Extractions, Contents, Antioxidant Activities and Compositions of Free and Bound Phenols from Kidney Bean Seeds Represented by 'Yikeshu' Cultivar in Cold Region.

To thoroughly understand the profile of phenolic phytochemicals in kidney bean seeds cultivated in a cold region, the extractions, contents, antioxidant activities, compositions of free and bound phenols in the seed coat and cotyledon, and also relevant color attributes, were investigated. The results indicated that ultrasound-assisted extraction was an efficient method for free phenols. The bound phenols in seed coat and cotyledon were released more efficiently by alkali-acid and acid-alkali sequential hydrolysis, respectively. Under the optimized extractions, total phenols (TPC), flavonoids (TFC), and anthocyanins (TAC) ranged in 7.81-32.89 mg GAE/g dw, 3.23-15.65 mg RE/g dw, and 0-0.21 mg CE/g dw in the whole seeds of the five common kidney beans. There was a big difference in phenolic distribution between red and white seeds. From whole seed, the phenols in the four red cultivars mainly existed in free state (78.84%) and seed coat (71.56%), while the phenols in the white 'Sark' divided equally between free (51.18%) and bound (48.82%) states and consisted chiefly in cotyledon (81.58%). The correlation analyses showed that the antioxidant activities were significantly and positively correlated with TPC and TFC. The phenolic attributes were closely associated with the color of the seed coat. Red seeds had higher total contents of phenols than white seeds. TAC had a positively significant correlation with redness. Brightness and yellowness showed a negatively significant correlation with TPC, TFC, and antioxidant capacities, which were necessarily linked with redness degree and spot in red seeds. The spotted red 'Yikeshu' with the most outstanding performance on phenolic attributes was selected to analyze phenolic compounds with UHPLC-QE-MS. Among the 85 identified phenolics, 2 phenolic acids and 10 flavonoids were dominant. The characteristic phenolics in free and bound states were screened in both seed coat and cotyledon, respectively. The available information on the phenolic profile may expand the utilization of kidney beans as a nutritional ingredient in the food industry.

ABLRI: A program for calculating the long-range interaction energy between two monomers in their non-degenerate states.

An accurate description of the long-range (LR) interaction is essential for understanding the collision between cold or ultracold molecules. However, to our best knowledge, there lacks a general approach to construct the intermolecular potential energy surface (IPES) between two arbitrary molecules and/or atoms in the LR region. In this work, we derived analytical expressions of the LR interaction energy, using the multipole expansion of the electrostatic interaction Hamiltonian and the non-degenerate perturbation theory. To make these formulae practical, we also derived the independent Cartesian components of the electrostatic properties, including the multipole moments and polarizabilities, of the monomer for a given symmetry using the properties of these components and the group-theoretical methods. Based on these newly derived formulae, we developed a FORTRAN program, namely ABLRI, which is capable of calculating the interaction energy between two arbitrary monomers both in their non-degenerate electronic ground states at large separations. To test the reliability of this newly developed program, we constructed IPESs for the electronic ground state of H2O-H2 and O2-H systems in the LR region. The interaction energy computed by our program agreed well with the ab initio calculation, which shows the validity of this program.

Impact of Geometric Phase on Dynamics of Complex-Forming Reactions: H + O2 → OH + O.

Reaction dynamics on the ground electronic state might be significantly influenced by conical intersections (CIs) via the geometric phase (GP), as demonstrated for activated reactions (i.e., the H + H2 exchange reaction). However, there have been few investigations of GP effects in complex-forming reactions. Here, we report a full quantum dynamical study of an important reaction in combustion (H + O2 → OH + O), which serves as a proving ground for studying GP effects therein. The results reveal significant differences in reaction probabilities and differential cross sections (DCSs) obtained with and without GP, underscoring its strong impact. However, the GP effects are less pronounced for the reaction integral cross sections, apparently due to the integral of the DCS over the scattering angle. Further analysis indicated that the cross section has roughly the same contributions from the two topologically distinct paths around the CI, namely, the direct and looping paths.

Highly sensitive optical fiber pressure sensor based on the FPI and Vernier effect via femtosecond laser plane-by-plane writing technology.

