The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons.

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals' cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

Synergistic Construction of Sub-Nanometer Channel Membranes through MOF-Polymer Composites: Strategies and Nanofiltration Applications.

The selective separation of small molecules at the sub-nanometer scale has broad application prospects in the field, such as energy, catalysis, and separation. Conventional polymeric membrane materials (e.g., nanofiltration membranes) for sub-nanometer scale separations face challenges, such as inhomogeneous channel sizes and unstable pore structures. Combining polymers with metal-organic frameworks (MOFs), which possess uniform and intrinsic pore structures, may overcome this limitation. This combination has resulted in three distinct types of membranes: MOF polycrystalline membranes, mixed-matrix membranes (MMMs), and thin-film nanocomposite (TFN) membranes. However, their effectiveness is hindered by the limited regulation of the surface properties and growth of MOFs and their poor interfacial compatibility. The main issues in preparing MOF polycrystalline membranes are the uncontrollable growth of MOFs and the poor adhesion between MOFs and the substrate. Here, polymers could serve as a simple and precise tool for regulating the growth and surface functionalities of MOFs while enhancing their adhesion to the substrate. For MOF mixed-matrix membranes, the primary challenge is the poor interfacial compatibility between polymers and MOFs. Strategies for the mutual modification of MOFs and polymers to enhance their interfacial compatibility are introduced. For TFN membranes, the challenges include the difficulty in controlling the growth of the polymer selective layer and the performance limitations caused by the "trade-off" effect. MOFs can modulate the formation process of the polymer selective layer and establish transport channels within the polymer matrix to overcome the "trade-off" effect limitations. This review focuses on the mechanisms of synergistic construction of polymer-MOF membranes and their structure-nanofiltration performance relationships, which have not been sufficiently addressed in the past.

Effects of ethyl palmitate on the release of aroma compounds in propanediol-ethanol solution and its mechanisms.

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

Identification of genetic variants controlling diosgenin content in Dioscorea zingiberensis tuber by genome-wide association study.

BACKGROUND: Diosgenin is an important steroidal precursor renowned for its diverse medicinal uses. It is predominantly sourced from Dioscorea species, particularly Dioscorea zingiberensis. Dioscorea zingiberensis has an ability to accumulate 2-16% diosgenin in its rhizomes. In this study, a diverse population of 180 D. zingiberensis accessions was used to evaluate the genomic regions associated with diosgenin biosynthesis by the genome wide association study approach (GWAS). RESULTS: The whole population was characterized for diosgenin contents from tubers by gas chromatography mass spectrometry. The individuals were genotyped by the genotyping-by-sequencing approach and 10,000 high-quality SNP markers were extracted for the GWAS. The highest significant marker-trait-association was observed as an SNP transversion (G to T) on chromosome 10, with 64% phenotypic variance explained. The SNP was located in the promoter region of CYP94D144 which is a member of P450 gene family involved in the independent biosynthesis of diosgenin from cholesterol. The transcription factor (TF) binding site enrichment analysis of the promoter region of CYP94D144 revealed NAC TF as a potential regulator. The results were further validated through expression profiling by qRT-PCR, and the comparison of high and low diosgenin producing hybrids obtained from a bi-parental population. CONCLUSIONS: This study not only enhanced the understanding of the genetic basis of diosgenin biosynthesis but also serves as a valuable reference for future genomic investigations on CYP94D144, with the aim of augmenting diosgenin production in yam tubers.

Unlocking Dynamic Solvation Chemistry and Hydrogen Evolution Mechanism in Aqueous Zinc Batteries.

Understanding the interfacial hydrogen evolution reaction (HER) is crucial to regulate the electrochemical behavior in aqueous zinc batteries. However, the mechanism of HER related to solvation chemistry remains elusive, especially the time-dependent dynamic evolution of the hydrogen bond (H-bond) under an electric field. Herein, we combine in situ spectroscopy with molecular dynamics simulation to unravel the dynamic evolution of the interfacial solvation structure. We find two critical change processes involving Zn-electroplating/stripping, including the initial electric double layer establishment to form an H2O-rich interface (abrupt change) and the subsequent dynamic evolution of an H-bond (gradual change). Moreover, the number of H-bonds increases, and their strength weakens in comparison with the bulk electrolyte under bias potential during Zn2+ desolvation, forming a diluted interface, resulting in massive hydrogen production. On the contrary, a concentrated interface (H-bond number decreases and strength enhances) is formed and produces a small amount of hydrogen during Zn2+ solvation. The insights on the above results contribute to deciphering the H-bond evolution with competition/corrosion HER during Zn-electroplating/stripping and clarifying the essence of electrochemical window widened and HER suppression by high concentration. This work presents a new strategy for aqueous electrolyte regulation by benchmarking the abrupt change of the interfacial state under an electric field as a zinc performance-enhancement criterion.

Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats.

