Stereodynamic control of nonadiabatic processes in low-energy Be+(2P) + H2 (v = 0, j = 2) collisions.

Controlling the relative arrangement of colliding molecules is crucial for determining the dynamical outcomes of chemical processes and has emerged as a hot spot of experimental research. Here, the quantum scattering calculations are conducted to investigate the stereodynamic control in collisions between Be+(2P) and H2 (v = 0, j = 2), which undergo nonadiabatic transitions to the electronic ground state. Stereodynamic preparation is achieved by controlling the initial alignment of the H2 bond axis relative to the scattering frame. For product BeH+ in the reactive process, the differential cross sections (DCSs) are significantly enhanced in the forward and sideways hemispheres when the alignment angle ß is 60°. For the product H2 in the quenching channel, the ß = 0° preparation can result in a more than one-fold increase in the DCS at a polar scattering angle of 0°. Furthermore, varying the alignment angle ß also has noteworthy effects on the rotational-state distributions of BeH+ products. Specifically, ß = 0° preparation can induce the disappearance of the bimodal distribution of rotational states at a collision energy of 0.05 eV.

Optimization of Cohesive Parameters in the Interfacial Transition Zone of Rubberized Concrete Based on the Response Surface Method.

Rubber concrete has been applied to a certain extent in fatigue-resistant structures due to its good durability. Based on a cohesive model of rubber composed of a five-phase material containing mortar, aggregate, rubber, aggregate-mortar interfacial transition zone (ITZ), and rubber-mortar ITZ, this paper studies the influence of the cohesive parameters in the rubber-mortar ITZ on the fatigue problem of rubber concrete on the mesoscopic scale. As the weak part of cement-based composite materials, the ITZ has a great influence on the mechanical properties and durability of concrete, but the performance of the ITZ is difficult to test in macro experiments, resulting in difficulties in determining its simulation parameters. Based on the cohesive model with a rubber content of 5%, this study uses Monofactor analysis and the Plackett-Burman test to quickly and effectively determine the primary and secondary influences of the cohesive model parameters in the rubber-mortar ITZ; further, the response surface method is used to optimize the cohesive parameters in the rubber-mortar ITZ, and the numerical simulation results after optimizing the cohesive parameters are compared and analyzed with the simulation results before optimization. The results show that, under the setting of the optimized parameters, the simulation results of each item of the optimal cohesive model parameters in the rubber-mortar ITZ are in line with the reality and closer to the experimental data, and they are also applicable to rubber concrete models with different rubber dosing.

Ten-Year Follow-Up of Lung Cancer Patients with Resected Stage IA Invasive Non-Small Cell Lung Cancer.

OBJECTIVE: The purpose of this study was to assess 10-year follow-up outcomes after surgical resection in patients with stage IA invasive non-small cell lung cancer (NSCLC) based on postoperative pathological diagnosis. METHODS: Patients with stage IA invasive NSCLC who underwent resection between December 2008 and December 2013 were reviewed. Patients were categorized into the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO), and solid groups based on consolidation to tumor ratio (CTR). Postoperative survival and risk of recurrence and developing secondary primary lung cancer were analyzed in each group. RESULTS: Among the 645 stage IA invasive NSCLC, the 10-year overall survival and recurrence-free survival rate was 79.38% and 77.44%, respectively. The 10-year overall survival for pGGO, mGGO, and solid group of patients was 95.08%, 86.21%, and 72.39%, respectively. The respective recurrence-free survival rate was 100%, 89.82%, and 65.83%. Multivariable Cox regression analysis associated tumor size and GGO components with recurrence and younger age, and tumors with GGO components were associated with longer overall survival. The cumulative incidence curve indicated no recurrence of GGO lung cancer ≥ 5 years postoperatively. Our cohort indicated that the number and stations of dissected lymph node did not influence long-term prognosis of IA invasive NSCLC. CONCLUSIONS: Recurrence of invasive stage IA NSCLC with GGO was more prevalent in patients with tumor size >1 cm and CTR > 0.5, occurring within 5 years after surgery. This will provide important evidence for follow-up strategies in these patients.

The influence of stereodynamical control on the nonadiabatic effects in the D + HD (v = 1, j = 2) → D2 + H reaction.

