Enhancing spleen-targeted mRNA delivery with branched biodegradable tails in lipid nanoparticles.

The application of mRNA therapy is constrained by the current lipid nanoparticles' (LNPs) inability to target non-liver tissues. In this study, we demonstrate that ionizable lipids equipped with branched and biodegradable tails enhance the selective delivery of mRNA to the spleen, particularly to antigen-presenting cells. This approach offers novel insights into how the chemical structure of LNPs influences their organ-specific targeting capabilities.

Factors Associated with Patient-Caregiver Concordance about Life-Sustaining Treatment Preferences among Advanced Cancer Patients: A Cross-Sectional Study.

OBJECTIVES: Concordance of preferences for end-of-life care regarding patients between patients with advanced cancer and family caregivers can improve the likelihood of honoring dying patients' wishes. However, there is a dearth of knowledge in mainland China. The purpose of this study was to examine patient-family caregiver concordance about patients' life-sustaining treatment preferences and associated factors among patients with advanced cancer in China. METHODS: From September 2019 to December 2021, a convenience sample of 406 dyads of advanced cancer patient-family caregiver were recruited from 2 tertiary hospitals in Wuhan, China. Participants completed a questionnaire about patient's preferences for life-sustaining treatment, respectively. The concordance was assessed by percent agreement and kappa coefficients. Associated factors were identified by univariate analysis and binary logistic regression. RESULTS: The average concordance rate on the preferences for life-sustaining treatment was 56.1%, ranging from 52.9% to 59.3%. Factors associated with a higher level of patient-family caregiver concordance were following: patients who were married, whose educational levels were at college or above, who had not been informed of diagnosis by a physician, who had been informed of the effects and side effects of related drugs by a physician, and who cared for a seriously ill family member or friend and caregivers whose educational level were primary or below. CONCLUSIONS: The patient-family caregiver concordance about patients' life-sustaining treatment preferences among patients with advanced cancer was poor. Patients' and caregivers' understanding of life-sustaining treatment and its efficacy in end-of-life should be facilitated. Relevant conversation should be encouraged between patients and caregivers, thus providing value-concordant end-of-life care for patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Health professionals need to carry out advanced care planning in oncology departments on mainland China to encourage patients and caregivers to discuss patients' end-of-life care preferences. Facilitating patients' and caregivers' understanding of life-sustaining treatment preferences may help improve the patient-caregiver concordance on life-sustaining treatment preferences among patients with advanced cancer.

Parental Mediation, Digital Media Usage, and Health Literacy: An Exploration Among Chinese Elementary School Students.

This study examines the relationship between parental interactions, digital media usage, and health literacy among 19,386 elementary students (ages 6-11) in Guangdong Province, China, using the framework of parental mediation theory. Path analysis revealed that increased digital media usage is associated with decreased health literacy, particularly for short video platforms, which exhibit a significant negative correlation (ß = -.335). Parental interaction was found to significantly reduce the use of instant messaging apps (ß = -.007) and short video platforms (ß = -.008), with the influence being moderated by the student's residence status (boarding or non-boarding). The findings highlight the importance of frequent parental interaction in limiting digital media usage and enhancing health literacy among children. This study suggests that parental mediation theory should pay closer attention to environmental or living status factors, as they can significantly influence its mechanisms of action. Overall, this research contributes to the discourse on digital behavior in childhood and offers evidence-based insights for improving educational and health literacy strategies.

Metformin combined with cisplatin reduces anticancer activity via ATM/CHK2-dependent upregulation of Rad51 pathway in ovarian cancer.

Ovarian cancer (OC) is the deadliest malignancy of the female reproductive system. The standard first-line therapy for OC involves cytoreductive surgical debulking followed by chemotherapy based on platinum and paclitaxel. Despite these treatments, there remains a high rate of tumor recurrence and resistance to platinum. Recent studies have highlighted the potential anti-tumor properties of metformin (met), a traditional diabetes drug. In our study, we investigated the impact of met on the anticancer activities of cisplatin (cDDP) both in vitro and in vivo. Our findings revealed that combining met with cisplatin significantly reduced apoptosis in OC cells, decreased DNA damage, and induced resistance to cDDP. Furthermore, our mechanistic study indicated that the resistance induced by met is primarily driven by the inhibition of the ATM/CHK2 pathway and the upregulation of the Rad51 protein. Using an ATM inhibitor, KU55933, effectively reversed the cisplatin resistance phenotype. In conclusion, our results suggest that met can antagonize the effects of cDDP in specific types of OC cells, leading to a reduction in the chemotherapeutic efficacy of cDDP.

