Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review.

RATIONALE: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS: Diagnosis and treatment of Hu-PNS. DIAGNOSES: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.

Geriatric nutritional risk index is associated with the occurrence of acute kidney injury in critically ill patients with acute heart failure.

Background: During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited. Methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p < 0.001). Multivariate COX regression analysis indicated that a high GNRI (adjusted HR 0.62, p < 0.001) was associated with a reduced risk of AKI during hospitalization in AHF patients. The final subgroup analysis demonstrated no significant interaction of GNRI in all subgroups except for diabetes subgroup and ventilation subgroup (P for interaction: 0.057-0.785). Conclusion: Our study findings suggest a correlation between GNRI and the occurrence of acute kidney injury in patients hospitalized with acute heart failure.

Structural mechanism of voltage-gated sodium channel slow inactivation.

Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.

Structural Pharmacology of TRPV4 Antagonists.

The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small-molecule antagonists, which may facilitate future drug discovery targeting TRPV4.

Upregulation of coagulation factor V by glucocorticoid in the preovulatory follicles of zebrafish.

Increased cortisol levels in the preovulatory follicular fluid suggests a role of glucocorticoid in human ovulation. However, the mechanisms through which cortisol regulates the ovulatory process remain poorly understood. In this study, we examined the upregulation of f5 mRNA by glucocorticoid and its receptor (Gr) in the preovulatory follicles of zebrafish. Our findings demonstrate a significant increase in 11ß-hydroxysteroid dehydrogenase type 2 (hsd11b2), a cortisol response gene, in preovulatory follicles. Additionally, hydrocortisone exerts a dose- and time-dependent upregulation of f5 mRNA in these follicles. Importantly, this stimulatory effect is Gr-dependent, as it was completely abolished in gr-/- mutants. Furthermore, site-directed mutagenesis identified a glucocorticoid response element (GRE) in the promoter of zebrafish f5. Interestingly, successive incubation of hydrocortisone and the native ovulation-inducing steroid, progestin (17α,20ß-dihydroxy-4-pregnen-3-one, DHP), further enhanced f5 expression in preovulatory follicles. Overall, our results indicate that the dramatic increase of f5 expression in preovulatory follicles is partially attributable to the regulation of glucocorticoid and Gr.

Exosomes Derived from Human Palatal Mesenchymal Cells Mediate Intercellular Communication During Palatal Fusion by Promoting Oral Epithelial Cell Migration.

Purpose: Exosomes are important "messengers" in cell-cell interactions, but their potential effects on palatal fusion are still unknown. This study aimed to explore the role and mechanism of exosomes derived from palatal mesenchymal cells in epithelial-mesenchymal communication during palatogenesis. Methods: The expression of exosome marker CD63 and CD81 in palatal cells during palatogenesis was detected by immunofluorescence staining. After being purified from the supernatant of human embryonic palatal mesenchymal (HEPM) cells, exosomes (HEPM-EXO) were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. HEPM-EXO were co-cultured with human immortalized oral epithelial cells (HIOEC). The effects of HEPM-EXO on the cell proliferation, migration, apoptosis and epithelial-mesenchymal transition (EMT) of HIOEC were evaluated. The proteins encapsulated in HEPM-EXO were analyzed by proteomic analysis. Results: The extensive expression of CD63 and CD81 in palatal epithelial and mesenchymal cells were continuously detected during E12.5~E14.5, suggesting that exosomes were involved in the process of palatal fusion. The expression of CD63 was also observed in the acellular basement membrane between the palatal epithelium and the mesenchyme in vivo, and HEPM-EXO could be internalized by HIOEC in vitro, suggesting that exosomes are potent to diffuse through the cellular tissue boundary to mediate palatal cell-cell communication. Exposure of HEPM-EXO to HIOEC substantially inhibited the proliferation and stimulated the migration of HIOEC, but had no significant effect on cell apoptosis and EMT. Proteomic analysis revealed the basic characteristics of the proteins in HEPM-EXO and that exosomal THBS1 may potentially regulate the cell behaviors of HIOEC, which needs further verification. Gene ontology (GO) analysis uncovered that the proteins highly expressed in HEPM-EXO are closely related to wound healing, implying a promising therapeutic opportunity of HEPM-EXO in tissue injury treatment with future studies. Conclusion: HEPM-EXO mediated cell-cell communication by regulating cell proliferation and migration of oral epithelial cells during palatogenesis.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Effects of temperature and initial pH on the growth of four dominant cyanobacteria species in biological soil crusts.

