Combined effects of thermal environment and gene regulation on metabolic enzyme activities of major metabolic tissues in a winter-breeding amphibian.

Variations in thermal environments can provoke diverse physiological responses in amphibians. Despite extensive studies on the thermal sensitivity of amphibian metabolic physiology, including enzyme activity at different temperatures, the rationale for selecting specific metabolic enzymes and their relationship with gene expression remains unclear. Cytochrome c oxidase (CCO), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) are key metabolic enzymes within the primary metabolic regulatory tissues of animals. Through a comparative analysis of the effects of two different thermal conditions (12 and 18 °C) on the activities and mRNA expression levels of these enzymes within the kidney and liver tissues of a winter-breeding amphibian (Leptobrachium liui), with the field group during the breeding season as the control, we provide insights into the interplay between temperature and gene expression. The mRNA levels of CCO subunits 1 (cox1), 2 (cox2), and 3 (cox3), and LDH subunit A (ldha) were significantly higher in the kidney than in the liver of all individuals. High-temperature acclimation resulted in significantly decreased expression levels of cox1-3, ldha, and SDH complex flavoprotein subunit A (sdha) in the kidney. In the liver, the expression levels of sdha and ldha significantly reduced under high-temperature treatment, whereas cox3 expression increased. SDH and LDH activities displayed tissue-specific variations, while no significant differences in CCO activity were observed between tissues. CCO, SDH, and LDH activities in both liver and kidney tissues significantly declined after high-temperature acclimation, but simultaneously increased with up-regulated gene expression, indicating that the thermal environment and corresponding gene expression combined affect the activities of these metabolic enzymes. In conclusion, the thermal environment is a key factor affecting the physiological and biochemical responses of L. liui. Prolonged exposure to high temperatures during the breeding season could inhibit the activity of primary metabolic enzymes in the winter-breeding amphibian.

The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer.

Zeb1, a key epithelial-mesenchymal transition (EMT) regulator, has recently been found to be involved in M2 macrophage polarization in the tumor immune microenvironment, thereby promoting tumor development. However, the underlying mechanism of Zeb1-induced M2 macrophage polarization remains largely unexplored. To identify the potential role of Zeb1 in remodeling the tumor immune microenvironment in breast cancer, we crossed the floxed Zeb1 allele homozygously into PyMT mice to generate PyMT;Zeb1cKO (MMTV-Cre;PyMT;Zeb1fl/fl ) mice. We found that the recruitment of M2-type tumor-associated macrophages (TAMs) was significantly reduced in tumors from PyMT;Zeb1cKO mice, and their tumor suppressive effects were weakened. Mechanistically, Zeb1 played a crucial role in transcriptionally promoting the production of Cxcl1 in tumor cells. In turn, Cxcl1 activated the Cxcr2-Jak-Stat3 pathway to induce M2 polarization of TAMs in a paracrine manner, which eventually led to T-cell inactivation and impaired the antitumor immune response in breast cancer. Our results collectively revealed an important role of Zeb1 in remodeling the tumor microenvironment, suggesting a novel therapeutic intervention for the treatment of advanced breast cancer.

Correlation between iron deposition and cognitive function in mild to moderate Alzheimer's disease based on quantitative susceptibility mapping.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressively worsening cognitive decline and memory loss. Excessive iron accumulation produces severe cognitive impairment. However, there are no uniform conclusions about changes in brain iron content in AD. This study aimed to investigate the iron content of the deep brain nuclei in AD, and its correlation with cognitive function. Methods: Thirty-one patients with mild to moderate AD, 17 patients with mild cognitive impairment (MCI), and 20 age-, sex-, and education-matched healthy controls (HC) were collected. The QSM was used to quantify the magnetic susceptibility values of the caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and dentate nucleus, and to analyze the differences that existed between the three groups. As well as the correlation between the magnetic susceptibility values and cognitive function was calculated. Results: The magnetic susceptibility values of bilateral globus pallidus, left putamen, and bilateral substantia nigra were significantly higher in AD patients than in HC, and the magnetic susceptibility values of the right globus pallidus were significantly higher in AD patients than in MCI (all p < 0.05). The magnetic susceptibility values of the left dentate nucleus in the AD group were negatively correlated with the writing function of the MMSE subitem (r = -0.42, p = 0.020), and the magnetic susceptibility values of the left caudate nucleus and right dentate nucleus were significantly and negatively correlated with the naming function and language function of the MoCA subitem, respectively (r = -0.43, p = 0.019; r = -0.36, p = 0.048). Conclusion: Magnetic susceptibility values based on QSM correlate with cognitive function are valuable in discriminating AD from MCI and AD from HC.

