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Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R2) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R2increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

Polymer-derived SiBCN ceramics (PDCs-SiBCN) are promising ultrahigh-temperature ceramics owing to their excellent high-temperature oxidation resistance and electromagnetic wave (EMW)-absorbing capability. In this paper, the microstructure evolutions, the dielectric properties, and EMW absorption properties of Y2O3-doped SiBCN ceramics were investigated. The results reveal that Y2O3acting as a catalyst promotes the formation of SiC, BN(C), and graphite crystalline phases in the SiBCN ceramics, and these crystalline phases are constructed as conduction phases and polarization phases to enhance the EMW-adsorbing properties. The minimum reflection loss (RLmin) reaches −42.22 dB at 15.28 GHz, and the effective absorption bandwidth is 4.72 GHz (13.28–18.00 GHz). In addition, there is only 0.56 wt % mass loss for the Y2O3-doped SiBCN ceramics when they are heated from ambient temperature to 1500 °C in air, indicating that the Y2O3-doped SiBCN ceramics obtain excellent oxidation resistance at high temperature. We believe that rare metal oxidation is beneficial for the growth of crystalline phases in the PDCs, resulting in high EMW-absorbing properties and oxidation resistance. Thus, the research extends a novel method and design strategy for microstructure regulation and property enhancement of PDCs.

An excited-state intramolecular proton transfer-based fluorescent sensor was designed and synthesized for ratiometric sensing of cellular pH viathe protonation/deprotonation of sulfonamide moiety, which can be employed to monitor the intracellular pH fluctuation under oxidative stress.

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development, disease diagnosis, and basic theoretical research. Aminopeptidase N (APN), as a representative tumor biomarker with anti-tumor potential, still lacks a high-precision theranostic probe specifically targeting it. In this study, a novel quaternity design strategy for APN theranostic probe was developed. This proposed strategy utilizes advanced machine learning and molecular dynamics simulations, and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments. Through this strategy, a unique “Off–On” theranostic probe, ABTP-DPTB, was ingeniously constructed to light up APN through fluorescence restoration, relying on conformation-induced effects and solvent restriction. Differ from the common diagnostic probes, the intelligent design with non-substrated linkage makes ABTP-DPTBfor long-term in-situimaging. The fabricated probe was used for detecting and inhibiting APN in various environments, with a better in vitroinhibitory than golden-standard drug bestatin.

The nonstationary roles of regional forcings from alongshore wind stress and sea level pressure (SLP) in driving low‐frequency (interannual‐to‐decadal) sea level variability along the U.S. east coast for the 1959–2020 period are investigated. The role of regional forcings increases with time north of Cape Hatteras particularly during summer when their contributions to the variance of observed summertime coastal sea level anomalies increase by approximately 58%–87% from 1959–1989 to 1990–2020. The enhanced impact of regional forcings in recent decades results from an increase in the Inverted Barometer (IB) effect that act constructively with alongshore wind stress especially during summer, and to a lesser extent for the Gulf of Maine during fall. The summertime North Atlantic Oscillation (NAO) is largely responsible for the increased IB effect, owing to the stronger NAO‐associated low SLP anomalies centered around the Mid‐Atlantic Bight in recent decades compared to earlier decades. Alongshore wind stress and sea level pressure (SLP) are important regional forces in driving low‐frequency (interannual‐to‐decadal) sea level anomalies along the U.S. east coast. The roles of these regional forcings, however, vary with time, season, and region, which can shift the location and change the frequency and intensity of coastal flooding. In this study, we find that regional forcings contribute more to observed sea level variability north of Cape Hatteras in recent decades (1990–2020) compared to earlier decades (1959–1989), particularly during summer. The increased role of regional forcings results from SLP variability via the Inverted Barometer (IB) effect, which exhibits a significant upward trend during summer with lower (higher) SLP raising (suppressing) sea level. The North Atlantic Oscillation (NAO) is largely responsible for the increased role of IB effect because the lower SLP anomalies related to the NAO have become more prominent north of Cape Hatteras in recent decades. Although winter NAO has been shown to be important for affecting the coastal sea level anomalies, it is the summer NAO effect that is enhanced via the IB effect, accounting for the enhanced regional forcing in recent decades. The sea‐level variance explained by regional forcings increases with time north of Cape Hatteras due to the Inverted Barometer effectLower sea level pressure centered around Mid‐Atlantic Bight favors more contributions of the Inverted Barometer effect in recent decadesThe summertime North Atlantic Oscillation is largely responsible for the increased role of the Inverted Barometer effect The sea‐level variance explained by regional forcings increases with time north of Cape Hatteras due to the Inverted Barometer effect Lower sea level pressure centered around Mid‐Atlantic Bight favors more contributions of the Inverted Barometer effect in recent decades The summertime North Atlantic Oscillation is largely responsible for the increased role of the Inverted Barometer effect