In this paper, a highly sensitive pressure sensor based on fiber-optic Fabry-Perot interferometers (FPIs) and the Vernier effect (VE) is proposed and experimentally demonstrated. We employ a closed capillary-based F P I s for the sensing cavity, and an F P I r created through femtosecond laser refractive index modulation for the reference cavity, which remains impervious to pressure changes. Connecting these two FPIs in series produces a VE-based cascaded sensor with a clear spectral envelope. The femtosecond laser micromachining technique provides precise control over the length of F P I r and facilitates adjustments to the VE's amplification degree. Experimental results reveal significant pressure sensitivities of -795.96p m/M P a and -3219.91p m/M P a, respectively, representing a 20-fold and 80-fold improvement compared to F P I s (-39.80p m/M P a). This type of sensor has good sensitivity amplification and, due to its all-fiber structure, can be a promising candidate for high-temperature and high-pressure sensing, especially in harsh environments.

Deciphering the Enhancing Impact of Exogenous Brassinolide on Physiological Indices of Melon Plants under Downy Mildew-Induced Stress.

Melon (Cucumis melo L.) is a valuable horticultural crop of the Cucurbitaceae family. Downy mildew (DM), caused by Pseudoperonospora cubensis, is a significant inhibitor of the production and quality of melon. Brassinolide (BR) is a new type of phytohormone widely used in cultivation for its broad spectrum of resistance- and defense-mechanism-improving activity. In this study, we applied various exogenous treatments (0.5, 1.0, and 2.0 mg·L-1) of BR at four distinct time periods (6 h, 12 h, 24 h, and 48 h) and explored the impact of BR on physiological indices and the genetic regulation of melon seedling leaves infected by downy-mildew-induced stress. It was mainly observed that a 2.0 mg·L-1 BR concentration effectively promoted the enhanced photosynthetic activity of seedling leaves, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis similarly exhibited an upregulated expression of the predicted regulatory genes of photosystem II (PSII) CmHCF136 (MELO3C023596.2) and CmPsbY (MELO3C010708.2), thus indicating the stability of the PSII reaction center. Furthermore, 2.0 mg·L-1 BR resulted in more photosynthetic pigments (nearly three times more than the chlorophyll contents (264.52%)) as compared to the control and other treatment groups and similarly upregulated the expression trend of the predicted key enzyme genes CmLHCP (MELO3C004214.2) and CmCHLP (MELO3C017176.2) involved in chlorophyll biosynthesis. Meanwhile, the maximum contents of soluble sugars and starch (186.95% and 164.28%) were also maintained, which were similarly triggered by the upregulated expression of the predicted genes CmGlgC (MELO3C006552.2), CmSPS (MELO3C020357.2), and CmPEPC (MELO3C018724.2), thereby maintaining osmotic adjustment and efficiency in eliminating reactive oxygen species. Overall, the exogenous 2.0 mg·L-1 BR exhibited maintained antioxidant activities, plastid membranal stability, and malondialdehyde (MDA) content. The chlorophyll fluorescence parameter values of F0 (42.23%) and Fv/Fm (36.67%) were also noticed to be higher; however, nearly three times higher levels of NPQ (375.86%) and Y (NPQ) (287.10%) were observed at 48 h of treatment as compared to all other group treatments. Increased Rubisco activity was also observed (62.89%), which suggested a significant role for elevated carbon fixation and assimilation and the upregulated expression of regulatory genes linked with Rubisco activity and the PSII reaction process. In short, we deduced that the 2.0 mg·L-1 BR application has an enhancing effect on the genetic modulation of physiological indices of melon plants against downy mildew disease stress.

Isotope Effects on State-to-State Photodissociation Dynamics of D2S in Its First Absorption Band.