Comparison of minimal access and open breast surgery: a propensity score-matched study on postoperative immune function in breast cancer.

BACKGROUND: Minimal access breast surgery (MABS) is commonly employed in the management of breast cancer, but there is limited research on the postoperative immune function associated with MABS. OBJECTIVE: This study aimed to assess the postoperative immune function in breast patients who underwent MABS or conventional open breast surgery (COBS). METHODS: We retrospectively analyzed the medical records of 829 breast cancer patients treated with either MABS or COBS at a single hospital between January 2020 and June 2023. Among them, 116 matched pairs were obtained through 1:1 propensity score matching (PSM). Flow cytometry was used to measure the percentages of CD3+, CD4+, and CD8+ cells, as well as the CD4+/CD8+ ratio, on three different time points: preoperative day 1 (PreD1), postoperative day 1 (PostD1), and postoperative day 7 (PostD7). RESULTS: Both the MABS and COBS groups demonstrated a significant reduction in the percentages of CD3+, CD4+, and CD8+ cells, along with the CD4+/CD8+ ratio, from PreD1 to PostD1. Interestingly, the MABS group showed a reversal of these parameters, returning to preoperative levels by PostD7. Conversely, the COBS group showed an increase in these parameters from PostD1 to PostD7, but they still remained significantly lower than preoperative levels at PostD7. CONCLUSION: MABS treatment may result in reduced postoperative immune suppression and faster recovery of preoperative immune function compared to COBS in patients.

Microorganisms in the rumen and intestine of camels have the ability to degrade 2-amino-3-methylimidazo[4, 5-f]quinoline.

Heterocyclic amines (HAs) are a group of mutagenic and carcinogenic compounds produced from the processing of high-protein foods, which include 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) showing the strongest carcinogenic effect. Camels are able to digest HAs in foods, which provide rich microbial resources for the study. Thus, camel rumen and intestinal microbiota were used to degrade IQ, and the dominant microorganisms and their degradation characteristics were investigated. After three generations of culture with IQ as the sole carbon source, the highest abundance in rumen and intestinal microbes was found in the Proteobacteria phylum. The strains of third generation of the rumen contents were mainly attributed to the genera Brevundimonas and Pseudomonas, and the dominant genera in intestine were Ochrobactrum, Bacillus, and Pseudomonas. Microorganisms were further isolated and purified from the third generation cultures. These 27 strains from the rumen (L1-L27) and 23 strains from the intestine (C1-C23) were obtained. Among them, four strains with the most effective degrading abilities were as follows: L6 (28.55% of IQ degrading rate) and C1 (25.19%) belonged to the genus Ochrobactrum, L15 (23.41%) belonged to the genus Pseudomonas, and C16 (20.89%) were of the genus Bacillus. This study suggested the application of abundant microbial resources from camels' digestive tract to biodegrade foodborne toxins.

Validity of the Chinese multimorbidity-weighted index in measuring disease burden using health check-ups data in primary care.

BACKGROUND: As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. METHODS: The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). RESULTS: One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. CONCLUSIONS: CMWI, calculated based on primary care's routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients' health risks in primary care.

EEG-DG: A Multi-Source Domain Generalization Framework for Motor Imagery EEG Classification.

