Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption.

The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na+ reabsorption kinetics by SGLT1/2. For area under the plasma concentration-time curve, maximum plasma concentration, and cumulative EMP excretion in urine, the predicted values fell within a range of 0.5-2.0 when compared to observed data. Additionally, the simulated UGE data also matched well with the clinical data, further validating the accuracy of the model. According to the simulations, SGLT1 and SGLT2 contributed approximately 13% and 87%, respectively, to RGR in the absence of EMP. However, in the presence of EMP at doses of 2.5 and 10 mg, the contribution of SGLT1 to RGR significantly increased to approximately 76%-82% and 89%-93%, respectively, in patients with type 2 diabetes mellitus. Furthermore, the model supported the understanding that the compensatory effect of SGLT1 is the underlying mechanism behind the moderate inhibition observed in total RGR. The PBPK-UGE model has the capability to accurately predict the PK and UGE time profiles in humans. Furthermore, it provides a comprehensive analysis of the specific contributions of SGLT1 and SGLT2 to RGR in the presence or absence of EMP.

Fluid-structure interaction study on the causes of mending material damage after sigmoid sinus wall reconstruction.

BACKGROUND AND OBJECTIVE: Sigmoid Sinus (SS) Wall Reconstruction (SSWR) is the mainstream treatment for pulsatile tinnitus (PT), but it has a high risk of recurrence. The damage of mending material is the key cause of recurrence, and its hemodynamic mechanism is still unclear. The purpose of this study was to investigate the hemodynamic causes of mending material breakage. METHODS: In this study, six patient-specific geometric models were reconstructed based on the data of the computed tomography angiography (CTA). The transient fluid-structure coupling method was performed to clarify the hemodynamic state of sigmoid sinus and the biomechanical state of the mending material. The distribution of stress and displacement and the flow pattern were calculated to evaluate the hemodynamic and biomechanics difference at the mending material area. RESULTS: The area of blood flow impact in some patients (2/6) was consistent with the damaged location of the mending material. The average stress (6/6) and average displacement (6/6) of damaged mending material were higher than those of complete mending material. All (6/6) patients showed that the high-stress and high-displacement proportion of the DMM region was higher than that of the CMM region. Moreover, the average stress fluctuation (6/6) and average displacement (6/6) fluctuation degree of damaged mending material is larger than that of complete mending material. CONCLUSIONS: The impact of blood and the uneven stress and displacement fluctuation of the mending material may be the causes of mending material damage. High stress and high displacement might be the key causes of the mending material damage.

Hemodynamic assessments of unilateral pulsatile tinnitus with jugular bulb wall dehiscence using 4D flow magnetic resonance imaging.