Biological soil crusts are of great significance for environment health and sustainable development in arid and semi-arid areas. Cyanobacteria, Microcoleus vaginatus, Scytonema sp., Nostoc sp., and Anabaena sp. are the dominant species in microbial community of biological soil crusts worldwide. Considering their broad application prospect, it is meaningful to cultivate them extensively. We examined the effects of temperature (10, 20, 25, 30, 35 ℃) and initial pH (4, 6, 8, 10, 12) on biomass and solution pH towards the four species of cyanobacteria with liquid culture in laboratory. The results showed that the biomass of the four cyanobacterial species grew slowly under 20 ℃, and that all species could grow in 25-35 ℃, with the highest growth rate at 25 and 30 ℃. The optimum culture temperature of different cyanobacterial species was slightly different. The optimum culture temperature was 25-30 ℃ for Scytonema sp. and Nostoc sp., and 30 ℃ for M. vaginatus and Anabaena sp. The four cyanobacterial species had a strong ability to adjust solution pH and proliferate in five different initial pH conditions. The highest maximum biomass and specific growth rate were recorded in the culture environment with initial pH of 4, while the lowest maximum biomass and specific growth rate were observed in initial pH of 12. Our results would provide scientific basis for the propagation of dominant cyanobacteria in biological soil crusts.

Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams.

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors.

The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

A cross-sectional study of factors influencing left ventricular myocardial work in peritoneal dialysis patients.

Objectives: To evaluate myocardial work in peritoneal dialysis patients by pressure-strain loop. To analyze the factors influencing myocardial work in peritoneal dialysis patients with preserved ejection fraction. Methods: We collected clinical data on possible effects on myocardial work in 105 maintenance peritoneal dialysis patients with preserved ejection fraction and applied ultrasonic pressure-strain loops to obtain the left ventricular global constructive work (GCW), Global work index (GWI), global work waste (GWW), and global work efficiency (GWE) of the patients. Then, the clinical data and myocardial work indices were statistically described and correlated. Results: Left ventricular hypertrophy was observed in 78 % of peritoneal dialysis patients with left ventricular ejection fraction preservation. There is a correlation between the left ventricular mass index and myocardial work indices (P < 0.05). On multiple linear regression analysis, systolic blood pressure (SBP), IL-6, and hemoglobin correlated with GCW(P < 0.05); SBP and IL-6 correlated with GWI(P < 0.05); homocysteine, SBP, TNF-α, and hemoglobin correlated with GWW(P < 0.05); homocysteine, TNF-α and hemoglobin correlated with GWE (P < 0.05). Conclusions: Using noninvasive pressure-strain loops to assess left ventricular myocardial work can provide information on cardiac function more consistent with pathophysiological changes than conventional ejection fraction. Hypertension, anemia, hyperhomocysteinemia, and inflammation influence left ventricular myocardial work in peritoneal dialysis patients, and they selectively affect one or more myocardial work indices.

Clinical internship environment and caring behaviours among nursing students: A moderated mediation model.

BACKGROUND: Caring behaviour is critical for nursing quality, and the clinical internship environment is a crucial setting for preparing nursing students for caring behaviours. Evidence about how to develop nursing students' caring behaviour in the clinical environment is still emerging. However, the mechanism between the clinical internship environment and caring behaviour remains unclear, especially the mediating role of moral sensitivity and the moderating effect of self-efficacy. RESEARCH OBJECTIVE: This study aimed to examine the mediating effect of moral sensitivity and the moderating function of self-efficacy on the association between the clinical internship environment and caring behaviours. RESEARCH DESIGN: A cross-sectional design used acceptable validity scales. The hypothesised moderated mediation model was tested in the SPSS PROCESS macro. PARTICIPANTS AND RESEARCH CONTEXT: This survey collected data from 504 nursing students in an internship at a teaching hospital in Changsha, China. ETHICAL CONSIDERATIONS: This study was pre-approved by the ethics committee of the medical school (No. E2022210). Informed consent was obtained from all students. RESULTS: The clinical internship environment (B = 0.450, 95% CI = [0.371, 0.530]) and moral sensitivity (B = 1.352, 95% CI = [1.090, 1.615]) had positive direct effects on nursing students' caring behaviours. Clinical internship environment also indirectly influenced students' caring behaviours via moral sensitivity (B = 0.161, 95% CI = [0.115, 0.206]). In addition, self-efficacy played a moderating role between the clinical internship environment and caring behaviours (B = 0.019, 95% CI = [0.007, 0.031]), as well as the relationship between the clinical internship environment and moral sensitivity (B = 0.006, 95% CI = [0.003, 0.010]). CONCLUSION: Moral sensitivity mediates the effect of the clinical internship environment on caring behaviour, and self-efficacy strengthens both direct and indirect effects. This study emphasises the importance of self-efficacy in developing moral sensitivity and caring behaviours in nursing students.

