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Abstract Arma chinensis is a natural enemy that preys on various species and can suppress agricultural and forest pests in the orders Lepidoptera and Coleoptera. Here, we aimed to determine the genome of A. chinensis assembled at the chromosome-level using PacBio and Hi-C technologies. The assembled genome was 986 Mb, with a contig N50 of 2.40 Mb, scaffold N50 of 134.98 Mb, and BUSCO completeness of 96.10%. Hi-C data aided in anchoring the assembly onto seven chromosomes. A sequence of ~ 496.2 Mb was annotated as a repeat element, constituting 51.15% of the genome. We functionally annotated 84.79% of 20,853 predicted protein-encoding genes. This high-quality A. chinensis genome provides a novel genomic resource for future research on Pentatomidae insects.

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells. Utilizing PEFUU, hierarchical composite nanofiber patch (HCNP) was fabricated, simulating the natural microstructure of the tendon-to-bone interface with an aligned-random alignment. The incorporation of enzymatic hydrolysate derived from decellularized Wharton jelly tissue into the random layer could further enhance cartilage regeneration at the tendon-to-bone interface. Via rat RCT repairing model, HCNP possessing prolonged anti-inflammatory properties uniquely facilitated physiological healing at the tendon-to-bone interface's microstructure. The alignment of fibers was restored, and histologically, the characteristic tripartite distribution of collagen I – collagen II - collagen I was achieved. This study offers a universal approach to the functionalization of degradable polymers and provides a foundational reference for their future applications in promoting the in vivo regeneration of musculoskeletal tissues.

Amidst the global burden of viral pneumonia, mitigating the excessive inflammatory response induced by viral pneumonia has emerged as a significant challenge. Pneumovirus infections can lead to the persistent activation of M1 macrophages, culminating in cytokine storms that exacerbate pulmonary inflammation and contribute to the development of pulmonary fibrosis. Mitochondria, beyond their role as cellular powerhouses, are pivotal in integrating inflammatory signals and regulating macrophage polarization. Mitochondrial damage in alveolar macrophages is postulated to trigger excessive release of reactive oxygen species (ROS), thereby amplifying macrophage-mediated inflammatory pathways. Recent investigations have highlighted the anti-inflammatory potential of Daphnetin, particularly in the context of cardiovascular and renal disorders. This review elucidates the mechanisms by which viral infection-induced mitochondrial damage promotes ROS generation, leading to the phenotypic shift of alveolar macrophages towards a pro-inflammatory state. Furthermore, we propose a mechanism whereby Daphnetin attenuates inflammatory signaling by inhibiting excessive release of mitochondrial ROS, thus offering mitochondrial protection. Daphnetin may represent a promising pharmacological intervention for viral pneumonia and could play a crucial role in addressing future pandemics.

Abstract Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH)2/NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm−2). Importantly, thanks to the “transferred” oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H2-integrated CO2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness.

Individuals with high-level spinal cord injuries often face significant challenges in performing essential daily tasks due to their motor impairments. Consequently, the development of reliable, hands-free human-computer interfaces (HCI) for assistive devices is vital for enhancing their quality of life. However, existing methods, including eye-tracking and facial electromyogram (FEMG) control, have demonstrated limitations in stability and efficiency. To address these shortcomings, this paper presents an innovative hybrid control system that seamlessly integrates gaze and FEMG signals. When deployed as a hybrid HCI, this system has been successfully used to assist individuals with high-level spinal cord injuries in performing activities of daily living (ADLs), including tasks like eating, pouring water, and pick-and-place. Importantly, our experimental results confirm that our hybrid control method expedites the performance in pick-place tasks, achieving an average completion time of 34.3 s, which denotes a 28.8% and 21.8% improvement over pure gaze-based control and pure FEMG-based control, respectively. With practice, participants experienced up to a 44% efficiency improvement using the hybrid control method. This state-of-the-art system offers a highly precise and reliable intention interface, suitable for daily use by individuals with high-level spinal cord injuries, ultimately enhancing their quality of life and independence.

Grand canonical Monte Carlo (GCMC) simulations were used to analyse the effect of -O-Li, -NH2, -SH, -F, -COOH, and -NO2 functional groups on the adsorption and separation of pure CO2 and a mixture of CO2 and CH4. The metal–organic framework (MOF) skeleton was structurally optimized using the Forcite and Dmol 3 modules. First, the GCMC method was employed to simulate the adsorption of pure CO2 by functionalized Mg-MOF-74 at 298 K and 10–3000 kPa. The results illustrated that -O-Li, -NH2, and -SH groups increased the CO2 adsorption below 101 kPa and followed the order Li-O-Mg-MOF-74 > NH2-Mg-MOF-74 > SH-Mg-MOF-74. When the pressure was >101 kPa, the adsorption capacity of Mg-MOF-74 was higher than that of functionalized Mg-MOF-74. Then, the adsorption capacity and selectivity of functionalized Mg-MOF-74 in the CO2/CH4 mixture were investigated at 298 K and 10–3000 kPa. The results showed that the introduction of -O-Li, -NH2, and -SH groups increased the CO2 selectivity of Mg-MOF-74 within the range of 10–1440 kPa and followed the order Li-O-Mg-MOF-74 > NH2-Mg-MOF-74 > SH-Mg-MOF-74.

The cooling role of phase change materials (PCMs) has emerged as a promising solution for battery thermal management systems (BTMS). However, issues such as high phase change temperature, low thermal conductivity, and easy leakage have been the long-term bottlenecks in the application of phase change materials. Herein, a composite phase change materials (CPCMs) is prepared by incorporating a mixture of lauric acid (LA) and paraffin (PA) with an expanded graphite (EG) thermally conductive unit. The mixture of lauric acid and paraffin provides latent heat, whereas expanded graphite enhances the thermal conductivity while preventing the leakage of lauric acid and paraffin. As expected, the lauric acid–paraffin–expanded graphite-based composite phase change materials demonstrate the high thermal conductivity of 1.22 W/(m k), the elevated melting enthalpy of 146.9 J/g, as well as the relatively low melting temperature of 36.1 °C. When used as a cooling system for battery thermal management systems, composite phase change materials can keep the maximum temperature of the battery below 43 °C with a temperature difference of 1.96 °C only, while ensuring the long-term cycling stability of the battery. Therefore, composite phase change materials with such a remarkable performance provide a promising and effective solution for battery thermal management systems.