Stereodynamics is a field that studies the influence of the alignment or orientation of colliding partners on the results of collisions. At present, the intersection of nonadiabatic effects and stereodynamics remains to be explored. In this study, we theoretically demonstrate significant stereodynamical effects in the D + HD (v = 1, j = 2) → D2 + H reaction within the collision energy range of 0.01-2.99 eV by using the time-dependent wave packet method. It is found that the stereodynamical control not only facilitates the reaction but also allows precise control of the products over a range of different scattering angles. The analysis at the state-to-state level reveals that the nonadiabatic effects are stronger in the parallel configuration than in the perpendicular configuration. By topological approach to separate the two reaction pathways at the conical intersection, the scattering amplitude of the roaming pathway in the parallel configuration is larger than that of the perpendicular configuration, which leads to more dramatic nonadiabatic features in the collision with parallel configuration.

In-depth understanding of transport behavior of sulfided nano zerovalent iron/reduced graphene oxide@guar gum slurry: Stability and mobility.

Nanoscale zero-valent iron (NZVI), which has the advantages of small particle size, large specific surface area, and high reactivity, is often injected into contaminated aquifers in the form of slurry. However, the prone to passivation and agglomeration as well as poor stability and mobility of NZVI limit the further application of this technology in fields. Therefore, sulfided NZVI loaded on reduced graphene oxide (S-NZVI/rGO) and guar gum (GG) with shear-thinning properties as stabilizers were used to synthesize S-NZVI/rGO@GG slurries. SEM, TEM, and FT-IR confirmed that the dispersion and anti-passivation of NZVI were optimized in the coupled system. The stability and mobility of the slurry were improved by increasing the GG concentration, enhancing the pH, and decreasing the ionic strength and the presence of Ca2+ ions, respectively. A modified advection-dispersion equation (ADE) was used to simulate the transport experiments considering the strain and physicochemical deposition/release. Meanwhile, colloidal filtration theory (CFT) demonstrated that Brownian motion plays a dominant role in the migration of S-NZVI/rGO@GG slurry, and the maximum migration distance can be increased by appropriately increasing the injection rate. Extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory showed that the excellent stability and migration of S-NZVI/rGO@GG slurry mainly came from the GG spatial forces. This study has important implications for the field injection of S-NZVI/rGO@GG slurry. According to the injection parameters, the injection range of S-NZVI/rGO@GG slurry is effectively controlled, which lays the foundation for the promotion of application in actual fields.

Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism.

The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.

PLS-based gene subset augmentation and tumor-specific gene identification.

In the study of tumor disease pathogenesis, the identification of genes specifically expressed in disease states is pivotal, yet challenges arise from high-dimensional datasets with limited samples. Conventional gene (feature) selection methods often fall short of capturing the complexity of gene-phenotype and gene-gene interactions, necessitating a more robust analysis method. To address these challenges, a gene subset augmentation strategy is proposed in this paper. Our approach introduces diverse perturbation mechanisms to generate distinct gene subsets. The partial least squares-based multiple gene measurement algorithm considers gene-phenotype and gene-gene correlations, identifying differentially expressed genes, including those with weak signals. The constructed gene networks derived from the augmented subsets unveil regulatory patterns, enabling association analysis to explore gene associations comprehensively. Our algorithm excels in identifying small-sized gene subsets with strong discriminative power, surpassing traditional methods that yield a single gene subset. Unlike conventional approaches, our algorithm reveals a spectrum of different gene subsets and their weakly differentially expressed genes. This nuanced perspective aids in unraveling the molecular characteristics and specific expression patterns of tumor genes. The versatility of our approach not only contributes to the advancement of tumor-specific gene identification but also holds promise for addressing challenges in various fields characterized by high-dimensional datasets and limited samples. The Python implementation is available at http://github.com/wenjieyou/PLSGSA.

GPR65 sensing tumor-derived lactate induces HMGB1 release from TAM via the cAMP/PKA/CREB pathway to promote glioma progression.