Background: Pulsatile tinnitus (PT) is a type of tinnitus characterized by a rhythmic sound that is synchronous with the heartbeat. One of the possible causes of PT is the jugular bulb wall dehiscence (JBWD). However, the hemodynamics of this condition are not well understood. To elucidate this issue, the present study aimed to compare the blood flow of PT patients with JBWD, PT patients with sigmoid sinus wall dehiscence (SSWD), and volunteers. Methods: A retrospective case-control study was conducted, which enrolled patients with unilateral PT who had undergone both computed tomography angiography (CTA) and four-dimensional (4D) flow magnetic resonance imaging (MRI) examinations at the Department of Otolaryngology-Head and Neck Surgery of Beijing Friendship Hospital affiliated to Capital Medical University between January 2019 and July 2023. After excluding the possible causes of PT, the patients were divided into the JBWD group and SSWD group according to the presence or absence of JBWD and/or SSWD. Finally, 11 female unilateral PT patients with JBWD (JBWD group, 11sides), 22 age- and side-matched female patients with SSWD (SSWD group, 22 sides), and 22 age-matched female volunteers (volunteer group, 36 sides) were enrolled. The area, maximum voxel velocity (Vv-max), maximum velocity (Vmax), average velocity (Vavg), and average blood flow rate (Q) were measured in the transverse sinuses (TSs), sigmoid sinuses (SSs), and jugular bulb (JB). The vortex flow pattern was also assessed. Fisher's exact test and Bonferroni correction were used for count data, with P<0.017 was considered statistically significant. Shapiro-Wilk test, one-way analysis of variance (ANOVA), Kruskal-Wallis H test, paired-samples t-test, and Wilcoxon matched-pairs signed-rank test were used for continuous variables depending on the distribution and variance of the data. The P<0.05 and corrected P<0.05 was considered statistically significant. Results: The area and Q of TSs and JB on the symptomatic side were higher than those on the contralateral side in the JBWD group (TSs: Parea=0.004, Pflow=0.002; JB: Parea=0.034, Pflow=0.018). The area was larger and velocities were lower in the JBWD group at the TSs than the SSWD group (Parea=0.004, PVv-max=0.009, PVmax=0.021, PVavg=0.026), and velocities were higher at the distal TSs and SSs than the volunteer group (TSs: PVv-max=0.042, PVmax=0.046, PVavg=0.040; SSs: PVv-max=0.007, PVmax=0.001, PVavg=0.001). At the JB, the JBWD group also had higher Vv-max than the volunteer group (P=0.012). The occurrence rate of vortex at JB in the JBWD group was higher than both the JBWD and the volunteer groups (P=0.002<0.017 and P=0.009<0.017, respectively). Conclusions: The blood flow of the intracranial venous sinus was different between the JBWD group and the SSWD group. The indicators that can differentiate include Vv-max, Vmax, Vavg, vortex, and TSs cross-sectional area.

Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.

Comparative study of the sensitivity of ultra-high-resolution CT and high-resolution CT in the diagnosis of isolated fenestral otosclerosis.

PURPOSE: To compare the diagnostic sensitivity of ultra-high-resolution computed tomography (U-HRCT) and HRCT in isolated fenestral otosclerosis (IFO). METHODS: A retrospective analysis was conducted on 85 patients (85 ears) diagnosed with IFO between October 2020 and November 2022. U-HRCT (0.1 mm thickness) was performed for 20 ears, HRCT (0.67 mm thickness) for 45 ears, and both for 20 ears. The images were evaluated by general radiologists and neuroradiologists who were blinded to the diagnosis and surgical information. The diagnostic sensitivity of U-HRCT and HRCT for detecting IFO was compared between the two groups. RESULTS: Excellent inter-observer agreement existed between the two neuroradiologists (Cohen's κ coefficient 0.806, 95% CI 0.692-0.920), with good agreement between the general radiologists (Cohen's κ coefficient 0.680, 95% CI 0.417-0.943). U-HRCT had a sensitivity of 100% (40/40 ears) for neuroradiologists and 87.5% (35/40 ears) for general radiologists, significantly higher than HRCT (89.2% [58/65 ears] for neuroradiologists; 41.5% [27/65 ears] for general radiologists) (p = 0.042, p' < 0.000). General radiologists' sensitivity with HRCT was significantly lower compared to neuroradiologists (p < 0.000), but no significant difference was observed when general radiologists switched to U-HRCT (p = 0.152). Among the 20 ears that underwent both examinations, U-HRCT detected lesions smaller than 1 mm in 5 ears, whereas HRCT's sensitivity for neuroradiologists was 40% (2/5 ears), significantly lower than for lesions larger than 1 mm (93.3%, 14/15 ears, p = 0.032). CONCLUSION: U-HRCT exhibits higher sensitivity than HRCT in diagnosing IFO, suggesting its potential as a screening tool for suspected otosclerosis patients. CRITICAL RELEVANCE STATEMENT: Ultra-high-resolution computed tomography has the potential to become a screening tool in patients with suspected otosclerosis and to bridge the diagnostic accuracy gap between general radiologists and neuroradiologists. KEY POINTS: • U-HRCT exhibits higher sensitivity than HRCT in the diagnosis of IFO. • U-HRCT has a significant advantage in the detection of less than 1 mm IFO. • U-HRCT has the potential to be used for screening of patients with suspected otosclerosis.