State-to-state photodissociation dynamics of D2S in its first absorption band were explored by utilizing recently developed diabatic potential energy surfaces (PESs). Quantum dynamics calculations, involving the first two strongly coupled 1A″ states, were executed employing a Chebyshev real wavepacket method. The nonadiabatic channel via the conical intersection (CI) is facile, direct, and fast, leading to the production of rotationally and vibrationally cold SD(X̃2Π). The calculated absorption spectrum, product state distributions, and angular distributions are in reasonable agreement with the experimental results, although some discrepancies exist at 193.3 nm. Compared with H2S, there are obvious isotope effects on rotational state distributions for D2S photodissociation in its first absorption band. Moreover, we scrutinize the variation of product state distributions as a function of photon energy and the vibrational mediated photodissociation of the parent molecule. Due to the diverse shapes of the three fundamental vibrational wave functions, photoexcited wavepackets access distinct segments of the upper-state PES, resulting in a disparate absorption spectrum and ro-vibrational distributions via the nonadiabatic transition. This study provides a comprehensive figure of the isotopic effect and wavelength dependence on the photofragmentation behaviors from D2S photodissociation, which should attract more experimental and theoretical attention to this prototypical system.

Dynamics studies for the multi-well and multi-channel reaction of OH with C2H2 on a full-dimensional global potential energy surface.

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive manifestation of nonalcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the growing knowledge of NASH and HCC, the association between the two conditions remains to be fully explored. Bioinformatics has emerged as a valuable approach for identifying disease-specific feature genes, enabling advancements in disease prediction, prevention, and personalized treatment strategies. MATERIALS AND METHODS: In this study, we utilized CellChat, copy number karyotyping of aneuploid tumors (CopyKAT), consensus Non-negative Matrix factorization (cNMF), Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), Monocle, spatial co-localization, single sample gene set enrichment analysis (ssGSEA), Slingshot, and the Scissor algorithm to analyze the cellular and immune landscape of NASH and HCC. Through the Scissor algorithm, we identified three cell types correlating with disease phenotypic features and subsequently developed a novel clinical prediction model using univariate, LASSO, and multifactor Cox regression. RESULTS: Our results revealed that macrophages are a significant pathological factor in the development of NASH and HCC and that the macrophage migration inhibitory factor (MIF) signaling pathway plays a crucial role in cellular crosstalk at the molecular level. We deduced three prognostic genes (YBX1, MED8, and KPNA2), demonstrating a strong diagnostic capability in both NASH and HCC. CONCLUSION: These findings shed light on the pathological mechanisms shared between NASH and HCC, providing valuable insights for the development of novel clinical strategies.

Matrix-Variate Regression for Sparse, Low-Rank Estimation of Brain Connectivities Associated With a Clinical Outcome.

OBJECTIVE: We address the problem of finding brain connectivities that are associated with a clinical outcome or phenotype. METHODS: The proposed framework regresses a (scalar) clinical outcome on matrix-variate predictors which arise in the form of brain connectivity matrices. For example, in a large cohort of subjects we estimate those regions of functional connectivities that are associated with neurocognitive scores. We approach this high-dimensional yet highly structured estimation problem by formulating a regularized estimation process that results in a low-rank coefficient matrix having a sparse set of nonzero entries which represent regions of biologically relevant connectivities. In contrast to the recent literature on estimating a sparse, low-rank matrix from a single noisy observation, our scalar-on-matrix regression framework produces a data-driven extraction of structures that are associated with a clinical response. The method, called Sparsity Inducing Nuclear-Norm Estimator (SpINNEr), simultaneously constrains the regression coefficient matrix in two ways: a nuclear norm penalty encourages low-rank structure while an l1 norm encourages entry-wise sparsity. RESULTS: Our simulations show that SpINNEr outperforms other methods in estimation accuracy when the response-related entries (representing the brain's functional connectivity) are arranged in well-connected communities. SpINNEr is applied to investigate associations between HIV-related outcomes and functional connectivity in the human brain. CONCLUSION AND SIGNIFICANCE: Overall, this work demonstrates the potential of SpINNEr to recover sparse and low-rank estimates under scalar-on-matrix regression framework.

Formation Mechanisms of Electronically Excited Nitrogen Molecules from N + N2 and N + N + N Collisions Revealed by Full-Dimensional Potential Energy Surfaces.

