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Here we report the asymmetric total syntheses of two rearranged tigliane diterpenoids, euphordraculoate A and pedrolide. A reductive dihydroxylation cascade and Nazarov cyclization were performed to generate euphordraculoate A, which was subjected to a cascade of Eu‐promoted dienyl enolization, intramolecular Diels–Alder reaction and enol‐ketone tautomerization to afford pedrolide, a pathway consistent with our proposal for the biogenesis of pedrolide. [ABSTRACT FROM AUTHOR]

Here we report the asymmetric total syntheses of two rearranged tigliane diterpenoids, euphordraculoate A and pedrolide. A reductive dihydroxylation cascade and Nazarov cyclization were performed to generate euphordraculoate A, which was subjected to a cascade of Eu‐promoted dienyl enolization, intramolecular Diels–Alder reaction and enol‐ketone tautomerization to afford pedrolide, a pathway consistent with our proposal for the biogenesis of pedrolide. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are common hematological malignancies in adults. Despite considerable research advances, the development of standard therapies, supportive care, and prognosis for the majority of AML and ALL patients remains poor and the development of new effective therapy is urgently needed. Here, it is reported that activation of thermogenic adipose tissues (TATs) by cold exposure or β3‐adrenergic receptor agonists markedly alleviated the development and progression of AML and ALL in mouse leukemia models. TAT activation (TATA) monotherapy substantially reduces leukemic cells in bone marrow and peripheral blood, and suppresses leukemic cell invasion, including hepatomegaly and splenomegaly. Notably, TATA therapy prolongs the survivals of AML‐ and ALL‐bearing mice. Surgical removal of thermogenic brown adipose tissue (BAT) or genetic deletion of uncoupling protein 1 (UCP1) largely abolishes the TATA‐mediated anti‐leukemia effects. Metabolomic pathway analysis demonstrates that glycolytic metabolism, which is essential for anabolic leukemic cell growth, is severely impaired in TATA‐treated leukemic cells. Moreover, a combination of TATA therapy with chemotherapy produces enhanced anti‐leukemic effects and reduces chemotoxicity. These data provide a new TATA‐based therapeutic paradigm for the effective treatment of AML, ALL, and likely other types of hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: As populations live longer, there is a progressive increase in chronic degenerative diseases, particularly those related to the musculoskeletal system. Sarcopenia is characterized by loss of skeletal muscle mass, muscle strength, and loss of physical function. It is a common disease in older adults associated with various adverse health outcomes. There is a lack of bioindicators to screen for sarcopenia. Albumin and lymphocyte counts are commonly used to assess the degree of malnutrition, and blood routine, lipids, and thyroid function are relatively easy to obtain as part of a routine physical examination. Therefore, finding blood markers that can screen for sarcopenia is essential. Our primary aim was to explore whether the bioindicators of body composition, lymphocytes, albumin, lipids, and thyroid hormones are associated with sarcopenia, and a secondary aim was to investigate changes in these indicators after an intensive lifestyle intervention preliminarily. Methods: 60 subjects were selected from Runda and Bailian community health centers in Suzhou, China. They underwent body composition analysis and tested lymphocyte, albumin, lipid, and thyroid hormone levels. The 30 sarcopenia subjects underwent a 3-month intensive lifestyle intervention program. At the end of the intervention, we rechecked the bioindicators. Statistical analyses were performed in IBM SPSS v26.0. Results: The blood indices of sarcopenia subjects were generally lower in albumin, non-high-density lipoprotein cholesterol (non-HDL-C), and free triiodothyronine (FT3). Body mass index (BMI)(r = 0.6266, p < 0.0001), fat-free mass (r = 0.8110, p < 0.0001), basal metabolism (r = 0.7782, p < 0.0001), and fat mass (r = 0.3916, p = 0.0020) were positively correlated with appendicular skeletal muscle index (ASMI). Higher BMI and FT3 were associated with lower odds of sarcopenia, while higher fat mass was associated with higher odds of sarcopenia. After a 3-month intensive intervention, sarcopenia subjects had a significant increase in BMI, ASMI, lymphocyte, and albumin levels, and an increase in FT3, but with a non-significant difference (p = 0.342). Conclusions: Low BMI, FT3, and high fat mass were associated with sarcopenia. Intensive lifestyle intervention can significantly improve ASMI, BMI, lymphocytes, albumin, and FT3 in sarcopenia subjects, which is favorable for delaying the progression of sarcopenia. Trial registration: This study was retrospectively registered on ClinicalTrials.gov, registration number NCT06128577, date of registration: 07/11/2023. [ABSTRACT FROM AUTHOR]

AlCoCrFeNi2.1 eutectic high‐entropy alloy was introduced to join Cf/SiC composite by spark plasma sintering technique. The influence of holding times on microstructure, shear strength and fracture behavior of the joints was studied. When held for 7 min, the typical microstructure of the Cf/SiC‐AlCoCrFeNi2.1‐Cf/SiC joint was Cf/SiC composite → CrSi2 + FCC + Al8Cr5 + graphite → CrSi2 + FCC + Al8Cr5 → CrSi2 + FCC + Al8Cr5 + graphite → Cf/SiC composite. As the holding time extended, the Ni–Si and Fe–Si brittle phases in the joint gradually reduced, and the diffusion transition layer continued to thicken. The maximum joint strength was 23.9 MPa, which was obtained at 1450°C for 7 min. Analyzed by scanning electron microscopy and energy dispersive spectroscopy, the fracture modes of the joints joined at different holding times were all brittle fracture. [ABSTRACT FROM AUTHOR]