The effect of tamoxifen as an adjuvant therapy for breast cancer on apolipoproteins and lipoprotein(a) concentrations in women: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Tamoxifen has been used in the management of breast cancer. The available evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins is controversial. Hence, this meta-analysis of randomized controlled trials (RCTs) was conducted to increase the quality of evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins. METHODS: Eligible RCTs published up to September 2023 were carefully selected following a comprehensive search. Thereafter, a meta-analysis was conducted using a random-effects model and the results were presented as the weighted mean difference (WMD) with a 95 % confidence interval (CI). RESULTS: The results from the random-effects model indicated a rise in ApoA-I (WMD: 16.24 mg/dL, 95 % CI: 5.35, 27.12, P = 0.003), and a decrease in ApoB (WMD: -9.37 mg/dL, 95 % CI: -15.16, -3.59, P = 0.001) and lipoprotein(a) (WMD: -3.24 mg/dL, 95 % CI: -5.66, -0.83, P < 0.001) concentrations following tamoxifen administration in women. Furthermore, a more pronounced decrease in ApoB (WMD: -12.86 mg/dL, 95 % CI: -19.78, -5.93, P < 0.001) and elevation in ApoA-1 levels (WMD: 51.97 mg/dL, 95 % CI: 45.89, 58.05, P < 0.001) were identified in a single study on patients with breast cancer. CONCLUSION: The current meta-analysis demonstrated an increase of ApoA-I and a decrease of ApoB and lipoprotein(a) levels after treatment with tamoxifen in women.

Autophagy in Oligodendrocyte Lineage Cells Controls Oligodendrocyte Numbers and Myelin Integrity in an Age-dependent Manner.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.

Two complete mitochondrial genomes of Boulenophrys (Anura: Megophryidae: Megophryinae): characteristics and phylogenetic implications.

The Chinese horned toads, Boulenophrys boettgeri (Boulenger, 1899) and Boulenophrys kuatunensis (Pope, 1929), are two captivating species within the family Megophryidae, which inhabit the mountainous streams in the Eastern of China. In this study, two new complete mitochondrial genomes of B. boettgeri and B. kuatunensis were sequenced, assembled, and annotated using next-generation sequencing. The length of mitochondrial genomes of B. boettgeri and B. kuatunensis was 16,597 and 17,921 bp, respectively, with both containing 13 protein coding genes, 22 tRNA genes, two rRNA genes, and one putative control region. Phylogenetic relationships based on protein-coding mitochondrial genes showed that the two Boulenophrys species formed a cluster with other Boulenophrys species. The two new sequences provide valuable insights into the mitochondrial genomes of these two species, offering important data for understanding the phylogenetic relationships of the genus Boulenophrys.

Multimodal Resonances of a Rectangular Planar Dielectric Elastomer Actuator and Its Application in a Robot with Soft Bristles.

Inspired by the fact that flying insects improve their power conversion efficiency through resonance, many soft robots driven by dielectric elastomer actuators (DEAs) have achieved optimal performance via first-order modal resonance. Besides first-order resonance, DEAs contribute to multiple innovative functions such as pumps that can make sounds when using multimodal resonances. This study presents the multimodal resonance of a rectangular planar DEA (RPDEA) with a central mass bias. Using a combination of experiments and finite element modeling (FEM), it was discerned that under a prestretch of 1.0 × 1.1, the first-, second-, and third-order resonances corresponded to vertical vibration, rotation along the long axis, and rotation along the short axis, respectively. In first-order resonance, superharmonic, harmonic, and subharmonic responses were activated, while only harmonic and subharmonic responses were observed in the second- and third-order resonances. Further investigations revealed that prestretching tended to inhibit third-order resonance but could elevate the resonance frequencies of the first and second orders. Conveniently, both the experimental and FEM results showed that the frequencies and amplitudes of the multimodal resonances could be tuned by adjusting the amplitudes of the excitation signals, referring to the direct current (DC) amplitude and alternating current (AC) amplitude, respectively. Moreover, instead of linear vibration, we found another novel approach that used rotation vibration to drive a robot with soft bristles via hopping locomotion, showcasing a higher speed compared to the first-order resonance in our robot.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Genetic analysis of seven patients with inherited ichthyosis and Nagashima­type palmoplantar keratoderma.