Room-Temperature Magnetic Phase Transition in an Electrically Tuned van der Waals Ferromagnet.

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr_{1.2}Te_{2} observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8×10^{21} cm^{-3}. We observed nonmonotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr_{1.2}Te_{2}. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr_{1.2}Te_{2} is a significant step towards practical spintronic devices.

Molecular pathway of mitochondrial preprotein import through the TOM-TIM23 supercomplex.

Over half of mitochondrial proteins are imported from the cytosol via the pre-sequence pathway, controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. The mechanisms through which proteins are translocated via the TOM and TIM23 complexes remain unclear. Here we report the assembly of the active TOM-TIM23 supercomplex of Saccharomyces cerevisiae with translocating polypeptide substrates. Electron cryo-microscopy analyses reveal that the polypeptide substrates pass the TOM complex through the center of a Tom40 subunit, interacting with a glutamine-rich region. Structural and biochemical analyses show that the TIM23 complex contains a heterotrimer of the subunits Tim23, Tim17 and Mgr2. The polypeptide substrates are shielded from lipids by Mgr2 and Tim17, which creates a translocation pathway characterized by a negatively charged entrance and a central hydrophobic region. These findings reveal an unexpected pre-sequence pathway through the TOM-TIM23 supercomplex spanning the double membranes of mitochondria.

Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment.

This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model to predict the maximum plasma concentration (Cmax) and trough concentration (Ctrough) at steady-state of olaparib (OLA) in Caucasian, Japanese and Chinese. Furthermore, the PBPK model was combined with mean and 95% confidence interval to predict optimal dosing regimens of OLA when co-administered with CYP3A4 modulators and administered to patients with hepatic/renal impairment. The dosing regimens were determined based on safety and efficacy PK threshold Cmax (< 12,500 ng/mL) and Ctrough (772-2500 ng/mL). The population PBPK model for OLA was successfully developed and validated, demonstrating good consistency with clinically observed data. The ratios of predicted to observed values for Cmax and Ctrough fell within the range of 0.5 to 2.0. When OLA was co-administered with a strong or moderate CYP3A4 inhibitor, the recommended dosing regimens should be reduced to 100 mg BID and 150 mg BID, respectively. Additionally, the PBPK model also suggested that OLA could be not recommended with a strong or moderate CYP3A4 inducer. For patients with moderate hepatic and renal impairment, the dosing regimens of OLA were recommended to be reduced to 200 mg BID and 150 mg BID, respectively. In cases of severe hepatic and renal impairment, the PBPK model suggested a dosing regimen of 100 mg BID for OLA. Overall, this present PBPK model can determine the optimal dosing regimens for various clinical scenarios involving OLA.

Electric-field control of reversible electronic and magnetic transitions in two-dimensional oxide monolayer magnets.

Atomically thin oxide magnetic materials are highly desirable due to the promising potential to integrate two-dimensional (2D) magnets into next-generation spintronics. Therefore, 2D oxide magnetism is expected to be effectively tuned by the magnetic and electrical fields, holding prospective for future low-dissipation electronic devices. However, the electric-field control of 2D oxide monolayer magnetism has rarely been reported. Here, we present the realization of 2D monolayer magnetism in oxide (SrRuO3)1/(SrTiO3)N (N = 1, 3) superlattices that shows an efficient and reversible phase transition through electric-field controlled proton (H+) evolution. By using ionic liquid gating to modulate the proton concentration in (SrRuO3)1/(SrTiO3)1 superlattice, an electric-field induced metal-insulator transition was observed, along with gradually suppressed magnetic ordering and modulated magnetic anisotropy. Theoretical analysis reveals that proton intercalation plays a crucial role in both electronic and magnetic phase transitions. Strikingly, SrTiO3 layers can act as a proton sieve, which have a significant influence on proton evolution. Our work stimulates the tuning functionality of 2D oxide monolayer magnetism by voltage control, providing potential for future energy-efficient electronics.