This work reports six new full-dimensional adiabatic potential energy surfaces (PESs) of the N3 system (four 4A″ states and two 2A″ states) at the MRCI + Q/AVQZ level of theory that correlated to N2(X1Σg+) + N(4S), N2(X1Σg+) + N(2D), N2(A3Σu+) + N(4S), N2(B3Πg) + N(4S), N2(W3Δu) + N(4S), and N(4S) + N(4S) + N(4S) channels. The neural networks with a proper account of the nuclear permutation invariant symmetry of N3 were employed to fit the PESs based on about 4000 ab initio points. The accuracy of the PESs was validated by excellent agreement on the equilibrium bond length, vertical excitation energy, and dissociation energy with experimental values. Two possible mechanisms of the formation of N2(A) were found. One is that the collision occurs between N2(X) and N(4S) in the 14A″ state, followed by a nonadiabatic transition through the conical intersection with the 24A″ PES, resulting in the formation of the N2(A) + N(4S) product. The other takes place in the collision among three N(4S) atoms in the adiabatic 24A″ state, and then, N2(A) + N(4S) is formed. This is the first systematical research of the N3 system focusing on the formation of the excited states of N2 via both adiabatic and nonadiabatic pathways.

Quantum Dynamics of Photodissociation: Recent Advances and Challenges.

Recent advances in constructing accurate potential energy surfaces and nonadiabatic couplings from high-level ab initio data have revealed detailed potential landscapes in not only the ground electronic state but also excited ones. They enabled quantitatively accurate characterization of photoexcited reactive systems using quantum mechanical methods. In this Perspective, we survey the recent progress in quantum mechanical studies of adiabatic and nonadiabatic photodissociation dynamics, focusing on initial state control and product energy disposal. These new insights helped to understand quantum effects in small prototypical systems, and the results serve as benchmarks for developing more approximate theoretical methods.

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis.

Background: Ofatumumab is approved for treating relapsing multiple sclerosis (RMS). Examining tolerability will enable understanding of its risk-benefit profile. Objective: Report the tolerability profile of ofatumumab in RMS during treatment of up to 4 years and the effect of pre-medication. Methods: Cumulative data from the overall safety population included patients taking continuous ofatumumab or being newly switched from teriflunomide. Injection-related reactions (IRRs) by incidence and severity, and post-marketing surveillance data, with an exposure of 18,530 patient-years, were analyzed. Results: Systemic IRRs affected 24.7% of patients (487/1969) in the overall safety population; most (99.2% [483/487]) were mild (333/487) to moderate (150/487) in Common Terminology Criteria for Adverse Events severity; most systemic IRRs occurred after first injection. Local-site IRRs affected 11.8% (233/1969) and most (99.6% [232/233]) were mild/moderate. Incidence and severity of systemic and localized IRRs were similar between continuous and newly switched patients across repeated injections. Systemic IRR incidence and severity were not substantially affected by steroidal or non-steroidal pre-medication. Post-marketing surveillance identified no new tolerability issues. Conclusion: Ofatumumab is well tolerated, displays a consistent safety profile during continuous use or after switching from teriflunomide and does not require pre-medication. This enables home management of RMS with a high-efficacy treatment.

RNA-Seq Identified Putative Genes Conferring Photosynthesis and Root Development of Melon under Salt Stress.

Melon is an important fruit crop of the Cucurbitaceae family that is being cultivated over a large area in China. Unfortunately, salt stress has crucial effects on crop plants and damages photosynthesis, membranal lipid components, and hormonal metabolism, which leads to metabolic imbalance and retarded growth. Herein, we performed RNA-seq analysis and a physiological parameter evaluation to assess the salt-induced stress impact on photosynthesis and root development activity in melon. The endogenous quantification analysis showed that the significant oxidative damage in the membranal system resulted in an increased ratio of non-bilayer/bilayer lipid (MGDG/DGDG), suggesting severe irregular stability in the photosynthetic membrane. Meanwhile, root development was slowed down by a superoxidized membrane system, and downregulated genes showed significant contributions to cell wall biosynthesis and IAA metabolism. The comparative transcriptomic analysis also exhibited that major DEGs were more common in the intrinsic membrane component, photosynthesis, and metabolism. These are all processes that are usually involved in negative responses. Further, the WGCN analysis revealed the involvement of two main network modules: the thylakoid membrane and proteins related to photosystem II. The qRT-PCR analysis exhibited that two key genes (MELO3C006053.2 and MELO3C023596.2) had significant variations in expression profiling at different time intervals of salt stress treatments (0, 6, 12, 24, and 48 h), which were also consistent with the RNA-seq results, denoting the significant accuracy of molecular dataset analysis. In summary, we performed an extensive molecular and metabolic investigation to check the salt-stress-induced physiological changes in melon and proposed that the PSII reaction centre may likely be the primary stress target.

