict of interest: D.J. Stewart reports other (equity) from Northern Therapeutics, outside the submitted work. Conflict of interest: V. Contreras-Dominguez has nothing to disclose. Conflict of interest: M. Thakrar reports grants from Reata Pharmaceuticals, outside the submitted work; and advisory board work for Janssen Pharmaceuticals. Conflict of interest: D. Helmersen reports grants from Gilead, Janssen and United Therapeutics, outside the submitted work. Conflict of interest: R. Varughese has nothing to disclose. Conflict of interest: N. Hirani reports grants (paid to institution) from Bayer, United Therapeutics and Northern Therapeutics, grants (paid to institution) and other (advisory board membership) from Actelion/Janssen, outside the submitted work. Conflict of interest: F. Umar has nothing to disclose. Conflict of interest: R. Dunne has nothing to disclose. Conflict of interest: C. Doyle-Cox has nothing to disclose. Conflict of interest: J. Foxall has nothing to disclose. Conflict of interest: L. Mielniczuk reports grants and personal fees for lectures from Janssen, grants from Bayer, outside the submitted work., (Copyright ©The authors 2022.)

Lung cancer is the malignancy most commonly seen worldwide. Emerging evidences indicated that lncRNAs may serve as a prognosis marker and play important role in NSCLC tumor biology. In this work, we analyzed the prognosis value of RP11-10A14.5 using TCGA and GEPIA database and expression profiles using PCR and FISH assay. The biological roles of RP11-10A14.5 in cell growth and invasion were determined by in vitro and in vivo experiments. Expression of RP11-10A14.5 is correlated with increased clinical stage and poor survival prognosis. In vitro experiments revealed that RP11-10A14.5 was widely expressed in lung cancer cell lines and mainly distributed in the cytoplasm and enhanced the growth, invasion and migration ability of NSCLC cell lines. Immunofluorescence assay suggested that RP11-10A14.5 may promote EMT by downregulating E-cadherin and upregulating N-cadherin and Vimentin. Flow cytometry results suggested that RP11-10A14.5 did not significantly affect cell cycle function, but could significantly inhibit apoptosis which may further enhance metastasis cell survival. In conclusion, RP11-10A14.5 is associated with clinical stage and poor survival outcome, may serve as a diagnosis and prognosis predictor for LUAD. Further, RP11-10A14.5 could promote LUAD cell growth and metastasis., (© 2022. The Author(s).)

Objective: To explore the association between role overload (RO) and sleep maintenance insomnia (SMI), and the moderation effects of social support and social engagement (SE). Methods: We report a cross-sectional study using data drawn from the 2015 National Health and Aging Trends Study and National Study of Caregiving. We used multiple regression and controlled for demographics and potential confounders. Results: Nearly 45% of caregivers reported suffering from SMI during "some" and "more" nights within the past month with one half reporting "almost" or "every" night. RO was found positively associated with the risk of SMI. Instrumental support moderated the effect of RO on SMI overall, although moderation was limited to a subsample of adult children caregivers. Discussion: The sleep quality of dementia caregivers may be affected by RO, particularly for adult children caregivers. Increasing instrumental support may be beneficial to caregiver's sleep quality.

Herein, a bovine serum albumin-stabilized gold clusters-MnO 2 nanocomposite (BSA@AuNCs-MnO 2 ) was constructed. Manganese dioxide (MnO 2 ) was generated in situ on the gold clusters (BSA@AuNCs) based on the redox reaction between bovine serum albumin (BSA) and potassium permanganate (KMnO 4 ). The fluorescence of BSA@AuNCs can be quenched by the in-situ grown MnO 2 , which has strong light absorption ability. It is worth noting that the quenched fluorescence of the BSA@AuNCs can be restored in the presence of glutathione (GSH), and MnO 2 was reduced to Mn 2+ in return. Encouragingly, 1 μM GSH can cause a detectable fluorescence change. This sensitivity is comparable to other nanomaterials based fluorescent probes. Furthermore, this nanocomposite has obvious superiorities, such as good uniformity, simple preparation and mild reaction. The nanocomposite also has good stability and specificity, which can be further used for visualizing of intracellular GSH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A conductometric immunoassay protocol was designed for the sensitive detection of a liver cancer biomarker, alpha-fetoprotein (AFP), in biological fluids by using enzyme-conjugated nanometer-sized enzyme-doped silica beads. Initially, urease molecules were doped into nanosilica particles by using the reverse micelle method. Thereafter, arginase-labeled anti-AFP antibodies were covalently conjugated onto the surface of the synthesized nanoparticles. The immunoreaction was carried out in a monoclonal anti-AFP capture antibody-coated microplate with a sandwich-type assay format by using bienzyme-functionalized silica nanobeads as the recognition elements. Upon l-arginine introduction, the substrate was cleaved into urea and l-ornithine on the basis of the arginase enzymatic reaction, and the as-produced urea was then decomposed into ammonia (NH4+) and bicarbonate (HCO3-) ions by the doped urease, thus causing the variation in the local conductivity of the detection solution on an interdigitated conductometric transducer. Under optimal conditions, the developed immunosensing system exhibited good conductometric responses toward target AFP within a dynamic linear range of 0.01-100 ng mL-1 at a relatively low detection limit of 4.8 pg mL-1 based on the 3sB criterion. Importantly, good reproducibility, high specificity and acceptable method accuracy were acquired for the analysis of human serum specimens in liver cancer patients.