When water vapor comes into contact with a cold surface, it condenses into water droplets. This natural phenomenon is called breath figures (BFs). Interestingly, ordered BFs can be formed on a volatile liquid surface. Different volatile liquids can induce different BFs, but the growth process of ordered BFs is not fully understood. Although it is believed that BFs can form on the surface of a volatile liquid, such as dichloromethane, there is little experimental evidence to support this claim. Herein, the growth of BFs on a surface of pure dichloromethane without any polymer was observed in situ by an optical microscope (OM) in a static humid environment. The OM images were analyzed to obtain details, and the ordered breath figure arrays (BFAs) were observed on the volatile liquid surface. It is found that there are three distinct power-law growth exponents, and the growth of BFs followed a single droplet growth before coalescing. Moreover, it was observed that water droplets were rapidly moving throughout the water droplet growth. The growth dynamics of BFs on the volatile surface of pure dichloromethane have unique characteristics, which are different from the reported results on nonvolatile surfaces, volatile solutions with polymer, and pure carbon disulfide. These results provide direct evidence for ordered BFs from pure dichloromethane and help explain the mechanism of ordered BFs on volatile liquid surfaces. [ABSTRACT FROM AUTHOR]

In this paper, a novel dual-sparse parallel nested array (DS-PNA) is proposed for high-accuracy two-dimensional (2D) direction of arrival (DOA) estimation. The DS-PNA contains three subarrays, and the inter-antenna spacings of subarrays and those between subarrays are all enlarged with specific rates in 2D space (both of which are far larger than half-wavelength), for mutual coupling reduction and array aperture extension in physical array domain. Based on it, there is a systematic procedure to determine the number and positions of antennas in each subarray to achieve the maximum degrees of freedom in difference coarray domain, for improving the performance of DOA estimation. Numerical results are provided to demonstrate the superior performance of the DS-PNA for 2D DOA estimation over the state-of-the-art approaches, in the case of practical mutual coupling model. [ABSTRACT FROM AUTHOR]

For target detection and recognition in a complicated electromagnetic environment, the two-dimensional direction-of-arrival and polarization estimation using a polarization-sensitive array has been receiving increased attention. To efficiently improve the performance of such multi-parameter estimation in practice, this paper proposes a parallel synthetic coprime array with reduced mutual coupling and hardware cost saving and then presents a dimension-reduction compressive sensing-based estimation method. For the proposed array, the polarization types, numbers, and positions of antennas in each subarray are jointly considered to effectively mitigate mutual coupling in the physical array domain and to both enhance degrees of freedom and extend the aperture in the difference coarray domain with the limited physical antennas. By exploring the array configuration, the parameter estimation can be formulated as a block-sparse signal reconstruction problem, and then the one-dimensional sparse reconstruction algorithm is only used once to achieve multi-parameter estimation with automatic pair-matching. The theoretical analysis and simulation results are provided to demonstrate the superior performance of the proposed array and method over the existing techniques. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs' function by CE-sEVs. [ABSTRACT FROM AUTHOR]

The design and synthesis of catalysts loaded with active components has attracted considerable attention in current research owing to their exceptional catalytic performance. In this study, the focus was on the utilization of tin‐loaded ZA molecular sieves, possessing remarkable adsorption properties, alongside the catalytic activity of tin. These catalysts were successfully prepared and employed for the synthesis of poly(lactic acid) (PLA) from lactic acid derived from non‐food biomass. By modifying the treatment of ZA molecular sieves, the properties of tin‐loaded ZA molecular sieves were adjusted. The resulting catalysts exhibited a high tin capacity ranging from 2.29% to 2.81% and featured abundant mesoporous structures, providing a surface area of up to 341.2 m2 g−1. Regarding the preparation of PLA, our findings demonstrated that ZA‐III‐Sn2+ as a catalyst yielded PLA with a higher weight‐average molecular weight (Mw) up to 2.57 × 104 g mol−1 and a higher yield of 65.3% compared to other catalysts. Moreover, the most optimal catalytic effect was achieved by adding the catalyst in three separate stages. Moreover, the amount of catalyst, reaction temperature and reaction time were found to influence both the molecular weight and yield of PLA. This study not only provides a valuable strategy for the preparation of loaded catalysts for PLA production but also offers new insights into the overall preparation process of PLA. © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

In this paper, the relative positive center set of convex plane curves is introduced and described. As its applications, some geometric inequalities are proved. [ABSTRACT FROM AUTHOR]

This paper centers its attention on an anisotropic area-preserving flow with the goal of establishing the existence of smooth solutions to the even, planar logarithmic Minkowski problem by the asymptotic behavior of this flow. [ABSTRACT FROM AUTHOR]

We consider an anisotropic area-preserving nonlocal flow for closed convex plane curves, which is a generalization of the model introduced by Pan and Yang (J. Differential Equations 266 (2019), 3764–3786) when τ = 1. Under this flow, the evolving curve maintains its convexity and converges to a homothety of a smooth symmetric strictly convex plane curve in the C∞ sense. The analysis of the asymptotic behavior of this flow implies the possibility of deforming one curve into another within the framework of Minkowski geometry. [ABSTRACT FROM AUTHOR]