A series of Tb3+mono-doped and Ce3+-Tb3+co-doped Sr3Gd2(Si3O9)2phosphors with high thermal stability and quantum yields were successfully prepared via the solid state reaction. The as-prepared Sr3Gd2(Si3O9)2:Tb3+samples showed broad excitation spectrum from 250 to 400 nm and presented characteristic emission transitions 5D4→7FJ(J=6, 5, 4, 3) of Tb3+under 313 nm excitation, which were located at about 488, 541, 584 and 620 nm. The emission intensities of Tb3+rose steadily in Sr3Gd2(Si3O9)2host with the increase of Tb3+concentration even though Gd3+ions were completely replaced by Tb3+ions. The Ce3+ion as a sensitizer could efficiently improve the performance of Tb3+ion. First, with Ce3+co-doping, the excitation spectrum of Tb3+monitored at 541 nm showed a similar band that responds to the violet emission of Ce3+monitored at 416 nm. Second, the quantum yields of Sr3Gd2(Si3O9)2:Tb3+phosphors could be enhanced from 26.6% to 80.2% by co-doping Ce3+. Finally, the co-doping of Ce3+was also effective to improve the thermal stability of Sr3Gd2(Si3O9)2:Tb3+. As the temperature rose to 150 °C, the emission intensity of Tb3+remained at about 83.6% of that measured at room temperature, which was better than the commercial YAG:Ce phosphor in terms of their thermal quenching properties. These results indicated that the as-prepared Sr3Gd2(Si3O9)2:Tb3+,Ce3+samples could be used as green emission phosphors for possible applications in near ultraviolet based WLEDs.

Microwave-absorbing materials adapting to high temperatures and harsh environments are in great demand. Herein, a core–shelled Ti3AlC2@La2Zr2O7(TAC@LZO) composite was designed and fabricated by encapsulating the La2Zr2O7(LZO) thermal insulation ceramic on the surface of highly conductive Ti3AlC2(TAC) via chemical coprecipitation and subsequent heat treatment. The continuous LZO ceramic coating on the surface improved the oxidation resistance of the composite at 600 °C and modulated its dielectric properties. The TAC@LZO composite exhibited an excellent microwave absorption performance within the temperature range of 25–600 °C, minimum reflection loss (RLmin) < −55 dB, and effective absorption bandwidth (EAB, RL < −10 dB) of 4 GHz. This work presents an effective approach for developing stable high-temperature microwave absorbers from thermal insulation ceramics.

