Changes of lipid oxidation, volatile and taste-active compounds during pan-heating of pork belly.

This study investigated the mechanisms underlying the evolution and formation of aroma and taste-active compounds of pork belly in representative traditional pork cuisines during pan-heating. The results revealed that as the temperature increased to 110 ℃, the unsaturation of fatty acids decreased from 60.25 % to 58.71 %, while the content of free radicals and secondary oxidation products increased. At the later heating stages, the addition of spices and increased heating temperature (150 â„ƒ) led to continuous increments in the contents (from 958.20 µg/kg to 1511.88 µg/kg) and diversity of volatile compounds in pork belly, imparting the unique aroma. Additionally, the accumulation of low-molecular-weight peptides, free amino acids, and nucleotides not only provided the substrate for thermal reactions and their synergistic effects, but also contributed to the desired taste quality. These findings offered insights into the flavor formation mechanisms of traditional pork cuisines and provided direction for further research.

Magnetic topological materials in two-dimensional: theory, material realization and application prospects.

Two-dimensional (2D) magnetism and nontrivial band topology are both areas of research that are currently receiving significant attention in the study of 2D materials. Recently, a novel class of materials has emerged, known as 2D magnetic topological materials, which elegantly combine 2D magnetism and nontrivial topology. This field has garnered increasing interest, especially due to the emergence of several novel magnetic topological states that have been generalized into the 2D scale. These states include antiferromagnetic topological insulators/semimetals, second-order topological insulators, and topological half-metals. Despite the rapid advancements in this emerging research field in recent years, there have been few comprehensive summaries of the state-of-the-art progress. Therefore, this review aims to provide a thorough analysis of current progress on 2D magnetic topological materials. We cover various 2D magnetic topological insulators, a range of 2D magnetic topological semimetals, and the novel 2D topological half-metals, systematically analyzing the basic topological theory, the course of development, the material realization, and potential applications. Finally, we discuss the challenges and prospects for 2D magnetic topological materials, highlighting the potential for future breakthroughs in this exciting field.

Promotion or Inhibition Effects of Exogenous Glutathione-Degraded Amino Acids on the Formation of 2,3-Butanedione and Pyrazines via Varied Pathways of Interaction with α-Dicarbonyl Compounds Derived from N-(1-Deoxy-d-xylulos-1-yl)-alanine.

The contribution of glutathione (GSH) and free amino acids degraded from GSH to the generation of pyrazines and 2,3-butanedione was illustrated during their interaction in the thermal treatment of the Amadori compound of alanine and xylose (ARP). GSH-degraded amino acids, glutamic acid (Glu), cysteine (Cys), and glycine (Gly), but not pyroglutamic acid (pGlu), could effectively capture α-dicarbonyls to facilitate the formation of pyrazines when ARP was heated with GSH. Deoxypentosones, the precursors of 2,3-butanedione, were largely consumed in the ARP-GSH model by the interaction with GSH and its degradative Cys compared with the ARP model. The addition of GSH and deoxypentosones inhibited the further degradation of deoxypentosones, resulting in less formation of 2,3-butanedione and other α-dicarbonyl compounds. Meanwhile, the reaction between GSH-degraded Cys and deoxypentosones to form sulfur-containing compounds such as thiols accelerated the consumption of deoxypentosones; thereby, the formation of 2,3-butanedione was severely interfered. However, this inhibition was compensated for by the GSH-degraded Gly through the addition between Gly and MGO and the subsequent deamination. The involvement of exogenous GSH could simultaneously boost the yields of 2,3-butanedione and pyrazines compared with those of ARP heated alone. As the degree of GSH degradation strengthened in the ARP-thermal-degraded GSH models, the yields of both pyrazines and 2,3-butanedione steadily increased.

Computed tomography angiography-based radiomics model to identify high-risk carotid plaques.