New accurate diabatic potential energy surfaces for the two lowest 1A'' states of H2S and photodissociation dynamics in its first absorption band.

In this work, state-to-state photodissociation dynamics of H2S in its first absorption band has been studied quantum mechanically with a new set of coupled potential energy surfaces (PESs) for the first two 1A'' excited states, which were developed at the explicitly correlated internally contracted multi-reference configuration interaction level with the cc-pVQZ-F12 basis set and a large active space. The calculated absorption spectrum, product state distributions, and angular distributions are in excellent agreement with available experimental data, validating the accuracy of the PESs and the non-adiabatic couplings. Detailed analysis of the dynamics reveals that there are strong non-adiabatic couplings between the bound 11B1 and dissociative 11A2 states around the Franck-Condon region, leading to very fast predissociation to ro-vibrationally cold SH(X̃) fragments, during which marginal angular anisotropy of the PESs is involved. This study provides quantitatively accurate characterization of the electronic structure and detailed fragmentation dynamics of this prototypical photodissociation system, which is desirable for improving astrochemical modelling.

Accurate Full-Dimensional Global Diabatic Potential Energy Matrix for the Two Lowest-Lying Electronic States of the H + O2 ↔ HO + O Reaction.

A new and more accurate diabatic potential energy matrix (DPEM) is developed for the two lowest-lying electronic states of HO2, covering both the strong interaction region and reaction asymptotes. The ab initio calculations were performed at the Davidson corrected multireference configuration interaction level with the augmented correlation-consistent polarized valence quintuple-zeta basis set (MRCI+Q/AV5Z). The accuracy of the electronic structure calculations is validated by excellent agreement with the experimental HO2 equilibrium geometry, fundamental vibrational frequencies, and H + O2 ↔ OH + O reaction energy. Through the combination of an electronic angular momentum-method and a configuration interaction vector-based method, the mixing angle between the first two 2A″ states of HO2 was successfully determined. Elements of the 2×2 DPEM were fit to neural networks with a proper account of the complete nuclear permutation inversion symmetry of HO2. The DPEM correctly predicted the properties of conical intersection seams at linear and T-shape geometries, thus providing a reliable platform for studying both the spectroscopy of HO2 and the nonadiabatic dynamics for the H + O2 ↔ OH + O reaction.

The vibronic state dependent predissociation of H2S: determination of all fragmentation processes.

Photochemistry plays a significant role in shaping the chemical reaction network in the solar nebula and interstellar clouds. However, even in a simple triatomic molecule photodissociation, determination of all fragmentation processes is yet to be achieved. In this work, we present a comprehensive study of the photochemistry of H2S, derived from cutting-edge translational spectroscopy measurements of the H, S(1D) and S(1S) atom products formed by photolysis at wavelengths across the range 155-120 nm. The results provide detailed insights into the energy disposal in the SH(X), SH(A) and H2 co-fragments, and the atomisation routes leading to two H atoms along with S(3P) and S(1D) atoms. Theoretical calculations allow the dynamics of all fragmentation processes, especially the bimodal internal energy distributions in the diatomic products, to be rationalised in terms of non-adiabatic transitions between potential energy surfaces of both 1A' and 1A'' symmetry. The comprehensive picture of the wavelength-dependent (or vibronic state-dependent) photofragmentation behaviour of H2S will serve as a text-book example illustrating the importance of non-Born-Oppenheimer effects in molecular photochemistry, and the findings should be incorporated in future astrochemical modelling.

