Search

We sought to investigate the value of combining intrauterine cerebral blood flow changes with brain electrical activity examination in evaluating the prognosis of brain injury. A total of 90 preterm infants were enrolled and divided into 2 groups: the brain damaged preterm infants group (n = 55) and the nonbrain damaged preterm infants group (n = 35). The diagnostic efficacy of combining intrauterine cerebral blood flow changes with electroencephalogram (EEG) activity examination in predicting the prognosis of preterm infants with brain injury was evaluated using T-test. Pearson linear correlation was applied to analyze the relationship between fetal intrauterine cerebral blood flow changes combined with electrical activity examination and the prognosis of brain injury. Significant differences were seen in pulse index, the ratio of peak systolic velocity to end diastolic velocity ratio, and other indexes between the 2 groups (P < 0.05). The combined approach of intrauterine cerebral blood flow changes with EEG activity examination demonstrated significantly higher values for area under the curve, sensitivity and negative predictive value compared to using intrauterine cerebral blood flow changes or EEG activity examination alone (P < 0.05). A positive correlation was found between fetal intrauterine cerebral blood flow and electrical activity examination (P < 0.05). Combining the assessment of intrauterine cerebral blood flow changes with cerebral electrical activity examination proved beneficial in diagnosing the prognosis of brain injury and provided an important reference for early clinical intervention. [ABSTRACT FROM AUTHOR]

This paper investigates the attack estimation and state reconstruction problem for linear cyber–physical systems with state delay and simultaneous sensor and actuator attacks. Reduced-order observer is designed for the augmented system to simultaneously estimate the actuator attack, sensor attack and the state of system. By adopting the double integral term into the Lyapunov–Krasovskii functional and decomposing the cross term, the delay-dependent results are obtained. The method proposed in this paper can accurately estimate the state, actuator and sensor attacks simultaneously without additional design. Compared with the previous method, the time delay information is fully utilized and the conservation is greatly reduced. Finally, the correctness of the results is verified by simulation. • Delay-dependent conditions are obtained for cyber–physical systems with state delay. • Both attack estimation and state reconstruction are considered. • Actuator attacks, sensor attacks and system state are estimated simultaneously. [ABSTRACT FROM AUTHOR]

In this paper, we study a class of discrete-time cyber-physical systems (CPSs) with transmission delays and sparse malicious attacks on both input and output transmission channels, and present design methods for secure observer and controller. First, the states and sparse malicious attacks of the original system are reorganized into the states of the new system obtained by an improved augmentation method (rather than a singular augmentation method). Then, based on the new system, the states and attacks can be reconstructed simultaneously by the designed Luenberger-like observer. Furthermore, a novel dynamic output feedback (DOF) controller is proposed using the estimated values of the attacks, and a cone complementarity linearization (CCL) algorithm is designed to obtain the controller gains. The results show that the closed-loop system is stable in the sense of Lyapunov that both the estimation errors and the original system states will converge to a small neighborhood of the origin. In addition, the correlation results without delay are given. Finally, two examples are given to illustrate the effectiveness and superiority of the proposed method. • In addition to the sparse attacks that occur in both input and output channels, this paper also considers the transmission delays in both channels. • This paper introduces a multi-delay dynamic output feedback controller that transforms the inherently unstable original system into one that ultimately achieves Lyapunov stability. • In the case without transmission delay, compared with the results in previous researches, the proposed method of designing the observer and controller separately can reduce the difficulty of solving observer gains and controller gains, and enhance the feasibility. [ABSTRACT FROM AUTHOR]

The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon , exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms. This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway. SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot. SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C. SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects. [Display omitted] [ABSTRACT FROM AUTHOR]

