Microcirculatory dysfunction is a defining feature of septic shock and is strongly associated with mortality, yet its relationship to macrocirculatory haemodynamics remains poorly understood. In particular, the persistence of heterogeneous capillary perfusion despite restoration of blood pressure and cardiac output (termed haemodynamic incoherence) lacks a coherent mechanistic explanation. I developed a conceptual and computational model of the microcirculation in which network behaviour is constrained by three interacting variables: cardiac output, vasomotor state, and shear stress regulation. A network of one million parallel arterioles was simulated using physiologically plausible distributions of vessel radius. For each vessel, flow requirements were determined by an apparent shear target, reflecting endothelial sensing of shear rather than absolute physical values. Total cardiac output required to maintain network-wide shear was calculated as the sum of individual vessel demands. The model demonstrates that, for a given shear target, total flow requirements increase in proportion to the sum of vessel radii cubed, such that even modest global vasodilation produces a substantial increase in required cardiac output. Increasing the apparent shear target further amplifies this demand. When cardiac output is insufficient to meet these requirements, vessels experience low shear and undergo functional derecruitment, reducing total flow demand but resulting in marked heterogeneity and reduced functional capillary density. These behaviours reproduce key features of septic physiology, including the hyperdynamic circulation and microvascular shunting observed in severe sepsis. The model provides a unifying framework in which microcirculatory dysfunction emerges as an inevitable consequence of the interaction between vasodilation, flow limitation, and shear regulation, rather than as an independent pathological process. It further predicts that therapies which reduce global vasodilation or lower the apparent shear target may restore microvascular coherence without requiring supranormal cardiac output. This framework generates testable hypotheses and offers a physiologically grounded basis for reinterpreting haemodynamic management in septic shock.
The National Diabetes Prevention Program (DPP) is an evidence-based intervention proven to delay or prevent progression to type 2 diabetes, yet most at-risk people do not enroll. In Hawai'i, Native Hawaiian and Other Pacific Islander (NHOPI) and Filipino adults experience disproportionately high rates of prediabetes and diabetes but have low DPP enrollment. From July to October 2024, the Hawai'i State Department of Health launched Beat Diabetes, a statewide media campaign encouraging DPP enrollment among at-risk adults, with a focus on NHOPI and Filipino communities. This evaluation assessed whether campaign exposure was associated with self-reported likelihood of joining a DPP among Hawai'i adults at risk for diabetes, particularly NHOPI or Filipino adults. A postcampaign cross-sectional online survey was conducted from October to December 2024, with Hawai'i residents aged 35-64 years who reported at least 1 diabetes risk factor. NHOPI or Filipino adults were oversampled to determine campaign effectiveness among the target audience. The survey measured self-reported likelihood of joining a lifestyle change program (main outcome), campaign recall (main exposure), demographic characteristics, diabetes risk factors, and beliefs that could affect DPP enrollment likelihood, including intrinsic motivation, perceived inevitability of developing diabetes, and perceived health benefits of DPP participation. Three general linear regression models examined the association between campaign exposure and DPP enrollment likelihood ratings, adjusted for demographic characteristics, diabetes risk factors, and belief variables. A sensitivity analysis among just those diagnosed with prediabetes was conducted. A total of 860 adults completed the survey, with 34.7% (298/860) and 12.2% (105/860) self-identifying as NHOPI and Filipino, respectively. In total, 40% (346/860) reported campaign exposure. Exposed individuals had higher mean DPP enrollment likelihood ratings and higher inevitability belief scores than those not exposed. A large proportion of exposed respondents reported that enrolling in a DPP would "improve their health a lot." No significant differences in campaign exposure were observed across ethnicities. All 3 regression models showed a significant positive association between campaign exposure and DPP enrollment likelihood ratings. In the final adjusted model controlling for all covariates, significant predictors included campaign exposure (β=.52, P<.001), male gender (β=.34, P=.01), residence outside Honolulu County (β=.31, P=.02), motivation index scores (β=.38, P<.001), inevitability belief (β=.20, P<.001), and the belief that DPP improves health "a little" (β=.76, P<.001) or "a lot" (β=1.63, P<.001). The sensitivity analysis among those diagnosed showed exposure was not associated with likelihood ratings (β=.30, P=.27). Campaign exposure was associated with higher ratings of likelihood to join a DPP among at-risk adults with no prediabetes diagnosis. Perceived positive health impact of DPP participation was the strongest contributor to likelihood ratings. Campaigns aiming to increase awareness of DPP and intentions to join should promote DPP effectiveness and the urgency of preventative actions.
