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High or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and planar fault boundaries that enhance the ductility, but this has not been verified. Here, we integrate in situ nanomechanical testing with energy-filtered four-dimensional scanning transmission electron microscopy (4D-STEM) and directly observe the rejuvenation during cyclic mechanical loading in single crystal CrCoNi at room temperature. Surprisingly, stacking faults (SFs) and twin boundaries (TBs) are reversible in initial cycles but become irreversible after a thousand cycles, indicating SF energy reduction and rejuvenation. Molecular dynamics (MD) simulation further reveals that the local breakdown of SRO in the MEA triggers these SF reversibility changes. As a result, the deformation features in HEAs/MEAs remain planar and highly localized to the rejuvenated planes, leading to the superior damage tolerance characteristic in this class of alloys.

Abstract Ubiquitination is a post-translational modification (PTM), which is critical to maintain cell homeostasis. Ubiquitin-specific protease 24 (USP24) plays roles in various diseases, the mechanisms by which USP24 regulates hepatocellular carcinoma (HCC) remain poorly understood. In this study, USP24 is found to be significantly downregulated in HCC. Knocking down USP24 promotes HCC proliferation and migration, whereas USP24 overexpression inhibits HCC in vitro and in vivo. The endogenous interaction between USP24 and Beclin1 is confirmed. Mechanically, USP24 delays Beclin1 degradation by reducing its K48-linked ubiquitination, the effects of overexpressing USP24 on HCC proliferation can be partially reversed by silencing Beclin1. We find that increased autophagy is accompanied by ferroptosis in USP24 overexpressed HCC cells and USP24 increases the susceptibility of HCC to sorafenib. Collectively, this study highlights the critical role of USP24 in regulating autophagy-dependent ferroptosis by decreasing Beclin1 ubiquitination, suggesting that targeting USP24 may be a strategy for treating HCC.

In order to improve the photocatalytic performance of nano-noble metal materials, porous boron nitride nanosheets (h-BNNS) with high specific surface area were prepared by high temperature pyrolysis of the precursor using melamine and boric acid as raw materials. After vacuum impregnation of AgNO3, the nanosheets were added to polyvinylpyrrolidone (PVP) spinning solution. Ag/h-BNNS/PVP composite fiber film was prepared by electrospinning, and the composition, microstructure and photoelectrothermal properties of the composite fiber film were characterized. The Ag plasmon resonance effect significantly improves the visible light absorption and electron-hole pair separation efficiency of the composite fiber membrane. The results showed that silver nanoparticles (Ag NPs) were uniformly dispersed on the surface of the composite fibers, and the average particle size was less than 10 nm. In addition, the introduction of Ag NPs also improves the thermal stability of the membrane material. Based on the CO2 reduction model, the photocatalytic performance of the composite fiber membrane was investigated and tested. The results showed that the best photocatalytic activity of the composite fiber membrane was achieved when the calcination temperature was 250 ℃ and the Ag NPs content was 1.0% (CO yield was 300 μmol/(g·h)).The stability test showed that the CO yield of Ag/h-BNNS/PVP composite membrane was not less than 500 μmol/g after 10 cycles of use. Therefore, the efficient porous composite membrane catalyst prepared by doping Ag NPs to modify h-BNNS and loading Ag/h-BNNS composite particles in PVP fiber provides theoretical reference for future research on boron nitride based catalysts.