In East Asia, epidermal growth receptor factor (EGFR) mutations are the most prevalent and important biomarkers for treating patients with advanced lung cancer. However, as L858R doublet mutations are rare, commercially available EGFR tests may yield false-negative results. To determine whether the L858R mutation of the L858R-K860I and L858R-L861F doublet mutations could be identified using different types of EGFR detection tests and to describe the clinical response of patients with lung cancer with L858R doublet mutations to EGFR tyrosine kinase inhibitors (TKI). Information and samples from four patients with L858R doublet mutations, including three with L858R-K860I and one with L858R-L861F, were retrospectively collected from the archives of our department. For each case, the clinical response to EGFR-TKI was retrieved from the medical records. Archived formalin-fixed paraffin-embedded blocks were subjected to Sanger sequencing, the cobas and Idylla EGFR tests, the IntelliPlex-LCP-DNA assay, and AmoyDx PLC panel. L858R mutations were all detected by Sanger sequencing and the Idylla EGFR test but missed by the cobas assay. The AmoyDx PLC detected L858R only in cases with L858R-K860I while the IntelliPlex-LCP-DNA assay detected L858R in the case with L858R-L861F. Additionally, three of the patients, who had measurable tumors, showed partial responses to afatinib and osimertinib. The L858R mutation associated with L858R-K860I and L858R-L861F doublet mutations could be detected using Idylla but not cobas EGFR tests. Using next-generation sequencing analysis should be considered after initial negative reports from the cobas test, because patients with L858R doublet mutations may benefit from EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Lignin, as an abundant natural aromatic biopolymer, has a complex structure and poor solubility in most solvents, making it difficult to achieve high-value applications and becoming the largest "natural waste". In this work, two novel ternary deep eutectic solvents (DESs) consisting of choline chloride (ChCl)/lactic acid (LA) with ethylene glycol (EG) or γ-valerolactone (GVL) were designed for separating lignin from waste wheat straw. Results showed that the delignification efficiency of wheat straw treated with two ternary DESs (ChCl-LA-EG and ChCl-LA-GVL) was twice as high as that treated with ChCl-LA under mild conditions (90 °C, 4 h). The highest delignification efficiency of 83.12% was achieved by ChCl-LA-GVL treatment at 130 °C for 4 h. Moreover, ternary DESs extracted lignin exhibited lower molecular weight, better homogeneity, and remarkably higher antioxidant activities than that extracted from ChCl-LA. Furthermore, ternary DESs extracted lignin had more S units and inhibited the destruction of the lignin substructure at high temperature. Compared with ChCl-LA treatment, cellulose fiber treated with ChCl-LA-EG and ChCl-LA-GVL had less active sites, lower total surface energy, and more alkaline (electron donor) adsorption sites on cellulose fiber surface. Theory calculations further confirm that the addition of EG and GVL changes the hydrogen bond strength and electrostatic potential of the ChCl-LA system, thus promoting the separation of lignin. These results provide new insights for understanding the mechanism of lignin dissolution in DESs and for the design of advanced DESs for lignocellulosic biomass separation and valorization. [Display omitted] • Two ternary ChCl-LA-EG and ChCl-LA-GVL DES are designed. • The structural characteristics of DES regenerated lignin are investigated. • The microstructure of fiber after lignin removal is analyzed. • The addition of EG and GV changed the intermolecular interactions of DES. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-β-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR. • The expression of p53 was upregulated in the retina of db/db mice. • Retinal aging in db/db mice was significantly earlier than that in normal C57BL/6J mice. • Inhibiting p53 alleviates endothelial cell senescence. • p53 promotes the ubiquitination and degradation of FoxO3a through UBE2L6 and aggravates endothelial cell senescence. [ABSTRACT FROM AUTHOR]

The ethanol extracts of propolis-egg white protein (EEP-EWP) composite gels were prepared through thermal induction to investigate the impact of ethanol extract of propolis (EEP) addition on the physicochemical properties, structural characteristics, chemical forces and rheological properties of the composite gel. The results demonstrated that the composite gel containing 6% EEP exhibited a more compact and smooth microstructure, along with remarkable hardness (414.05 g) and water holding capacity (96.5%). Compared to the EWP gel, the hardness increased by 2.65 times and water holding capacity increased by 17.45%. Upon adding EEP, both energy storage modulus G′ and apparent viscosity initially increased before decreasing; β-sheet and β-turn content showed an initial increase followed by a decrease; however, α-helix and random coil content decreased initially before increasing again. Notably during gel formation, there was a significant increase in electrostatic interactions, hydrophobic groups, and disulfide bonds with subsequent decrease as EEP addition amounts increased (p < 0.05). This study expands the application range of propolis in novel gels while facilitating their development and utilization in low-fat or innovative functional products. [Display omitted] • Ethanol extract of propolis-egg white protein composite gel were prepared by thermal induction. • The composite gel with 6% ethanol extract of propolis had the best gel performance. • Ethanol extract of propolis can enhance electrostatic actions, hydrophobic bonds and disulfide bonds between egg white protein molecules. • Ethanolic extract of propolis can increase the β-sheets of egg white protein molecules while reducing random curls. [ABSTRACT FROM AUTHOR]