To improve the performance of underdetermined direction of arrival (DOA) estimation in the scenario of strong mutual coupling and unknown nonuniform noise, this paper presents a novel coprime polarization sensitive array (PSA) with limited antenna number and proposes a low-complexity DOA estimation method via iterative covariance matrix reconstruction. The proposed synthetic array is composed of two single-polarized subarrays with dipole or loop antennas. Owing to the polarization domain, it can efficiently reduce the mutual coupling between subarrays, which dominates the effect of mutual coupling in the existing coprime arrays. For effectively eliminating the nonuniform noise, the cross-covariance matrix between subarrays is utilized. Based on it, the full aperture and all degrees of freedoms of the difference coarray with holes are obtained, and then, initial DOAs are estimated by using orthogonal matching pursuit algorithm. The oblique projection operators depending on initial DOAs are constructed to fill holes in difference coarray, in order to generate a larger covariance matrix for refined angle estimation. Then, a fast iterative procedure associated with covariance matrix reconstruction is given to achieve final DOA estimation, for further enhancing estimation performance. Theoretical analysis and simulation results verify the effectiveness of the proposed array and method. [ABSTRACT FROM AUTHOR]

In wastewater treatment, a low C/N ratio highly inhibits the bioremoval of nitrogen, and commercial external carbon sources are widely used. In order to obtain an economical substitute, fermentation broth of spent mushroom substrates (SMS) was employed here as a carbon source for denitrification in a sequencing batch reactor (SBR). During the domestication process, the SMS fermentation broth-feeding treatment presented comparable nitrogen removal ability (74.44%) with a commercial carbon source group (77.99%). Rhodobacter, Lactobacillus and Pseudomonas were the dominant bacteria in the fermentation broth, and Saccharomycetales Gymnopilus dilepis was the dominant fungi. At the early domestication stage, the relatively high concentration of fermentation broth led to a much lower abundance of typical nitrate reductase genes than the control group. Furthermore, extracellular polymeric substance (EPS) formation was observed in the broth-feeding sample. The microbial structure dynamic was investigated, which showed a high influent effect when 20% fermentation broth was added. As domestication proceeded, similar dominant species in the control and broth-feeding treatments were observed. Overall, SMS fermentation broth can be used as a promising substitute to replace a costly commercial carbon source. [ABSTRACT FROM AUTHOR]

This letter proposes a novel parallel sparse nested array and then provides a matrix reconstruction‐based method with three steps, to enhance the performance of direction of arrival (DOA) estimation in practice. The spacings between the closest antennas along x‐ and y‐axes, are coprime and much greater than half‐wavelength in the proposed array, which contributes to efficiently eliminate the mutual coupling and achieve larger aperture with limited physical antennas. By using the oblique projection operator with iteration, the proposed method can employ all items of covariance matrix of the received data to construct a virtual covariance matrix with increased degrees of freedom, for effectively improving angle estimation performance. Then the unique and high‐accuracy DOA estimation is obtained via the coprime‐ness. The simulation results show the superiority of the proposed array and method for DOA estimation in the presence of mutual coupling and limited antennas. [ABSTRACT FROM AUTHOR]

Citrus harvesting is a labor‐intensive and time‐intensive task. As the global population continues to age, labor costs are increasing dramatically. Therefore, the citrus‐harvesting robot has attracted considerable attention from the business and academic communities. However, robotic harvesting in unstructured and natural citrus orchards remains a challenge. This study aims to address some challenges faced in commercializing citrus‐harvesting robots. We present a fully integrated, autonomous, and innovative solution for citrus‐harvesting robots to overcome the harvesting difficulties derived from the natural growth characteristics of citrus. This solution uses a fused simultaneous localization and mapping algorithm based on multiple sensors to perform high‐precision localization and navigation for the robot in the field orchard. Besides, a novel visual method for estimating fruit poses is proposed to cope with the randomization of citrus growth orientations. Further, a new end‐effector is designed to improve the success and conformity rate of citrus stem cutting. Finally, a fully autonomous harvesting robot system has been developed and integrated. Field evaluations showed that the robot could harvest citrus continuously with an overall success rate of 87.2% and an average picking time of 10.9 s/fruit. These efforts provide a solid foundation for the future commercialization of citrus‐harvesting robots. [ABSTRACT FROM AUTHOR]

Most existing lower-limb rehabilitation robots (LLRR) for stroke and postoperative rehabilitation are bulky and prone to misalignments between robot and human joints. These drawbacks hamper LLRR application, leading to poor arthro-kinematic compatibility. To address these challenges, this paper proposes a novel robot with portability and compliance features. The developed robot consists of an underactuated mechanism and a crus linkage, respectively corresponding to the hip and knee joints. The underactuated mechanism is a new type of remote center of motion (RCM) mechanism with two sets of contractible slider cranks that can reduce the misalignments between robot and human joints. The underactuated mechanism is then optimized using the particle swarm optimization method, and the developed robot's kinematic analysis is presented. The proposed robot can be simplified as a two-link mechanism with the ability to easily plan its trajectory using the modified Denavit–Hartenberg method. Finally, passive exercise trials demonstrate that the mismatch angles between the human and robot knee joints are less than 2.1% of the range of motion, confirming the feasibility and effectiveness of the proposed robot. [ABSTRACT FROM AUTHOR]