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole­exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis­like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis­associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.

Immunogenicity and safety of a recombinant Omicron BA.4/5-Delta COVID-19 vaccine ZF2202-A in Chinese adults.

BACKGROUND: The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. METHODS: A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. RESULTS: At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. CONCLUSIONS: The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines.

Neutralization of EG.5, EG.5.1, BA.2.86, and JN.1 by antisera from dimeric receptor-binding domain subunit vaccines and 41 human monoclonal antibodies.

BACKGROUND: The recently circulating Omicron variants BA.2.86 and JN.1 were identified with more than 30 amino acid changes on the spike protein compared to BA.2 or XBB.1.5. This study aimed to comprehensively assess the immune escape potential of BA.2.86, JN.1, EG.5, and EG.5.1. METHODS: We collected human and murine sera to evaluate serological neutralization activities. The participants received three doses of coronavirus disease 2019 (COVID-19) vaccines or a booster dose of the ZF2022-A vaccine (Delta-BA.5 receptor-binding domain [RBD]-heterodimer immunogen) or experienced a breakthrough infection (BTI). The ZF2202-A vaccine is under clinical trial study (ClinicalTrials.gov: NCT05850507). BALB/c mice were vaccinated with a panel of severe acute respiratory syndrome coronavirus 2 RBD-dimer proteins. The antibody evasion properties of these variants were analyzed with 41 representative human monoclonal antibodies targeting the eight RBD epitopes. FINDINGS: We found that BA.2.86 had less neutralization evasion than EG.5 and EG.5.1 in humans. The ZF2202-A booster induced significantly higher neutralizing titers than BTI. Furthermore, BA.2.86 and JN.1 exhibited stronger antibody evasion than EG.5 and EG.5.1 on RBD-4 and RBD-5 epitopes. Compared to BA.2.86, JN.1 further lost the ability to bind to several RBD-1 monoclonal antibodies and displayed further immune escape. CONCLUSIONS: Our data showed that the currently dominating sub-variant, JN.1, showed increased immune evasion compared to BA.2.86 and EG.5.1, which is highly concerning. This study provides a timely risk assessment of the interested sub-variants and the basis for updating COVID-19 vaccines. FUNDING: This work was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, the Beijing Life Science Academy, the Bill & Melinda Gates Foundation, and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (CPSF).

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B).

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.

From Wigner hyperbolic rotation to fractional squeezing transformation.

Based on the usual Wigner-Weyl transformation theory we find that the Wigner hyperbolic rotation in phase space will map onto fractional squeezing operator in Hilbert space. The merit of Weyl ordering and the coherent state representation of Fresnel operator is used in our derivation.

Identification of gene biomarkers for brain diseases via multi-network topological semantics extraction and graph convolutional network.

BACKGROUND: Brain diseases pose a significant threat to human health, and various network-based methods have been proposed for identifying gene biomarkers associated with these diseases. However, the brain is a complex system, and extracting topological semantics from different brain networks is necessary yet challenging to identify pathogenic genes for brain diseases. RESULTS: In this study, we present a multi-network representation learning framework called M-GBBD for the identification of gene biomarker in brain diseases. Specifically, we collected multi-omics data to construct eleven networks from different perspectives. M-GBBD extracts the spatial distributions of features from these networks and iteratively optimizes them using Kullback-Leibler divergence to fuse the networks into a common semantic space that represents the gene network for the brain. Subsequently, a graph consisting of both gene and large-scale disease proximity networks learns representations through graph convolution techniques and predicts whether a gene is associated which brain diseases while providing associated scores. Experimental results demonstrate that M-GBBD outperforms several baseline methods. Furthermore, our analysis supported by bioinformatics revealed CAMP as a significantly associated gene with Alzheimer's disease identified by M-GBBD. CONCLUSION: Collectively, M-GBBD provides valuable insights into identifying gene biomarkers for brain diseases and serves as a promising framework for brain networks representation learning.