Direct air capture (DAC) technology plays a crucial role in mitigating the effects of global warming by capturing carbon dioxide (CO 2) directly from the atmosphere. A significant technical challenge for DAC is its high thermal energy consumption, which results in an unacceptable overall cost (600 $ t CO 2 – 1). The combination of a high-temperature heat pump (HTHP) and DAC system offers a substantial reduction in thermal energy consumption, decreased reliance on renewable energy sources, and enhanced DAC system flexibility. This study presents three distinct thermal integration strategies that combine an HTHP with solid adsorbent-based DAC and verifies their effectiveness in reducing energy consumption and CO 2 emissions compared to a traditional DAC system. Among them, the deeply integrated DAC-HTHP system (I-DAC) exploits low-grade adsorption heat and waste heat, providing direct heating and cooling energy to the DAC system via refrigerant condensation and evaporation processes. Simulation results indicate that the I-DAC system achieves an extremely low operating energy consumption of 2.77 GJ t CO 2 – 1 , representing a 69.5% reduction than traditional DAC under the same conditions. Consequently, the I-DAC offers a cost-effective (32.0–46.2 $ t CO 2 – 1) negative emission solution. We also demonstrate that the I-DAC is promising for wide application in cities to recycle waste heat and remove CO 2 from the air. The comprehensive implementation of the I-DAC in 105 cities could yield a net annual productivity of 980 MtCO 2. • Proposed a deeply thermal integrated DAC system (I-DAC) with waste heat recovery heat pump. • I-DAC achieved a 69.5% reduction in specific energy consumption compared to base-DAC. • I-DAC offers a cost-effective and scalable negative emission solution for climate change mitigation. • Successful implementation of I-DAC in 105 cities could yield a net annual capture capacity of 980 MtCO 2 by 2050. • Highlights the potential of I-DAC to recycle waste heat and remove CO 2 from the air, with policy implications [ABSTRACT FROM AUTHOR]

Preparation of novel ternary photocatalysts with heterojunction is a resultful and valid method for H 2 production from water splitting reaction under visible light irradiation at present. Herein, a NH 2 -MIL-125(Ti)/CdIn 2 S 4 semiconductor material was designed by a hydrothermal method and Pd added into NH 2 -MIL-125 to improve photocatalytic activity. The Pd/NH 2 -MIL-125(Ti)/CdIn 2 S 4 material presented the highest photocatalytic H 2 rate of 4.60 mmol·g−1·h−1, which was 31 times higher than that of pristine CdIn 2 S 4 and 16 times higher than that of pure NH 2 -MIL-125. The enhanced photocatalytic performance can be attributed to the intimate interfacial contact between NH 2 -MIL-125(Ti) and CdIn 2 S 4 , accelerating the charge transfer, as well as loaded Pd nanoparticles, which increasing the light-absorbing capacity and inhibiting electron hole recombination of NH 2 -MIL-125(Ti)/CdIn 2 S 4. The Pd/NH 2 -MIL-125(Ti)/CdIn 2 S 4 was acquired successfully and the construction of heterojunction, NH 2 -MIL-125(Ti)/CdIn 2 S 4 , have been proved by various representational means. This work provides a feasible application that construct heterogeneous nodes and ternary composite materials by hydrothermal for H 2 production from water splitting reaction under visible light irradiation. • A novel method for the construction of ternary structure composites is proposed. • Pd acts as electron traps to inhibit electron hole recombination. • The unique ternary structure expands the absorption range of visible light. • The ternary structure contributes to the efficient hydrogen production under visible light. [ABSTRACT FROM AUTHOR]