Background: Extracranial atherosclerosis is one of the major causes of stroke. Carotid computed tomography angiography (CTA) is a widely used imaging modality that allows detailed assessments of plaque characteristics. This study aimed to develop and test radiomics models of carotid plaques and perivascular adipose tissue (PVAT) to distinguish symptomatic from asymptomatic plaques and compare the diagnostic value between radiomics models and traditional CTA model. Methods: A total of 144 patients with carotid plaques were divided into symptomatic and asymptomatic groups. The traditional CTA model was built by the traditional radiological features of carotid plaques measured on CTA images which were screened by univariate analysis and multivariable logistic regression. We extracted and screened radiomics features from carotid plaques and PVAT. Then, a support vector machine was used for building plaque and PVAT radiomics models, as well as a combined model using traditional CTA features and radiomics features. The diagnostic value between radiomics models and traditional CTA model was compared in identifying symptomatic carotid plaques by Delong method. Results: The area under curve (AUC) values of traditional CTA model were 0.624 and 0.624 for the training and validation groups, respectively. The plaque radiomics model and PVAT radiomics model achieved AUC values of 0.766, 0.740 and 0.759, 0.618 in the two groups, respectively. Meanwhile, the combined model of plaque and PVAT radiomics features and traditional CTA features had AUC values of 0.883 and 0.840 for the training and validation groups, respectively, and the receiver operating characteristic curves of combined model were significantly better than those of traditional CTA model in the training group (P<0.001) and validation group (P=0.029). Conclusions: The combined model of the radiomics features of carotid plaques and PVAT and the traditional CTA features significantly contributes to identifying high-risk carotid plaques compared with traditional CTA model.

Phase transformation of Cr(VI) host-mineral driven by citric acid-aided mechanochemical approach for advanced remediation of chromium ore processing residue-contaminated soil.

The slow release of Cr(VI) from chromium ore processing residue-contaminated soil (COPR-soil) poses a significant environmental and health risk, yet advanced remediation techniques are still insufficient. Here, the slow-release behavior of Cr(VI) in COPR-soil is observed and attributed to the embedded Cr(VI) in the lattice of vaterite due to the isomeric substitution of CrO42- for CO32-. A citric acid-aided mechanochemical approach with FeS2/ZVI as reductive material was developed and found to be highly effective in remediating COPR-soil. Almost all Cr(VI) in COPR-soil, including Cr(VI) embedded in the minerals, are reduced with a reduction efficiency of 99.94%. Cr(VI) reduction kinetics indicate that the Cr(VI) reduction rate constant in the presence of citric acid was 4.8 times higher compared to its absence. According to the Raman spectroscopy, X-ray diffraction (XRD), and Electron Probe X-ray Micro-Analyzer (EPMA) analysis, the reduction of Cr(VI) embedded in vaterite was mainly attributed to the citric acid-induced protonation effect. That is, under the protonation effect, the embedded Cr(VI) could be released from vaterite through its phase transformation to calcite, whose affinity to Cr(VI) is low. While the reduction of released Cr(VI) could be promoted due to the complexation of citric acid with disulfide groups on FeS2/ZVI. The results of long-term stability tests demonstrated that the remediated COPR-soil exhibited excellent long-term stability, which may also be associated with improved utilization of available carbon and electron donors by the Cr(VI) reducing bacteria (Proteobacteria)-dominated microbial community in the presence of citric acid, thereby promoting to establish a stable reducing microenvironment. Collectively, these findings will further our understanding of the reduction remediation of COPR-soil, especially in the case of Cr(VI) embedded in minerals.

Regulated Formation of Inhibited Color and Enhanced Flavor Derived from Heated 2-Threityl-Thiazolidine-4-Carboxylic Acid with Additional Cysteine Targeting at Different Degradation Stages.