Despite the undeniable improvements made by research and therapy that have led to better prognosis and quality of life for many cancer patients, when the prognosis remains unfavorable, both in terms of survival and residual quality of life, the risk of suicide increases. If depression or another psychiatric disorder arises, the reconstruction of the causal link is more straightforward. The path appears less straightforward when this evidence is lacking, and one must question the awareness of the inevitability of the prognosis. Starting from cases of occupational neoplastic disease, in which annuity holders committed suicide, the Authors reconstruct the correct investigative methodology to follow for reconstructing the causal link, necessary to ensure Inail protection to the heirs. According to evidence-based medicine, the admissibility in the specific case of what is postulated in general must be evaluated. This requires some fundamental requirements: the diagnosis of occupational disease with unfavorable prognosis; the precise and documented knowledge of one's fate by the insured (through the development or not of a psychiatric illness already diagnosed and documented at the time of death); the absence of pre-existing (or subsequent) alternative causes independent of the occupational disease. The methodological framework adopted for neoplasias with unfavorable prognosis could also be applied to traumatic events that cause severe and drastic irreversible impairment in the subject's autonomy or to diseases that involve a progressive and worsening loss of autonomy, but in this case, the need for a well-documented psychiatric disorder, causally correlated to the consequences of the accident/disease, within which to inscribe the suicidal behavior, appears unavoidable. Some reflections from the Inail indemnity perspective must be formulated in recently observed cases of "assisted suicide," to understand how the Institute should behave if the subject's choice is related to the disability derived from a work accident or occupational disease. The Authors finally emphasize the importance of interventions useful for preventing suicidal events, measures that INAIL is beginning to implement, as demonstrated by the recent Implementation Agreement with the National Council of the Order of Psychologists.
Converting food waste (FW) into a high-value-added chemical product, lactic acid (LA), through anaerobic fermentation provides a sustainable route for waste management and biorefining. The C/N ratio has been widely studied because it critically influences LA fermentation. However, most existing studies focus on low substrate concentrations, which inevitably lead to low LA levels, making downstream separation and purification economically unfavorable. This study investigated the effects of different C/N ratios (10, 15, 20, and 25) on LA production in an open fermentation system operated at a high substrate concentration (162.7 g TCOD/L, 35 °C, 150 rpm, uncontrolled pH). Results showed that lowering the C/N ratio from 25 to 10 resulted in a 1.4-fold increase in LA production, reaching a peak concentration of 25.0 g/L, and promoted a dominant lactic acid bacteria (LAB) community (from 82.8% to 95.5%). Mechanistic analysis indicates that, under conditions of high substrate concentration, a low C/N ratio promotes an increase in LA yield; this is attributed to the fact that an abundant nitrogen source accelerates the rate of substrate hydrolysis and increases the relative abundance of key metabolic genes. Further statistical analysis revealed that proteins and potassium promoted LA production, whereas lipids inhibited it. This work elucidated the effects and underlying mechanisms of the C/N ratio on LA production from FW under high substrate concentration, thereby providing further insights into the high-value utilization of FW.