The issues related to microstructure and its effects on functional properties of electroceramics become increasingly prominent with the progressive downscaling of electronics. In this study, temperature-dependent dielectric and impedance data of BaTiO 3 (BT), Sr-doped BT (BST) and layer-structured BaBi 4 Ti 4 O 15 (BBTO) ceramics are systematically investigated to reveal the effects of doping and perovskite layering on the dielectric relaxation and conduction processes at high temperatures. By using complex impedance spectroscopy, it is demonstrated that the ceramics are electrically heterogeneous structures displaying a non-ideal Debye-like behavior at high temperatures. Using a suitable equivalent circuit model, the impedance diagrams at different temperatures are simulated and the refined values of macroscopic resistance and capacitance are used for the identification and characterization of particular microstructural regions (grains, grain boundaries, interfaces, etc.). The approach of combining the impedance, electric modulus and permittivity formalisms is demonstrated to be effective in explaining the peculiarities of the electrical charge transport mechanism and relaxation in the grains, grain boundaries and interface layers of the ceramics. • Electrical response of ferroelectric ceramics is described by the impedance, electric modulus and permittivity formalisms. • Band transport dominates long-range (non-localized) DC conduction in grains and grain boundaries. • Short-range transport occurs predominantly at interfaces through thermally activated hopping. • Sr-doping and perovskite layering reduce activation energies for the band conduction and dielectric relaxation. • Hopping mechanism is responsible for AC conductivity and low-frequency Maxwell-Wagner-type relaxation. [ABSTRACT FROM AUTHOR]

In this paper, we developed a novel composites of alginate hydrogel and hollow silica microspheres microsphere (SA@SiO 2) for drug delivery, in which a protective silicon shell encloses the alginate hydrogel to form a core–shell structure. Research results showed that the drug delivery system has broad-spectrum controlled-release performance for different types of molecules, and the controlled-release time can exceed 40 h. [Display omitted] • A novel kind of alginate hydrogel microspheres with a protective silicon shell were prepared. • This composite core–shell hydrogel microspheres (SA@SiO 2) showed broad-spectrum controlled-release performance for different types of molecules with satisfied drug roading rate. • The controlled-release time of the SA@SiO 2 composites can exceed 40 h. Sodium alginate hydrogel has been widely used in the field of controlled-release. In this paper, in order to prevent the negative effect of fast degradation and explosive release of pure sodium alginate hydrogel in the drug delivery process, we developed a novel alginate hydrogel supported by hollow silica microsphere for drug delivery. Briefly, the drugs were fused with sodium alginate and the hollow silica microspheres followed by ion crosslinking to form a composite hydrogel microsphere with a core–shell structure (SA@SiO 2). The structure and morphology of the composite hydrogel were characterized by Fourier infrared spectroscopy (FT-IR), thermogravimetric analysis (TG), scanning electron microscope (SEM), transmission electron microscope (TEM) along with fluorescence microscope. On this basis, using three different types of organic compounds (rhodamine B, Indocyanine green and salicylic acid) as model molecules, the controlled-release performance of the SA@SiO 2 microspheres were investigated in detail. The research results show that the drug delivery system has broad-spectrum controlled-release performance for different types of molecules, and the controlled-release time can exceed 40 h. At the same time, the pH- responsive property of the sodium alginate hydrogel endows the delivery system with a certain targeting function. This study provides a new strategy for constructing an efficient targeted drug controlled-release system. [ABSTRACT FROM AUTHOR]