In order to exert the synergistic photocatalytic effect of nano-noble metal and polymer matrix, hexagonal boron nitride nanosheets (h-BNNS) were doped with C and O elements by RGO to obtain porous doped boron nitride materials (BCNO), and silver nanoparticles (Ag NPs) were loaded on BCNO matrix by hydrothermal method to prepare BCNO/Ag composites. The composition, microstructure and photocatalytic properties of the composites were characterized. The photocatalytic properties of BCNO/Ag composites were tested by reducing CO2 to CO as a reaction model. The results show that boron nitride modified by nonmetal doping still has a stable polycrystalline structure; After loading Ag NPs, the plasma resonance effect of Ag NPs not only significantly enhances the absorption ability of BCNO matrix to ultraviolet-visible light, but also improves the separation efficiency of its photogenerated carriers; During the preparation of composite materials, the composite material obtained with the addition of 3.0% silver and the calcination temperature of the composite sample at 130 ℃ exhibits the best photocatalytic performance, and the conversion rate of CO2 to CO is 4.68 μmol/（g·h）. Therefore, h-BNNS modified by doping can better stably load nano-precious metals, thus giving full play to the synergistic photocatalytic performance of Ag nanoparticle and BCNO, which provides a theoretical basis for the effective composite and performance research of organic-inorganic nanophotocatalyst.

ObjectiveBiomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP).MethodsThe narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies.ResultsTo answer the need for measuring biomechanical performance, our "Results" section describes the spectrum of technologies that have been developed and are being used within BACPAC.Conclusion and future directionsThe outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.

BackgroundMelanoma, a malignant tumor of the skin, presents challenges in its treatment process involving modalities such as surgery, chemotherapy, and targeted therapy. However, there is a need for an ideal model to assess prognosis and drug sensitivity. Programmed cell death (PCD) modes play a crucial role in tumor progression and has the potential to serve as prognostic and drug sensitivity indicators for melanoma.MethodsWe analyzed 13 PCD modes including apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, disulfidptosis, and alkaliptosis. These modes were used to construct a model that incorporated genes related to these 13 PCD modes to establish a cell death index (CDI) to conduct prognosis analysis. Transcriptomic, genomic, and clinical data were collected from cohorts including TCGA-SKCM, GSE19234, and GSE65904 to validate this model.ResultsA CDI consisting of ten gene signatures was established using machine learning algorithms and divided into two groups based on CDI values. The high CDI group exhibited relatively lower numbers of immune-infiltrating cells and showed resistance to commonly used drugs such as docetaxel and axitinib. Our validation results demonstrated good discrimination in PCA analysis between CDI groups, and melanoma patients with higher CDI values had worse postoperative prognoses (all p < 0.01).ConclusionThe CDI model, incorporating multiple PCD modes, accurately predicts the clinical prognosis and drug sensitivity of melanoma patients.

Abstract Objectives To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). Materials and Methods This multi‐institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre‐operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow‐up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. Results From January 2015 to July 2022, 68 renal AML patients were studied—41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non‐TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non‐TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non‐TSC patient discontinued treatment due to side‐effects. Most patients (92.7% TSC, 85.2% non‐TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow‐up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. Conclusion Everolimus was effective and well‐tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

ABSTRACT Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients’ gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.IMPORTANCEThis study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.

Using simulated patients to mimic 9 established noncommunicable and infectious diseases, we assessed ChatGPT’s performance in treatment recommendations for common diseases in low- and middle-income countries. ChatGPT had a high level of accuracy in both correct diagnoses (20/27, 74%) and medication prescriptions (22/27, 82%) but a concerning level of unnecessary or harmful medications (23/27, 85%) even with correct diagnoses. ChatGPT performed better in managing noncommunicable diseases than infectious ones. These results highlight the need for cautious AI integration in health care systems to ensure quality and safety.

Research efforts on permanganate (Mn(VII)) combined with redox-mediator (RM), have received increasing attention due to their significant performance for bisphenol-A (BPA) removal. However, the mechanisms underpinning BPA degradation remain underexplored. Here we show the overlooked interactions between RM and BPA during permanganate oxidation by introducing an RM—N-hydroxyphthalimide (NHPI). We discovered that the concurrent generation of MnO2 and phthalimide-N-oxyl (PINO) radical significantly enhances BPA oxidation within the pH range of 5.0–6.0. The detection of radical cross-coupling products between PINO radicals and BPA or its derivatives corroborates the pivotal role of radical cross-coupling in BPA oxidation. Intriguingly, we observed the formation of an NHPI-BPA complex, which undergoes preferential oxidation by Mn(VII), marked by the emergence of an electron-rich domain in NHPI. These findings unveil the underlying mechanisms in the Mn(VII)/RM system and bridge the knowledge gap concerning BPA transformation via complexation. This research paves the way for further exploration into optimizing complexation sites and RM dosage, significantly enhancing the system's efficiency in water treatment applications.