Peptic ulcer bleeding (PUB) is the most common cause of non-variceal upper gastrointestinal bleeding, although its incidence is decreasing worldwide. Current epidemiological evidence demonstrates the positive influence of Helicobacter pylori eradication on outcomes, owing to the widespread introduction of proton pump inhibitor (PPI) treatment. However, PUB is still commonly encountered in clinical settings given the increasing indications for nonsteroidal anti-inflammatory drugs, anticoagulants, and antiplatelet agents in the aging population. Regardless of advancements made in the endoscopic approach and pharmacological treatment, upper gastrointestinal bleeding has an inevitable mortality rate ranging from 7% to 11%. Endoscopic treatment is recommended for peptic ulcers with current bleeding, vessel exposure, or clotting. However, the development of effective high-dose PPIs has resulted in a decrease in rebleeding events after endoscopic treatment. Pharmacological management consisting of post-endoscopic treatment was more effective than pre-endoscopic treatment. As PPIs ensure that gastric acidity remains above pH 6, they are essential treatments for PUB. This review aimed to investigate the current strategies for PUB pharmacological management.
Over the past two centuries, the atmospheric concentrations of greenhouse gases (GHGs) have reached unprecedented levels because of population growth and urbanization, uncontrolled industrialization, deforestation and agricultural expansion. While agricultural expansion is inevitable, accelerating in-situ soil storage via adsorption is perhaps one of the most feasible strategies for GHG abatement. For this purpose, naturally occurring and modified forms of clays and zeolites are abundant, cost-effective, and well-characterized materials that have demonstrated significant potential for GHG emission mitigation. This state-of-the-art review examines literature from the past-decade to evaluate the efficacy of clay and zeolite-based materials in mitigating GHGs, with a focus on their application in agricultural systems. It evaluates the effects of these materials on soil health, particularly their role in altering soil physicochemical properties and nutrient availability. Although numerous studies have explored the adsorption capacity of clays and zeolites for GHG emission mitigation purposes, there is a significant research gap regarding their applications within the agricultural sector. The lack of field-scale trials and variation and validation studies is exacerbating this gap. In this context, innovative solutions involving raw and synthetic clays and zeolites in on-farm operations and agricultural soils show promise but require deeper studies. This review therefore addresses this gap and highlights relevant strategies and methodologies.
The inevitable adhesion and accumulation of oily pollutants on membrane interfaces throughout the oil-water separation processes lead to severe performance degradation, underscoring the urgent need for effective and energy-saving antifouling strategies. Herein, a nucleation-directed mineralization strategy is developed to prepare a Cu3(PO4)2 mineralized nanofiber membrane (PAN/CuP) with a micro/nanoparticulate architecture. By preanchoring copper ions onto carboxyl-functionalized electrospun polyacrylonitrile nanofibers as nucleation sites, a uniform and robust mineralized layer is controllably grown, imparting exceptional surface hydrophilicity and underwater superoleophobicity. The phosphate-rich mineral coating endows the PAN/CuP membrane with strong hydration capability, enabling complete oil detachment without prewetting treatment. Under gravity-driven or ultralow-pressure conditions (∼0.01 MPa), the membrane achieves efficient separation of both immiscible oil-water mixtures and surfactant-stabilized emulsions, with separation efficiencies exceeding 99.4%. Benefiting from its robust antifouling capability, the PAN/CuP membrane stably sustains a high flux of 447.3-763 L m-2 h-1 throughout 300 min of continuous cross-flow filtration of oil-in-water emulsions. The fouled membrane can be readily restored by simple water rinsing, attaining a flux recovery ratio (FRR) > 99.2% and an irreversible fouling ratio below 1%, demonstrating nearly complete fouling reversibility. This work provides a robust and energy-efficient strategy for constructing high-performance mineralized nanofiber membranes, offering new insights into the design of advanced antifouling membranes for practical oily wastewater treatment.