BACKGROUND: Lactate has emerged as a critical regulator within the tumor microenvironment, including glioma. However, the precise mechanisms underlying how lactate influences the communication between tumor cells and tumor-associated macrophages (TAMs), the most abundant immune cells in glioma, remain poorly understood. This study aims to elucidate the impact of tumor-derived lactate on TAMs and investigate the regulatory pathways governing TAM-mediated tumor-promotion in glioma. METHODS: Bioinformatic analysis was conducted using datasets from TCGA and CGGA. Single-cell RNA-seq datasets were analyzed by using UCSC Cell Browser and Single Cell Portal. Cell proliferation and mobility were evaluated through CCK8, colony formation, wound healing, and transwell assays. Western blot and immunofluorescence staining were applied to assess protein expression and cell distribution. RT-PCR and ELISA were employed to identify the potential secretory factors. Mechanistic pathways were explored by western blotting, ELISA, shRNA knockdown, and specific inhibitors and activators. The effects of pathway blockades were further assessed using subcutaneous and intracranial xenograft tumor models in vivo. RESULTS: Elevated expressions of LDHA and MCT1 were observed in glioma and exhibited a positive correlation with M2-type TAM infiltration. Lactate derived from glioma cells induced TAMs towards M2-subtype polarization, subsequently promoting glioma cells proliferation, migration, invasion, and mesenchymal transition. GPR65, highly expressed on TAMs, sensed lactate-stimulation in the TME, fueling glioma cells malignant progression through the secretion of HMGB1. GPR65 on TAMs triggered HMGB1 release in response to lactate stimulation via the cAMP/PKA/CREB signaling pathway. Disrupting this feedback loop by GPR65-knockdown or HMGB1 inhibition mitigated glioma progression in vivo. CONCLUSION: These findings unveil the intricate interplay between TAMs and tumor cells mediated by lactate and HMGB1, driving tumor progression in glioma. GPR65, selectively highly expressed on TAMs in glioma, sensed lactate stimulation and fostered HMGB1 secretion via the cAMP/PKA/CREB signaling pathway. Blocking this feedback loop presents a promising therapeutic strategy for GBM.

General Model for Predicting Response of Gas-Sensitive Materials to Target Gas Based on Machine Learning.

Gas sensors play a crucial role in various industries and applications. In recent years, there has been an increasing demand for gas sensors in society. However, the current method for screening gas-sensitive materials is time-, energy-, and cost-consuming. Consequently, an imperative exists to enhance the screening efficiency. In this study, we proposed a collaborative screening strategy through integration of density functional theory and machine learning. Taking zinc oxide (ZnO) as an example, the responsiveness of ZnO to the target gas was determined quickly on the basis of the changes in the electronic state and structure before and after gas adsorption. In this work, the adsorption energy and electronic and structural characteristics of ZnO after adsorbing 24 kinds of gases were calculated. These computed features served as the basis for training a machine learning model. Subsequently, various machine learning and evaluation algorithms were utilized to train the fast screening model. The importance of feature values was evaluated by the AdaBoost, Random Forest, and Extra Trees models. Specifically, charge transfer was assigned importance values of 0.160, 0.127, and 0.122, respectively, ranking as the highest among the 11 features. Following closely was the d-band center, which was presumed to exert influence on electrical conductivity and, consequently, adsorption properties. With 5-fold cross-validation using the Extra Tree accuracy, the 24-sample data set achieved an accuracy of 88%. The 72-sample data set achieved an accuracy of 78% using multilayer perceptron after 5-fold cross-validation, with both data sets exhibiting low standard deviations. This verified the accuracy and reliability of the strategy, showcasing its potential for rapidly screening a material's responsiveness to the target gas.

The prevalence of oral frailty among older adults: a systematic review and meta­analysis.