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.

More than expected: extracellular waveforms and functional responses in monkey LGN.

Unlike the exhaustive determination of cell types in the retina, key populations in the lateral geniculate nucleus of the thalamus (LGN) may have been missed. Here, we have begun to characterize the full range of extracellular neuronal responses in the LGN of awake monkeys using multi-electrodes during the presentation of colored noise visual stimuli to identify any previously overlooked signals. Extracellular spike waveforms of single units were classified into seven distinct classes, revealing previously unrecognized diversity: four negative-dominant classes that were narrow or broad, one triphasic class, and two positive-dominant classes. Based on their mapped receptive field (RF), these units were further categorized into either magnocellular (M), parvocellular (P), koniocellular (K), or non-RF (N). We found correlations between spike shape and mapped RF and response characteristics, with negative and narrow spiking waveform units predominantly associated with P and N RFs, and positive waveforms mostly linked to M RFs. Responses from positive waveforms exhibited shorter latencies, larger RF sizes, and were associated with larger eccentricities in the visual field than the other waveform classes. Additionally, N cells, those without an estimated RF, were consistently responsive to the visually presented mapping stimulus at a lower and more sustained rate than units with an RF. These findings suggest that the LGN cell population may be more diverse than previously believed.

CO electrolysis to multicarbon products over grain boundary-rich Cu nanoparticles in membrane electrode assembly electrolyzers.

Producing valuable chemicals like ethylene via catalytic carbon monoxide conversion is an important nonpetroleum route. Here we demonstrate an electrochemical route for highly efficient synthesis of multicarbon (C2+) chemicals from CO. We achieve a C2+ partial current density as high as 4.35 ± 0.07 A cm-2 at a low cell voltage of 2.78 ± 0.01 V over a grain boundary-rich Cu nanoparticle catalyst in an alkaline membrane electrode assembly (MEA) electrolyzer, with a C2+ Faradaic efficiency of 87 ± 1% and a CO conversion of 85 ± 3%. Operando Raman spectroscopy and density functional theory calculations reveal that the grain boundaries of Cu nanoparticles facilitate CO adsorption and C - C coupling, thus rationalizing a qualitative trend between C2+ production and grain boundary density. A scale-up demonstration using an electrolyzer stack with five 100 cm2 MEAs achieves high C2+ and ethylene formation rates of 118.9 mmol min-1 and 1.2 L min-1, respectively, at a total current of 400 A (4 A cm-2) with a C2+ Faradaic efficiency of 64%.

Comparative effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide formation in potato chips.

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.

Multichannel highly secure wireless communication system with information camouflage capability.

Information metasurface has shown great potential in wireless communications owing to its ability to flexibly control electromagnetic waves. However, it is still a big challenge to achieve high-security and large-channel capacity wireless communications by a simple system. Here, we propose a space-polarization-division multiplexing secure wireless communication system with information camouflage capability based on the information metasurface, which can realize multichannel encrypted wireless communications with different polarization coding strategies independently and simultaneously. A polarization mask key is introduced to encrypt the target message, and the cipher message is further concealed behind a cover image with steganography and sent to the user by using the polarization modulation strategy. Different polarization mask keys can be adopted in each individual communication by changing the polarization coding strategy to enhance the system security. The proposed scheme integrates computational algorithm encryption and physical layer security together and thus has the advantages of high security, large channel capacity, and strong camouflage ability.

Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy.

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI.

GmTCP40 Promotes Soybean Flowering under Long-Day Conditions by Binding to the GmAP1a Promoter and Upregulating Its Expression.

Soybean [Glycine max (L.) Merr.] is a short-day (SD) plant that is sensitive to photoperiod, which influences flowering, maturity, and even adaptation. TEOSINTE-BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factors have been shown to regulate photoperiodic flowering. However, the roles of TCPs in SD plants such as soybean, rice, and maize remain largely unknown. In this study, we cloned the GmTCP40 gene from soybean and investigated its expression pattern and function. Compared with wild-type (WT) plants, GmTCP40-overexpression plants flowered earlier under long-day (LD) conditions but not under SD conditions. Consistent with this, the overexpression lines showed upregulation of the flowering-related genes GmFT2a, GmFT2b, GmFT5a, GmFT6, GmAP1a, GmAP1b, GmAP1c, GmSOC1a, GmSOC1b, GmFULa, and GmAG under LD conditions. Further investigation revealed that GmTCP40 binds to the GmAP1a promoter and promotes its expression. Analysis of the GmTCP40 haplotypes and phenotypes of soybean accessions demonstrated that one GmTCP40 haplotype (Hap6) may contribute to delayed flowering at low latitudes. Taken together, our findings provide preliminary insights into the regulation of flowering time by GmTCP40 while laying a foundation for future research on other members of the GmTCP family and for efforts to enhance soybean adaptability.