The long-term ecological impact of total phosphorus (TP) in fluvial systems is well-established, prompting its inclusion in water quality regulations worldwide. Due to the strong affinity between sediment and phosphorus, certain regulatory protocols recommend pretreating water samples using methods such as shaking or clarification. Recent studies have noted discrepancies between these methods, but their comparisons were experimental and did not consider sediment conditions altered by dam construction. This study aims to investigate how the shaking and clarification methods differ under varying sediment conditions associated with inflow-outflow scenarios. Using the globally representative, dam-regulated Yellow and Yangtze rivers as case studies, we conducted comparative analyses of TP determined by both methods, based on consecutive field measurements and long-term hydrological data. The shaking method indicated substantial reductions in TP (up to 63.75%) from inflow to outflow sites. In contrast, the clarification method yielded much smaller reductions, and during flood seasons it even showed an increase (up to 35.89%). These discrepancies in methodology may lead to substantial underestimation of reservoir TP retention from the perspective of reservoir-induced sediment regime shifts. By integrating theoretical analysis with field data, we demonstrate that this discrepancy is inevitable: the clarification method significantly underestimates TP under inflow condition characterized by coarse sediment or high sediment concentration (S), whereas this underestimation becomes negligible under outflow condition featuring fine sediment or low S. In order to keep a consistent measurement in TP under varying sediment conditions and thereby evaluate the TP retention effect of dams more objectively, we recommend adopting the shaking method for complete TP quantification. This work provides fundamental insights into TP measurement that are crucial for managing river ecosystems.
Hypertension-mediated organ damage (HMOD) represents a critical and dynamic stage on the cardiovascular continuum, serving as the primary mechanistic link between sustained arterial pressure elevation and major adverse cardiovascular and renal events. HMOD is often subclinical at first occurrence and is a systemic, cumulative process, representing structural and functional injury of the heart, brain, kidneys, and vasculature. This narrative review synthesises current evidence on the pathogenesis and clinical sequelae of HMOD, specifically focusing on the interplay between chronic haemodynamic load, endothelial dysfunction, oxidative stress, neurohormonal activation, inflammation, and microvascular remodelling. Key manifestations such as left ventricular hypertrophy, hypertensive nephrosclerosis, cerebral small vessel disease, and arterial stiffness can be regarded as dynamic and partly modifiable phenomena of subclinical injury rather than inevitable sequelae of long-standing hypertension. This review aims to summarise contemporary detection and risk stratification approaches, drawing on the 2023 European Society of Hypertension (ESH) and 2024 European Society of Cardiology (ESC) guidelines, combining imaging and biomarker-based assessment. Evidence supporting organ protection as an important therapeutic objective is also reviewed, with particular attention to regression of left ventricular mass and reduction in albuminuria as treatment endpoints associated with improved prognosis beyond blood pressure reduction alone. Finally, unresolved issues such as causal versus associative properties of candidate biomarkers, comparative validity of vascular indices, and heterogeneity in organ-specific response to therapy are critically analysed. The overarching goal of this review is to support a clinically applicable framework for early HMOD detection and organ-protective treatment strategies in routine hypertension care.
Achieving simultaneously high operational stability and low-voltage operation is critical for the practical deployment of organic field-effect transistors (OFETs) in flexible and integrated electronics. However, the heterogeneous organic semiconductors (OSCs)/dielectric interface, where carriers are transported, inevitably introduces defects originating from structural and energetic disorder that lead to instability. Here, we demonstrate that the insulating alkyl chains could serve as a dielectric component to fabricate alkylated OFETs. This interface-free OSC/dielectric configuration reduces interfacial defects and enables efficient charge transport with intrinsic structural passivation. Under this configuration, the 2,9-didecyldinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (C10-DNTT) FET exhibits operational stability over 10,000 s and an ultrahigh intrinsic gain of 7.52 × 104. The corresponding inverters show exceptional static (gains of 127.6 and noise margin of 95.3% at VDD = 2.5 V) and dynamic characteristics (signal-delay time constants of 50 μs at VDD = 1 V), with negligible shift over 50 switch cycles, demonstrating excellent electrical performance and reliability of low-voltage organic circuits. This molecular-level OSC/dielectric integration strategy provides a general pathway for addressing key limitations for the practical deployment of OFETs in flexible and integrated electronics.