BACKGROUND: In recent years, oral frailty was proposed as a new concept regarding dental and oral health in older adults. Poor oral health is linked to preserving general health and has become a geriatric public health problem that deeply affects healthy aging. While in present, evidence on the prevalence associated with oral frailty in older adults remains unclear. OBJECTIVE: To systematically evaluate the prevalence of oral frailty among older adults, stratified by relevant factors such as gender, source, study design, region, and the evaluation scales for oral frailty and provide an evidence-based foundation for healthcare professionals and policymakers to formulate relevant measures. METHODS: Ten electronic databases were systematically searched from inception to September 2023, including PubMed, Web of Science, Embase, PsycINFO, The Cochrane Library, CINAHL, China National Knowledge Infrastructure Database (CNKI), Chinese Biomedical Database (Sinomed), Weipu Database, and Wanfang database. Based on the Stata 15.0 software package, a random effect model was used to calculate the pooled prevalence of oral frailty among older adults. In addition, sensitivity analysis, subgroup analysis, and meta-regression were conducted based on different study characteristics to detect heterogeneity sources. Funnel plots, Begg's and Egger's tests were used to evaluate the publication bias. RESULTS: Eighteen studies with a total of 12,932 older adults were included for meta-analysis. The pooled prevalence of oral frailty and oral pre-frailty was 24% (95% CI: 20-28%) and 57% (95% CI: 52-61%) respectively. Based on different assessment tools of oral frailty, the pooled prevalence of oral frailty was higher when using the OFI-8 scale (44.1%; 95% CI: 35.4-52.8%) than the OFI-6 scale (18.3%; 95% CI: 15.8-20.8%) or OF checklist (22.1%; 95% CI: 17.4-26.7%). The prevalence of oral frailty was higher among older adults in females (23.8%; 95% CI: 18.4-29.2%), hospital settings (31%, 95% CI: 16.6-45.5%), cross-sectional design (26.7%, 95% CI: 19.2-34.2%), and China (45.9%, 95% CI: 34.4-57.3%). CONCLUSIONS: Our study showed that oral frailty was common among older adults and various characteristics may affect its prevalence. Thus, healthcare professionals and policymakers should take oral frailty seriously in clinical practice and program planning and develop more preventive measures for oral frailty among older adults.

Spectral analysis of environmental microplastic polyethylene (PE) using average spectra.

In this study, microplastic samples from surface seawater of Tokyo Bay were collected, polyethylene (PE) microplastics were used to calculate carbonyl index (CI), and average spectra of PE were analyzed and compared with a previous study applying agitation during chemical treatment. It was found that PE and polypropylene (PP) were the predominant polymer type in the samples. Among PE samples, fragments were the most commonly observed shape, with white being the dominant color. Deviations were found in the average spectra among different shapes and colors when compared to the standard PE spectrum. A comparison of the average spectra between the two datasets suggests that pronounced peaks related to oxidation are most likely resulted from agitation during the chemical treatment. Additionally, it was found a closer spectral resemblance between the sample spectra and the spectrum of standard sample of oxidized PE (PEOx) than with the standard PE spectrum, suggesting that using the oxidized PE as a reference spectrum might be more effective for identification. These findings highlight the complex factors affecting the spectral properties of microplastics and highlight the importance of understanding these variations to enhance the accuracy of microplastic identification workflows and understanding of environmental fate of microplastics.

State-to-State Quantum Dynamics Study of Intramolecular Isotope Effects on Be(1S) + HD (v0 = 2, j0 = 0) → BeH/BeD + H/D Reaction.

The dynamic mechanisms and intramolecular isotope effects of the Be(1S) + HD (v0 = 2, j0 = 0) → BeH/BeD + H/D reaction are studied at the state-to-state level using the time-dependent wave packet method on a high-quality potential energy surface. This reaction can proceed along the indirect pathway that features a barrier and a deep well or the smooth direct pathway. The reaction probabilities, total and state-resolved integral cross sections, and differential cross sections are analyzed in detail. The calculated dynamics results show that both of the products are mainly formed by the dissociation of a collinear HBeD intermediate when the collision energy is slightly larger than the threshold. As the collision energy increases, the BeH + D channel is dominated by the direct abstraction process, whereas the BeD + H channel mainly follows the complex-forming mechanism.

Incidence and influencing factors of urinary incontinence in stroke patients: A meta-analysis.