DNA topoisomerase II inhibition potentiates osimertinib's therapeutic efficacy in EGFR-mutant non-small cell lung cancer models.

Development of effective strategies to manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the treatment of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), is urgently needed. This study reports that DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide, synergistically decreased cell survival, with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells; suppressed the growth of osimertinib-resistant tumors; and delayed the emergence of osimertinib-acquired resistance. Mechanistically, osimertinib decreased Topo IIα levels in EGFRm NSCLC cells by facilitating FBXW7-mediated proteasomal degradation, resulting in induction of DNA damage; these effects were lost in osimertinib-resistant cell lines that possess elevated levels of Topo IIα. Increased Topo IIα levels were also detected in the majority of tissue samples from patients with NSCLC after relapse from EGFR tyrosine kinase inhibitor treatment. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their susceptibility to osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.

Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

Polysaccharide hydrogel containing silver nanoparticle@catechol microspheres with photothermal, antibacterial and anti-inflammatory activities for infected-wounds repair.

Anti-infection hydrogels have recently aroused enormous attraction, particularly in the treatment of chronic wounds. Herein, silver nanoparticle@catechol formaldehyde resin microspheres (Ag@CFRs) were fabricated by one-step hydrothermal method and subsequently encapsulated in hydrogels which were developed by Schiff base reaction between aldehyde groups in oxidized hyaluronic acid and amino groups in carboxymethyl chitosan. The developed polysaccharide hydrogel exhibited microporous structure, high swelling capacity, favorable mechanical strength, enhanced tissue adhesion and photothermal activities. Additionally, the hydrogel not only ensured long-term and high-efficiency antibacterial performance (99.9 %) toward E. coli and S. aureus, but also realized superior cytocompatibility in vitro. Moreover, based on the triple antibacterial strategies endowed by chitosan, silver nanoparticles and the photothermal properties of catechol microspheres, the composite hydrogel exhibited excellent anti-infection function, significantly downregulated inflammatory factors (TNF-α and IL-1ß) and promoted in vivo infected-wound healing. These results demonstrated that the polysaccharide hydrogel containing Ag@CFRs has great potential for infected-wounds repair.

Changed nocturnal levels of stress-related hormones couple with sleep-wake states in the patients with chronic insomnia disorder: A clinical pilot study.

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.

Visualizing and Regulating Dynamic Evolution of Interfacial Electrolyte Configuration during De-solvation Process on Lithium-Metal Anode.

Acting as a passive protective layer, solid-electrolyte interphase (SEI) plays a crucial role in maintaining the stability of the Li-metal anode. Derived from the reductive decomposition of electrolytes (e.g., anion and solvent), the SEI construction presents as an interfacial process accompanied by the dynamic de-solvation process during Li-metal plating. However, typical electrolyte engineering and related SEI modification strategies always ignore the dynamic evolution of electrolyte configuration at the Li/electrolyte interface, which essentially determines the SEI architecture. Herein, by employing advanced electrochemical in situ FT-IR and MRI technologies, we directly visualize the dynamic variations of solvation environments involving Li+-solvent/anion. Remarkably, a weakened Li+-solvent interaction and anion-lean interfacial electrolyte configuration have been synchronously revealed, which is difficult for the fabrication of anion-derived SEI layer. Moreover, as a simple electrochemical regulation strategy, pulse protocol was introduced to effectively restore the interfacial anion concentration, resulting in an enhanced LiF-rich SEI layer and improved Li-metal plating/stripping reversibility.

Photo-modulated activation of organic bases enabling microencapsulation and on-demand reactivity.

A method is developed for facile encapsulation of reactive organic bases with potential application for autonomous damage detection and self-healing polymers. Highly reactive chemicals such as bases and acids are challenging to encapsulate by traditional oil-water emulsion techniques due to unfavorable physical and chemical interactions. In this work, reactivity of the bases is temporarily masked with photo-removable protecting groups, and the resulting inactive payloads are encapsulated via an in situ emulsion-templated interfacial polymerization method. The encapsulated payloads are then activated to restore the organic bases via photo irradiation, either before or after being released from the core-shell carriers. The efficacy of the photo-activated capsules is demonstrated by a damage-triggered, pH-induced color change in polymeric coatings and by recovery of adhesive strength of a damaged interface. Given the wide range of potential photo-deprotection chemistries, this encapsulation scheme provides a simple but powerful method for storage and targeted delivery of a broad variety of reactive chemicals, promoting design of diverse autonomous functionalities in polymeric materials.

Constructing the Polymer Molecules to Regulate the Electrode/Electrolyte Interface to Enhance Lithium-Metal Battery Performance.

Lithium-ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single-functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile-butyl hexafluoro methacrylate- poly (ethylene glycol) methacrylate- methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4-hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF- and Li3N-rich is formed at the cathode-electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm-2, the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g-1, with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium-metal batteries.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.