Cryo-EM and femtosecond spectroscopic studies provide mechanistic insight into the energy transfer in CpcL-phycobilisomes.

Phycobilisomes (PBS) are the major light harvesting complexes of photosynthesis in the cyanobacteria and red algae. CpcL-PBS is a type of small PBS in cyanobacteria that transfers energy directly to photosystem I without the core structure. Here we report the cryo-EM structure of the CpcL-PBS from the cyanobacterium Synechocystis sp. PCC 6803 at 2.6-Å resolution. The structure shows the CpcD domain of ferredoxin: NADP+ oxidoreductase is located at the distal end of CpcL-PBS, responsible for its attachment to PBS. With the evidence of ultrafast transient absorption and fluorescence spectroscopy, the roles of individual bilins in energy transfer are revealed. The bilin 1Iß822 located near photosystem I has an enhanced planarity and is the red-bilin responsible for the direct energy transfer to photosystem I.

Prediction for Plasma Trough Concentration and Optimal Dosing of Imatinib under Multiple Clinical Situations Using Physiologically Based Pharmacokinetic Modeling.

(1) Purpose: This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the trough concentration (C trough) of imatinib (IMA) at steady state in patients and to explore the role of free concentration (f up), α1-acid glycoprotein (AGP) level, and organic cation transporter 1 (OCT1) activity/expression in clinical efficacy. (2) Methods: The population PBPK model was built using physicochemical and biochemical properties, metabolizing and transporting kinetics, tissue distribution, and human physiological parameters. (3) Results: The PBPK model successfully predicted the C trough of IMA administered alone in chronic phase (CP) and accelerated phase (AP) patients, the C trough of IMA co-administered with six modulators, and C trough in CP patients with hepatic impairment. Most of the ratios between predicted and observed data are within 0.70-1.30. Additionally, the recommendations for dosing adjustments for IMA have been given under multiple clinical uses. The sensitivity analysis showed that exploring the f up and AGP level had a significant influence on the plasma C trough of IMA. Meanwhile, the simulations also revealed that OCT1 activity and expression had a significant impact on the intracellular C trough of IMA. (4) Conclusion: The current PBPK model can accurately predict the IMA C trough and provide appropriate dosing adjustment recommendations in a variety of clinical situations.

Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization.

The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space (IMS) and functions to promote the solubilization of various mitochondrial proteins. Loss-of-function CLPB mutations are associated with a few human diseases with neutropenia and neurological disorders. Unlike canonical AAA+ proteins, CLPB contains a unique ankyrin repeat domain (ANK) at its N-terminus. How CLPB functions as a disaggregase and the role of its ANK domain are currently unclear. Herein, we report a comprehensive structural characterization of human CLPB in both the apo- and substrate-bound states. CLPB assembles into homo-tetradecamers in apo-state and is remodeled into homo-dodecamers upon substrate binding. Conserved pore-loops (PLs) on the ATPase domains form a spiral staircase to grip and translocate the substrate in a step-size of 2 amino acid residues. The ANK domain is not only responsible for maintaining the higher-order assembly but also essential for the disaggregase activity. Interactome analysis suggests that the ANK domain may directly interact with a variety of mitochondrial substrates. These results reveal unique properties of CLPB as a general disaggregase in mitochondria and highlight its potential as a target for the treatment of various mitochondria-related diseases.

Rapid screening and in vivo target occupancy quantitative evaluation of xanthine oxidase inhibitors based on drug-target binding kinetics research strategy: A case study of Chrysanthemum morifolium Ramat.

