Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.

Aims: Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes. Methods: A Chinese infertile man with MMAF and PCD was enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify potential causative genes and mutations. Results: A novel homozygous missense mutation (c.1450G>A; p.E484K) of CCDC40 was finally identified and Sanger sequencing confirmed that the patient carried the homozygous mutation, which was inherited from his parents. We reported the first homozygous missense CCDC40 mutation in infertile men with MMAF but had other milder PCD symptoms. Conclusion: Our findings not only broaden the disease-causing mutation spectrum of CCDC40 but also provide new insight into the correlation between CCDC40 mutations and MMAF.

Understanding the dynamics of microplastics transport in urban stormwater runoff: Implications for pollution control and management.

The transport of microplastics (MPs) from urban environments to water resources via stormwater runoff poses significant concerns due to its adverse impacts on water safety and aquatic ecosystems. This study presents a modeling approach aimed at understanding the transport mechanisms of MPs in an urban residential setting, considering settling and buoyant MPs. To consider the effect of MP shapes, the settling velocity of various settling MPs in shapes of fibers, films, and fragments was calculated. Using an analogy of sediment transport, a Rouse number criterion was used to analyze the transport of MPs. For buoyant MPs, it was assumed that they transport as wash-load as soon as they float in the water and the travel time for them to reach the storm drain was determined. The calculation of settling velocity revealed the influence of shape on the settling velocity of MPs was particularly pronounced as the equivalent diameter of the MPs increased. The transport mechanism for the smallest settling MPs, irrespective of their shapes, density, and depth of flow, was wash-load. However, for larger MPs, the shape and size distribution of settling MPs, along with the depth of flow and slope significantly influenced their transport mechanisms compared to sediment particles. The influence of weathering on the MPs' transport mechanisms depended on their sizes and shapes. The site-specific characteristics, including slope and surface friction, significantly influenced the velocity of stormwater runoff and, consequently, the extent of MP transport during rain events. Moreover, an evaluation of the transport mechanism of settling MPs was conducted using the reported field data on MP abundance in road dust collected from residential and traffic sites. This study underscores the complexity of MP transport dynamics and provides a foundation for developing targeted strategies to mitigate MP pollution in urban environments.

Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction.

Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL's prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

How COVID-19 Information Fear of Missing out Increases the Risk of Depression and Anxiety: Roles of Resilience and Personality Types.

During major health emergencies (e.g., the COVID-19 pandemic) people often fear missing relevant information. COVID-19 information fear of missing out (FOMO) is a phenomenon where people feel anxiety about losing control of COVID-19-related information. The present study aimed to examine how COVID-19 information FOMO relates to mental health (e.g., depression and anxiety), the mediating role of resilience, and the moderating role of personality types during the COVID-19 pandemic. We surveyed 1442 Chinese undergraduates (Mage = 21.68 ± 2.35 years) on the relevant variables. The results showed that COVID-19 information FOMO was positively associated with depression and anxiety, and resilience mediated these associations. Latent profile analysis (LPA) identified three personality types (undercontrolled, adaptive, and overcontrolled). Personality types moderated the mediation models, in which the indirect effects were only significant in the participants classified in the undercontrolled group rather than the participants classified in the other two groups. This study told us that undergraduates' mental health, particularly that of the undercontrollers, should be paid attention to when responding to a major public health emergency (e.g., the COVID-19 pandemic).

Quantifying the CO2 sink intensity of large and small saline lakes on the Tibetan Plateau.

This study quantitatively evaluates the carbon dioxide (CO2) sink intensity of a large saline lake (area > 2000 km2) and a small saline lake (area 1.4 km2) on the Tibetan Plateau (TP), alongside an alpine meadow, by analysing their net ecosystem exchange (NEE) figures obtained by eddy covariance (EC) measurements. Specifically, the "large lake" exhibits an NEE value of -122.51 g C m-2 yr-1, whereas the small lake has an NEE value of -47.17 g C m-2 yr-1. The alpine meadow, in contrast, demonstrates an NEE value of -128.18 g C m-2 yr-1. Through standardization of the eddy flux data processing and accounting for site-specific conditions with a wind direction filter and footprint analysis, the study provides robust estimates of CO2 sink intensity. The "large lake" was found to absorb CO2 primarily during non-icing cold periods with minimal exchange occurring during ice-covered season, whereas the "small lake" showed no significant CO2 exchange throughout the year. On the other hand, alpine meadows engaged in CO2 uptake during the vegetative growth season but showed weak CO2 release in winter. CO2 uptake in lakes is mainly controlled by ice barrier and chemical processes, while biological processes dominate the alpine meadow. The carbon sink intensity of the TP's saline lakes is estimated to be 1.87-3.01 Tg C yr-1, smaller than the previous reported estimations. By evaluating the CO2 sink intensity of different lakes, the study highlights the importance of saline lakes in regional carbon balance assessments. It specifically points out the differential roles lakes of various sizes play in the carbon cycle, thereby enriching our understanding of carbon dynamics in high-altitude lacustrine ecosystems.