Predicting Drug-Protein Interactions through Branch-Chain Mining and multi-dimensional attention network.

Identifying drug-protein interactions (DPIs) is crucial in drug discovery and repurposing. Computational methods for precise DPI identification can expedite development timelines and reduce expenses compared with conventional experimental methods. Lately, deep learning techniques have been employed for predicting DPIs, enhancing these processes. Nevertheless, the limitations observed in prior studies, where many extract features from complete drug and protein entities, overlooking the crucial theoretical foundation that pharmacological responses are often correlated with specific substructures, can lead to poor predictive performance. Furthermore, certain substructure-focused research confines its exploration to a solitary fragment category, such as a functional group. In this study, addressing these constraints, we present an end-to-end framework termed BCMMDA for predicting DPIs. The framework considers various substructure types, including branch chains, common substructures, and specific fragments. We designed a specific feature learning module by combining our proposed multi-dimensional attention mechanism with convolutional neural networks (CNNs). Deep CNNs assist in capturing the synergistic effects among these fragment sets, enabling the extraction of relevant features of drugs and proteins. Meanwhile, the multi-dimensional attention mechanism refines the relationship between drug and protein features by assigning attention vectors to each drug compound and amino acid. This mechanism empowers the model to further concentrate on pivotal substructures and elements, thereby improving its ability to identify essential interactions in DPI prediction. We evaluated the performance of BCMMDA on four well-known benchmark datasets. The results indicated that BCMMDA outperformed state-of-the-art baseline models, demonstrating significant improvement in performance.

Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine's blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6's N- and C-termini binding to Slack's C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack's C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of 'Slack as an isolated target' for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.

Subjective quality of life and schizophrenia: results from a large cohort study based in Chinese primary care.

INTRODUCTION: Much confusion exists between health-related QoL (HRQoL) scales and subjective QoL (SQoL) scales. One method to avoid confusion is use of a single question that asks What is your quality of life? or similar. This study explored the relationship between biopsychosocial factors and high SQoL, SQoL stability, and factors associated with improving SQoL. METHOD: We conducted a large cohort study of community-dwelling Chinese adults with schizophrenia, with two data points (2015-2016 (N = 742), 2017-2018 (N = 491)). Demographic and clinically related items and a comprehensive suite of published measures were collected. Direct logistic regressions were used to explore links between biopsychosocial factors and high SQoL and Improvement in SQoL across time. RESULTS: Sample at Baseline: Male = 62.3%; Med age = 38.5 years; Med Age at illness onset = 24 years; SQoL Mode = neither poor nor good. Three independent variables predicted high SQoL at T1. Contemporary age and the presence of clinically relevant symptoms had a negative relationship with high SQoL; insight had a positive relationship with high SQoL. SQoL changed significantly across time with a modest effect size. Age at illness onset was the single independent variable linked to improving SQoL favoring being older at the time of illness onset. DISCUSSION/CONCLUSIONS: SQoL can be high and changeable. While symptomology and illness insight may affect SQoL self-appraisals at single points in time, only age of illness onset was connected with improving SQoL. Thus, public health measures to delay illness onset are important. In addition, care about the distinction between HRQoL and SQoL in study design and choice of measures is necessary and will depend on the purpose and context.

Increases in computationally predicted deleterious variants of unknown significance and sperm mtDNA copy numbers may be associated with semen quality.

BACKGROUND: Mitochondria are essential for sperm motility because they provide the energy required for the movement. Changes in sperm mtDNA, such as point mutations, large-scale deletions, or copy number variations, may interfere with ATP production and reduce sperm motility. However, it is not clear if changes in mtDNA are linked to semen quality. OBJECTIVES: To explore the association between sperm mitochondrial DNA (mtDNA) changes and semen quality. MATERIALS AND METHODS: Sixty-five oligo and/or astheno and/or terato patients (O/A/T) patients and 41 controls were recruited from couples undergoing assisted reproduction. Semen and blood samples were collected from the same individual on the day of oocyte retrieval to extract, isolate and purify mtDNA for next-generation sequencing. mtDNA copy numbers were assessed in 64 patient and 39 control sperm DNA samples using quantitative real-time PCR. The 4977 bp deletion was assessed in 20 patient and 20 control sperm DNA samples using polymerase chain reaction. RESULTS: The mtDNA of patients was more likely to carry pathogenic variants or variants of unknown significance (VUSs) (P = 0.091) with higher heteroplasmy levels (P < 0.05) than that of controls. Interestingly, 33.85% of O/A/T patients (22 out of 65) lacked unique variants in their spermatozoa. but presented an exceptionally high mtDNA copy number (P < 0.0001). Moreover, we observed a decrease in the heteroplasmy level of common mtDNA variants shared by somatic and gamete cells (P < 0.0001) and the emergence of a very large number of de novo mtDNA variants with low-level heteroplasmy in spermatozoa. DISCUSSION AND CONCLUSION: The increases in the number of computationally predicted deleterious VUS and mtDNA copies in spermatozoa may be associated with semen quality. Exposure to environmental mutation pressure that causes novel mtDNA variants with low-level heteroplasmy may occur during spermatogenesis. Furthermore, when a certain harmful threshold is reached, male germ cells may degrade mtDNA with mutations and replicate the correct mtDNA sequence to maintain the mitochondrial function in spermatozoa.