Global mean sea level (GMSL) has been rising since the last century, posing a serious challenge for the coastal areas. A variety of regression models have been utilized for determining GMSL rise over the past one hundred years, resulting in a large spread of sea level rise rates and multidecadal variations. In this study, we develop a new nonparametric noise model that is data‐dependent and considers overfitting due to regression. The noise model is used to determine whether one regression model has significantly better skill than others over the period 1900–2010. The choices of background noise and GMSL reconstruction influence whether two sea level models can be statistically distinguished. With our new nonparametric noise spectra, the differences of model skills in explaining sea level variance are significant only in 34% of model comparisons. However, stepwise trends with three inflection points are significantly more skillful than the linear, quadratic, or exponential trend for most GMSL reconstructions, suggesting the importance of multidecadal variability of sea level rise in the twentieth century. Nevertheless, stepwise trend models cannot be distinguished from models with a long‐term harmonic oscillation, indicating that the shape of multidecadal variability is not conclusive. The multidecadal variability is also significant in the steric and barystatic sea level contributions and is related to both natural and anthropogenic forcings. GMSL predictions based on regression fits in the twentieth century underestimate the sea level rise rate over the period 2011–2020 because the sea level acceleration in the recent decade (2011–2020) is not well represented. Global mean sea level (GMSL) has been rising since the last century under a warming climate. Understanding both the mean rate and how it is accelerating is important for future management of coastal areas. Various regression models have typically been used to detect the rates of sea level change. As different regression models imply different rates and their consequences for future sea level projections are very different, it is important to distinguish their skills in explaining sea level variance. In addition, different GMSL time series estimated from historical tide‐gauge data also imply different rise rates and long‐term variations. In this study, we develop a new noise model that is data‐dependent and considers the underestimation of noise energy due to regression. Based on the new noise model, comparisons between different regression models indicate that the exact shape of sea level change cannot be determined with any confidence. Nevertheless, the multidecadal variability of sea level rise is significant in the GMSL. Cautions must be taken when regression models are used to predict the GMSL rise because regression fits to the GMSL in the twentieth century underestimate the sea level rise in the recent decade (2011–2020). A new nonparametric noise model is developed to distinguish skills of regression models for global mean sea levelAn accurate estimate of background noise and global mean sea level reconstruction is important for distinguishing sea level modelsThe multidecadal variability of sea level rise is significant, but its exact shape is not conclusive over the period 1900–2010 A new nonparametric noise model is developed to distinguish skills of regression models for global mean sea level An accurate estimate of background noise and global mean sea level reconstruction is important for distinguishing sea level models The multidecadal variability of sea level rise is significant, but its exact shape is not conclusive over the period 1900–2010

Earlier studies in the Northeast Pacific (NEP) suggest that the local and remote sea level responses are important for the large‐scale, low‐frequency sea level variability, but the relative importance of the two processes remains unclear. In this study, we develop a novel sea level model driven by wind, buoyancy and eddy forcing to examine their relative roles in the NEP. Based on the new model, a diagnostic equation for sea level that is an alternative to the conventional method of characteristics is formed. The wind, buoyancy and eddy forcing account for the sea level variability in different regions. Sea level variability is primarily controlled by the wind forcing in the central to the northeast of the NEP, by the local buoyancy forcing in the southeast region between 210°E and 230°E, and by the eddy forcing in the southwest of the NEP. In addition, the diagnosis demonstrates that the local sea level response is more important than the remote response over most of the NEP, while the remote sea level response could play an important role in the southwest portion of the NEP. In the Northeast Pacific (NEP), the low‐frequency sea level variability is not only an important component for predicting the future sea level change but also an integrated measure of climate variability over this region. It can respond to the local and remote external forcing. However, the importance of different driving forces and the relative role of the local and remote sea level response in determining the low‐frequency sea level variability are not conclusive. In this study, the sea level variability is diagnosed with a new developed sea level model. Winds, surface heat and freshwater fluxes and intense eddy activities contribute to the sea level variability in different regions. Sea level variability is primarily driven by the winds in the central to the northeast of the NEP, by the local surface heat and freshwater fluxes in the southeast of the NEP, and by the eddy forcing in the southwest of the NEP. Moreover, our results suggest that the local sea level response is more important than the remote sea level response over most of the NEP. A new sea level model driven by wind, buoyancy and eddy forcing is proposedWind, buoyancy and eddy forcing account for the sea level variability in different regions of the Northeast PacificThe local sea level response is more important than the remote response over most of the Northeast Pacific except in the southwest A new sea level model driven by wind, buoyancy and eddy forcing is proposed Wind, buoyancy and eddy forcing account for the sea level variability in different regions of the Northeast Pacific The local sea level response is more important than the remote response over most of the Northeast Pacific except in the southwest

A simply way was proposed to prepare solid-phase microextraction (SPME) fiber with cation-exchange functional groups by the thermally initiated radical polymerization of poly(butadiene-maleic acid) (PBMA) copolymer onto a silica capillary. The capacity of the fiber coating could be easily controlled by fabricating successive layers of PBMA. The performance of the fiber combined with ion chromatography was evaluated by choosing Mg2+and Ca2+as model analytes; ~13 and ~51-fold enrichment factors for Mg2+and Ca2+were obtained, respectively.