BACKGROUND: The incidence of stroke in China ranks first in the world and is the leading cause of death and disability in adults. Urinary incontinence is an independent risk factor leading to poor prognosis of stroke. However, studies on the incidence of urinary incontinence in stroke patients and its influencing factors are different, fluctuate greatly, and there is no unified basis. OBJECTIVE: To quantitatively analyze the incidence of urinary incontinence in stroke patients and its related influencing factors, and further make public health strategic decisions to reduce the occurrence of adverse outcomes. METHODS: Computer searches were conducted in PubMed, Medline, Web of Science, Cochrane Library, Embase, CLNAHL Complete, China National Knowledge Infrastructure (CNKI), Chinese Biomedical database(CBM), Wan Fang Database, VIP Database, observational studies such as cohort studies, case-control studies or cross-sectional studies on the incidence or influencing factors of urinary incontinence in stroke patients from the establishment of the database to the publication in August 2023. Studies selection, quality evaluation and data extraction were conducted independently by two researchers according to the established search strategy. Stata 14.0 statistical software was used for meta-analysis. RESULTS: A total of 21 manuscripts were included, with a cumulative sample size of 7327 cases, including 2887 patients with urinary incontinence. Meta-analysis results showed that the incidence of urinary incontinence in stroke patients was 38% [95% confidence interval (34%, 41%)], including married patients and lacunar infarction were the protective factors for urinary incontinence in stroke patients, while age, chaperone, low educational level, chronic cough, lesion sites (parietal lobe, frontal lobe, and temporal lobe), stroke type (cerebral hemorrhage, subarachnoid hemorrhage and cerebral hemorrhage complicated with subarachnoid hemorrhage), dysfunction (aphasia dyslexia, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, the higher the NIHSS score, the lower the Bachmann index (BI) score, OCSP classification (total anterior circulation infarction) and other 11 items were risk factors for urinary incontinence in stroke patients. CONCLUSION: The incidence of urinary incontinence in stroke patients is 38%. Marriage and lacunar infarction are the protective factors of urinary incontinence. Age, carer, low educational level, chronic cough, lesion site (parietal, frontal and temporal lobes), stroke type (cerebral hemorrhage, subarachnoid hemorrhage, cerebral hemorrhage combined with subarachnoid hemorrhage), dysfunction (aphasia and dysarthria syndrome, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, and higher NIHSS score, Lower BI score and OCSP classification (total anterior circulation infarction) were risk factors for urinary incontinence in stroke patients.

The association between chronotype profile and temporomandibular disorders among college students.

BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.

Cadmium Exposure Induces Apoptosis and Necrosis of Thyroid Cells via the Regulation of miR-494-3p/PTEN Axis.

Cadmium (Cd) exposure is a persistent pollution problem, necessitating caution in using cadmium-expelling complexing agents. Currently, there is no targeted therapy to treat Cd poisoning. The thyroid gland is a major endocrine organ that directly regulates thyroid hormones involved in various physiological processes and is a target organ for Cd accumulation. Herein, the effects of Cd exposure on swine thyroid glands were investigated. Six-week-old male pigs were randomly divided into the Cd and control groups. The control group was fed a normal diet containing 0 mg Cd/kg, while the Cd group was fed a diet containing 20 mg Cd/kg (CdCl2) for 40 days. The regulation mechanism of phosphatase and tensin homolog (PTEN) microRNA-494-3p (miR-494-3p) was evaluated to determine the toxic effects of Cd exposure on free radicals' cleaner. Notably, heat shock proteins (HSPs) were triggered as defense agents against Cd. Cd exposure increased the enzyme activity of superoxide dismutase1(SOD1) and SOD2, catalase (CAT), and glutathione (GSH), and the endoplasmic reticulum stress in thyroid cells. Histopathological staining, RT-qPCR, and Western Blot assays were further employed to detect possible apoptosis and necroptosis of thyroid cells induced by Cd exposure. The assays revealed increased thyroid inflammatory injury, fibrosis, and apoptosis caused by Cd exposure. This study demonstrates the role of microRNAs in regulating Cd toxicity in pig thyroid tissue and provides evidence of Cd's negative effects. It further provides an assessment of the toxicological impact of Cd as an environmental endocrine disruptor (ED) that threatens public health and safety, which forms a basis for the development of Cd poisoning treatment therapies.

Theoretical study on photoinduced charge transfer in one-photon and two-photon absorption of branching oligofluorenes.

Oligofluorenes have been identified as very promising two-photon absorption (TPA) materials and present great application potential for the fabrication of nonlinear optical devices, but the TPA mechanism and corresponding electron excitation properties have not been studied. Here, the photoinduced charge transfer characteristics of V-shaped and Y-shaped branching oligofluorenes that consist of two and three fluorene units in each branch during one-photon absorption (OPA) and TPA processes are analyzed theoretically using the density functional theory and visualization sum-over-states model. The calculated results show that the OPA intensity and TPA cross-section are significantly enhanced by increasing the branch length or changing the structure from V-shaped to Y-shaped. The long-distance charge transfer only occurs on the second transition of TPA at high excited states. Compared to Y-shaped molecules, V-shaped structures exhibit a stronger cooperative effect among the different branches.

Unveiling Quantum Interference in the D+ + H2 Nonadiabatic Reaction Dynamics at Low Collision Energies.