This study explored the addition of cysteine (Cys) affecting the color formation of heated 2-threityl-thiazolidine-4-carboxylic acid (TTCA) models under different reaction conditions and pointed out that temperature was considered to be the key parameter influencing the color inhibition behavior of Cys on TTCA reaction models. Results revealed that additional Cys not only controlled the reaction progress and blocked the formation pathway of browning but also changed the formation rate, intensity, and profile of the flavor generated from the TTCA reaction model. Meanwhile, the mechanism of Cys simultaneously regulating the formation of color and flavor was revealed through monitoring of the characteristic downstream products during TTCA degradation and model reaction systems. At the initial stage, the additional Cys acted as a color inhibitor before the deoxyxylosone degradation, preventing the formation of downstream browning precursors. With the continuous depletion of Cys as well as the generation of furans or α-dicarbonyl compounds, Cys became a flavor enhancer to act on the browning precursors and to provide more sulfur/nitrogen elements for the TTCA thermal reaction system. Therefore, Cys had the potential to act as both color inhibitor and flavor fortifier to match with TTCA for the preparation of a light-colored flavoring base with a desired flavor during thermal processing.

Realization of high-order topological phase transition in 2D metal-organic frameworks.

In two-dimensional (2D) scale, controllable topological phase transition between a conventional topological quantum state and a higher-order one has been a challenge currently. Herein, based on first-principles, we report 2D metal-organic frameworks (MOFs) are ideal choice for realizing such topological phase transition. Taking MOF candidate Pd3(C6S6)2 as an example, a semimetallic band structure is present at the equilibrium state. Under moderate compressive strain, it features a nontrivial energy gap and corner states, which is evidenced as a second-order topological insulator (SOTI). In addition, the band order for its low-energy bands switches at moderate tensile strain, during which topological phase transition from SOTI and topological semimetal to double Weyl semimetal (DWSM) happens, accompanied by the change in real Chern number form ν_R=1 to ν_R=0. At the critical point for the phase transition, the system can be characterized as a 2D pseudospin-1 fermion. Beside Pd3(C6S6)2, we further identify the ferromagnetic monolayer Fe3(C6S6)2 can also take the DWSM-to-SOTI phase transition, where the topological fermions and corresponding edge/corner states could be fully spin-polarized. This work has for the first time realized topological transition between conventional topological quantum state and a higher-order one in both nonmagnetic and magnetic MOFs.

APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFß-mediated checkpoints.

The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD-astrocyte cross-talk associated with ß-amyloid (Aß) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8-transforming growth factor-ß (TGFß) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD-astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4-ITGB8-TGFß pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8-TGFß signaling provides a promising therapeutic intervention for AD.

NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of ß- or γ-Branched Chiral Aromatic N-Heterocycles.

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access to a library of chiral ß- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- and atom-economies, and generating two kinds of chiral products through one synthetic strategy. Furthermore, the possible reaction mechanism was extensively investigated using numerous control experiments and density functional theory calculations.

Drumhead surface states promoted hydrogen evolution reactions in type-II nodal-line topological catalyst Mg3Bi2.

An excellent catalyst generally meets three indicators: high electron mobility, high surface density of states and low Gibbs free energy (ΔG) [H. Luo et al. Nat. Rev. Phys., 2022, 4, 611-624]. Recent studies have confirmed that topological materials exhibit more advantages than conventional precious metals with regard to the above-mentioned indicators. Herein, based on DFT calculations and symmetry analysis, we discovered for the first time that the topological surface states of Mg3Bi2 with a Kagome lattice promote hydrogen evolution reactions (HERs). In particular, there exists a snake-like type-II nodal loop (NL), located on kz = 0 plane in Mg3Bi2. Besides, the NL forms a topologically protected drumhead surface state on the (001) surface. It was found that the ΔG (0.176 eV) value of the (001) surface is comparable to that of the precious metal Pt. Then, through hole doping and strain regulation, it was found that the catalytic activity of Mg3Bi2 is closely related to the drumhead surface state formed by NL. With the above-mentioned results, this study not only provides a promising candidate material for hydrogen electrolysis, but also deepens our understanding of the dominant factors of NL semimetals for the catalytic activity.