New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model.

OBJECTIVE: The high mortality rate of gastric cancer, traditionally managed through surgery, underscores the urgent need for advanced therapeutic strategies. Despite advancements in treatment modalities, outcomes remain suboptimal, necessitating the identification of novel biomarkers to predict sensitivity to immunotherapy. This study focuses on utilizing single-cell sequencing for gene identification and developing a random forest model to predict immunotherapy sensitivity in gastric cancer patients. METHODS: Differentially expressed genes were identified using single-cell RNA sequencing (scRNA-seq) and gene set enrichment analysis (GESA). A random forest model was constructed based on these genes, and its effectiveness was validated through prognostic analysis. Further, analyses of immune cell infiltration, immune checkpoints, and the random forest model provided deeper insights. RESULTS: High METTL1 expression was found to correlate with improved survival rates in gastric cancer patients (P = 0.042), and the random forest model, based on METTL1 and associated prognostic genes, achieved a significant predictive performance (AUC = 0.863). It showed associations with various immune cell types and negative correlations with CTLA4 and PDCD1 immune checkpoints. Experiments in vitro and in vivo demonstrated that METTL1 enhances gastric cancer cell activity by suppressing T cell proliferation and upregulating CTLA4 and PDCD1. CONCLUSION: The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.

Lipidomics analysis of bone marrow in a mouse model of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.

Effects of low protein feed on hepato-intestinal health and muscle quality of grass carp (Ctenopharyngodon idellus).

In this study, grass carp (33.28 ± 0.05 g) were fed three diets for 8 weeks: control (crude protein [CP] 30%, crude lipid [CL] 6%), low protein (LP; CP16%, CL6%), and low protein with high-fat (LPHF; CP16%, CL10%). The final body weight decreased in the LP and LPHF groups compared to the Control (P < 0.05). Liver triglycerides, total cholesterol, and nonesterified fatty acids were higher in the LP group than the Control, whereas these indexes in the LPHF group were higher than those in the LP group (P < 0.05). The LP group had intestinal barrier damage, while the LPHF group had a slight recovery. TNF-α, IL-8, and IL-1ß content were lower in the LP group than in the Control (P < 0.05), and even higher in the LPHF group (P < 0.05). The expressions of endoplasmic reticulum stress-related genes Activating transcription factor 6 (ATF-6) and Glucose-regulated protein (GRP78) were higher in the LPHF group against the LP group (P < 0.05). The IL-1ß and TNF-α content negatively correlated with intestinal Actinomycetes and Mycobacterium abundance (P < 0.05). The muscle fiber diameter was smaller in both the LP and LPHF groups than the control (P < 0.05), with the LP group showing metabolites related to protein digestion and absorption, and LPHF group exhibiting metabolites related to taste transmission. The results demonstrate reducing dietary protein affects growth, causing liver lipid accumulation, reduced enteritis response, and increased muscle tightness, while increasing fat content accelerates fat accumulation and inflammation.

How adult children experience and cope with their parents' diagnosis of multiple myeloma: A qualitative exploration.