Motor imagery EEG classification plays a crucial role in non-invasive Brain-Computer Interface (BCI) research. However, the performance of classification is affected by the non-stationarity and individual variations of EEG signals. Simply pooling EEG data with different statistical distributions to train a classification model can severely degrade the generalization performance. To address this issue, the existing methods primarily focus on domain adaptation, which requires access to the test data during training. This is unrealistic and impractical in many EEG application scenarios. In this paper, we propose a novel multi-source domain generalization framework called EEG-DG, which leverages multiple source domains with different statistical distributions to build generalizable models on unseen target EEG data. We optimize both the marginal and conditional distributions to ensure the stability of the joint distribution across source domains and extend it to a multi-source domain generalization framework to achieve domain-invariant feature representation, thereby alleviating calibration efforts. Systematic experiments conducted on a simulative dataset, BCI competition IV 2a, 2b, and OpenBMI datasets, demonstrate the superiority and competitive performance of our proposed framework over other state-of-the-art methods. Specifically, EEG-DG achieves average classification accuracies of 81.79% and 87.12% on datasets IV-2a and IV-2b, respectively, and 78.37% and 76.94% for inter-session and inter-subject evaluations on dataset OpenBMI, which even outperforms some domain adaptation methods. Our code is available at https://github.com/zxchit2022/EEG-DG for evaluation.

Development and validation of a nomogram for breast cancer-related lymphedema.

To establish and validate a predictive model for breast cancer-related lymphedema (BCRL) among Chinese patients to facilitate individualized risk assessment. We retrospectively analyzed data from breast cancer patients treated at a major single-center breast hospital in China. From 2020 to 2022, we identified risk factors for BCRL through logistic regression and developed and validated a nomogram using R software (version 4.1.2). Model validation was achieved through the application of receiver operating characteristic curve (ROC), a calibration plot, and decision curve analysis (DCA), with further evaluated by internal validation. Among 1485 patients analyzed, 360 developed lymphedema (24.2%). The nomogram incorporated body mass index, operative time, lymph node count, axillary dissection level, surgical site infection, and radiotherapy as predictors. The AUCs for training (N = 1038) and validation (N = 447) cohorts were 0.779 and 0.724, respectively, indicating good discriminative ability. Calibration and decision curve analysis confirmed the model's clinical utility. Our nomogram provides an accurate tool for predicting BCRL risk, with potential to enhance personalized management in breast cancer survivors. Further prospective validation across multiple centers is warranted.

Geographical variation in dementia prevalence across China: a geospatial analysis.

Background: Dementia poses great health and social challenges in China. Dementia prevalence may vary across geographic areas, while comparable estimations on provincial level is lacking. This study aims to estimate dementia prevalence by provinces across China, taking into account risk factors of individual level and potential spatial correlation of provinces. Methods: In this study, 17,176 adults aged 50 years or older were included from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS 2018), covering 28 provinces, autonomous regions and municipalities. To improve provincial representativeness, we constructed provincial survey weights based on China 7th census (2020). The prevalence of dementia and 95% Bayesian credible intervals (BCIs) were estimated using a Bayesian conditional autoregressive (CAR) model with spatially varying coefficients of covariates. Findings: The weighted prevalence of dementia at provincial level in China in 2018 ranged from 2.62% (95%BCI: 1.70%, 3.91%) to 13.53% (95%BCI: 8.82%, 20.93%). High dementia prevalence was concentrated in North China, with a prominent high-high cluster, while provinces of low prevalence were concentrated on East and South China, characterized by a low-low cluster. Ordered by the median estimation of prevalence, the top 10% of provinces, include Xinjiang, Jilin, and Beijing. Meanwhile, Fujian, Zhejiang, and Guangdong rank among the last. The association between dementia prevalence and drinking, smoking, social isolation, physical inactivity, hearing impairment, hypertension, and diabetes exhibits provincial variation. Interpretation: Our study identifies a geospatial disparity in dementia prevalence and risk factor effects across China's provinces, with high-high and low-low clusters in some northern and southern provinces, respectively. The findings emphasize the need for targeted strategies, such as addressing hypertension and hearing impairment, in specific regions for more effective dementia prevention and treatment. Funding: National Science Foundation of China/the Economic and Social Research Council, UK Research and Innovation joint call: Understanding and Addressing Health and Social Challenges for Ageing in the UK and China. UK-China Health And Social Challenges Ageing Project (UKCHASCAP): present and future burden of dementia, and policy responses (grant number 72061137003, ES/T014377/1).

High-Fidelity and Efficient Pluralistic Image Completion with Transformers.