Caviar yield, caviar color, and body weight are crucial economic traits in sturgeon breeding. Understanding the molecular mechanisms behind these traits is essential for their genetic improvement. In this study, we performed whole-genome sequencing on 673 Russian sturgeons, renowned for their high-quality caviar. With an average sequencing depth of 13.69×, we obtained approximately 10.41 million high-quality single nucleotide polymorphisms (SNPs). Using a genome-wide association study (GWAS) with a single-marker regression model, we identified SNPs and genes associated with these traits. Our findings revealed several candidate genes for each trait: caviar yield: TFAP2A, RPS6KA3, CRB3, TUBB, H2AFX, morc3, BAG1, RANBP2, PLA2G1B, and NYAP1; caviar color: NFX1, OTULIN, SRFBP1, PLEK, INHBA, and NARS; body weight: ACVR1, HTR4, fmnl2, INSIG2, GPD2, ACVR1C, TANC1, KCNH7, SLC16A13, XKR4, GALR2, RPL39, ACVR2A, ADCY10, and ZEB2. Additionally, using the genomic feature BLUP (GFBLUP) method, which combines linkage disequilibrium (LD) pruning markers with GWAS prior information, we improved genomic prediction accuracy by 2%, 1.9%, and 3.1% for caviar yield, caviar color, and body weight traits, respectively, compared to the GBLUP method. In conclusion, this study enhances our understanding of the genetic mechanisms underlying caviar yield, caviar color, and body weight traits in sturgeons, providing opportunities for genetic improvement of these traits through genomic selection.

We describe an iridium-catalyzed ortho-selective C–H borylation of unprotected anilines. The employing strong σ-donating cyclometalated mesoionic carbene as C^C bidentate ligand is crucial for the high ortho-selectivity. Computational studies support outer-sphere X–H···Oboryl hydrogen bond interactions, which are strengthened by bidentate C^C ligand introduction. The method shows broad substrate scope and high functional group tolerance.

To enhance gas drainage in the soft and hard interbedded (SHI) coal seam, it’s necessary to unload the in-situ stress and improve its gas migration performance. In this research, a directional hydraulic flushing (DHF) technology was carried out. The stress-unloading and gas migration improvement mechanism was analyzed through numerical simulation, and systematic engineering tests were conducted to verify the gas drainage effect. The results show that the improvement of gas migration performance in the SHI coal seam is caused by a combined effect of seepage-improving and diffusion-improving. After DHF, stress-unloading and plastic failure could be achieved both in the soft coal (SC) sublayer and in the hard coal (HC) sublayer. However, the gas diffusion capacity improves significantly in the SC sublayer, while the gas seepage capacity improves notably in the HC sublayer. Meanwhile, the stress-unloading and gas migration improvement effect improves with the flushing radius and the thickness of the SC sublayer. Besides, after adopting the DHF technology, the gas drainage effect improved markedly. The borehole number dropped by 49%, the gas drainage ratio increased from 26.0% to 48.2%, and the average coal roadway excavation speed increased from 2.4 to 5.6 m/d.

The scalable fabrication of cost-efficient bifunctional catalysts with enhanced hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance plays a significant role in overall water splitting in hydrogen production fields. MoSe2 is considered to be one of the most promising candidates because of its low cost and high catalytic activity. Herein, hierarchical nitrogen-doped carbon networks were constructed to enhance the catalytic activity of the MoSe2-based materials by scalable free-drying combined with an in situ selenization strategy. The rationally designed carbonaceous network-encapsulated MoSe2 composite (MoSe2/NC) endows a continuous honeycomb-like structure. When utilized as a bifunctional electrocatalyst for both HER and OER, the MoSe2/NC electrode exhibits excellent electrochemical performance. Significantly, the MoSe2/NC‖MoSe2/NC cells require a mere 1.5 V to reach a current density of 10 mA cm−2 for overall water splitting in 1 M KOH. Ex situ characterizations and electrochemical kinetic analysis reveal that the superior catalytic performance of the MoSe2/NC composite is mainly attributed to fast electron and ion transportation and good structural stability, which is derived from the abundant active sites and excellent structural flexibility of the honeycomb-like carbon network. This work offers a promising pathway to the scalable fabrication of advanced non-noble bifunctional electrodes for highly efficient hydrogen evolution.

Inductive power transfer (IPT) technology is used in various applications owing to its safety features, robust environmental adaptability, and convenience. In some special applications, the charging pads are required to be as compact as possible to accommodate practical spatial requirements, and even size requirements dictate that the diameter of the charging pad matches the air gap. However, such requirements bring about a decrease in the transmission efficiency, power, and tolerance to misalignment of the system. In this paper, by comparing a double-sided inductor–capacitor–capacitor (LCC), double-sided inductor–capacitor–inductor (LCL), series–series (SS), and inductor–capacitor–capacitor–series (LCC-S) compensation topologies in IPT systems, we identified a double-sided LCC compensation topology that is suitable for weak coupling coefficients. Furthermore, this study modeled and simulated the typical parameters of coreless coils in circular power pads, such as the number of coil layers, turns, wire diameter, and wire spacing, to enhance the mutual inductance of the magnetic coupler during misalignment and long-distance transmission. A wireless charging system with 640 W output power was built, and the experimental results show that a maximum dc-dc efficiency of over 86% is achieved across a 200 mm air gap when the circular power pad with a diameter of 200 mm is well aligned. The experimental results show that using a suitable compensation topology and optimizing the charging pad parameters enables efficient IPT system operation when the coupling coefficient is 0.02.