PURPOSE: The aim of this study was to understand and explore the caregiving experience of adult children of patients with multiple myeloma (MM) during diagnosis and initial treatment based in Chinese filial piety culture. METHODS: A descriptive phenomenology study was conducted to investigate semi-structured interview responses from the adult children (N = 22) of MM patients within three months after diagnosis. Colaizzi's descriptive analysis framework was employed to analyze data. This study was reported following the COREQ checklist. RESULTS: Four themes and twelve subthemes were identified from the interviews. (1) Commitment to filial piety. Participants subconsciously fulfilled their commitment to filial piety by supporting their parents, obeying their wishes, providing emotional comfort, and protecting them from harm. (2) Experiencing multiple dilemmas. They faced challenges such as difficult treatment decisions, insufficient caregiving preparation, emotional distress, and role conflict. (3) Benefiting from setbacks. The caregiving experience allowed participants to cherish the present more and to establish a new view of life. (4) Adaptive coping. Family supports and self-adaptation are effective coping strategies to achieve their good psychosocial adaptation. CONCLUSIONS: Our study provides a culturally sensitive perspective on the caregiving experience of adult children of patients with MM. This study found that Chinese culture, especially filial piety culture, influenced the experiences and coping strategies of MM caregivers. Healthcare providers should focus on the challenges faced by adult children and develop various strategies to help them cushion the burden and adjust to caregiving roles, such as supportive care programs, meaning-centered psychotherapy, and family-centered medical communication interventions.

Segmentation of bone surface from ultrasound using a lightweight network UBS-Net.

Objective. Ultrasound-assisted orthopaedic navigation held promise due to its non-ionizing feature, portability, low cost, and real-time performance. To facilitate the applications, it was critical to have accurate and real-time bone surface segmentation. Nevertheless, the imaging artifacts and low signal-to-noise ratios in the tomographical B-mode ultrasound (B-US) images created substantial challenges in bone surface detection. In this study, we presented an end-to-end lightweight US bone segmentation network (UBS-Net) for bone surface detection.Approach. We presented an end-to-end lightweight UBS-Net for bone surface detection, using the U-Net structure as the base framework and a level set loss function for improved sensitivity to bone surface detectability. A dual attention (DA) mechanism was introduced at the end of the encoder, which considered both position and channel information to obtain the correlation between the position and channel dimensions of the feature map, where axial attention (AA) replaced the traditional self-attention (SA) mechanism in the position attention module for better computational efficiency. The position attention and channel attention (CA) were combined with a two-class fusion module for the DA map. The decoding module finally completed the bone surface detection.Main Results. As a result, a frame rate of 21 frames per second (fps) in detection were achieved. It outperformed the state-of-the-art method with higher segmentation accuracy (Dice similarity coefficient: 88.76% versus 87.22%) when applied the retrospective ultrasound (US) data from 11 volunteers.Significance. The proposed UBS-Net for bone surface detection in ultrasound achieved outstanding accuracy and real-time performance. The new method out-performed the state-of-the-art methods. It had potential in US-guided orthopaedic surgery applications.

Effects of sleep-disordered breathing on serum lipid levels in children:a case control study.

BACKGROUND: Sleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese. METHODS: This was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays. RESULTS: A total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group. CONCLUSIONS: SDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG. TRIAL REGISTRATION: ChiCTR1900026807(2019.10.23).

Ecological inferences on invasive carp survival using hydrodynamics and egg drift models.

Bighead carp (Hypophthalmichthys nobilis), silver carp (H. molitrix), black carp (Mylopharyngodon piceus), and grass carp (Ctenopharyngodon idella), are invasive species in North America. However, they hold significant economic importance as food sources in China. The drifting stage of carp eggs has received great attention because egg survival rate is strongly affected by river hydrodynamics. In this study, we explored egg-drift dynamics using computational fluid dynamics (CFD) models to infer potential egg settling zones based on mechanistic criteria from simulated turbulence in the Lower Missouri River. Using an 8-km reach, we simulated flow characteristics with four different discharges, representing 45-3% daily flow exceedance. The CFD results elucidate the highly heterogeneous spatial distribution of flow velocity, flow depth, turbulence kinetic energy (TKE), and the dissipation rate of TKE. The river hydrodynamics were used to determine potential egg settling zones using criteria based on shear velocity, vertical turbulence intensity, and Rouse number. Importantly, we examined the difference between hydrodynamic-inferred settling zones and settling zones predicted using an egg-drift transport model. The results indicate that hydrodynamic inference is useful in determining the 'potential' of egg settling, however, egg drifting paths should be taken into account to improve prediction. Our simulation results also indicate that the river turbulence does not surpass the laboratory-identified threshold to pose a threat to carp eggs.

Interfering with reconsolidation by rimonabant results in blockade of heroin-associated memory.

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6 hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder.

Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.

This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P  < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P <  0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P  < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).

Brain frailty associated with stroke events in anterior circulation large artery occlusion.