Image completion has made tremendous progress with convolutional neural networks (CNNs), because of their powerful texture modeling capacity. However, due to some inherent properties (e.g., local inductive prior, spatial-invariant kernels), CNNs do not perform well in understanding global structures or naturally support pluralistic completion. Recently, transformers demonstrate their power in modeling the long-term relationship and generating diverse results, but their computation complexity is quadratic to input length, thus hampering the application in processing high-resolution images. This paper brings the best of both worlds to pluralistic image completion: appearance prior reconstruction with transformer and texture replenishment with CNN. The former transformer recovers pluralistic coherent structures together with some coarse textures, while the latter CNN enhances the local texture details of coarse priors guided by the high-resolution masked images. To decode diversified outputs from transformers, auto-regressive sampling is the most common method, but with extremely low efficiency. We further overcome this issue by proposing a new decoding strategy, temperature annealing probabilistic sampling (TAPS), which firstly achieves more than 70× speedup of inference at most, meanwhile maintaining the high quality and diversity of the sampled global structures. Moreover, we find the full CNN architecture will lead to suboptimal solutions for guided upsampling. To render more realistic and coherent contents, we design a novel module, named texture-aware guided attention, to concurrently consider the procedures of texture copy and generation, meanwhile raising several important modifications to solve the boundary artifacts. Through dense experiments, we found the proposed method vastly outperforms state-of-the-art methods in terms of four aspects: 1) large performance boost on image fidelity even compared to deterministic completion methods; 2) better diversity and higher fidelity for pluralistic completion; 3) exceptional generalization ability on large masks and generic dataset, like ImageNet. 4) Much higher decoding efficiency over previous auto-regressive based methods.

Film-Forming Capability and Antibacterial Activity of Surface-Deacetylated Chitin Nanocrystals: Role of Degree of Deacetylation.

Developing sustainable food-active packaging materials is a major issue in food preservation applications. Chitin nanocrystals (ChNCs) are regarded as unique bioderived nanomaterials due to their inherent nitrogen moiety. By tuning the chemical functionality of this nanomaterial, it is possible to affect its properties, such as film-forming capability and antibacterial activity. In this work, surface-deacetylated chitin nanocrystals (D-ChNCs) with different degrees of deacetylation (DDs) were prepared by partial deacetylation of native chitin and subsequent acid hydrolysis, and their film-forming capability and antibacterial activity were studied systematically. The D-ChNCs showed favorable film-forming ability and antibacterial activity, which are closely related to their DD. With the increase in DD (from 5.7% to 45.4%), the formed transparent films based on ChNCs showed gradually increased elongation at break (from 0.5% to 2.5%) and water contact angle (from 25.5° to 87.0°), but decreased break strength (from 3.13 to 0.89 MPa), Young's modulus (from 0.84 to 0.24 MPa), and water vapor permeability (from 4.7 × 10-10 to 4.1 × 10-10g/m s Pa). Moreover, the antibacterial activity of the D-ChNCs against E. coli and S. aureus also increased with the increase of DD. This study also found that the depolarization and potential dissipation of the bacterial cell membrane induced by the contact between amino-rich D-ChNCs and bacteria through electrostatic attraction are the possible mechanisms causing bacterial cell death. This study provides a basis for understanding the effects of DD on the film-forming capability and antibacterial activity of ChNCs, which is conducive to the design of novel active packaging films based on ChNCs.

StyleRetoucher: Generalized Portrait Image Retouching with GAN Priors.

Creating fine-retouched portrait images is tedious and time-consuming even for professional artists. There exist automatic retouching methods, but they either suffer from over-smoothing artifacts or lack generalization ability. To address such issues, we present StyleRetoucher, a novel automatic portrait image retouching framework, leveraging StyleGAN's generation and generalization ability to improve an input portrait image's skin condition while preserving its facial details. Harnessing the priors of pretrained StyleGAN, our method shows superior robustness: a). performing stably with fewer training samples and b). generalizing well on the out-domain data. Moreover, by blending the spatial features of the input image and intermediate features of the StyleGAN layers, our method preserves the input characteristics to the largest extent. We further propose a novel blemish-aware feature selection mechanism to effectively identify and remove the skin blemishes, improving the image skin condition. Qualitative and quantitative evaluations validate the great generalization capability of our method. Further experiments show  StyleRetoucher's superior performance to the alternative solutions in the image retouching task. We also conduct a user perceptive study to confirm the superior retouching performance of our method over the existing state-of-the-art alternatives.