Catalytic Enantioselective Alkylation of Aldehydes with 3-Bromooxindoles.

An asymmetric conjugate addition of aldehydes with o-azaxylylene intermediates (indol-2-ones) from 3-bromooxindoles has been developed. The use of a novel spiro-pyrrolidine (SPD)-derived bifunctional N-sulfonylated amide catalyst is essential for a highly diastereo- and enantioselective transformation to provide a wide array of enantioenriched C3 quaternary oxindoles with structurally diverse ß-aldehyde appendages. Further application of this synthetic methodology enables the construction of the tricyclic cores of akuammiline-type alkaloids.

Interactions of arsenic exposure, arsenic metabolism with red blood cell folate on the risk of hypertension: NHANES 2007-2016.

PURPOSE: Arsenic exposure was associated with hypertension, and arsenic metabolism might be influenced by folate concentrations. Thus, this study aimed to explore the interaction between arsenic exposure and metabolism with folate concentrations on hypertension. METHODS: We studied 6643 adults aged 20 years and older who participated in the National Health and Nutrition Examination Survey from 2007 through 2016. Urinary total arsenic (UTAs), the percentage of urinary dimethylarsinic acid (DMA%), serum and red blood cell (RBC) folate were collected. Logistic regression and restricted cubic spline (RCS) analyses were performed to determine the association and dose-response relationship. Interaction analyses were conducted on both additive and multiplicative scales. RESULTS: UTAs (median: 7.05 µg/L) was positively associated with hypertension risk, and the adjusted OR was 1.44 (95% CI: 1.06-1.95) when comparing the third with the lowest quartile. And participants with the highest quintile of RBC folate had increased hypertension risk than those with the lowest quintile (adjusted OR = 1.43, 95% CI: 1.06-1.94). Significant additive interaction was observed between excessive RBC folate with high UTAs (AP = 0.323, 95% CI: 0.083-0.564) and low DMA% (AP = 0.381, 95% CI: 0.119-0.643) on hypertension risk. CONCLUSION: Our results suggested significant interactions between high UTAs and low DMA% with excessive RBC folate on hypertension risk.

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis dependent CKD. STUDY DESIGN: Prospective cohort study. SETTING: & Participants: 2,539 adults in the Chronic Renal Insufficiency Cohort Study. EXPOSURE: Frailty status assessed using five criteria (slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss). OUTCOMES: Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. ANALYTICAL APPROACH: Cause-specific hazards models. RESULTS: At study entry, mean age was 62 years, 46% were female, mean eGFR was 45.4 mL/min/1.73m2, and median urine protein was 0.2 mg/day. Frailty status was as follows: 12% frail, 51% pre-frail, and 37% non-frail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with non-frailty, both frailty and pre-frailty status were each associated with higher risk of an atherosclerotic event (HRs of 2.03 [95% CI, 1.41, 2.91] and 1.77 [95% CI, 1.35, 2.31], respectively) and incident heart failure (HRs 2.22 [95% CI, 1.59, 3.10] and 1.39 [95% CI, 1.07, 1.82], respectively), as well as higher risk of all-cause death (HRs of 2.52 [95% CI, 1.84, 3.45] and 1.76 [95% CI, 1.37, 2.24], respectively) and cardiovascular death (HRs of 3.01 [95% CI, 1.62, 5.62] and 1.78 [95% 1.06, 2.99], respectively). LIMITATIONS: Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. CONCLUSIONS: In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population.

Cascade N2 Reduction Process with DBD Plasma Oxidation and Electrocatalytic Reduction for Continuous Ammonia Synthesis.