The extraordinary work hardening ability and fracture toughness of the face-centered cubic (fcc) high-entropy alloys render them ideal candidates for many structural applications. Here, the deformation and failure mechanisms of an equiatomic CrCoNi medium-entropyalloy (MEA) were investigated by powerful laser-driven shock experiments. Multiscale characterization demonstrates that profuse planar defects including stacking faults, nanotwins, and hexagonal nanolamella were generated during shock compression, forming a three-dimensional network. During shock release, the MEA fractured by strong tensile deformation and numerous voids was observed in the vicinity of the fracture plane. High defect populations, nanorecrystallization, and amorphization were found adjacent to these areas of localized deformation. Molecular dynamics simulations corroborate the experimental results and suggest that deformation-induced defects formed before void nucleation govern the geometry of void growth and delay their coalescence. Our results indicate that the CrCoNi-based alloys are impact resistant, damage tolerant, and potentially suitable in applications under extreme conditions.

Purpose: This scoping review aimed to offer researchers and practitioners an understanding of artificial intelligence (AI) applications in physical activity (PA) interventions; introduce them to prevalent machine learning (ML), deep learning (DL), and reinforcement learning (RL) algorithms; and encourage the adoption of AI methodologies. Methods: A scoping review was performed in PubMed, Web of Science, Cochrane Library, and EBSCO focusing on AI applications for promoting PA or predicting related behavioral or health outcomes. AI methodologies were summarized and categorized to identify synergies, patterns, and trends informing future research. Additionally, a concise primer on predominant AI methodologies within the realm of PA was provided to bolster understanding and broader application. Results: The review included 24 studies that met the predetermined eligibility criteria. AI models were found effective in detecting significant patterns of PA behavior and associations between specific factors and intervention outcomes. Most studies comparing AI models to traditional statistical approaches reported higher prediction accuracy for AI models on test data. Comparisons of different AI models yielded mixed results, likely due to model performance being highly dependent on the dataset and task. An increasing trend of adopting state-of-the-art DL and RL models over standard ML was observed, addressing complex human–machine communication, behavior modification, and decision-making tasks. Six key areas for future AI adoption in PA interventions emerged: personalized PA interventions, real-time monitoring and adaptation, integration of multimodal data sources, evaluation of intervention effectiveness, expanding access to PA interventions, and predicting and preventing injuries. Conclusion: The scoping review highlights the potential of AI methodologies for advancing PA interventions. As the field progresses, staying informed and exploring emerging AI-driven strategies is essential for achieving significant improvements in PA interventions and fostering overall well-being.

This work studied the microstructure, mechanical properties and damping properties of Mg95.34Ni2Y2.66 and Mg95.34Zn1Ni1Y2.66 alloys systematically. The difference in the evolution of the long-period stacked ordered (LPSO) phase in the two alloys during heat treatment was the focus. The morphology of the as-cast Mg95.34Ni2Y2.66 presented a disordered network. After heat treatment at 773 K for 2 hours, the eutectic phase was integrated into the matrix, and the LPSO phase maintained the 18R structure. As Zn partially replaced Ni, the crystal grains became rounded in the cast alloy, and lamellar LPSO phases and more solid solution atoms were contained in the matrix after heat treatment of the Mg95.34Zn1Ni1Y2.66 alloy. Both Zn and the heat treatment had a significant effect on damping. Obvious dislocation internal friction peaks and grain boundary internal friction peaks were found after temperature-dependent damping of the Mg95.34Ni2Y2.66 and Mg95.34Zn1Ni1Y2.66 alloys. After heat treatment, the dislocation peak was significantly increased, especially in the alloy Mg95.34Ni2Y2.66. The annealed Mg95.34Ni2Y2.66 alloy with a rod-shaped LPSO phase exhibited a good damping performance of 0.14 at ε=10−3, which was due to the difference between the second phase and solid solution atom content. These factors also affected the dynamic modulus of the alloy. The results of this study will help in further development of high-damping magnesium alloys.