The climate crisis is not just an environmental issue; it's a profound public health emergency that is deeply affecting the mental well-being of young people, leading to widespread eco-anxiety. As the future frontline of healthcare, physiotherapy students will inevitably have to manage the health consequences of climate change. Yet, we know surprisingly little about how prepared they are specifically, how their own awareness of the crisis connects with their anxiety about the future. This exploratory study aimed to provide preliminary findings on the relationship between global climate change awareness and future anxiety among physiotherapy students in Turkey. We conducted a cross-sectional study with 394 physiotherapy students (mean age 21.3 ± 3.0; 74.6% female) from the state universities. Using an online survey, we gathered data on their demographic and social characteristics, along with their scores on two validated scales: the Awareness Scale of University Students About Global Climate Change (ASUSGCC) and the Future Anxiety Scale for University Students (FASUS). We analyzed the data using Pearson correlation to examine the relationship between climate change awareness and future anxiety, and univariable linear regression analyses to explore factors associated with climate change awareness. Overall, students reported a moderate level of climate change awareness (ASUSGCC mean: 3.4 ± 0.7) and a notable level of future anxiety (FASUS mean: 61.6 ± 8.6). We found a statistically significant, positive, but weak correlation between total climate awareness and total future anxiety (r = 0.168, p < 0.01). The regression analyses showed that several variables were statistically associated with higher awareness scores, although the explained variance was low. Female gender (β = 0.273, p = 0.001), environmental volunteering (β = 0.180, p = 0.019), and more frequent use of social media for climate-related information (β = 0.167, p = 0.001) were associated with higher climate change awareness. Higher total future anxiety was weakly but statistically significantly associated with higher awareness scores (β = 0.013, p = 0.001). In subscale-level analyses, Future Fear was also weakly associated with awareness (β = 0.009, p = 0.015). Previous environmental training was not significantly associated with climate change awareness (p = 0.466). Among physiotherapy students, climate change awareness was weakly but statistically significantly associated with future anxiety. Environmental volunteering and more frequent exposure to climate-related content on social media were also associated with higher awareness scores, whereas previous environmental training was not significantly associated with awareness. However, given the cross-sectional design and possible self-selection into volunteering, these findings should be interpreted as associations rather than evidence that volunteering increases awareness. Future longitudinal or intervention-based studies are needed to examine whether structured environmental engagement can improve climate literacy in physiotherapy education.
Conventional homogeneous hydrogels typically face an inherent trade-off between mechanical strength and lubrication performance. Achieving high load-bearing capacity requires dense crosslinking and tight chain entanglement, which inevitably restrict water uptake and suppress the formation of effective hydration layers. Herein, inspired by the anisotropic architecture of natural ligaments, we developed a robust lubricious hydrogel material (STOC-D) through synergistic spontaneous tensile orientation under confinement (STOC) processing and surface dissociation modification. The STOC process generates highly aligned polymer chains and densely packed microcrystalline domains that serve as robust physical crosslinks, effectively restricting chain slippage and crack propagation. This yields exceptional mechanical properties, including a tensile strength of 54.5 MPa, an elastic modulus of 62.7 MPa, and a tear energy of 25.7 kJ m-2. Subsequent surface dissociation creates a modulus gradient featuring a soft, highly hydrated outer layer rich in dangling chains, which enables rapid water infiltration and the formation of a stable hydration lubrication layer. As a result, the STOC-D hydrogel achieves ultralow coefficients of friction against both metallic and biological surfaces. Furthermore, in vitro cytotoxicity and in vivo subcutaneous implantation studies confirm its excellent biocompatibility. By successfully decoupling bulk mechanical reinforcement from surface hydration, this strategy overcomes the longstanding strength-lubrication trade-off in hydrogels, offering a promising method for load-bearing biomedical applications.