Chrysanthemum morifolium Ramat. is a kind of food and drug dual-use traditional Chinese medicine possessing multiple pharmacological and biochemical benefits. In our study, a rapid and high-throughput method based on Surface plasmon resonance (SPR) biosensor technology was developed and verified for screening potential xanthine oxidase (XOD) inhibitors exemplarily in the Chrysanthemum morifolium Ramat. Coupled with ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS), 14 XOD-binders were identified. In the SPR-based biosensor and molecular docking analysis, most compounds exhibited a strong affinity and binding kinetic property (association rate constant, Kon and dissociation rate constant, Koff) for XOD and could be regarded as potential inhibitors. More importantly, to further accurately assess target occupancy of candidate compounds in vivo, a mathematical model was established and verified involving three crucial intrinsic kinetic processes (Pharmacokinetics, Binding kinetic and Target kinetic). Overall, the proposed screening and assessment strategy could be proved an effective theoretical basis for further pharmacodynamic evaluation.

CT evaluation of unilateral pulsatile tinnitus with jugular bulb wall dehiscence.

OBJECTIVES: To investigate the imaging features of unilateral pulsatile tinnitus (PT) with jugular bulb wall dehiscence (JBWD). METHODS: Computerized tomography angiography images of unilateral PT patients were reviewed between 2019 and 2021. Thirty-one symptomatic JBWD patients without sigmoid sinus wall dehiscence (SSWD) were included. Thirty-eight patients with SSWD were used as the control group. The prevalence of JBWD was calculated. The area and height of the jugular bulb, the extent of dehiscence, the presence of jugular bulb diverticulum, posterior condylar emissary vein (PCEV), oblique occipital sinus (OOS), venous outflow laterality (VOL), the degree of transverse sinus stenosis (TSS), and the pituitary height to sella turcica ratio were compared between the two groups. RESULTS: The prevalence of JBWD was 12.1%, and JBWD was established as a causative diagnosis in 5.0% of unilateral PT patients. There were no statistical differences in the gender, symptomatic side, or VOL between the two groups. The area of the jugular bulb was larger and the height was higher (parea < 0.001, pheight = 0.005). The prevalence of jugular bulb diverticulum was higher in the JBWD group (p = 0.002). The degree of symptomatic TSS was less severe (p < 0.001), and the prevalence of bilateral TSS was lower in the JBWD group (p < 0.001). The pituitary height to sella turcica ratio was greater (p = 0.004), the prevalence of PCEV (p = 0.014) was lower, and OOS (p = 0.015) was greater in the JBWD group. CONCLUSIONS: The correlating factors of PT with JBWD and PT with SSWD are significantly different. These findings can further facilitate early and efficient PT treatment. KEY POINTS: • The incidence of jugular bulb dehiscence (JBWD) accounted for approximately 12.1% in pulsatile tinnitus (PT) patients, and JBWD was established as a causative diagnosis in 5.0% of PT patients. • PT required large blood flows and abnormal flow patterns, whether in JBWD or sigmoid sinus wall dehiscence groups. • JBWD causing PT has some unique characteristic findings on CT.

A new method for assessing transverse sinus stenosis with CT venography based on the venous trans-stenotic pressure gradient.

BACKGROUND: Evaluation of the transverse sinus stenosis (TSS) is essential for TSS-related diseases. OBJECTIVE: To investigate a new method for the quantitative assessment of TSS based on the correlation between TSS and trans-stenotic pressure gradient (TPG). METHODS: Patients with unilateral pulsatile tinnitus with or without idiopathic intracranial hypertension were retrospectively included. All patients underwent CT venography and venous manometry and were confirmed to have TSS. The cross-sectional diameter/area of TSS, the poststenotic and prestenotic segments, and the superior sagittal sinus (SSS) were measured. The degree of TSS was calculated by dividing the diameter/area of TSS by the diameter/area of the poststenotic segment (M1/M2), prestenotic segment (M3/M4), and SSS (M5/M6). Partial correlation analysis (controlling for the effect of age, sex, outflow laterality, and contralateral stenosis) was performed to evaluate the correlation between M1-M6 and the TPG. Receiver operating characteristic curve analysis of M1-M6 for diagnosing a significant TPG (≥8 mm Hg) was performed. RESULTS: Ninety-nine patients met the inclusion criteria. The partial correlation coefficients between M1-M6 and the TPG were 0.60, 0.61, 0.43, 0.48, 0.39, and 0.54, respectively. The areas under the curve (AUCs) of M1-M6 for diagnosing a significant TPG were 0.81, 0.86, 0.68, 0.69, 0.64, and 0.72, respectively. The AUC of M2 was significantly larger than that of M3 (P=0.002), M4 (P<0.001), M5 (P=0.001), and M6 (P<0.001). CONCLUSIONS: Quantitatively assessing TSS by taking the ratio of the cross-sectional area of TSS to that of the poststenotic segment might be a more efficient method for predicting the TPG.