Introduction This retrospective study aimed to evaluate the prognostic value of [18F]FDG parameters in patients with visceral and bone metastatic hormone-sensitive prostate cancer (mHSPC).Patients and methods This analysis included the mHSPC patients who underwent [18F]FDG PET/CT at the initial diagnosis. Baseline characteristics were analyzed, and the uptake of [18F]FDG was quantified using SUVmax. Kaplan–Meier and Cox proportional hazard regression analysis were employed to evaluate the correlation between SUVmax and patient survival.Results Among the 267 patients enrolled, 90 (33.7%) presented with visceral metastases and 177 (66.3%) had bone metastases. The median follow-up for the visceral metastasis group was 35.5 months (IQR 26–53.8 months). The median overall survival for patients with lung, liver, or both metastases were 30, 21 and 17 months, respectively. Patients exhibiting higher [18F]FDG uptake in metastatic lesions experienced shorter overall survival (OS) in comparison to those with lower [18F]FDG uptake, both in the visceral metastases group (17 vs. 31 months, p = 0.002) and the bone metastases group (27.5 vs. 34.5 months, p

The use of an appropriate amount of anesthetic can prevent the sacrifice of oysters during experimental sampling or seedling rearing. In this study, we assessed the effects of air exposure and three concentrations of magnesium chloride (10, 40, and 70 g L–1) on the anesthetic efficiency for Crassostrea hongkongensis. We examined the recuperative capacity of the oysters post-tissue sampling. The results indicated that 36 h of air exposure could significantly enhance the anesthetic efficiency of C. hongkongensis while ensuring the oysters’ survival. A 40 g L–1 solution of magnesium chloride had the optimal anesthetic effect on C. hongkongensis across all oyster sizes. In addition, smaller oysters (119.10 g) had a higher relaxation rate than larger oysters (191.00 g). The oysters anesthetized with 40 g L–1 magnesium chloride also demonstrated the best recovery. No deaths were observed among the non-anesthetized oysters, anesthetized-recovered oysters, or non-recovered oysters during a seven-day post-farming period. In terms of live sampling, the control group (100 %), gonad group (100 %), mantle group (98.67 %), gill group (89.33 %), and adductor muscle group (97.33 %) all showed high survival rates after anesthesia. Observation of tissue growth post-sampling revealed the presence of focal green areas in tissues between days 7 and 14. By day 30, the adductor muscle and mantle tissues had fully healed, and the regrown tissue in the gills had approached its original length. A 40 g L–1 magnesium chloride solution had no significant effects on gametes in terms of fertilization rate, growth rate, and attachment rate. The present findings indicated that C. hongkongensis could be effectively anesthetized using a 40 g L–1 magnesium chloride solution following 36 h of aerial exposure. Post-anesthesia tissue and gamete sampling did not result in significant mortality, and the tissues had fully recovered within 30 days post-sampling. The anesthesia did not have any adverse effects on the progeny.

Interstitial oxygen embrittles titanium, particularly at cryogenic temperatures, which necessitates a stringent control of oxygen content in fabricating titanium and its alloys. Here, we propose a structural strategy, via grain refinement, to alleviate this problem. Compared to a coarse-grained counterpart that is extremely brittle at 77 K, the uniform elongation of an ultrafine-grained (UFG) microstructure (grain size ~ 2.0 µm) in Ti-0.3wt.%O is successfully increased by an order of magnitude, maintaining an ultrahigh yield strength inherent to the UFG microstructure. This unique strength-ductility synergy in UFG Ti-0.3wt.%O is achieved via the combined effects of diluted grain boundary segregation of oxygen that helps to improve the grain boundary cohesive energy and enhanced dislocation activities that contribute to the excellent strain hardening ability. The present strategy will not only boost the potential applications of high strength Ti-O alloys at low temperatures, but can also be applied to other alloy systems, where interstitial solution hardening results into an undesirable loss of ductility.