Although THA is routinely offered to patients age 85 years and older, surgeons might hesitate to operate on patients deemed "too young." This study tests whether such hesitancy reflects a consistent standard. (1) How much utility (net benefit) can be expected from THA, as a function of patient age and operation-related clinical variables? (2) What relative cost must be attributed to revision of a THA such that the imposition of this penalty renders the expected utility of the operation too low to justify it in younger people? A calculator was programmed using a state-transition Markov model to estimate the expected lifetime benefit of THA as a function of patient age and other user-specified parameters. A novel unit of benefit, the joint-adequate life year (JALY), was defined. One JALY is earned in each postoperative year that the patient has an intact prosthesis and adequate clinical outcome. JALYs can also be forfeited when a patient enters a revision state. Thus, previously accumulated JALYs may be partially or completely offset, resulting in a net lifetime total that is lower than the total years of an adequate outcome. Users of the calculator specify patient sex and age at the time of THA (we modeled sex rather than gender in order to be able to derive life expectancy from sex-specific life tables published by the Social Security Administration), the anticipated fraction of patients expected to have a clinically adequate outcome (termed here the "satisfaction fraction"), prosthetic life expectancy, the expected annual risk of revision attributed to catastrophic events such as fracture or infection, and a discount rate, which is used to convert future gains and losses to their net present value. The prosthetic life expectancy parameter was used to calculate an annual risk of needing revision for wear. Users also assign a negative value to the revision state, representing the number of JALYs that a patient would be willing to forgo to avoid that state. This penalty was applied in the first instance the failure state was encountered, and a value 1.5 times this penalty was applied for any subsequent encounter. The model was then interrogated to provide the expected JALYs earned as a function of failure-state penalties ranging from 0 to 40 JALYs. For this calculation, prosthetic life expectancy was set to 15 years, the anticipated satisfaction fraction was set to 90%, the annual rate of catastrophic failure was set to 0.5%, and no temporal discounting was applied. Sensitivity analyses were then performed for different values of prosthetic life expectancy, satisfaction fraction, catastrophic failure rate, second-revision penalty ratio, and with 2% and 10% temporal discounting applied. Based on the common use of THA in 85-year-old patients (a group with a life expectancy of about 6 years after THA), a benchmark of six JALYs was established, as logically no patient can have more "adequate joint years" than total years of life. We then determined the penalty that must be assigned to the revision state, such that a 45-year-old male's expected benefit would fall below this six-JALY benchmark. A cohort of 45-year-old males can be expected to earn 25 lifetime JALYs under the base case assumptions and a revision penalty of five JALYs. Lifetime JALYs for this cohort do not drop below the threshold of six until the revision penalty reaches 25 JALYs. Sensitivity analysis demonstrated that this finding was robust across wide variation in clinically plausible values for prosthetic life expectancy, satisfaction, failure rates, and discounting. Hesitation to offer THA to 45-year-old patients with impairing hip disease is logically inconsistent with the procedure's broad acceptance in 85-year-old patients. This is because under plausible assumptions of the clinical parameters, 45-year-old patients stand to accrue considerably more lifetime benefit. Indeed, even accounting for the inevitable failures younger patients may encounter (and the penalties these failures impose), such patients can expect to accrue more than six JALYs across their lifetimes unless implausibly large failure penalties are assumed. Level II, Economic and Decision Analyses.