A novel nomogram and recursive partitioning analysis for predicting cancer-specific survival of patients with subcutaneous leiomyosarcoma.

Accurately predicting prognosis subcutaneous leiomyosarcoma (LMS) is crucial for guiding treatment decisions in patients. The objective of this study was to develop prediction models for cancer-specific survival (CSS) in patients with subcutaneous LMS. The collected cases of diagnosed subcutaneous LMS were randomly divided into a training cohort and a validation cohort at a 6:4 ratio based on tumor location and histological code. The X-tile program was utilized to determine the optimal cutoff points for age index. Univariate and Cox multivariate regression analyses were conducted to identify independent risk factors for subcutaneous LMS patients. Nomograms were constructed to predict CSS, and their performance was assessed using C-index and calibration plots. Additionally, a decision tree model was established using recursive partitioning analysis to determine the total score for CSS prediction in subcutaneous LMS patients based on the nomogram model. A total of 1793 patients with subcutaneous LMS were found. X-tile software divides all patients into ≤ 61 years old, 61-82 years old, and ≥ 82 years old. The most important anatomical sites were the limbs (including the upper and lower limbs, 48.0%). Only 6.2% of patients received chemotherapy, while 44% had a history of radiotherapy and 92.9% underwent surgery. The independent risk factors for patients with subcutaneous LMS were age, summary stage, grade, and surgery. CSS was significantly decreased in patients with distant metastases, which showed the highest independent risk predictor (HR 4.325, 95% CI 3.010-6.214, p < 0.001). The nomogram prediction model of LMS was constructed based on four risk factors. The C-index for this model was 0.802 [95% CI 0.781-0.823] and 0.798 [95% CI 0.768-0.829]. The training cohort's 3-, 5-, and 10-year AUCs for CSS in patients with subcutaneous LMS were 0.833, 0.830, and 0.859, and the validation cohort's AUC for predicting CSS rate were 0.849, 0.830, and 0.803, respectively. Recursive segmentation analysis divided patients into 4 risk subgroups according to the total score in the nomogram, including low-risk group < 145, intermediate-low-risk group ≥ 145 < 176, intermediate-high-risk group ≥ 176 < 196, and high-risk group ≥ 196; The probability of the four risk subgroups is 9.1%, 34%, 49%, and 79% respectively. In this retrospective study, a novel nomogram or corresponding risk classification system for patients with subcutaneous LMS were developed, which may assist clinicians in identifying high-risk patients and in guiding the clinical decision.

Resting-state activity and functional connectivity of insula and postcentral gyrus related to psychological resilience in female depressed patients: A preliminary study.

BACKGROUND: Psychological resilience is a protective factor of depression. However, the neuroimaging characteristics of the relationship between psychological resilience and brain imaging in depression are not very clear. Our objectives were to explore the brain functional imaging characteristics of different levels of resilience in female patients with depression. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed on 58 female depressed patients. According to the resilience score, participants were divided into three groups: Low resilience (Low-res), Medium resilience (Med-res) and High resilience (High-res). We compared the differences in the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) among the three groups and correlated psychological resilience with ALFF and FC. RESULTS: According to ALFF, there was a higher activation in RI and RPG in the High-res compared with Med-res and Low-res, but no significant differences between Med-res and Low-res. The FC between the RPG and supramarginal gyrus (SG) in the High-res was significantly stronger than that in the Med-res and the Low-res, and the FC of the Med-res is stronger than that of the Low-res. Both ALFF and FC were positively correlated with the score of resilience. LIMITATIONS: The sample size of this study was relatively small and it lacked healthy controls. The results of this study could be considered preliminary. CONCLUSIONS: Among female patients with depression, patients with higher psychological resilience had higher resting state activation in the RI and RPG and had a stronger interaction between the RPG and the SG.