Due to the extremely high bond energy of N≡N (∼941 kJ/mol), the traditional Haber-Bosch process of ammonia synthesis is known as an energy-intensive and high CO2-emission industry. In this paper, a cascade N2 reduction process with dielectric barrier discharge (DBD) plasma oxidation and electrocatalytic reduction as an alternative route is first proposed. N2 is oxidized to be reactive nitrogen species (RNS) by nonthermal plasma, which would then be absorbed by KOH solution and electroreduced to NH4+. It is found that the production of NOx is a function of discharge length, discharge power, and gas flow rate. Afterward, the cobalt catalyst is used in the process of electrocatalytic reduction of ammonia, which shows high selectivity (Faradic efficiency (FE) above 90%) and high yield of ammonia (45.45 mg/h). Finally, the cascade plasma oxidation and electrocatalytic reduction for ammonia synthesis is performed. Also, the performance of the reaction system is evaluated. It is worth mentioning that a stable and sustainable ammonia production efficiency of 16.21 mg/h is achieved, and 22.16% of NOx obtained by air activation is converted into NH4+. This work provides a demonstration for further industrial application of ammonia production with DBD plasma oxidation and electrocatalytic reduction techniques.

Effect of Short-Term High-Temperature Stimuli on the Functional Response of Trichopria drosophilae (Matsumura).

Researchers have previously investigated the role of Trichopria drosophilae as a pupal parasitoid in the biological control of Drosophila suzukii in China. Here, we investigated the ability of T. drosophilae to parasitize D. suzukii pupae at different temperatures. To do this, we evaluated the functional response of T. drosophilae to D. suzukii pupae at different temperatures and investigated the specific effects of density on parasitism. The results show that the parasitic functional response of T. drosophilae under different high-temperature stimuli is Holling type II. After processing at 29 °C, the instantaneous search rate was 1.1611; the theoretical maximum parasitic value was 20.88 at 31 °C. The parasitic efficiency decreased with increasing stimulation temperature, as the host pupa density increased from 5 to 25, and the strongest search effect occurred at 0.87 at 27 °C. The searching effect of T. drosophilae at each temperature fell gradually with an increase in prey density from 5 to 25. At 31 °C, the theoretical parasitic maximum of T. drosophilae reached a maximum of 20.88 pupae. At this temperature, when a pair of T. drosophilae was placed in a pupa density of 50, its actual total number of parasites was 18.60.

Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer's disease.

Emerging evidence suggests that dysregulation of neuroinflammation, particularly that orchestrated by microglia, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Danger signals including dead neurons, dystrophic axons, phosphorylated tau, and amyloid plaques alter the functional phenotype of microglia from a homeostatic (M0) to a neurodegenerative or disease-associated phenotype, which in turn drives neuroinflammation and promotes disease. Thus, therapies that target microglia activation constitute a unique approach for treating AD. Here, we report that nasally administered anti-CD3 monoclonal antibody in the 3xTg AD mouse model reduced microglial activation and improved cognition independent of amyloid beta deposition. In addition, gene expression analysis demonstrated decreased oxidative stress, increased axogenesis and synaptic organization, and metabolic changes in the hippocampus and cortex of nasal anti-CD3 treated animals. The beneficial effect of nasal anti-CD3 was associated with the accumulation of T cells in the brain where they were in close contact with microglial cells. Taken together, our findings identify nasal anti-CD3 as a unique form of immunotherapy to treat Alzheimer's disease independent of amyloid beta targeting.

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Voriconazole in Chinese Kidney Transplant Patients.