The accuracy of bridge performance monitoring and evaluation is easily affected by unfavorable factors such as vehicle coupling and test noise. In order to accurately evaluate the dynamic response and health monitoring threshold of the bridge under different operating conditions, a time-varying dynamic vehicle group model including the main uniform mass and the coupling mass was established, and the influence of road roughness was considered in the coupling equation. A bridge monitoring strategy considering signal noise ratio and vehicle–bridge interaction was proposed, and the effectiveness of the monitoring strategy was verified by taking a simple supported beam as an example. The results showed that the proposed time-varying dynamic vehicle group model could accurately consider the influence of road roughness and estimate the threshold of health monitoring, and the proposed bridge monitoring strategy could filter out a large amount of low signal-to-noise ratio or meaningless data, thus saving computing resources and realizing the lightweight safety monitoring of bridges.

Pretreatment processes are essential for the preparation of biofuels from lignocellulosic feedstocks. Based on alkaline H2O2 pretreatment, photocatalytic alkaline H2O2 pretreatment (U-AHP) was investigated to examine the effects of reaction time, alkali concentration, and H2O2 concentration on the enzymatic digestion of corn stover. The optimum process conditions were determined by orthogonal tests: 1% NaOH, 2% H2O2, and reaction time of 8 h. Under these conditions, the lignin removal efficiency of UH-AHP was 90.2% and the saccharification yield was 94.7%. Furthermore, FT-IR, XRD, and SEM analyses showed that U-AHP pretreatment caused structural damage to the maize straw and increased the crystallinity of the cellulose, and it was speculated that the U-AHP pretreatment reaction was a complex mechanism, which might be a multiple synergistic reaction. This study shows that U-AHP pretreatment is a simple, green and effective method to promote lignin removal.

An efficient battery thermal management system (BTMS) can undoubtedly improve the performance and lifetime of lithium-ion batteries. In this study, a novel battery thermal cooling module (BCM) consisting of composite phase change material (CPCM) with carbon foam skeleton support material and a carbon fiber thermally conductive gasket (CFT) are proposed. Experimental results show that the combination of CPCM loaded on carbon foam and CFT provides significant cooling and temperature balancing benefits to the battery components, with peak temperature reductions of 25.13% and 27.83% at 1.3C and 1.5C, and maximum temperature differences for 1.5C remaining within 2.7 °C. The high enthalpy of the CPCM is the key to battery cooling. The addition of CFT reduces the interfacial thermal resistance and enhances phonon heat transfer, effectively controlling the uniformity of the battery surface temperature. Therefore, this study shows that the combined BTMS with BCM and CFT has a good temperature response and cooling effect. The BTMS achieves the dual modulation of CPCM with high enthalpy and carbon material with enhanced heat transfer, enabling intelligent and long-term stable operation. This material combination is expected to have a wide range of applications in battery materials, energy storage and other fields.

In recent years, nocturnal ozone enhancement (NOE) events have emerged as a prominent research focus in the field of the atmospheric environment. By using statistical analysis methods, we conducted a comparative investigation of nocturnal ozone concentrations and NOE events in Dongying, the central city of the Yellow River Delta, China, in 2022 and 2023, and further explored the effects of NOE events on O3 and PM2.5 on the same night and the subsequent day. The results showed that from 2022 to 2023, in Dongying, the annual average nocturnal ozone concentrations increased from 51 μg/m3 to 59 μg/m3, and the frequency of NOE events was higher in the spring, summer, and autumn, and lower in the winter. The NOE events not only exhibited promoting effects on nocturnal O3 and Ox, and on the daily maximum 8 h average concentration of O3 (MDA8-O3) on the same day (comparatively noticeable in summer and autumn), but also demonstrated a clear impact on nocturnal PM2.5 and PM2.5-bounded NO3− and SO42− (especially in winter). Additionally, the NOE events also led to higher concentrations of O3 and Ox, as well as higher MDA8-O3 levels during the subsequent day, with more observable impacts in the summer. The results could strengthen our understanding about NOE events and provide a scientific basis for the collaborative control of PM2.5 and O3 in urban areas in the Yellow River Delta in China.

Abstract Mixed insulation oil is considered as a desired substitute for traditional mineral oil. A novel 3‐element mixed insulation oil has been developed in our previous works, whose parameters satisfy the mineral oil standard (IEC 60296:2012). In the application of transformer oil, dissolved gas analysis is an effective method for insulation fault diagnosis. Thermal fault is a common and typical fault in transformers; however, the pyrolysis process and gas production characteristics of mixed insulation oil under thermal fault remain unknown. In this study, the pyrolysis process and gas production characteristics of 3‐element mixed insulation oil have been studied through simulation and experiments, and mineral oil is equally treated for comparison. Results show that the gas production characteristics of mixed oil are closely related to its base oils, and 3‐element mixed insulation oil generates more H2 and C2H6 under thermal fault, in which the percentage of H2 in the mixed oil is always three times that in the mineral oil. More CO2 is produced in mixed oil under thermal fault because of ester bonds; C2H4 is also a main characteristic gas for mixed insulation oil under thermal fault, and its proportion increases continuously with the increase of temperature. For mineral oil, the weight loss temperature in thermo‐gravimetric (TG) curve corresponds to evaporation rather than decomposition. Natural esters have poor thermal stability according to simulation results, but they possess high flash point and weight loss temperature in the TG curve primarily because of their large average molecular weight.

In order to investigate the control mechanism of composite phase change materials (PCM), a series of composite nano-phase change emulsion (NPCE) were prepared in this paper with high thermal conductivity, high heat storage and low supercooling using hexadecane, octadecane, hexadecanol, octadecanol and various metal nano-particles. Through the control mechanism, it is expected to adjust the phase transition range of NPCE to a desirable range. The NPCEs were characterized by particle size analyser, cryogenic transmission electron microscope (Cryo TEM), differential scanning calorimeter (DSC), thermal conductivity meter and rheometer. The results showed that the NPCEs was successfully prepared with uniform dispersion, great stability, low viscosity and narrow particle size distribution. DSC results showed that the latent heat of NPCE with 20 wt. % hexadecane was 55.86 kJ/kg. The supercooling degree of prepared NPCEs using 1.25 wt. % of hybrid nucleating agents was reduced by 81%. Metal oxides effectively improved the thermal conductivity of NPCEs. The thermal conductivity of the NPCEs with 1wt. % nano Al2O3 was 0.70 W/(m ⋅ K), which was increased by 21%. The viscosity of the NPCEs increased with the increase of metal oxide concentrations and decreased with the increase of temperature. Importantly the NPCEs presented a shear thinning effect and can be considered as Newtonian fluid after shear rate of 2 s−1, which had great potential in the thermal energy storage system.

Fischer–Tropsch to olefins (FTO) reaction is an important non-petrochemical route to produce light olefins. Iron is the most widely used and easily obtainable metal catalyst with great potential in FTO. Combine micro and relatively macro perspectives, this review briefly summarizes the recent research progress related to the synthesis of light olefins via Fe-based FTO catalysts by focusing on the addition of various supports and promoters, while elucidating the effects of novel catalyst configurations and preparation methods on catalytic performance. Finally, the future application and research of Fe-based catalysts applied in FTO are discussed.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L−1 vs. 4.26 ± 0.6 mmol L−1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min−1 vs. 34.75 ± 2.66 m min−1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg−1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

Systemic chronic inflammation (SCI) due to intrinsic immune over-activation is an important factor in the development of many noninfectious chronic diseases, such as neurodegenerative diseases and diabetes mellitus. Among these immune responses, macrophages are extensively involved in the regulation of inflammatory responses by virtue of their polarization plasticity; thus, dysregulation of macrophage polarization direction is one of the potential causes of the generation and maintenance of SCI. High-temperature demand protein A2 (HtrA2/Omi) is an important regulator of mitochondrial quality control, not only participating in the degradation of mis-accumulated proteins in the mitochondrial unfolded protein response (UPRmt) to maintain normal mitochondrial function through its enzymatic activity, but also participating in the regulation of mitochondrial dynamics-related protein interactions to maintain mitochondrial morphology. Recent studies have also reported the involvement of HtrA2/Omi as a novel inflammatory mediator in the regulation of the inflammatory response. HtrA2/Omi regulates the inflammatory response in BMDM by controlling TRAF2 stabilization in a collagen-induced arthritis mouse model; the lack of HtrA2 ameliorates pro-inflammatory cytokine expression in macrophages. In this review, we summarize the mechanisms by which HtrA2/Omi proteins are involved in macrophage polarization remodeling by influencing macrophage energy metabolism reprogramming through the regulation of inflammatory signaling pathways and mitochondrial quality control, elucidating the roles played by HtrA2/Omi proteins in inflammatory responses. In conclusion, interfering with HtrA2/Omi may become an important entry point for regulating macrophage polarization, providing new research space for developing HtrA2/Omi-based therapies for SCI.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC.

In order to investigate the causes of complex air pollution in coastal cities in the Bohai Rim of China, a one-month intensive field observation combined with model simulation was carried out in a typical city named Dongying in September 2022. The results showed that two PM2.5 and O3 complex pollution episodes occurred in Dongying in the observation period, with the primary pollutant being O3. Atmospheric photochemical reactions occurring under unfavorable meteorological conditions led to the production of O3 while at the same time facilitating the generation of nitrate, sulfate, and other secondary components of PM2.5 by enhancing the atmospheric oxidizing capacity, which promoted the formation of complex air pollution. It was worth noting that in the context of high pollutants emission, the occurrence of complex air pollution was more sensitive to the variation in meteorological conditions than to the change in pollutants emission. To continuously improve air quality and protect human health in Dongying, it is recommended that an effective regional joint air pollution prevention and control mechanism with neighboring cities should be established in the premise of effective local pollutants reduction, and special attention should be paid to the adverse effect of the air mass transportation from Bohai Bay.

The use of plastics in agriculture and in fisheries has been vital to increase food production and meet the demands of an increasingly growing global population. However, there are several drawbacks to the use of plastics in these industries. Most plastics used in agriculture are disposed of after one single use and are highly susceptible to weathering. Abandoned, lost, or discarded fishing gear cause considerable damage to marine life. Quantification of plastic waste generation in these industries is scarce or non-existent in the case of fisheries. In this paper, we estimate the amount of plastic waste generated by agriculture and fisheries at a regional scale, considering the South West of the UK as a case study. We followed a mass balance approach to quantify the potential plastic waste generated by these industries. We find a generation of 49 kt of plastic waste in agriculture, 47% of which has an unknown fate. We estimate 454 t/year of fishing gear waste, with unclear end-of-life pathways. A detailed quantitative understanding of plastic waste generation per sector at a regional scale is fundamental for tracking plastic waste flows, locating hotspots of pollution, and planning actions to reduce the amount of plastic waste along the chain of end-users.

Purpose – The literature review aims to facilitate a broader understanding of on-demand service platform operations management and proposes potential research directions for scholars. Design/methodology/approach – This study searches four databases for relevant literature on on-demand service platform operations management and selects 72 papers for this review. According to the research context, the literature can be divided into research on “a single platform” and research on “multiple platforms”. According to the research methods, the literature can be classified into “Mathematical Models”, “Empirical Studies”, “Multiple Methods” and “Literature Review”. Through comparative analysis, we identify research gaps and propose five future research agendas. Findings – This paper proposes five research agendas for future research on on-demand service platform operations management. First, research can be done to combine classic research problems in the field of operations management with platform characteristics. Second, both the dynamic and steady-state issues of on-demand service platforms can be further explored. Third, research employing mathematical models and empirical analysis simultaneously can be more fruitful. Fourth, more research efforts on the various interactions among two or more platforms can be pursued. Last but not least, it is worthwhile to examine new models and paths that have emerged during the latest development of the platform economy. Originality/value – Through categorizing the literature into two research contexts as well as classifying it according to four research methods, this article clearly shows the research progresses made so far in on-demand service platform operations management and provides future research directions.

Introduction: Traditional Chinese medicine (TCM) injections, as a relatively safe and low-cost treatment, have been widely used in the prevention and treatment of anthracyclines-induced cardiotoxicity in China. However, the quality of the relevant systematic reviews and meta-analyses published in recent years is uneven, so that the effectiveness and safety of TCM injections in preventing and treating anthracyclines-induced cardiotoxicity remain to be discussed. A systematic overview is therefore needed to provide a more advanced evidentiary reference for clinical practice. Methods: Eight Chinese and English databases were searched by computer to screen the meta-analyses/systematic reviews on the efficacy of traditional Chinese medicine injections for the prevention and treatment of anthracyclines-induced cardiotoxicity from the database establishment to October 2022. The methodological quality and evidence quality of outcome indicators included in the study were evaluated by AMSTAR 2 tool, PRISMA statement and GRADE classification. Results: A total of 7 articles were included in the study. The quality evaluation of AMSTAR 2 showed that 7 studies were extremely low-level; PRISMA stated that the evaluation results showed that the reports of 7 studies were of intermediate quality; The GRADE rating indicated that most of the evidence was of low quality. Conclusion: The methodological quality and evidence quality of meta-analysis/system evaluation concerning the prevention and treatment of anthracyclines-induced cardiotoxicity by Chinese medicine are currently low, and the effectiveness of Chinese medicine in the treatment of anthracyclines-induced cardiotoxicity needs more high-quality evidence-based evidence.

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. β-amyloid plaque (Aβ) deposition and hyperphosphorylated tau, as well as dysregulated energy metabolism in the brain, are key factors in the progression of AD. Many studies have observed abnormal iron accumulation in different regions of the AD brain, which is closely correlated with the clinical symptoms of AD; therefore, understanding the role of brain iron accumulation in the major pathological aspects of AD is critical for its treatment. This review discusses the main mechanisms and recent advances in the involvement of iron in the above pathological processes, including in iron-induced oxidative stress-dependent and non-dependent directions, summarizes the hypothesis that the iron-induced dysregulation of energy metabolism may be an initiating factor for AD, based on the available evidence, and further discusses the therapeutic perspectives of targeting iron.

Ovarian cancer is the most lethal gynecologic malignancy, and metastasis is the major cause of death in patients with ovarian cancer, which is regulated by the coordinated interplay of genetic and epigenetic mechanisms. Histone deacetylases (HDACs) are enzymes that can catalyze the deacetylation of histone and some non-histone proteins and that are involved in the regulation of a variety of biological processes via the regulation of gene transcription and the functions of non-histone proteins such as transcription factors and enzymes. Aberrant expressions of HDACs are common in ovarian cancer. Many studies have found that HDACs are involved in regulating a variety of events associated with ovarian cancer metastasis, including cell migration, invasion, and the epithelial–mesenchymal transformation. Herein, we provide a brief overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. In addition, we discuss the roles of HDACs in the regulation of ovarian cancer metastasis. Finally, we discuss the development of compounds that target HDACs and highlight their importance in the future of ovarian cancer therapy.

ObjectiveThe carbon fiber reinforced plastic (CFRP) propeller has such advantages as light weight, high strength, low vibration, low noise, corrosion resistance and fatigue resistance. In order to accurately ascertain the deformation and strain of CFRP propeller blades under hydrodynamic load, this paper proposes an online measurement method for CFRP propeller dynamic strain under submerged operation conditions.MethodFiber bragg grating (FBG) sensors are embedded in a CFRP propeller, and an underwater dynamic strain test system is built. Two types of test conditions are set: (1) the velocity is 0 m/s, and the rotation speed increases from 50 to 400 r/min; and (2) the rotation speed is 427 r/min, and the velocity increases from 0.0 to 1.6 m/s. The dynamic strain data of the CFRP propeller under the above conditions is obtained by the FBG sensors and analyzed in the time and spectrum domains.ResultsThe results show that, the dynamic strain frequencies of each FBG sensor on the CFRP propeller are the same and related to the rotation speed, while the dynamic strain amplitude of each FBG sensor has no obvious relationship with the rotation speed or velocity, but depends on the position of the sensor, which reflects the structural mechanics features of the propeller.ConclusionThe underwater online dynamic strain test of the CFRP propeller is realized, and test results are reasonable and reliable. This provides an important empirical basis for the theoretical design and analysis of the CFRP propeller, which is of great significance for the study of its vibration noise and hydrodynamic performance.

Abstract Alkaline water electrolysis (AWE) is among the most developed technologies for green hydrogen generation. Despite the tremendous achievements in boosting the catalytic activity of the electrode, the operating current density of modern water electrolyzers is yet much lower than the emerging approaches such as the proton‐exchange membrane water electrolysis (PEMWE). One of the dominant hindering factors is the high overpotentials induced by the gas bubbles. Herein, the bubble dynamics via creating the superaerophobic electrode assembly is optimized. The patterned Co‐Ni phosphide/spinel oxide heterostructure shows complete wetting of water droplet with fast spreading time (≈300 ms) whereas complete underwater bubble repelling with 180° contact angle is achieved. Besides, the current collector/electrode interface is also modified by coating with aerophobic hydroxide on Ti current collector. Thus, in the zero‐gap water electrolyzer test, a current density of 3.5 A cm−2 is obtained at 2.25 V and 85 °C in 6 m KOH, which is comparable with the state‐of‐the‐art PEMWE using Pt‐group metal catalyst. No major performance degradation or materials deterioration is observed after 330 h test. This approach reveals the importance of bubble management in modern AWE, offering a promising solution toward high‐rate water electrolysis.

In this paper, a composite structure double layer phase change walls with expanded graphite (EG) was investigated. By adding the EG, the time needed for the phase change process and the wall to work was both accelerated. The effect of composite phase change walls on the indoor thermal comfort and building energy consumption were investigated experimentally. The results show that the double layer phase change wall with the EG can suppress the temperature fluctuation. In addition, it simulated the cooling and heating loads with or without phase change walls based on the climatic conditions in Shanghai. The results show that the heating load in winter is reduced by more than 15%. The simulated values are consistent with the experimental values, and the temperature deviation at the same measuring point within the same period is small. The maximum temperature change between the experimental and simulated values is less than 1 °C. The double layer phase change wall with the EG can reduce the temperature fluctuation and improve the indoor thermal comfort.

Phyllanthi Fructus (PF), the edible fruits of Phyllanthus emblica L., serves as an important resource for some health products, foods and drugs due to its high safety and sufficient nutritional value. In recent years, in vivo and in vitro experiments have been conducted to reveal the active components of PF. More than 180 compounds have been isolated and identified from the PF so far, primarily including tannins, phenolic acids, flavonoids, terpenoids, polysaccharides, fatty acids and amino acids. In traditional Chinese medicine (TCM), PF is used to cure several diseases such as bronchitis, asthma, diabetes, peptic ulcer, hepatopathy, leprosy, and jaundice. Consistent with ethnopharmacology, numerous modern studies have demonstrated that the extracts or monomeric compounds derived from PF exhibit various pharmacological effects including anti-oxidation, anti-bacteria, anti-inflammation, anti-tumour, anti-virus, immunity improvement, hypoglycemic and hypolipidemic effects, and multiple organ protective protection. Toxicological studies on PF indicated the absence of any adverse effects even at a high dose after oral administration. Due to strict quality control, these pharmacological activities and the safety of PF greatly improve the development and utilization of products. Our comprehensive review aims to summarize the phytochemistry, pharmacological effects, toxicology, and product development of PF to provide theoretical guidance and new insights for further research on PF in the future.

There is increasing evidence for the key role of the immune microenvironment in the occurrence and development of hepatocellular carcinoma. As an important component of the immune microenvironment, the polarization state and function of macrophages determine the maintenance of the immunosuppressive tumor microenvironment. Hepatocellular carcinoma tumor-derived exosomes, as information carriers, regulate the physiological state of cells in the microenvironment and control cancer progression. In this review, we focus on the role of the exosome content in disease outcomes at different stages in the progression of hepatitis B virus/hepatitis C virus-induced hepatocellular carcinoma. We also explore the mechanism by which macrophages contribute to the formation of hepatocellular carcinoma and summarize the regulation of macrophage functions by the heterogeneity of exosome loading in liver cancer. Finally, with the rise of exosome modification in immunotherapy research on hepatocellular carcinoma, we summarize the application prospects of exosome-based targeted drug delivery.

ObjectiveTo assess the economic evaluation of margetuximab plus chemotherapy over trastuzumab plus chemotherapy for women with pretreated ERBB2-positive advanced breast cancer in the United States (US) and China.MethodsBased on the SOPHIA trial, a three-state Markov model was developed to compare the cost and efficacy of margetuximab to trastuzumab for previously treated women with ERBB2-positive advanced breast cancer. The model inputs were derived from existing literature and the US life table. Primary outcomes included lifetime costs in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty.ResultsThe base case analyses demonstrated that margetuximab plus chemotherapy had an increasing cost of $68,132 and $20,540 over trastuzumab plus chemotherapy in the US and China, respectively, with a gain of 0.11 and 0.09 QALYs both favored margetuximab. The ICERs for two treatment strategies were $260,176 in the US and $630,777 in China, resulting in a poor cost-effectiveness at their respective threshold of willingness to play. One-way sensitivity analyses showed that the results to be most sensitive to the price of margetuximab and that of trastuzumab. And an 11 and 82% price reduction of margetuximab would make this regimen cost-effective in the US and China, respectively.ConclusionIn the US and China, margetuximab plus chemotherapy is not likely to be cost-effective for women with pretreated ERBB2-positive advanced breast cancer, whereas price reduction effectively improves insufficient cost-effectiveness.

Mitochondrial transcription termination factor (mTERF) is a DNA-binding protein that is encoded by nuclear genes, ultimately functions in mitochondria and can affect gene expression. By combining with mitochondrial nucleic acids, mTERF regulates the replication, transcription and translation of mitochondrial genes and plays an important role in the response of plants to abiotic stress. However, there are few studies on mTERF genes in tomato, which limits the in-depth study and utilization of mTERF family genes in tomato stress resistance regulation. In this study, a total of 28 mTERF gene family members were obtained through genome-wide mining and identification of the tomato mTERF gene family. Bioinformatics analysis showed that all members of the family contained environmental stress or hormone response elements. Gene expression pattern analysis showed that the selected genes had different responses to drought, high salt and low temperature stress. Most of the genes played key roles under drought and salt stress, and the response patterns were more similar. The VIGS method was used to silence the SLmTERF13 gene, which was significantly upregulated under drought and salt stress, and it was found that the resistance ability of silenced plants was decreased under both kinds of stress, indicating that the SLmTERF13 gene was involved in the regulation of the tomato abiotic stress response. These results provide important insights for further evolutionary studies and contribute to a better understanding of the role of the mTERF genes in tomato growth and development and abiotic stress response, which will ultimately play a role in future studies of tomato gene function.

Lithium-ion batteries have become the primary electrical energy storage device in commercial and industrial applications due to their high energy/power density, high reliability, and long service life. It is essential to estimate the state of health (SOH) of batteries to ensure safety, optimize better energy efficiency and enhance the battery life-cycle management. This paper presents a comprehensive review of SOH estimation methods, including experimental approaches, model-based methods, and machine learning algorithms. A critical and in-depth analysis of the advantages and limitations of each method is presented. The various techniques are systematically classified and compared for the purpose of facilitating understanding and further research. Furthermore, the paper emphasizes the prospect of using a knowledge graph-based framework for battery data management, multi-model fusion, and cooperative edge-cloud platform for intelligent battery management systems (BMS).

Seawater electrolysis is promising for grid-scale H2 production without freshwater reliance, but high energy costs and detrimental Cl chemistry reduce its practical potential. Here, authors developed an energy-saving hybrid seawater electrolyzer for chlorine-free H2 production and N2H4 degradation.

Intelligent transformation of manufacturers requires smart logistics transformation collaboration, which improves competitiveness. In this study, we construct a Stackelberg game model based on the mutual influence and restriction in the relationship between a manufacturer and a logistics service provider (LSP) undergoing smart logistics transformation. We investigate whether cost-sharing (CS) or revenue-sharing (RS) contracts can coordinate the supply chain and suggest a hybrid CS–RS contract to improve performance. We find that, compared with decentralized options, CS and RS contracts achieve a higher level of smart logistics transformation. While the coordination and effectiveness of CS contracts are superior to those of RS contracts, neither can fully coordinate the supply chain. The proposed hybrid CS–RS contract allows the manufacturer to share the LSP’s costs before the transformation and its partial revenue after transformation, so that the LSP can reduce its service charge, thereby achieving full supply chain coordination.

Sturgeons are ancient and endangered species whose populations have been greatly reduced over the past few centuries due to habitat destruction and overfishing for the production of expensive caviar. All sturgeon species are listed in CITES Appendix II to limit their trade; therefore, accurate species identification is crucial. In this study, we performed whole-genome resequencing of five sturgeon species, including Kaluga sturgeon (H. dauricus), Siberian sturgeon (A. baerii), Sterlet sturgeon (A. ruthenus), Russian sturgeon (A. gueldenstaedtii), and Amur sturgeon (A. schrenckii), to obtain species-specific InDel-based nucleotide sequences for Kaluga sturgeon. Through whole-genome screening within these five sturgeon species, we developed methods for the rapid identification of Kaluga sturgeon germplasm. Using dominant/co-dominant molecular markers designed for Huso dauricus, purebred or hybrid samples can be identified through a PCR reaction. These markers allow for the precise identification of Kaluga sturgeon lineages from at least seven sturgeon species (H. dauricus, A. schrenckii, A. ruthenus, A. baerii, A. gueldenstaedtii, A. stellatus, and H. huso) and their hybrids. This development is expected to have a positive effect on both the sturgeon trade and the conservation of sturgeon germplasm resources.

Background: Erythroferrone (ERFE) is a hormone identified recently as a master regulator connecting iron homeostasis and erythropoiesis. Serum ERFE concentrations significantly increase in animals and humans with normal or impaired kidney function after receiving exogenous erythropoiesis-stimulating agents (ESAs), which suggests it might be a predictive factor for erythropoiesis. To evaluate whether ERFE is an early, sensitive biomarker for long-term erythropoietic effects of ESAs, we investigated the relationship between ERFE dynamics and time courses of major erythropoietic responses to ESA treatment.Methods: Healthy rats received single dose and multiple doses (thrice a week for 2 weeks) of recombinant human erythropoietin (rHuEPO) at three dose levels (100, 450, and 1350 IU/kg) intravenously. The rHuEPO and ERFE concentrations in plasma were determined at a series of time points after dosing. Erythropoietic effects including red blood cell count and hemoglobin concentrations were continuously monitored for 24 days (single dose) or 60 days (multiple doses). The expansion of erythroblasts in bone marrow was quantified by flow cytometry analysis.Results: ERFE significantly increased within a few hours and return to baseline at 24 h after rHuEPO treatment. The ERFE response was enhanced after repeated treatment, which was consistent with the observed expansion of erythroblasts in the bone marrow. In addition, the dynamics of ERFE showed double peaks at approximately 2 and 10 h after rHuEPO stimulation, and the ERFE baseline displayed a significant circadian rhythm. There was a strong positive correlation between peak values of short-term ERFE responses and the long-term hemoglobin responses.Conclusion: The stimulated release of ERFE is a rapid process within 24 h. The second peak in the ERFE response to rHuEPO suggests the presence of a feedback mechanism counterregulating the ESA stimulation. The early increase of ERFE at 2 h appears to be a predictor of the hemoglobin response at 14 days after single dose of rHuEPO. Under multiple-dose regimen, the enhanced ERFE responses still correlate with the peak hemoglobin responses. The ERFE baseline also exhibits a circadian rhythm.

Aconitine is one of the main bioactive and toxic ingredients of Aconitum species. Increasingly, aconitine has been reported to induce neurotoxicity. However, whether aconitine has effects on the dopaminergic nervous system remains unclear. In this study, zebrafish embryos at 6-days postfertilization were exposed to aconitine at doses of 0.5, 1, and 2 μM for 24 h, and SH-SY5Y cells were treated with 50, 100, and 200 μM of aconitine for 24 h. Results demonstrated that aconitine treatment induced deformities and enhanced the swimming behavior of zebrafish larvaes. Aconitine exposure suppressed cell proliferation and increased the number of reactive oxygen species and apoptosis in zebrafish larvaes and SH-SY5Y cells. Aconitine altered the levels of dopamine and its metabolites by regulating the expression of genes and proteins related to dopamine synthesis, storage, degradation, and reuptake in vivo and in vitro. Moreover, aconitine activated the AC/cAMP/PKA pathway by activating the dopamine D1 receptor (D1R) and inhibiting the dopamine D2 receptor (D2R) to disturb intracellular calcium homeostasis, eventually leading to the damage of nerve cells. Furthermore, the D1R antagonist SCH23390 and D2R agonist sumanirole pretreatment effectively attenuated the excitatory state of larvaes. Sumanirole and PKA antagonist H-89 pretreatment effectively decreased intracellular Ca2+ accumulation induced by aconitine in vivo. SCH23390 and sumanirole also reduced aconitine-induced cytotoxicity by inhibiting the AC/cAMP/PKA pathway in vitro. These results suggested that dopamine homeostasis imbalance and dopamine receptors (DRs)-mediated AC/cAMP/PKA pathway activation might be vital mechanisms underlying aconitine-induced neurological injury.

The synthesis of 4,5-diiodo-1,3-dimesityl-1,2,3-triazolium salts with different anions have been developed. These triazolium salts show diverse aggregation via halogen bonding between C–I bonds and anions. Triazolium with halide anions exists as a tetramer with saddle conformation. Triazolium tetrafluoroborate exists as a trimer with Chinese lantern shape conformation. Triazolium trifluoroacetate and acetate exist as dimers, respectively, while the former shows boat conformation and the latter forms rectangle conformation. Triazolium salts form a linear polymer with polyiodide.

Sorafenib has attracted much attention as the first drug approved by the FDA for the treatment of advanced hepatocellular carcinoma (HCC). Because of the drug tolerance, the overall outcomes were far from satisfactory. Current studies suggest that changes in glucose metabolism induced by sorafenib are the pivotal resistant mechanism of HCC cells, but the specific regulatory mechanism remains unclear, which makes it difficult to increase drug sensitivity by targeting glycolysis. As a metabolic-recycling pathway, autophagy regulates multiple important pathways involved in cell survival and death. In this study, we found the expression of key autophagy proteins were closely related to the prognosis and progression of HCC patients. Based on in vitro experiments, our studies showed sorafenib induced autophagy in HCC cells. Inhibition of autophagy by chloroquine could significantly increase the sensitivity of HCC cells to sorafenib and reverse the enhancement of glycolysis. Furthermore, sorafenib-induced autophagy promoted the deacetylase activity of HDAC6 by degrading p62, which promoted the activity of PKM2 by regulating the acetylation of its critical substrate HSP90. In this study, we investigated the role of autophagy-induced HDAC6 in regulating the key glycolytic enzyme PKM2, which may be helpful to clarify the relationship between autophagy and glycolysis in a sorafenib-resistant mechanism. Targeting p62/HDAC6/HSP90 could herald a potential improvement in HCC therapy.

ObjectiveTo date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role in patients with septic shock.MethodsThirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study. Baseline information and clinical outcomes were obtained prospectively. Lactylation levels of all proteins and H3K18 from peripheral blood mononuclear (PBMC) were determined by western blotting and serum levels of inflammatory cytokines by flow cytometry. Arginase-1 (Arg1) and Krüppel-like factor-4 (Klf4) mRNA expression was evaluated by quantitative real-time PCR (qRT-PCR).ResultsLactylation was found to be an all-protein post-translational modification and was detected in PBMCs from both healthy volunteers and critically ill patients, with a significantly higher relative density in shock patients (t=2.172, P=0.045). H3K18la was expressed in all subjects, including healthy volunteers, with the highest level in septic shock patients (compared with non-septic shock patients, critically ill without shock patients and healthy volunteers P=0.033, 0.000 and 0.000, respectively). Furthermore, H3K18la protein expression correlated positively with APACHE II scores, SOFA scores on day 1, ICU stay, mechanical ventilation time and serum lactate (ρ=0.42, 0.63, 0.39, 0.51 and 0.48, respectively, ρ=0.012, 0.000, 0.019, 0.003 and 0.003, respectively). When we matched patients with septic shock and with non-septic shock according to severity, we found higher H3K18la levels in the former group (t=-2.208, P =0.040). Moreover, H3K18la exhibited a close correlation with procalcitonin levels (ρ=0.71, P=0.010). Patients with high H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels (ρ=0.33, 0.37, 0.62, 0.55, 0.65, 0.49 and 0.374 respectively, P=0.024, 0.011, 0.000, 0.000, 0.000 and 0.000 respectively). H3K18la expression also displayed a positive correlation with the level of Arg1 mRNA (ρ=0.561, P=0.005).ConclusionsLactylation is an all-protein post-translational modification occurring in both healthy subjects and critically ill patients. H3K18la may reflect the severity of critical illness and the presence of infection. H3K18la might mediate inflammatory cytokine expression and Arg1 overexpression and stimulate the anti-inflammatory function of macrophages in sepsis.

Recombinant human erythropoietin (rHuEPO) is one of the most effective drugs for the treatment of anemia in patients with chronic kidney disease. However, EPO-resistance is an important contributor to the increased risk of adverse effects. We previously showed that EPO treatment could induce precursor cell depletion, resulting in EPO-resistance. We further found that the combination of EPO with romiplostim, a thrombopoietin receptor agonist that can stimulate the expansion of hematopoietic stem cells, can treat EPO-resistance. In this study, we performed interspecies pharmacodynamic (PD) scaling of this combination therapy for human dose prediction. The pharmacokinetic parameters of both rHuEPO and romiplostim in humans were obtained from previous studies. The PD parameters obtained in rats were scaled to humans using allometric equations. The relationship between PD parameters of the megakaryocyte lineage from rats, monkeys, and humans was in agreement with those from the literature on allometric scaling. The PD response was translated to humans based on allometric scaling and agreed with the observed data. These parameters were used to simulate hemoglobin and platelet response in humans. RHuEPO 50 IU/kg thrice weekly and romiplostim 1 μg/kg once every 4 weeks from the second week is the recommended combination dosing regimen according to the model prediction. Our work successfully scaled the PD of rHuEPO and romiplostim monotherapy from rats to humans. The predicted dosing regimen of each drug in the combination therapy is less intensive than the approved starting dose of each drug, which supports additional evaluations of the combination therapy in humans.

Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk.

Triclosan (TCS), a ubiquitous antimicrobial agent, has been frequently detected in wild fish, leading to concerns regarding TCS safety in the aquatic environment. The present work aims to investigate the TCS-mediated effects on various tissues (the liver, gills, brain, and testes) of wild-sourced adult mosquitofish based on histological analysis and transcriptome. Severe morphological injuries were only found in the liver and gills. The histopathological alterations in the liver were characterized by cytoplasmic vacuolation and degeneration, eosinophilic cytoplasmic inclusions, and nuclear polymorphism. The gill lesions contained epithelial lifting, intraepithelial edema, fusion and shortening of the secondary lamellae. Consistently, the numbers of differently expressed genes (DEGs) identified by transcriptome were in the order of liver (1627) > gills (182) > brain (9) > testes (4). Trend-aligned histopathological and transcriptomic changes in the 4 tissues, suggesting the tissue-specific response manner of mosquitofish to TCS, and the liver and gills were the target organs. TCS interrupted many biological pathways associated with lipogenesis and lipid metabolism, transmembrane transporters, protein synthesis, and carbohydrate metabolism in the liver, and it induced nonspecific immune response in the gills. TCS-triggered hepatotoxicity and gills damnification may lead to inflammation, apoptosis, diseases, and even death in mosquitofish. TCS showed moderate acute toxicity and bioaccumulative property on mosquitofish, suggesting that prolonged or massive use of TCS may pose an ecological risk.