SO2 Photodissociation at 193 nm Directly Forms S(3P) + O2(3Σg-): Implications for the Archean Atmosphere on Earth.

It is well-documented that photodissociation of SO2 at λ = 193 nm produces O(3Pj) + SO X(3Σ-). We provide experimental evidence of a new product channel from one-photon absorption producing S(3Pj) + O2 X(3Σg-) in 2-4% yield. We probe the reactant and all products with time-resolved photoelectron photoion coincidence spectroscopy. High-level ab initio calculations suggest that the new product channel can only occur on the ground-state potential energy surface through internal conversion from the excited state, followed by isomerization to a transient SOO intermediate. Classical trajectories on the ground-state potential energy surface with random initial conditions qualitatively reproduce the experimental yields. This unexpected photodissociation pathway may help reconcile discrepancies in sulfur mass-independent fractionation mechanisms in Earth's geologic history, which shape our understanding of the Archean atmosphere and the Great Oxygenation Event in Earth's evolution.

A method for reducing thermal injury during the ureteroscopic holmium laser lithotripsy.

Objective: Many studies have demonstrated the heat effect from the holmium laser lithotripsy can cause persistent thermal injury to the ureter. The purpose of this study was to elucidate the use of a modified ureteral catheter with appropriate firing and irrigation to reduce the thermal injury to the "ureter" during the ureteroscopic holmium laser lithotripsy in vitro. Methods: An in vitro lithotripsy was performed using a modified catheter (5 Fr) as the entrance for the irrigation and the holmium laser fiber while using the remaining space in the ureteroscopic channel as an outlet. Different laser power settings (10 W, 20 W, and 30 W) with various firing times (3 s, 5 s, and 10 s) and rates of irrigation (15 mL/min, 20 mL/min, and 30 mL/min) were applied in the experiment. Temperature changes in the "ureter" were recorded with a thermometer during and after the lithotripsy. Results: During the lithotripsy, the local highest mean temperature was 60.3 °C and the lowest mean temperature was 26.7 °C. When the power was set to 10 w, the temperature was maintained below 43 °C regardless of laser firing time or irrigation flow. Regardless of the power or firing time selected, the temperature was below 43 °C at the rate of 30 mL/min. There was a significant difference in temperature decrease when continuous 3 s drainage after continuous firing (3 s, 5 s, or 10 s) compared to with not drainage (p<0.05) except for two conditions of 0.5 J×20 Hz, 30 mL/min, firing 5 s, and 1.0 J×10 Hz, 30 mL/min, firing 5 s. Conclusion: Our modified catheter with timely drainage reducing hot irrigation may significantly reduce the local thermal injury effect, especially along with the special interrupted-time firing setting during the simulated holmium laser procedure.

Phenolic features and anthocyanin profiles in winemaking pomace and fresh berries of grapes with different pedigrees.

The total contents and antioxidant activities of phenolic compounds as well as anthocyanin profiles were analyzed and compared in fresh berries and fermented pomace of three grape cultivars with different pedigrees. The phenolic contents and antioxidant activities decreased significantly in skins (p < 0.05), while relatively large amounts of them were retained in seeds after fermentative maceration. Fermentative maceration also had a significant impact on the anthocyanin compositions. The proportions of anthocyanins with more stable structures, such as malvidin derivatives, methylated, diglucosides and nonacylated anthocyanins, increased significantly in the pomace skins (p < 0.05). There were obvious differences in phenolic features and anthocyanin profiles among the three cultivars. 'NW196', a wine hybrid of Vitis vinifera and V. quinquangularis, was characterized by the highest total anthocyanin contents and degree of diglucosylation. The results obtained in this study could contribute to the primary data for the development and utilization of winemaking pomace, especially from local non-Vitis vinifera grapes.

Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial.

INTRODUCTION: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. METHODS: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg. Frequent sNfL sampling (14 time points over 12 weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions was compared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. RESULTS: In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. CONCLUSIONS: sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. CLINICALTRIALS: GOV: NCT03560739. CLASSIFICATION OF EVIDENCE: This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity.