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1.
Sci Rep ; 14(1): 12921, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839809

ABSTRACT

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan-Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS.


Subject(s)
Mouth Neoplasms , Nutrition Assessment , Humans , Female , Male , Mouth Neoplasms/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Aged , Prognosis , Retrospective Studies , Middle Aged , Geriatric Assessment/methods , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Nutritional Status , Aged, 80 and over , Kaplan-Meier Estimate , Disease-Free Survival , ROC Curve , Risk Factors , Proportional Hazards Models , Risk Assessment/methods
2.
Commun Biol ; 7(1): 551, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720110

ABSTRACT

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.


Subject(s)
Colorectal Neoplasms , Epigenome , Fusobacterium Infections , Fusobacterium nucleatum , Oxygen , Transcriptome , Humans , Fusobacterium nucleatum/genetics , Fusobacterium nucleatum/physiology , Fusobacterium nucleatum/pathogenicity , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , HCT116 Cells , Fusobacterium Infections/genetics , Fusobacterium Infections/microbiology , Fusobacterium Infections/metabolism , Oxygen/metabolism , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic
3.
Cytokine ; 180: 156609, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38781871

ABSTRACT

BACKGROUND: We aim to deal with the Hub-genes and signalling pathways connected with Sepsis-associated encephalopathy (SAE). METHODS: The raw datasets were acquired from the Gene Expression Omnibus (GEO) database (GSE198861 and GSE167610). R software filtered the differentially expressed genes (DEGs) for hub genes exploited for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Hub genes were identified from the intersection of DEGs via protein-protein interaction (PPI) network. And the single-cell dataset (GSE101901) was used to authenticate where the hub genes express in hippocampus cells. Cell-cell interaction analysis and Gene Set Variation Analysis (GSVA) analysis of the whole transcriptome validated the interactions between hippocampal cells. RESULTS: A total of 161 DEGs were revealed in GSE198861 and GSE167610 datasets. Biological function analysis showed that the DEGs were primarily involved in the phagosome pathway and significantly enriched. The PPI network extracted 10 Hub genes. The M2 Macrophage cell decreased significantly during the acute period, and the hub gene may play a role in this biological process. The hippocampal variation pathway was associated with the MAPK signaling pathway. CONCLUSION: Hub genes (Pecam1, Cdh5, Fcgr, C1qa, Vwf, Vegfa, C1qb, C1qc, Fcgr4 and Fcgr2b) may paticipate in the biological process of SAE.

4.
Neurosci Bull ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819707

ABSTRACT

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

5.
Molecules ; 29(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38792041

ABSTRACT

Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li+) to form Li2O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.

6.
ACS Appl Mater Interfaces ; 16(19): 25148-25159, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38695364

ABSTRACT

Green electromagnetic interference (EMI) shielding materials not only require high shielding effectiveness (SE) and low reflection but also need to be recyclable after damage; however, it is challenging to strike a balance in practice. Here, a polyacrylamide (PAM) composite composed of numerous chemically cross-linked PAM@carbon nanotube (cPAM@CNT) core-shell particles featuring rich wrinkled microstructures was prepared using an adsorption-drying-shrinking strategy. The wrinkled microstructures enable the incident electromagnetic waves (EMWs) to undergo attenuation within the composites, achieving an average EMI SE of 67.5 dB in the X band. Due to the hygroscopicity of hydrophobically associated PAM (hPAM, an adhesive for cPAM@CNTs core-shell particles), the average EMI SE of the composites further increased to 83.2 dB after exposure to 91% relative humidity for 24 h, with only a 2.7 dB low reflection. Additionally, the composites also demonstrated excellent Joule heating, photothermal performance, and recyclability, which exhibit substantial promise for advanced EMI shielding applications.

7.
BMC Genomics ; 25(1): 530, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816813

ABSTRACT

BACKGROUND: Skeletal muscle development and fat deposition have important effects on meat quality. The study of regulating skeletal muscle development and fat deposition is of great significance in improving the quality of carcass and meat. In the present study, whole transcriptome sequencing (including RNA-Seq and miRNA-Seq) was performed on the longissimus dorsi muscle (LDM) of Jinfen White pigs at 1, 90, and 180 days of age. RESULTS: The results showed that a total of 245 differentially expressed miRNAs were screened in any two comparisons, which may be involved in the regulation of myogenesis. Among them, compared with 1-day-old group, miR-22-5p was significantly up-regulated in 90-day-old group and 180-day-old group. Functional studies demonstrated that miR-22-5p inhibited the proliferation and differentiation of porcine skeletal muscle satellite cells (PSCs). Pearson correlation coefficient analysis showed that long non-coding RNA (lncRNA) LOC106505926 and CXXC5 gene had strong negative correlations with miR-22-5p. The LOC106505926 and CXXC5 were proven to promote the proliferation and differentiation of PSCs, as opposed to miR-22-5p. In terms of mechanism, LOC106505926 functions as a molecular sponge of miR-22-5p to modulate the expression of CXXC5, thereby inhibits the differentiation of PSCs. In addition, LOC106505926 regulates the differentiation of porcine preadipocytes through direct binding with FASN. CONCLUSIONS: Collectively, our results highlight the multifaceted regulatory role of LOC106505926 in controlling skeletal muscle and adipose tissue development in pigs and provide new targets for improving the quality of livestock products by regulating skeletal muscle development and fat deposition.


Subject(s)
Cell Differentiation , Lipogenesis , MicroRNAs , Muscle Development , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , Muscle Development/genetics , Swine , MicroRNAs/genetics , MicroRNAs/metabolism , Lipogenesis/genetics , Cell Differentiation/genetics , Cell Proliferation , Satellite Cells, Skeletal Muscle/metabolism , Satellite Cells, Skeletal Muscle/cytology , Muscle, Skeletal/metabolism , Muscle, Skeletal/growth & development , Cells, Cultured
8.
Viruses ; 16(5)2024 04 29.
Article in English | MEDLINE | ID: mdl-38793587

ABSTRACT

A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases.


Subject(s)
Fish Diseases , Flatfishes , Genome, Viral , Papillomaviridae , Parvoviridae Infections , Parvovirus , Phylogeny , Animals , Fish Diseases/virology , Fish Diseases/mortality , China , Flatfishes/virology , Parvoviridae Infections/veterinary , Parvoviridae Infections/virology , Parvovirus/genetics , Parvovirus/isolation & purification , Parvovirus/classification , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Papillomavirus Infections/virology , Papillomavirus Infections/veterinary , In Situ Hybridization, Fluorescence
9.
Phys Rev Lett ; 132(19): 191901, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38804936

ABSTRACT

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

10.
Heliyon ; 10(7): e28198, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596020

ABSTRACT

Statement of problem: AI technology presents a variety of benefits and challenges for educators. Purpose: To investigate whether ChatGPT and Google Bard (now is named Gemini) are valuable resources for generating multiple-choice questions for educators of dental caries. Material and methods: A book on dental caries was used. Sixteen paragraphs were extracted by an expert consultant based on applicability and potential for developing multiple-choice questions. ChatGPT and Bard language models were used to produce multiple-choice questions based on this input, and 64 questions were generated. Three dental specialists assessed the relevance, accuracy, and complexity of the generated questions. The questions were qualitatively evaluated using cognitive learning objectives and item writing flaws. Paired sample t-tests and two-way analysis of variance (ANOVA) were used to compare the generated multiple-choice questions and answers between ChatGPT and Bard. Results: There were no significant differences between the questions generated by ChatGPT and Bard. Moreover, the analysis of variance found no significant differences in question quality. Bard-generated questions tended to have higher cognitive levels than those of ChatGPT. Format error was predominant in ChatGPT-generated questions. Finally, Bard exhibited more absolute terms than ChatGPT. Conclusions: ChatGPT and Bard could generate questions related to dental caries, mainly at the cognitive level of knowledge and comprehension. Clinical significance: Language models are crucial for generating subject-specific questions used in quizzes, tests, and education. By using these models, educators can save time and focus on lesson preparation and student engagement instead of solely focusing on assessment creation. Additionally, language models are adept at generating numerous questions, making them particularly valuable for large-scale exams. However, educators must carefully review and adapt the questions to ensure they align with their learning goals.

11.
Oncoimmunology ; 13(1): 2340154, 2024.
Article in English | MEDLINE | ID: mdl-38601319

ABSTRACT

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.


Subject(s)
AMP-Activated Protein Kinase Kinases , Adenocarcinoma of Lung , Lung Neoplasms , Humans , NF-E2-Related Factor 2/genetics , Kelch-Like ECH-Associated Protein 1/genetics , Oxidation-Reduction , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Immunotherapy , Mutation , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , T-Lymphocytes , CD8-Positive T-Lymphocytes , Tumor Microenvironment/genetics , DNA Helicases , Nuclear Proteins , Transcription Factors
12.
World J Gastrointest Oncol ; 16(3): 1046-1058, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38577462

ABSTRACT

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

13.
J Transl Med ; 22(1): 326, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566102

ABSTRACT

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Gastrointestinal Microbiome , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Immunotherapy , ErbB Receptors/genetics , Anti-Bacterial Agents/therapeutic use
14.
Oncologist ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688457

ABSTRACT

BACKGROUND: Treatment options for T1/2N0M0 anal squamous cell carcinoma include chemotherapy, radiotherapy, chemoradiotherapy, and local excision, although the optimal treatment method has not been determined. METHODS: The National Cancer Institute Surveillance, Epidemiology and Results database was used to search and screen 1465 patients with cT1/2N0M0 anal squamous cell carcinoma who were clinically diagnosed between 2004 and 2016. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression analysis was performed to screen independent prognostic factors and build a nomogram survival prediction model. According to the risk score, patients were divided into low, medium, and high risk groups using X-tile software. RESULTS: Age, sex, grade and cT stage were identified as independent prognostic factors for cT1/2N0M0 anal squamous cell carcinoma and were included in the nomogram to construct a prediction model. The C-index of the model was 0.770 [95% confidence interval (CI), 0.693-0.856], which was higher than the C-index of T stage 0.565 (95% CI, 0.550-0.612). Low-risk patients benefited from local resection, moderate-risk patients benefited from radiotherapy, and high-risk patients benefited from radiotherapy or chemoradiotherapy. This was confirmed using external validation data from the center. CONCLUSION: The nomogram developed in this study effectively and comprehensively evaluated the prognosis of patients with cT1/2N0M0 squamous cell carcinoma of the anal canal. Local excision is recommended for low risk patients, radiotherapy for moderate-risk patients, and radiotherapy or chemoradiotherapy for high-risk patients.

15.
Elife ; 122024 Apr 22.
Article in English | MEDLINE | ID: mdl-38648100

ABSTRACT

Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks. Here, we conducted ChIP-seq analyses focusing on histone marks indicative of active enhancers (H3K27ac) and active promoters (H3K4me3), alongside RNA-seq, using frontal cortex samples from antipsychotic-free (AF) and antipsychotic-treated (AT) individuals with schizophrenia, as well as individually matched controls (n=58). Schizophrenia subjects exhibited thousands of neuronal and non-neuronal epigenetic differences at regions that included several susceptibility genetic loci, such as NRG1, DISC1, and DRD3. By analyzing the AF and AT cohorts separately, we identified schizophrenia-associated alterations in specific transcription factors, their regulatees, and epigenomic and transcriptomic features that were reversed by antipsychotic treatment; as well as those that represented a consequence of antipsychotic medication rather than a hallmark of schizophrenia in postmortem human brain samples. Notably, we also found that the effect of age on epigenomic landscapes was more pronounced in frontal cortex of AT-schizophrenics, as compared to AF-schizophrenics and controls. Together, these data provide important evidence of epigenetic alterations in the frontal cortex of individuals with schizophrenia, and remark for the first time on the impact of age and antipsychotic treatment on chromatin organization.