CrCoNi-based medium- and high-entropy alloys display outstanding damage tolerance, especially at cryogenic temperatures. In this study, we examined the fracture toughness values of the equiatomic CrCoNi and CrMnFeCoNi alloys at 20 kelvin (K). We found exceptionally high crack-initiation fracture toughnesses of 262 and 459 megapascal-meters½ (MPa·m½) for CrMnFeCoNi and CrCoNi, respectively; CrCoNi displayed a crack-growth toughness exceeding 540 MPa·m½ after 2.25 millimeters of stable cracking. Crack-tip deformation structures at 20 K are quite distinct from those at higher temperatures. They involve nucleation and restricted growth of stacking faults, fine nanotwins, and transformed epsilon martensite, with coherent interfaces that can promote both arrest and transmission of dislocations to generate strength and ductility. We believe that these alloys develop fracture resistance through a progressive synergy of deformation mechanisms, dislocation glide, stacking-fault formation, nanotwinning, and phase transformation, which act in concert to prolong strain hardening that simultaneously elevates strength and ductility, leading to exceptional toughness.

Abstract The transition metal‐catalyzed multi‐component cross‐electrophile sulfonylation, which incorporates SO2 as a linker within organic frameworks, has proven to be a powerful, efficient, and cost‐effective means of synthesizing challenging alkyl–alkyl sulfones. Transition metal catalysts play a crucial role in this method by transferring electrons from reductants to electrophilic organohalides, thereby causing undesirable side reactions such as homocoupling, protodehalogenation, β‐hydride elimination, etc. It is worth noting that tertiary alkyl halides have rarely been demonstrated to be compatible with current methods owing to various undesired side reactions. In this work, a zinc‐promoted cross‐electrophile sulfonylation is developed through a radical‐polar crossover pathway. This approach enables the synthesis of various alkyl–alkyl sulfones, including 1°‐1°, 2°‐1°, 3°‐1°, 2°‐2°, and 3°‐2° types, from inexpensive and readily available alkyl halides. Various functional groups are well tolerated in the work, resulting in yields of up to 93%. Additionally, this protocol has been successfully applied to intramolecular sulfonylation and homo‐sulfonylation reactions. The insights gained from this work shall be useful for the further development of cross‐electrophile sulfonylation to access alkyl–alkyl sulfones.

The aging process profoundly impacts the systemic milieu, with specific blood-borne factors playing critical roles in its regulation. Platelet Factor 4 (PF4), released by platelets, has emerged as a novel blood-borne factor that contributes to the rejuvenation of aging brains in rodents. However, the age-related disparity in PF4 levels in humans remains poorly understood. To explore the relationship between PF4 and the natural aging process in humans, we collected peripheral blood (PB) samples from young (23.40 ± 2.13 years, n = 15) and elderly (75.23 ± 4.19 years, n = 13) individuals, along with cord blood (CB) samples (n = 15). ELISA analysis revealed higher PF4 levels in platelet-rich plasma lysate from young PB compared with that from elderly PB. Consistent with this, qPCR results demonstrated the highest PF4 expression in young PB among the three groups. In addition, FACS analysis showed increased expression of CXCR3 in mononuclear cells of young PB, indicating a greater responsiveness to PF4. Finally, our RNA-sequencing analysis corroborated platelets as a sensitive element during the natural aging process, and indicated platelets play a pivotal role in antioxidant response during aging, as evidenced by significant enrichment of several age-related pathways. These findings reveal that, alongside PF4 levels, platelets undergo substantial alterations during aging. Taken together, our data identified age-related disparities in platelets and PF4-related elements during natural aging and underscored the potential of targeting platelet modulation as an intervention in the aging process.