The efficacy of metformin for the treatment of psoriasis: a meta-analysis study.

Introduction: Metformin has potential in treating patients with psoriasis, and this meta-analysis aims to explore the impact of metformin supplementation on treatment efficacy for psoriasis. Material and methods: The PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of metformin on treatment efficacy for patients with psoriasis. Results: Three RCTs were included in the meta-analysis. Overall, compared with control intervention for psoriasis, metformin intervention resulted in significantly increased psoriasis area severity index (PASI) 75% reduction (odds ratio (OR) = 22.02; 95% confidence interval (CI): 2.12 to 228.49; p = 0.01), and erythema, scaling and induration (ESI) 75% reduction (OR = 9.12; 95% CI: 2.13 to 39.02; p = 0.003), and was associated with substantially decreased fasting plasma glucose (FPG, standard mean difference (SMD) = -0.59; 95% CI: -0.92 to -0.26; p = 0.0005), triglycerides (SMD = -0.92; 95% CI: -1.38 to -0.47; p < 0.0001), total cholesterol (SMD = -0.77; 95% CI: -1.22 to -0.32; p = 0.00008), and low-density lipoprotein (LDL, SMD = -0.67; 95% CI: -1.12 to -0.23; p = 0.003). Conclusions: Metformin supplementation effectively improves treatment efficacy and metabolic syndrome in psoriasis patients.

Gene Polymorphisms and Expression of NRG1, DAOA, and DISC1 Genes in a Chinese Han Population with an Ultra-High Risk for Psychosis.

Purpose: Although there is previous evidence supporting that ultra-high risk (UHR) for psychosis transformation is associated with NRG1, DAOA, and DISC1 genes, there have been no relevant studies in the Chinese population. The objective of the current study was to explore the gene polymorphism and expression of NRG1, DAOA, and DISC1 genes in a Han population with UHR for psychosis in China. Methods: Eighteen UHR individuals, 61 first-degree relatives of patients with schizophrenia (FDR), 55 first-episode psychosis individuals (FEP), and 61 healthy controls (HC) were enrolled in the study. The genotypes at four loci of the NRG1 gene, four loci of the DAOA gene, and two loci of the DISC1 gene were tested for all subjects, and mRNAs of NRG1 and DISC1 were examined and analyzed in a pairwise comparison among the four groups. Statistical analysis of genetics was performed using snpStats software. For the case-control association analysis, a single site association study, epistatic effect analysis, and haplotype analysis were used to explore the association of the above genes. Results: This study found that rs3918341 in the DAOA gene was associated with susceptibility to UHR by single site association analysis. Epistatic effect analysis results showed that the NRG1 gene interacted with the DAOA gene and DISC1 gene in the susceptibility to UHR. Haplotype association analysis showed that all haplotypes were not significantly associated with UHR. NRG1 mRNA was significantly downregulated in the UHR group compared with the HC group as well as the FEP group. Conclusion: Our preliminary results show that NRG1, DAOA, and DISC1 genes may play a role in psychosis onset, opening the way to the identification of prognostic biomarkers.

Heterogeneous influence of neighborhood features on community satisfaction: a comparative study in Beijing's urban and suburban communities.

Introduction: Community satisfaction contributes to urban planning, community development, and policy formulation. Yet, we lack comprehensive knowledge about how different neighborhood features impact satisfaction, especially across diverse community types. Methods: Relied on a sample of 4,009 respondents in Beijing, this study examines the influence of neighborhood features on community satisfaction through neighborly interactions, focusing on the heterogeneity between urban and suburban communities, using structural equation models. Results: The results reveal that community service and community management exert significant influences on community satisfaction, primarily mediated by the role of neighborly interactions. Then, transportation convenience positively influences community satisfaction in urban areas, while no housing property has a negative effect in suburban communities. Discussion: These results highlight varied neighborhood effects on community satisfaction, informing tailored urban planning and policies that address unique traits and requirements of different communities.

Investigating Doxorubicin's mechanism of action in cervical cancer: a convergence of transcriptomic and metabolomic perspectives.

Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin's therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.