Layer-Number-Dependent Magnetism and Anomalous Hall Effect in van der Waals Ferromagnet Fe5GeTe2.

Realization of ferromagnetism in the two-dimensional (2D) van der Waals (vdW) crystals opens up a vital route to understand the magnetic ordering in the 2D limit and to design novel spintronics. Here, we report enriched layer-number-dependent magnetotransport properties in the vdW ferromagnet Fe5GeTe2. By studying the magnetoresistance and anomalous Hall effect (AHE) in nanoflakes with thicknesses down to monolayer, we demonstrate that while the bulk crystals exhibit soft ferromagnetism with an in-plane magnetic anisotropy, hard ferromagnetism develops upon thinning, and a perpendicular easy-axis anisotropy is realized in bilayer flakes, which is accompanied by a pronounced enhancement of AHE because of extrinsic mechanisms. For the monolayer flakes, the hard ferromagnetism is replaced by spin-glass-like behavior, in accordance with the localization effect in the 2D limit. Our results highlight the thickness-based tunability of the magnetotransport properties in the atomically thin vdW magnets that promises engineering of high-performance spintronic devices.

Identification, Screening, and Comprehensive Evaluation of Novel DPP-IV Inhibitory Peptides from the Tilapia Skin Gelatin Hydrolysate Produced Using Ginger Protease.

PURPOSE: Inhibition of dipeptidyl peptidase-IV (DPP-IV) is an effective therapy for treating type II diabetes (T2D) that has been widely applied in clinical practice. We aimed to evaluate the DPP-IV inhibitory properties of ginger protease hydrolysate (GPH) and propose a comprehensive approach to screen and evaluate DPP-IV inhibitors. METHODS: We evaluated the in vitro inhibitory properties of fish skin gelatin hydrolysates produced by five proteases, namely, neutral protease, alkaline protease, bromelain, papain, and ginger protease, toward DPP-IV. We screened the most potent DPP-IV inhibitory peptide (DIP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with in silico analysis. Next, surface plasmon resonance (SPR) technology was innovatively introduced to explore the interactions between DPP-IV and DIP, as well as the IC50. Furthermore, we performed oral administration of DIP in rats to study its in vivo absorption. RESULTS: GPH displayed the highest degree of hydrolysis (20.37%) and DPP-IV inhibitory activity (65.18%). A total of 292 peptides from the GPH were identified using LC-MS/MS combined with de novo sequencing. Gly-Pro-Hyp-Gly-Pro-Pro-Gly-Pro-Gly-Pro (GPXGPPGPGP) was identified as the most potent DPP-IV inhibitory peptide after in silico screening (Peptide Ranker and molecular docking). Then, the in vitro study revealed that GPXGPPGPGP had a high inhibitory effect on DPP-IV (IC50: 1012.3 ± 23.3 µM) and exhibited fast kinetics with rapid binding and dissociation with DPP-IV. In vivo analysis indicated that GPXGPPGPGP was not absorbed intact but partially, in the form of dipeptides and tripeptides. CONCLUSION: Overall, the results suggested that GPH would be a natural functional food for treating T2D and provided new ideas for searching and evaluating potential antidiabetic compounds. The obtained GPXGPPGPGP can be structurally optimized for in-depth evaluation in animal and cellular experiments.