Fully converged nonadiabatic dynamics calculations of the D+ + H2 → H+ + HD reaction are performed at low temperatures using the time-dependent wave packet approach based on a set of precise 3 × 3 diabatic potential energy surfaces (PESs) ( Phys. Chem. Chem. Phys., 2021, 23, 7735-7747, DOI: 10.1039/D0CP04100A). The D+ + H2 reaction is mediated by a dense manifold of resonances associated with the deep potential well on the ground-state PES. The calculated results show that the nonadiabatic coupling can affect the resonance positions, deviating from the expectation based solely on adiabatic considerations. Furthermore, significant forward-backward asymmetry in total differential cross sections (DCSs) is revealed, which is markedly influenced by nonadiabatic effects. The nonadiabatic effects not only affect the contribution of partial waves in the reaction but also make the interference patterns in the DCSs change significantly.

Efficacy and safety of 48 weeks of guselkumab for patients with Crohn's disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial.

BACKGROUND: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. METHODS: We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn's disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting. FINDINGS: Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respectively. In the placebo group, 15 patients were in CDAI clinical response at week 12 and continued placebo; of these, nine (60%) were in clinical remission at week 48. 44 patients in the placebo group were not in CDAI clinical response at week 12 and crossed over to ustekinumab; of these, 26 (59%) were in clinical remission at week 48. Up to week 48, adverse events frequencies in the safety population (n=360) were 46 (66%) of 70 patients (464·9 events per 100 patient-years of follow-up) in the placebo group, 163 (74%) of 220 patients (353·1 per 100 patient-years) in the three guselkumab groups combined, and 60 (85%) of 71 patients (350·7 per 100 patient-years) in the ustekinumab group. Among patients treated with guselkumab or ustekinumab, the most frequently reported infections up to week 48 were nasopharyngitis (25 [11%] of 220 guselkumab recipients, 12 [11%] of 114 ustekinumab recipients) and upper respiratory infections (13 [6%] guselkumab recipients, eight [7%] ustekinumab recipients). After week 12, one patient who responded to placebo induction and two guselkumab-treated patients had serious infections. No active tuberculosis, opportunistic infections, or deaths occurred. INTERPRETATION: Patients receiving guselkumab intravenous induction and subcutaneous maintenance treatment achieved high rates of clinical and endoscopic efficacy up to week 48. No new safety concerns were identified. FUNDING: Janssen Research & Development.

UHPLC-MS/MS-based lipidomics for the evaluation of the relationship between lipid changes and Zn-protoporphyrin formation during Nuodeng ham processing.

The effects of changes in lipids on the formation of Zn-protoporphyrin (ZnPP) during the processing of Nuodeng ham were analyzed using a lipidomics approach based on UHPLC-MS/MS. The Nuodeng ham samples had a strong fluorescence emission peak at 590 nm, and the fluorescence intensity increased with the processing time. Lipid profiles were mainly affected by processing time. A total of 5 lipid classes were detected, of which glycerophospholipids (GP) and glycerolipids (GL) were the most abundant lipids. Fifty differential lipid compounds were screened, which were mainly GP and GL. Correlation analysis showed that 13 differential lipid compounds were significantly positively correlated with ZnPP content, and they contained more linoleic acid and oleic acid branch chains. Meanwhile, all triglycerides (TG) were negatively correlated with heme content, and they were enriched in stearic acid and palmitic acid branch chains. These findings can deepen the understanding of the relationship between ZnPP and lipids.

Accessing the intrinsic factors of carbonyl index of microplastics: Physical and spectral properties, baseline correction, calculation methods, and their interdependence.

Carbonyl index (CI) is a measure of the degradation status of microplastics. While many studies address environmental factors of microplastic degradation, intrinsic factors like physical properties, spectral properties, baseline correction, and CI calculation methods are less explored. This research focused on these aspects using surface seawater samples. We found that color and shape have limited dependence on particle size or signal-to-noise ratio (SNR). Baseline correction can significantly alter CI values, with the direction of the shift depending on the methods used. Additionally, most CI values before and after baseline correction and those calculated using different methods tend to be strongly correlated. Using the selected CI calculation methods, we found that CI values varied significantly by shape and color. CI's relation to the similarity between the sample and its pristine form suggests an alternative degradation measure. Our findings emphasize the need for standardized CI calculation methods.