• An online-offline coupled rumor propagation model incorporating the higher-order group interactions and the social adaptation is proposed. • Both the online and offline network layers integrate the higher-order group interactions via simplicial complexes. • Individuals' macroscopic attitudes toward rumors are represented as superposition states of positive and negative attitudes via quantum cellular automata. • Mean-field theory is used to derive the basic regeneration number, the rumor-free equilibrium, and the rumor-prevalence equilibrium. With the development of the Internet, the influence of rumors is more widespread. Studying the propagation law of rumors is an effective way to reduce the damage of rumors. We therefore propose a new two-layer rumor propagation model, which simultaneously introduces simplicial complexes into the online and offline network layers and considers the social adaptation of individuals. We derive the basic regeneration number, the rumor-free equilibrium, and the rumor-prevalence equilibrium using mean-field theory, and verify their accuracy through extensive computer simulations. The results show that the inclusion of higher-order interactions in both layers leads to richer dynamical phenomena. Specifically, higher-order interactions lead to bistable states, discontinuous transitions, and the coexistence of multiple rumor-prevalence equilibria, and increasing the infection parameter within a certain range reduces the outbreak size of rumors in another layer. In addition, a higher speed and degree of social adaptation, a stronger strength of coupled propagation enhancement effect, and a weaker strength of coupled recovery enhancement effect significantly increase the spread speed and size of rumors. Finally, we present and analyze two intervention strategies: improving public media literacy and building a truth space. We find that both intervention strategies can reduce the spread size and speed of rumors, but the synergy of two intervention strategies is more effective. [ABSTRACT FROM AUTHOR]

In this study, two proteins with antioxidant activity, WLZP1F1G2 and WLZP1F1G3, were firstly isolated from the shell of Arca inflata, one source of Walengzi, a traditional Chinese medicine. This study used a green, traditional decoction extraction method coupled with column chromatography technique for protein extraction and purification. The protein types were determined by comparing their amino acid sequences from the transcriptome database of A. inflata. Then, a number of techniques including UV, FT-IR, circular dichroism, scanning electron microscopy and atomic force microscopy were used to characterize the structural properties of WLZP1F1G2 and WLZP1F1G3. WLZP1F1G2 was a type of ferritin while WLZP1F1G3 was a type of promyosin. They both shown good temperature stability and pH tolerance. WLZP1F1G2 and WLZP1F1G3 were tested for their antioxidant capacity in both in vitro and in vivo experiments. They all had good ability to clear ABTS, DPPH, and oxygen free radicals. And they all showed good Fe2+ chelating properties. Additionally, in vivo tests on wild-type Caenorhabditis elegans revealed that WLZP1F1G2 and WLZP1F1G3 both had effective anti-aging properties. These results raised the possibility that WLZP1F1G2 and WLZP1F1G3 could function as food preservatives and antioxidants. [Display omitted] • Proteins were extracted from Walengzi using a green and environmental friendly method. • Amino acid sequences of WLZP1F1G2 and WLZP1F1G3 were identified by LC-MS/MS. • WLZP1F1G2 and WLZP1F1G3 could clear free radicals related to aging in vivo. • WLZP1F1G2 and WLZP1F1G3 had certain anti-aging activity in Caenorhabditis elegans. • WLZP1F1G2 and WLZP1F1G3 were promising antioxidants. [ABSTRACT FROM AUTHOR]

Coral bleaching events are becoming increasingly common worldwide, causing widespread coral mortality. However, not all colonies within the same coral taxa show sensitivity to bleaching events, and the current understanding of the metabolic mechanisms underlying thermal bleaching in corals remains limited. We used untargeted metabolomics to analyze the biochemical processes involved in the survival of two bleaching phenotypes of the common corals Pavona decussata and Acropora pruinosa , during a severe bleaching event in the northern South China Sea in 2020. During thermal bleaching, P. decussata and A. pruinosa significantly accumulated energy products such as succinate and EPA, antioxidants and inflammatory markers, and reduced energy storage substances like glutamate and thymidine. KEGG analysis revealed enrichment of energy production pathways such as ABC transporters, nucleotide metabolism and lipid metabolism, suggesting the occurrence of oxidative stress and energy metabolism disorders in bleached corals. Notably, heat stress exerted distinct effects on metabolic pathways in the two coral species, e.g., P. decussata activating carbohydrate metabolism pathways like glycolysis and the TCA cycle, along with amino acid metabolism pathways, whereas A. pruinosa significantly altered the content of multiple small peptides affected amino acid metabolism. Furthermore, the osmoregulatory potential of corals correlates with their ability to survive in heat-stress environments in the wild. This study provides valuable insights into the metabolic mechanisms linked to thermal tolerance in reef-building corals, contributes to the understanding of corals' adaptive potential to heat stress induced by global warming and lays the foundation for developing targeted conservation strategies in the future. • Metabolic profiles differed between unbleached and bleached corals. • Bleached corals consumed energy reserves like nucleotides and lipids. • Coral bleaching led to oxidative damage and immune response activation. • Osmotic substances were crucial in coral response to heat stress. • New insights into metabolic response of reef-building corals to heat stress. [ABSTRACT FROM AUTHOR]

In this hydrological study, we developed a Transformer-based model to forecast urban river discharges and predict flood peaks, crucial for flood mitigation in urban areas prone to inundation. Utilizing daily precipitation data from 63 meteorological stations and flow data from hydrological stations, we established a correlation using the Random Forest method to determine the lag time between precipitation and flow. The model, enhanced with alternative loss functions – Weighted MSE Loss (WMSE), Huber Loss (Hloss), and Quantile Loss (Qloss) – instead of traditional Mean Squared Error (MSE), aims to project daily flow rates for seven days. Our findings indicate that Hloss significantly reduces absolute errors in peak value predictions, while WMSE improves linear correlation in forecasting. The accuracy remains stable for the initial four days, with a decrease from the fifth day. This approach, integrating diverse loss functions, presents a novel method for accurately predicting river discharges, offering vital insights for proactive flood management. • Unique loss functions tailored to amplify peak flow event prediction accuracy. • Novel integration of DSW preprocessing with Transformer for hydrology forecasting. • Lag time optimization using Random Forest, enhancing input data synchronization. • Advanced seven-day flow forecasting leveraging data from 63 meteorological stations. • Dynamic model update strategy proposed for long-term hydrological shifts. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatases PTPN2 and PTPN1 (also known as PTP1B) have been implicated in a number of intracellular signaling pathways of immune cells. The inhibition of PTPN2 and PTPN1 has emerged as an attractive approach to sensitize T cell anti-tumor immunity. Two small molecule inhibitors have been entered the clinic. Here we report the design and development of compound 4 , a novel small molecule PTPN2/N1 inhibitor demonstrating nanomolar inhibitory potency, good in vivo oral bioavailability, and robust in vivo antitumor efficacy. [Display omitted] • PTPN2 and PTPN1 are crucial modulators of immune oncology that have been shown to promote tumorigenesis by attenuating tumor-directed immunity. • The development of PTPN2/PTPN1 inhibitors has been slowed down by the challenges of unfavorable pharmacokinetics due to the highly cationic active site and the relative shallow nature of the protein surface. • SAR optimization of ABBV-CLS-484 resulted in a novel PTPN2/PTPN1 small molecule inhibitor with nanomolar potency and improved oral bioavailability across different species. [ABSTRACT FROM AUTHOR]

[Display omitted] • A one-dimensional whole-loop CFB dynamic model was established with the flow properties. • The model explicitly depicts the solids throughput behavior at the cyclone and standpipe. • Factors affecting the dynamic characteristics of CFB boiler under load regulation were discussed. • An optimization on a 135 MW CFB boiler demonstrated a maximum load ramp rate of about 4 %/min. CFB boilers face an increasing significance for load change rate in China. However, there is currently a lack of mechanistic understanding on limitation on fast peak shaving. Based on the mass and energy balance in the full loop, this paper conducts a dynamic model to describe the coupling effect of gas–solid two-phase flow, heat transfer, and combustion processes under load regulation conditions. In particular, the material throughput pattern of cyclone and standpipe are systemically described. Finally, the model was validated by field test data in a 135 MW commercial CFB boiler. On this basis, the impact of factors such as the draining ash strategy and adding/discharging circulating ash on the load regulation characteristics of the boiler were deeply explored, and a comprehensive optimization solution was proposed. The results showed that the boiler's ramp could be maximized to about 4 %/min after adopting this solution. [ABSTRACT FROM AUTHOR]