Prostate cancer development and progression depend on androgen receptor (AR) signaling. Therefore, androgen-deprivation therapy (ADT) and AR signaling inhibitors (ARSIs) are standard therapies for advanced or metastatic disease. Although these treatments are initially effective, prostate cancer inevitably progresses to a lethal stage termed castration-resistant prostate cancer (CRPC). In the majority of patients, CRPC occurs via reactivation of AR signaling (CRPC-AR). However, lineage plasticity is a hallmark of cancer that drives AR-independent CRPC phenotypes in a subset of patients. One subtype of AR-negative CRPC is neuroendocrine prostate cancer (NEPC), which transforms from CRPC-AR by losing the characteristic AR-driven luminal epithelial identity and gaining neuroendocrine identity. Another AR-negative CRPC subtype lacks AR and neuroendocrine features and has therefore been classified as double-negative prostate cancer (DNPC). Chromatin modifications, alterations in three-dimensional (3D) genome structure, and expression of transcriptional regulators are crucial for controlling lineage states and modulating AR-dependent and AR-independent phenotypes in CRPC. Here, we highlight how high-resolution investigations of the 3D genome have revealed interdependence between chromatin architecture and transcriptional regulation, offering novel insights into the mechanisms of CRPC progression and context-specific targets for therapeutic intervention.
Simultaneous trajectory tracking and obstacle avoidance are critical capabilities for unmanned underwater vehicles (UUVs). However, implementing these tasks on digital processors inevitably introduces discretization errors and time delays. Most existing continuous-time methods suffer from significant performance degradation when directly applied to discrete-time systems. Therefore, achieving high-precision control in the discrete-time domain remains a considerable challenge. To address this issue, a robust discrete-time dual-loop control architecture is proposed in this paper. First, a discrete-time distributed model predictive control (DMPC) scheme serves as the outer-loop kinematic controller, solving an online optimization problem to generate collision-free velocity commands. To guarantee closed-loop stability, discrete LQR-based terminal constraints are strictly incorporated. Furthermore, slack variables are introduced to dynamically relax these constraints during obstacle evasion maneuvers. This strategy effectively resolves the inherent conflict between theoretical stability and recursive feasibility in cluttered environments. Second, a discrete-time sliding mode controller (DSMC) is developed for the inner dynamic loop, where a specialized reaching law is designed to strictly confine state fluctuations within a minimal quasi-sliding mode band. In addition, a discrete disturbance observer (DDOB) is introduced to estimate and compensate for the effects of time-varying ocean current disturbances. Extensive simulation results demonstrate that the proposed framework achieves superior tracking accuracy, high computational efficiency, and reliable obstacle avoidance. Furthermore, rigorous theoretical analysis ensures global system stability under discrete-time implementation constraints.
In practice, optimal consensus control for multiagent systems (MASs) is strictly constrained by limited communication bandwidth. Therefore, dynamic encoding-decoding mechanisms are designed to address this issue. However, unknown nonlinear dynamics inevitably generate uncertainties during the encoding-decoding process, which may lead to quantizer saturation and consequently affect consensus performance. To address this challenge, this article proposes an online reinforcement learning (RL) control strategy based on a novel model-decoupled dynamic encoding-decoding mechanism. Distinct from existing schemes relying on model parameters, the proposed mechanism features a model-decoupled architecture where the encoder and decoder structures are constructed without embedding explicit system dynamics. To handle the unknown system model, a novel online identifier is designed to actively compensate for dynamic uncertainties faced by the encoding-decoding mechanism, theoretically guaranteeing quantizer nonsaturation and ensuring data validity. Based on this reliable quantization communication, a distributed value iteration (VI) algorithm is developed to obtain optimal policies using solely decoded state information, eliminating the dependence on control policies of neighbors. Simulation studies on a heterogeneous UAV-UGV formation verify the robustness and effectiveness of the proposed method.
Targeting HR-positive breast cancer via the inhibition of CDK4 and CDK6 has become the standard of care. However, progression inevitably occurs, and emerging data suggest the implication of CDK2 in this resistance mechanism. As part of our efforts to target this resistance, we embarked on a medicinal chemistry campaign to selectively inhibit CDK2 over the broadly essential CDK1. In order to obtain selectivity against CDK1, we utilized a molecular dynamics approach focused on interaction with a conserved lysine in the active site. Additionally, we uncovered a unique mechanism of clearance driven by both metabolism and efflux in rats and demonstrated that we could counter efflux-driven clearance with high permeability. Our efforts resulted in compound 19, which was potent against CDK2, exhibited good selectivity vs CDK4 and CDK1, and had pharmacokinetic properties that enabled evaluation in a CDK2 xenograft model of cancer, where it achieved nearly 80% tumor growth inhibition.