The circadian clock in animals and humans plays crucial roles in multiple physiological processes. Disruption of circadian homeostasis causes detrimental effects. Here, it is demonstrated that the disruption of the circadian rhythm by genetic deletion of mouse brain and muscle ARNT‐like 1 (Bmal1) gene, coding for the key clock transcription factor, augments an exacerbated fibrotic phenotype in various tumors. Accretion of cancer‐associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive myoCAFs, accelerates tumor growth rates and metastatic potentials. Mechanistically, deletion of Bmal1 abrogates expression of its transcriptionally targeted plasminogen activator inhibitor‐1 (PAI‐1). Consequently, decreased levels of PAI‐1 in the tumor microenvironment instigate plasmin activation through upregulation of tissue plasminogen activator and urokinase plasminogen activator. The activated plasmin converts latent TGF‐β into its activated form, which potently induces tumor fibrosis and the transition of CAFs into myoCAFs, the latter promoting cancer metastasis. Pharmacological inhibition of the TGF‐β signaling largely ablates the metastatic potentials of colorectal cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Together, these data provide novel mechanistic insights into disruption of the circadian clock in tumor growth and metastasis. It is reasonably speculated that normalization of the circadian rhythm in patients provides a novel paradigm for cancer therapy. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is an acute infectious haemorrhagic fever of pigs caused by African swine fever virus (ASFV). Aloe-emodin (Ae) is an active ingredient of Chinese herbs with antiviral, anticancer, and anti-inflammatory effects. We investigated the antiviral activity and mechanism of action of Ae against ASFV using Real-time quantitative PCR (qPCR), western blotting, and indirect immunofluorescence assays. Ae significantly inhibited ASFV replication. Furthermore, transcriptomic analysis revealed that ASFV infection activated the NF-κB signaling pathway in the early stage and the apoptosis pathway in the late stage. Ae significantly downregulated the expression levels of MyD88, phosphor-NF-κB p65, and pIκB proteins as well as the mRNA levels of IL-1β and IL-8 in porcine alveolar macrophages (PAMs) infected with ASFV, thereby inhibiting the activation of the NF-κB signaling pathway induced by ASFV. Flow cytometry and western blot analysis revealed that Ae significantly increased the percentage of ASFV-induced apoptotic cells. Additionally, Ae promoted apoptosis by upregulating the expression levels of cleaved-caspase3 and Bax proteins and downregulating the expression levels of Bcl-2 proteins. This suggests that Ae promotes apoptosis by inhibiting the NF-κB pathway, resulting in inhibition of ASFV replication. These findings have further improved therapeutic reserves for the prevention and treatment of ASF. [ABSTRACT FROM AUTHOR]

Mechanically compressible energy devices represent one of the most promising candidates for powering flexible and portable electronics, but often suffer from their limited stability of performance under high compressive strains. We here demonstrate a type of reduced graphene oxide/carbon nanotubes (RGO/CNTs) composite aerogel with high conductivity and compressive strength for elastic energy conversion and storage devices with high performance. The catalyst for growth of CNTs is loaded in the RGO aerogel by a simple solution method, and then, highly aligned CNT arrays are directly grown among RGO layers through chemical vapor deposition. The pillared CNT arrays between lamellar RGO layers provide the RGO/CNTs aerogel with extremely high conductivity (214.7 S m−1) and compressive strength (73.6 kPa), which are superior to most previously reported results. With using the RGO/CNTs derived composite aerogels as electrodes, the achieved supercapacitors not only exhibit high specific capacitance (215.5 mF cm−3), but also show outstanding compression stability without performance degradation even after 15 000 repeated compression cycles. Furthermore, the piezoelectric nanogenerator based on the RGO/CNTs-derived aerogel can deliver a stable piezoelectric voltage of 0.6 V and excellent stability. This lamellar/pillared RGO/CNTs aerogel can be used as an efficient platform to load other functional materials for other elastic electronics with high performance. [ABSTRACT FROM AUTHOR]

This paper will establish the asymptotic behavior of an anisotropic area‐preserving flow which shows the existence of smooth solutions of the planar Lp$L_p$ Minkowski problem for p≠0$p\ne 0$. [ABSTRACT FROM AUTHOR]