Preparation of Dendrobium officinale Polysaccharide by Lactic Acid Bacterium Fermentation and Its Protective Mechanism against Alcoholic Liver Damage in Mice.

Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were →4)-ß-D-Manp(1→, →4)-ß-Glcp(1→, ß-D-Manp(1→, and ß-D-Glcp(1→. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1ß to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.

Toward a Medication Information Literacy Indicator System for Older Adults: A Delphi Study.

BACKGROUND: The safety of medication use among older adults is a growing concern, given the aging population. Despite widespread attention, the exploration of medication literacy in older adults, particularly from the perspective of information literacy, is in its nascent stages. METHODS: This study utilized the existing literature to define medication information literacy (MIL) as a theoretical framework. A two-round Delphi survey was conducted to identify the essential components of a MIL indicator system for older adults. The analytic hierarchy process (AHP) was then used to assign weights to each indicator. RESULTS: The study observed relatively high response rates in both rounds of the questionnaire, which, along with expert authority coefficients (Cr) of 0.86 and 0.89, underscores the credibility and expertise of the panellists. Additionally, Kendall's coefficient of concordance (Kendall's W) ranging from 0.157 to 0.33 (p < 0.05) indicates a consensus among experts on the identified indicators. Utilizing the Delphi process, a MIL indicator system for older adults was developed, comprising five primary and 23 secondary indicators. These indicators were weighted, with medication information cognition and acquisition emerging as pivotal factors in enhancing medication literacy among older adults. CONCLUSIONS: This study developed a MIL indicator system tailored for older adults using the Delphi approach. The findings can inform healthcare professionals in providing customized medication guidance and assist policymakers in crafting policies to enhance medication safety among older adults. PATIENT OR PUBLIC CONTRIBUTION: Patient and public engagement played a pivotal role in the development of our medication information literacy indicator system for older adults. Their involvement contributed to shaping research questions, facilitating study participation, and enriching evidence interpretation. Collaborations with experts in geriatric nursing, medicine, and public health, along with discussions with caregivers and individuals with lived experience, provided invaluable insights into medication management among older adults. Their input guided our research direction and ensured the relevance and comprehensiveness of our findings.

The dynamics and control of a multi-lingual rumor propagation model with non-smooth inhibition mechanism.

In this paper, the dynamic behaviors and control strategies of a rumor propagation model are studied in multi-lingual environment. First, an S2E2I2R rumor propagation model is proposed, which incorporates a non-smooth inhibition mechanism. Meanwhile, the existence and stability of the equilibrium are analyzed, grounded in the spreader threshold of the government intervention. Finally, the optimal control and the event-triggered impulsive control strategies are proposed to mitigate the spread of rumors, and the comparison of their effectiveness is further presented by the numerical simulation and a practical case.

Reduced expression of cathepsin F predicts poor prognosis in patients with clear cell renal cell carcinoma.

Abnormalities in the extracellular matrix (ECM) play important roles in the regulation and progression of clear cell renal cell carcinoma (ccRCC). The cysteine cathepsin is one of the major proteases involved in ECM remodeling and has been shown to be aberrantly expressed in multiple cancer types. However, the clinical significance and biological function of distinct cysteine cathepsins in ccRCC remain poorly understood. In this study, several bioinformatics databases, including UALCAN, TIMER, GEPIA and the Human Protein Atlas datasets, were used to analyze the expression and prognostic value of different cysteine cathepsin family members in ccRCC. We found that the expression level of CTSF was downregulated in tumor tissues and closely related to the poor survival of ccRCC patients. Further in vitro experiments suggested that CTSF overexpression suppressed the proliferation and migration of ccRCC cells. Moreover, the expression of CTSF was shown to be associated with several immune-infiltrating cells and immunomodulators in ccRCC. These results indicated that CTSF might be a promising diagnostic and prognostic marker in ccRCC.

The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.

MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.

Impairment in acquisition of conditioned fear in people with depressive symptoms.

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.