OBJECTIVE: To investigate the factors associated with brain frailty and the effect of brain frailty in patients with anterior circulation large artery occlusion (AC-LAO). METHODS: 1100 patients with AC-LVO consecutively admitted to the Second Hospital of Hebei Medical University, North China between June 2016 and April 2018 were retrospectively analyzed. The variables associated with brain frailty and stroke outcome were analyzed by ANOVA analysis, the Mann-Whitney U test and multiple linear regression. Based on previous research. Brain frailty score comprises 1 point each for white matter hyperintensity (WMH), old infarction lesions, and cerebral atrophy among 983 participants with baseline brain magnetic resonance imaging or computed tomography. RESULTS: Among AC-LAO participants, baseline brain frailty score ≥ 1 was common (750/983, 76.3%). Duration of hypertension > 5 years (mean difference [MD] 0.236, 95% CI 0.077, 0.395, p = 0.004), multiple vessel occlusion (MD 0.339, 95% CI 0.068, 0.611, p = 0.014) and basal ganglia infarction (MD -0.308, 95% CI -0.456, -0.160, p < 0.001) were independently associated with brain frailty score. Brain frailty score was independently associated with stroke events, and higher brain frailty scores were associated with higher rates of stroke events (p < 0.001). However, brain frailty has no independent effect on short-term outcome of ACI in AC-LAO patients. CONCLUSIONS: In AC-LAO patients, older age, duration of hypertension > 5 years, and multiple vessel occlusion influenced the brain frailty score. Brain frailty score was independently associated with the occurrence of stroke events in AC-LAO patients.

High-Performance Room Temperature Ammonia Sensors Based on Pure Organic Molecules Featuring B-N Covalent Bond.

Exploring organic semiconductor gas sensors with high sensitivity and selectivity is crucial for the development of sensor technology. Herein, for the first time, a promising chemiresistive organic polymer P-BNT based on a novel π-conjugated triarylboron building block is reported, showcasing an excellent responsivity over 30 000 (Ra/Rg) against 40 ppm of NH3, which is ≈3300 times higher than that of its B-N organic small molecule BN-H. More importantly, a molecular induction strategy to weaken the bond dissociation energy between polymer and NH3 caused by strong acid-base interaction is further executed to optimize the response and recovery time. As a result, the BN-H/P-BNT system with rapid response and recovery times can still exhibit a high responsivity of 718, which is among the highest reported NH3 chemiresistive sensors. Supported by in situ FTIR spectroscopy and theoretical calculations, it is revealed that the N-H fractions in BN-H small molecule promoted the charge distribution on phenyl groups, which increases charge delocalization and is more conducive to gas adsorption in such molecular systems. Notably, these distinctive small molecules also promoted charge transfer and enhanced electron concentration of the P-BNT sensing polymer, thus achieving superior B-N-containing organic molecules with excellent sensing performance.

Regulation of histone acetylation by garcinol blocks the reconsolidation of heroin-associated memory.

Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.

Epistasis in neurotransmitter receptors linked to posttraumatic stress disorder and major depressive disorder comorbidity in traumatized Chinese.

Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD-MDD comorbidity. Methods: Four groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD-MDD comorbidity. NPY2R (rs4425326), NPY5R (rs11724320), DRD2 (rs1079597), and DRD3 (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene-environment interaction (G × E), and gene-gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD-MDD comorbidity as a reference. Results: The results demonstrated that compared to PTSD-MDD comorbidity, epistasis (G × G) NPY2R-DRD2 (rs4425326 × rs1079597) affects low symptoms (ß = -0.66, OR = 0.52 [95% CI: 0.32-0.84], p = 0.008, pperm = 0.008) and predominantly PTSD (ß = -0.56, OR = 0.57 [95% CI: 0.34-0.97], p = 0.037, pperm = 0.039), while NPY2R-DRD3 (rs4425326 × rs6280) impacts low symptoms (ß = 0.82, OR = 2.27 [95% CI: 1.26-4.10], p = 0.006, pperm = 0.005) and predominantly depression (ß = 1.08, R = 2.95 [95% CI: 1.55-5.62], p = 0.001, pperm = 0.001). The two G × G effects are independent. Conclusion: NPY and dopamine receptor genes are related to the genetic etiology of PTSD-MDD comorbidity, whose specific mechanisms can be studied at multiple levels.