Triboelectric nanogenerators (TENGs) can efficiently convert weak mechanical energy into electricity, making them suitable for small-scale and distributed power supply demanded by the Internet of Things. However, the inevitable friction and wear not only cause high energy dissipation and low triboelectrification efficiency but also severely limit the device's lifetime and reliability. Here, a wear-free structural superlubricity TENG (SSL-TENG) is designed using the graphite-SiO2 pair. By achieving an atomic-level friction interface via micromachining, the device operates in a stable SSL state with a near-zero coefficient of friction (0.0034). As compared to mosaic charge distribution in previous studies, the intimate contact at the SSL interface suppresses air breakdown, enabling a unipolar charge distribution, which yields a high charge density of 0.47 mC/m2 and a 106-fold enhancement in triboelectrification efficiency. Simultaneously, the SSL-TENG demonstrates stable output performance for over 1.1×105 cycles without wear. This work provides a fundamental strategy to eliminate interfacial friction and the air-breakdown limit, paving the way for ultra-reliable and high-output energy harvesting.
Lattice oxygen redox (LOR) provides a compelling avenue to boost the oxygen evolution reaction by circumventing the scaling relationship of oxygen intermediates. However, its intrinsic oxidative pathway inevitably accelerates structural degradation, especially in aggressive seawater. Herein, we present a unique localized LOR buffering strategy to overcome the abovementioned activity-stability trade-off using interstitial boron-doped high-entropy selenide as a model electrocatalyst. Combined experimental and theoretical investigations demonstrate that interstitial boron crucially promotes localized LOR within the reconstructed oxyhydroxide layer, which triggers dynamic, quasi-reversible valence oscillations in adjacent Ni centers. This adaptive electron exchange effectively mitigates the irreversible over-oxidation and dissolution of the active sites while strengthening metal-oxygen covalency for continuous site regeneration. Concurrently, the selectively formed stronger B-Co-Se covalent framework, along with the rapid formation of chloride-repelling selenate layers, further preserves the lattice against corrosive attack. Thus, the catalyst sustains >1000 h of stable operation at 500 mA cm-2 with its overpotential remarkably decreasing by 180 mV in alkaline seawater. This work establishes a transferable valence-adaptation strategy for designing self-stabilizing electrocatalysts in extreme electrolytic environments.
Graphite positive electrode-based anion-intercalation aqueous dual-ion batteries using bis(trifluoromethanesulfonyl)imide anion intercalations show the potential because of the high discharge plateau (>1.4 V vs. the standard hydrogen electrode at 25 °C ± 2 °C) for anion chemistry. However, currently, the electrochemical performance of aqueous dual-ion batteries based on bis(trifluoromethanesulfonyl)imide anion intercalation can only be achieved in highly concentrated salt electrolytes. This dependence on high anion concentration to activate intercalation inevitably leads to high costs and prevents operation at low temperatures (e.g., < -20 °C). In this context, we explore a hydrogel electrolyte rich in dipole molecules, incorporating only 1 M lithium bis(trifluoromethanesulfonyl)imine and 2 M zinc chloride, with expanded electrochemical stability windows (>4.6 V at -40 °C) to activate bis(trifluoromethanesulfonyl)imide anion insertion into the graphite positive electrode through high-voltage scanning to 3.0 V. The assembled aqueous dual-ion batteries based on bis(trifluoromethanesulfonyl)imide anion intercalation demonstrate high discharge plateaus of 1.9 V at -20 °C and 1.7 V at -40 °C, along with a specific energy of 595 Wh kg-1 (normalized to the 1 mg cm-2 of the graphite positive electrode).