Numerical circulation modeling and observational studies have been conducted to understand the Loop Current (LC) system behaviors in the Gulf of Mexico (GoM). One of the factors that may influence the LC are upstream eddies from within the Caribbean Sea. By combining satellite altimetry, sea surface salinity and ocean color data, we demonstrate that mesoscale eddies from the western tropical Atlantic Ocean can eventually make their way to the Gulf of Mexico and likely affect the LC. In addition, our study shows that freshwater of Amazon and Orinoco River origin trapped within mesoscale eddies can also enter the GoM, potentially affecting the GoM stratification. This study provides insights into understanding variations of the LC system and showcases the roles of mesoscale eddies in connecting the open ocean and regional seas. The Loop Current (LC) is the dominant large‐scale oceanic process in the Gulf of Mexico (GoM). However, the mechanism for variations of the LC system is still unsolved. Here, we show that some mesoscale eddies originated in the tropical Atlantic Ocean can pass through the Caribbean Sea and eventually enter the GoM. These remotely generated eddies could be an important upstream factor affecting the behavior of the LC. Also, freshwater and other materials (e.g., chlorophyll) trapped in the eddies could reach the GoM as well. In addition to advancing the understanding of the LC system, this study provides an explicit example showing eddies can serve as a route connecting regional seas and the open ocean. Some eddies from the Atlantic Ocean can ultimately reach the Gulf of Mexico and likely affect the Loop CurrentFreshwater of Amazon and Orinoco River origin and other materials trapped in eddies could reach the Gulf of MexicoWeakening and strengthening of the long‐propagating eddies are mostly related to the variation of bathymetry Some eddies from the Atlantic Ocean can ultimately reach the Gulf of Mexico and likely affect the Loop Current Freshwater of Amazon and Orinoco River origin and other materials trapped in eddies could reach the Gulf of Mexico Weakening and strengthening of the long‐propagating eddies are mostly related to the variation of bathymetry

Coupling between the surface and near‐bottom currents in the Gulf of Mexico (GoM) has been reported in many case studies. However, geographical variations of this coupling need more examination. In this study, surface geostrophic currents derived from satellite‐observed sea surface height and subsurface currents from a collection of deep ocean moorings are used to examine the surface and bottom coupling in different parts of the GoM. The short‐period (30–90 days) fluctuations generated by the Loop Current (LC) and the LC eddies (LCEs) have a more vertically coherent structure and stronger deep ocean expressions than the long‐period fluctuations (>90 days). In addition, the strength of the coupling is modulated by the long‐period variations of the LC and LCE sheddings. Moreover, the surface and bottom coupling varies geographically. In the LC region, the surface fluctuations along the eastern side of the LC are important in causing the bottom current fluctuations through baroclinic instability under the LC and through traveling topographic Rossby waves (TRWs) north of the LC. In the central deep GoM, the bottom currents are affected by the upper fluctuations of the northern LC through both local baroclinic instability and remote TRW propagation. In the northwestern GoM, the bottom current fluctuations are largely related to the remote surface variability from the west side of the LC by TRWs propagating northwestward. This study will help us better understand mechanisms of the bottom current fluctuations that are important for the dispersal of deep ocean materials and properties. Bottom currents in the Gulf of Mexico (GoM) are important in many ways, such as transporting fish larvae and spilled oil. However, in contrast to surface currents that are easily derived from the abundant satellite observations, our understanding of the bottom currents is very limited. In this study, the relationships between surface and near‐bottom current fluctuations in different parts of the GoM are investigated by combining a collection of historical near‐bottom current measurements and satellite data. The results show that the bottom current variability is linked to local processes such as current instability or remote processes through planetary wave propagation. The surface and bottom coupling is mainly related to the short‐period variability generated along the Loop Current and the Loop Current eddies and has a significant influence on the bottom currents. Although the long‐period fluctuations have weak bottom expressions, they can modulate the strength of the short‐period coupling. Studying the coupling between the surface and bottom current fluctuations in the GoM can advance our understanding of mechanisms of the bottom currents that are important for the deep ocean ecosystem and industrial operations. Surface and bottom currents in the Gulf of Mexico can be coupled locally by baroclinic instability and remotely by topographic Rossby wavesFluctuations generated along the Loop Current have stronger deep ocean expressions at the period of 30–90 days than at longer periodsSurface and bottom coupling in the Gulf of Mexico varies geographically and is modulated by the Loop Current and the Loop Current eddies