BACKGROUND: The effect of drug-drug interaction (DDI) between tacrolimus and voriconazole on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. OBJECTIVE: The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-voriconazole DDI in Chinese kidney transplant patients. METHODS: All kidney transplant patients were divided into combination and non-combination groups based on whether tacrolimus was combined with or without voriconazole. Each group was subdivided into CYP3A5 expresser (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 nonexpresser (CYP3A5*3/*3). A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between combination and non-combination groups, respectively. Tacrolimus C0/D was also compared between CYP3A5 expresser and nonexpresser in both groups. RESULTS: The C0/D values of tacrolimus were significantly different between CYP3A5 expresser and nonexpresser in combination group (378.20 [219.38, 633.48] ng/mL/[mg/kg/d] vs 720.00 [595.35, 1681.50] ng/mL/[mg/kg/d], P = 0.0010). Either in CYP3A5 expresser or nonexpresser, we found a statistically significant difference in tacrolimus C0/D between combination and non-combination group (P < 0.0001). The increase in CYP3A5 nonexpresser was 1.38 times higher than that in CYP3A5 expresser (320.93% vs 232.19%). CONCLUSION AND RELEVANCE: The median C0/D values were 90.38% higher in kidney transplant recipients with CYP3A5*3/*3 genotype than in those with CYP3A5*1/*1 or CYP3A5*1/*3 genotype when treated with both tacrolimus and voriconazole. A CYP3A5 genotype-dependent DDI was found between tacrolimus and voriconazole. Therefore, personalized therapy accounting for CYP3A5 genotype detection and therapeutic drug monitoring is necessary for kidney transplant patients when treating with tacrolimus and voriconazole.

AI-Based Optimal Treatment Strategy Selection for Female Infertility for First and Subsequent IVF-ET Cycles.

Over the last 20 years, China's infertility rate has risen from 3% to 12.5%-15%. Infertility has become the third largest disease following cancer and cardiovascular disease. Then, the in vitro fertilization and embryo transfer (IVF-ET) becomes more and more important in infertility treatment field. However, the reported success rate for IVT-ET is 30%-40% and costs are gradually rising. Meanwhile, to increase success rates and decrease costs, the optimal selection of the IVF-ET treatment strategy is crucial. In a clinical work, the IVF-ET treatment strategy selection is always based on the experience of the doctor without a uniform standard. To solve this important and complex problem, we proposed an artificial intelligence (AI)-based optimal treatment strategy selection system to extract implicit knowledge from clinical data for new and returning patients, by mimicking the IVF-ET process and analysing a myriad of treatment decisions. We demonstrated that the performance of the model was different in 10 AI classification algorithms. Hence, we need to select the optimal method for predicting patient pregnancy result in different IVF-ET treatment strategies. Moreover, feature ranking is determined in the proposed model to measure the importance of each patient characteristics. Therefore, better advice can be provided for individual patient characteristics, doctors can provide more valid suggestions regarding certain patient characteristics to improve the accuracy of diagnosis and efficiency.

Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.

OBJECTIVES: Fibroblast-like synoviocytes (FLS) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLS in relapse and remission RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs. METHODS: Combining single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three relapse RA patients and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using qPCR and multiplex immunohistochemistry (HC). We further targeted the critical signals in vitro and in vivo using collage-induced arthritis (CIA) model in rats. RESULTS: Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLS from relapse RA patients where mIHC confirmed the increased expression of FGF10. While the type I interferon pathway was also activated in the lining FLS, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by siRNA in FLS significantly reduced the expression of RANKL. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGFR1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. CONCLUSION: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.

Tailing Optical Pulling Force on a Metal-Dielectric Hybrid Dimer with Electromagnetic Coupling.

In this work, we demonstrate that optical pulling forces (OPFs) can be induced by a hybrid dimer consisting of a Si nanoparticle (NP) and a coated nanoparticle with a gain core and Au shell under normal plane wave illumination. Analytical theory reveals that the underlying physical mechanism relies on interactions between the electric dipole (ED) modes excited in the NPs. As compared with the individual NP, it is found that the magnitude of optical force can be enlarged by almost three orders for the Si NP and one order for the coated gain NP in the coupled dimer. In addition, we find that the OPFs exerted on the NPs are heavily dependent on the gain level of the core materials, the incident polarization angle and the sizes of the NPs. More interestingly, we find that the OPF can also be exerted on a trimer system consisting of two identical Si NPs and a coated NP arranged in a line. The related results could be used to propose a versatile platform for manipulating NPs.