Coalbed methane extraction promotes energy exploitation and alleviates the greenhouse effect. This study aimed to analyze the technical potential of a high‐pressure gas–liquid two‐phase jet in increasing coalbed permeability and promoting coalbed methane extraction. A well‐designed experimental setup was used to investigate the erosion characteristics of a high‐pressure gas–liquid two‐phase jet. Through the shock pressure monitoring and erosion tests of the jet, the effects of pump pressure, mixer structure, and nozzle structure on the shock pressure and rock‐breaking performance were studied, and the rock‐breaking mechanism of the high‐pressure gas–liquid two‐phase jet was examined. The results showed that the nonuniformity of mixing and the expansibility of high‐pressure gas continually alters high‐pressure gas–liquid two‐phase jets between single and multiple streams, which makes the jet show obvious pulse effects and considerably improves the rock‐breaking performance. Furthermore, reasonable air pump pressure and water pump pressure settings significantly increase the shock area, whereas the maximum shock pressure only decreases slightly. Although the shock pressure of a high‐pressure gas–liquid two‐phase jet decreases with the increase in air pump pressure, its shock efficiency first increases and then decreases with the increase in air pump pressure. To improve the erosion efficiency of a high‐pressure gas–liquid two‐phase jet, the settings of the air pump pressure and water pump pressure is crucial, but the optimal air pump pressure differs for different water pump pressures. Additionally, the greater the angle between the gas and liquid inlets, the greater the energy loss of the fluid during the mixing. Finally, the rock‐breaking performance showed that the optimal nozzle structure is the single‐cone nozzle. [ABSTRACT FROM AUTHOR]

For a convex domain, two Chernoff type inequalities concerning the k-order width are proved by using Fourier series, and one of which is an extension of the Chernoff–Ou–Pan inequality (Pacific J Math 284:393–401, 2010). Furthermore, stability properties for these inequalities can also be obtained in the Hausdorff and L 2 metrics, respectively. [ABSTRACT FROM AUTHOR]

Microbial fatty acids are synthesized by Type II fatty acid synthase and could be tailored by acyl-ACP thioesterase. With the prospects of medium-chain fatty-acid-derivative biofuels, the selectivity of thioesterase has been studied to control the fatty acid product chain length. Here, we report an alternative approach by manipulating the acyl carrier protein portion of acyl-ACP to switch the chain length propensity of the thioesterase. It was demonstrated that ChFatB2 from Cuphea hookeriana preferred C10-ACP to C8-ACP with ACP from E. coli, while converting preference to C8-ACP with ACP from Cuphea lanceolate. Circular dichroism (CD) results indicated that the C8-EcACP encountered a 34.4% α-helix increment compared to C10-EcACP, which resulted in an approximate binding affinity decrease in ChFatB2 compared to C10-EcACP. Similarly, the C10-ClACP2 suffered a 45% decrease in helix content compared to C8–ClACP2, and the conformational changes resulted in an 18% binding affinity decline with ChFatB2 compared with C10-ClACP2. In brief, the study demonstrates that the ACP portion of acyl-ACP contributes to the selectivity of acyl-ACP thioesterase, and the conformational changes of EcACP and ClACP2 switch the chain length preference of ChFatB2 between C8 and C10. The result provides fundamentals for the directed synthesis of medium-chain fatty acids based on regulating the conformational changes of ACPs. [ABSTRACT FROM AUTHOR]

Water scarcity is a worldwide problem. Recycled municipal wastewater is considered a useful alternative to the conventional types of water resources. In this study, a shallow constructed wetland (SCW) with porous filter material and Rotala rotundifolia was used for advanced municipal sewage treatment. The wetland without plant was set as the control (SCW-C). The pollutant removal performance of the system at different hydraulic retention times (HRTs) was investigated. The diversity of the microbial community was analyzed, and the fate of nutrients, mainly N and P, in the system was discussed. Results showed that SCW was efficient in pollutant removal. Effluent concentrations of chemical oxygen demand (COD), total phosphorus (TP), and ammonium nitrogen (NH4+-N) were 15.0–23.6, 0.19–0.28, and 0.83–1.16 mg/L, separately, with average removal efficiencies of 61.2%, 46.3%, and 88.1% at HRT 18 h, which met the requirements of type IV water set by the environmental quality standards for surface water in China. The richness and evenness of the bacterial community were significantly higher in the plant-rooted SCW. They increased along with the system. The dominant genera in the system were phosphate-solubilizing bacteria, nitrifying bacteria, and denitrifying bacteria. The P in the influent mainly flowed to the substrate and plant. At the same time, most N was removed by nitrification and denitrification. These findings suggested that the SCW could remove pollutants from the municipal sewage effluent and meet the standard requirement at low HRT. [ABSTRACT FROM AUTHOR]

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.Research Design and Methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis.Results: Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease-related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease-related factors were predominant for diabetes occurring after pancreatitis.Conclusions: Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention. [ABSTRACT FROM AUTHOR]

The article in Advanced Science discusses how activating thermogenic adipose tissues (TATs) through cold exposure or β3‐adrenergic receptor agonists can effectively prevent and treat acute myeloid leukemia and acute lymphoblastic leukemia in mice. The study suggests that targeting tissues outside of cancer could be a potential therapy for leukemia. The cover art depicts a TAT troop attacking a leukemia cell in a wintry setting. [Extracted from the article]

Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy. [Display omitted] • Voluntary exercise increases miR-29a-3p in muscle-derived EVs in patients with cancer • MiR-29a-3p-containing EVs accumulate in tumors and inhibit collagen components • Exercise or collagen inhibition leads to tumor inflammation and sensitizes immunotherapy Luo et al. report that voluntary exercise sensitizes immunotherapy in mouse models and patients with cancer by releasing muscle-derived miR-29a-3p-containing EVs. These EVs accumulate in tumor tissue and inhibit collagen components, leading to an inflammatory tumor immune microenvironment and sensitizing immunotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet–induced circulating β-hydroxybutyrate (β-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-β-hydroxybutyrate dehydrogenase (BDH)–mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked β-OHB–induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body–MCT1–BDH–histone acetylation–platelet biogenesis axis in megakaryocytes and propose a nontoxic, low-cost dietary intervention for combating CIT. Ketones for chemo: Ketones for chemoChemotherapy can reduce platelet counts in patients with cancer, in turn limiting treatment efficacy. Xie et al. report that ketogenesis-induced β-hydroxybutyrate mitigated this chemotherapy-induced thrombocytopenia by altering histone acetylation and gene transcription to promote platelet production. A ketogenic diet alleviated thrombocytopenia in mouse models treated with chemotherapy, and modestly increased platelet counts in healthy volunteers, suggesting potential relevance for clinical treatment. —CAC [ABSTRACT FROM AUTHOR]

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1–6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1—the key mediator for BAT-thermogenesis—ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells. [ABSTRACT FROM AUTHOR]

Continuous passive motion (CPM) machines are commonly used after various knee surgeries, but information on tibiofemoral forces (TFFs) during CPM cycles is limited. This study aimed to explore the changing trend of TFFs during CPM cycles under various ranges of motion (ROM) and body weights (BW) by establishing a two-dimensional mathematical model. TFFs were estimated by using joint angles, foot load, and leg–foot weight. Eleven healthy male participants were tested with ROM ranging from 0° to 120°. The values of the peak TFFs during knee flexion were higher than those during knee extension, varying nonlinearly with ROM. BW had a significant main effect on the peak TFFs and tibiofemoral shear forces, while ROM had a limited effect on the peak TFFs. No significant interaction effects were observed between BW and ROM for each peak TFF, whereas a strong linear correlation existed between the peak tibiofemoral compressive forces (TFCFs) and the peak resultant TFFs (R2 = 0.971, p < 0.01). The proposed method showed promise in serving as an input for optimizing rehabilitation devices. [ABSTRACT FROM AUTHOR]

In this paper, a hyperspectral (HS) image super-resolution (SR) approach based on attention convolutional bi-long short-term memory (ConvBiLSTM) network is proposed, aiming to explore the collaborative spatial and spectral attention characteristics, thereby enhancing the spatial resolution of HS image. ConvBiLSTM network combines the spatial feature mining and sequential predicting abilities of convolutional neural network and recurrent neural network, respectively. We adapt the ConvBiLSTM network for our super-resolution purpose by regarding each band as a single frame of sequential data, and propose a band-sharing spatial-channel attention-combined ConvBiLSTM SR method to intensify the saliency features. Moreover, a spatial-regularized loss function is presented to further promote the fidelity of the super-resolved HS image. Experiments on four HS data sets show that the proposed approach outperforms some state-of-the-art HS image SR techniques, from the aspect of spectral fidelity. [ABSTRACT FROM AUTHOR]

The nitrite removal pathway in Acinetobacter sp. TX5 was explored through the key gene identification and the corresponding enzyme purification, after which the capability to reduce nitrite by immobilized beads was investigated in a fixed-bed reactor. Results revealed that a nosZ gene encoding nitrous oxide reductase (N2OR) exists in TX5 cells, and a N2OR responsible for the reduction of N2O to N2 was purified successfully with a molecular weight of 70.05 kDa, a purification fold of 16.30 and a recovery rate of 5.17%. For TX5 immobilization, the optimal values of polyvinyl alcohol (PVA), spent mushroom substrate (SMS) and Aci (TX5) obtained by response surface methodology (RSM) were 6.32%, 2.92% and 4.57%, respectively. In a fixed-bed reactor packed with immobilized TX5, the removal efficiency (RE) achieved 90% (at 50 h) for NO 2 − -N and 85% (at 96 h) for total nitrogen (TN). On the basis of these results, a nitrite removal pathway in TX5 was proposed. Overall, Acinetobacter sp. TX5 might be a promising candidate for nitrite removal with an ability to suppress N2O accumulation. [ABSTRACT FROM AUTHOR]

Asymmetric supercapacitors (ASCs) with high working voltages, power density, and long cyclic life have attracted widespread interest. Along with their rapid charge process, the ASCs also exhibit fast self‐discharge behavior, which remains a big challenge. Unfortunately, very limited studies have been focused on this crucial issue. Here, a flexible asymmetric supercapacitor with excellent electrochemical performance and ultra‐long self‐discharge time is reported, which is enabled by designing a bilayer heterogeneous polymer electrolyte (HPE) of polyanions/polycations between the positive electrode and the negative electrode. The developed HPE‐based ASCs exhibit comparable electrochemical performance with those of ASCs by using homogeneous polymer electrolytes. The existing repulsive force between the charged polyelectrolytes and the movable ions can efficiently restrict the diffusion and the redistribution of the small ions, which gives the fully charged HPE‐based ASC an extremely long self‐discharge time of 110 h as the open‐circuit voltage decreases to half of its original value, over ten times longer than the devices based on homogeneous polymer electrolytes. This work indicates that the self‐discharge rate of ASCs can be efficiently suppressed by using the heterogeneous polymer electrolyte, which is helpful in the context of broadening their applications in the field of flexible electronics. [ABSTRACT FROM AUTHOR]

The vanadium‐supramolecules and their derivatives are in high demand because of their huge potential applications in various fields, especially as electrodes for supercapacitors and batteries. However, the complex synthesis process is still a significant challenge. Furthermore, for these self‐assembly processes, the early reaction stages, intermediates, and details of reaction kinetics are still unknown. Here, an efficient approach of rapid cooling for large‐scale fabrication of melamine‐ammonium metavanadate (C3H6N6‐NH4VO3) supramolecular nanoribbons is reported, and the corresponding nucleation and growth process are visualized by using an in situ polarizing microscope. The thermally induced nucleation takes place within tens of seconds, and once the nucleus is formed, C3H6N6 and NH4VO3 begin to assemble into nanoribbons under thermal control and grow epitaxial around the already‐formed nuclei. The growth process is much slower than the nucleation, until all small molecules are consumed. Rapid heat induction (rapid cooling) and shear force induction (stirring) help to form a uniform and wider 2D sheet rather than fibers or ribbons. After pyrolysis, the vanadium‐supramolecules derived vanadium nitride (VN)/carbon nanoribbons present a mesoporous structure, which endows the VN/carbon with high capacitance of 266.3 F g−1 at 0.5 A g−1. In addition, the relationship between various structures and their properties is systematically investigated. [ABSTRACT FROM AUTHOR]

Recognition of specific antigens expressed in cancer cells is the initial process of cytolytic T cell‐mediated cancer killing. However, this process can be affected by other non‐cancerous cellular components in the tumor microenvironment. Here, it is shown that interleukin‐33 (IL‐33)‐activated macrophages protect melanoma cells from tumor‐infiltrating lymphocyte‐mediated killing. Mechanistically, IL‐33 markedly upregulates metalloprotease 9 (MMP‐9) expression in macrophages, which acts as a sheddase to trim NKG2D, an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, subsets of CD4+ T cells, iNKT cells, and γδ T cells. Further, MMP‐9 also cleaves the MHC class I molecule, cell surface antigen‐presenting complex molecules, expressed in melanoma cells. Consequently, IL‐33‐induced macrophage MMP‐9 robustly mitigates the tumor killing‐effect by T cells. Genetic and pharmacological loss‐of‐function of MMP‐9 sheddase restore T cell‐mediated cancer killing. Together, these data provide compelling in vitro and in vivo evidence showing novel mechanisms underlying the IL‐33‐macrophage‐MMP‐9 axis‐mediated immune tolerance against cancer cells. Targeting each of these signaling components, including IL‐33 and MMP‐9 provides a new therapeutic paradigm for improving anticancer efficacy by immune therapy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC‐sEVs in cartilage and low bioavailability of MSC‐sEVs after intra‐articular injection. To overcome this, a strategy to reverse the surface charge of MSC‐sEVs by modifying the MSC‐sEVs with a novel cationic amphiphilic macromolecule namely ε‐polylysine‐polyethylene‐distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC‐sEVs (PPD‐sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD‐sEVs than unmodified MSC‐sEVs to chondrocytes was demonstrated. More importantly, PPD‐sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC‐sEVs. Intra‐articular injection of PPD‐sEVs into a mouse OA model showed significantly improved bioavailability than MSC‐sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra‐articular bioavailability of MSC‐sEVs and has a great potential to accelerate the clinical practice of MSC‐sEVs based OA therapy. [ABSTRACT FROM AUTHOR]

Most anticancer drugs with broad toxicities are systematically administrated to cancer patients and their distribution in tumors is extremely low owing to hypoxia, which compromises the therapeutic efficacies of these cancer drugs. Consequently, a preponderant proportion of cancer drugs is distributed in off-target-healthy tissues, which often causes severe adverse effects. Precision cancer therapy without overdosing patients with drugs remains one of the most challenging issues in cancer therapy. Here, a novel concept of nanopoxia is presented, which is a tumor-hypoxia-based photodynamic nanoplatform for the release of therapeutic agents to achieve precision cancer therapy. Under tumor hypoxia, exposure of tumors to laser irradiation induces the fracture of polymer outer shell and produces anticancer reactive oxygen species, and switches 2D antimonene (Sb) nanomaterials to cytotoxic trivalent antimony to synergistically kill tumors. In preclinical cancer models, delivery of Sb nanomaterials to mice virtually ablates tumor growth without producing any detectable adverse effects. Mechanistically, the tumor hypoxiatriggered generation of trivalent antimony displays direct damaging effects on cancer cells and suppression of tumor angiogenesis. Together, the study provides a proof-of-concept of hypoxia-based precision cancer therapy by developing a novel nanoplatform that offers multifarious mechanisms of cancer eradication. [ABSTRACT FROM AUTHOR]

ZrB2‐SiC ceramics and Nb alloy were brazed at 1160°C for 60 min with CoFeNiCrCuTix high‐entropy alloy filler. The influence of Ti content on the interface structure and mechanical properties of ZrB2‐SiC/Nb joint was systematically studied. It is found that the rich‐Ti Laves phase was formed due to the addition of large atomic size Ti fill into the filler alloy or brazing joint, and its content increases with Ti content. The joint brazed by high‐entropy alloys filler without Ti can be divided into a tooth‐shaped Cr2B reaction layer and a central area composed of a eutectic mixed structure of FCC phase and rich‐Nb lamellar Laves phase. Ti and Nb are mutual solid solution elements. The increase of Ti content in the joint makes the FCC phase and the rich‐Nb lamellar Laves phase to transform into a big bulk Ti‐rich Laves phase and the quadrilateral (Ti, Nb)B phase. The tooth‐shaped Cr2B was disappeared. The residual stress generated in the joint during the brazing process tends to cause defects such as holes and microcracks in the bulk Ti‐rich brittle Laves phase. Therefore, with the addition of Ti, the normal temperature performance of the joint decreases from 216 MPa to 52 MPa. However, with the increase of Ti, the high‐temperature mechanical properties of the joint first decrease, and then increase. It was mainly due to the formation of rich‐Ti Laves phase and quadrilateral (Ti, Nb)B with excellent high‐temperature mechanical properties. When brazing with CoFeNiCrCuTi1.5 filler, the high‐temperature performance of the joint reached 92% of its room temperature performance. [ABSTRACT FROM AUTHOR]

Flexible supercapacitors have attracted increasing interest due to their high power density, long-term cycling life and excellent safety. Like other energy storage devices, flexible supercapacitors exhibit serious performance degradation as they work in extremely cold and/or sweltering climates, which greatly limit their practical applications. Here, we demonstrate a polymer hydrogel with high ionic conductivity for flexible supercapacitors with high performance and excellent climate tolerance. The wide temperature adaptability of the polymer hydrogel is enabled by introducing an additive of dimethyl sulfoxide, which can form abundant hydrogen bonds with water molecules and functional groups of polymer molecules. The optimized hydrogel exhibits high ionic conductivities of 0.82 and 1.12 S m−1 at −20 and 100 °C, respectively, comparable with that at room temperature. Using the polymer hydrogel as an electrolyte, the resulting supercapacitors not only show high electrochemical performance, but also exhibit high capacitance retention up to 91% and 85% at both low (−20 °C) and high (100 °C) temperatures, compared with that at room temperature. In addition, the developed supercapacitors possess excellent mechanical flexibility even at −20 °C. Polymer hydrogels with wide temperature tolerance could be easily functionalized and broadly used for other flexible energy devices and electronics working in harsh environments in the future. [ABSTRACT FROM AUTHOR]

Antiangiogenic tyrosine kinase inhibitors (AA‐TKIs) have become a promising therapeutic strategy for colorectal cancer (CRC). In clinical practice, a significant proportion of cancer patients temporarily discontinue AA‐TKI treatment due to recurrent toxicities, economic burden or acquired resistance. However, AA‐TKI therapy withdrawal‐induced tumour revascularization frequently occurs, hampering the clinical application of AA‐TKIs. Here, this study demonstrates that tumour perivascular cells mediate tumour revascularization after withdrawal of AA‐TKI therapy. Pharmacological inhibition and genetic ablation of perivascular cells largely attenuate the rebound effect of CRC vascularization in the AA‐TKI cessation experimental settings. Mechanistically, tumour perivascular cell‐derived extracellular vehicles (TPC‐EVs) contain Gas6 that instigates the recruitment of endothelial progenitor cells (EPCs) for tumour revascularization via activating the Axl pathway. Gas6 silence and an Axl inhibitor markedly inhibit tumour revascularization by impairing EPC recruitment. Consequently, combination therapy of regorafenib with the Axl inhibitor improves overall survival in mice metastatic CRC model by inhibiting tumour growth. Together, these data shed new mechanistic insights into perivascular cells in off‐AA‐TKI‐induced tumour revascularization and indicate that blocking the Axl signalling may provide an attractive anticancer approach for sustaining long‐lasting angiostatic effects to improve the therapeutic outcomes of antiangiogenic drugs in CRC. [ABSTRACT FROM AUTHOR]

Background. Osteoporosis is characterized by low bone mass, deterioration of bone tissue structure, and susceptibility to fracture. New and more suitable therapeutic targets need to be discovered. Methods. We collected osteoporosis-related datasets (GSE56815, GSE99624, and GSE63446). The methylation markers were obtained by differential analysis. Degree, DMNC, MCC, and MNC plug-ins were used to screen the important methylation markers in PPI network, then enrichment analysis was performed. ROC curve was used to evaluate the diagnostic effect of osteoporosis. In addition, we evaluated the difference in immune cell infiltration between osteoporotic patients and control by ssGSEA. Finally, differential miRNAs in osteoporosis were used to predict the regulators of key methylation markers. Results. A total of 2351 differentially expressed genes and 5246 differentially methylated positions were obtained between osteoporotic patients and controls. We identified 19 methylation markers by PPI network. They were mainly involved in biological functions and signaling pathways such as apoptosis and immune inflammation. HIST1H3G, MAP3K5, NOP2, OXA1L, and ZFPM2 with higher AUC values were considered key methylation markers. There were significant differences in immune cell infiltration between osteoporotic patients and controls, especially dendritic cells and natural killer cells. The correlation between MAP3K5 and immune cells was high, and its differential expression was also validated by other two datasets. In addition, NOP2 was predicted to be regulated by differentially expressed hsa-miR-3130-5p. Conclusion. Our efforts aim to provide new methylation markers as therapeutic targets for osteoporosis to better treat osteoporosis in the future. [ABSTRACT FROM AUTHOR]