Subject(s)
Antipsychotic Agents , Epigenesis, Genetic , Frontal Lobe , Schizophrenia , Humans , Schizophrenia/genetics , Schizophrenia/drug therapy , Schizophrenia/metabolism , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Frontal Lobe/metabolism , Frontal Lobe/drug effects , Male , Female , Middle Aged , Adult , Epigenomics , Aged , Histones/metabolism
16.
Bioresour Technol ; 400: 130668, 2024 May.
Article in English | MEDLINE | ID: mdl-38583677

ABSTRACT

This study examined the removal of typical antibiotics from simulated swine wastewater. Microalgae-bacteria/fungi symbioses were constructed using Chlorella ellipsoidea, endophytic bacteria (S395-2), and Clonostachys rosea as biomaterials. The growth, photosynthetic performance, and removal of three types of antibiotics (tetracyclines, sulfonamides, and quinolones) induced by four phytohormones were analyzed in each system. The results showed that all four phytohormones effectively improved the tolerance of symbiotic strains against antibiotic stress; strigolactones (GR24) achieved the best performance. At 10-9 M, GR24 achieved the best removal of antibiotics by C. elliptica + S395-2 + C. rosea symbiosis. The average removals of tetracycline, sulfonamide, and quinolone by this system reached 96.2-99.4 %, 75.2-81.1 %, and 66.8-69.9 %, respectively. The results of this study help to develop appropriate bio enhancement strategies as well as design and operate algal-bacterial-fungal symbiotic processes for the treatment of antibiotics-containing wastewater.


Subject(s)
Anti-Bacterial Agents , Microalgae , Plant Growth Regulators , Wastewater , Water Purification , Animals , Microalgae/drug effects , Wastewater/chemistry , Anti-Bacterial Agents/pharmacology , Swine , Water Purification/methods , Plant Growth Regulators/pharmacology , Water Pollutants, Chemical , Symbiosis/drug effects , Biodegradation, Environmental , Photosynthesis/drug effects , Chlorella/drug effects
17.
Cell Rep Methods ; 4(4): 100757, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38631345

ABSTRACT

Cross-disease genome-wide association studies (GWASs) unveil pleiotropic loci, mostly situated within the non-coding genome, each of which exerts pleiotropic effects across multiple diseases. However, the challenge "W-H-W" (namely, whether, how, and in which specific diseases pleiotropy can inform clinical therapeutics) calls for effective and integrative approaches and tools. We here introduce a pleiotropy-driven approach specifically designed for therapeutic target prioritization and evaluation from cross-disease GWAS summary data, with its validity demonstrated through applications to two systems of disorders (neuropsychiatric and inflammatory). We illustrate its improved performance in recovering clinical proof-of-concept therapeutic targets. Importantly, it identifies specific diseases where pleiotropy informs clinical therapeutics. Furthermore, we illustrate its versatility in accomplishing advanced tasks, including pathway crosstalk identification and downstream crosstalk-based analyses. To conclude, our integrated solution helps bridge the gap between pleiotropy studies and therapeutics discovery.


Subject(s)
Genetic Pleiotropy , Genome-Wide Association Study , Humans , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide
18.
J Xray Sci Technol ; 32(3): 549-568, 2024.
Article in English | MEDLINE | ID: mdl-38640141

ABSTRACT

BACKGROUND: Projection Domain Decomposition (PDD) is a dual energy reconstruction method which implements the decomposition process before image reconstruction. The advantage of PDD is that it can alleviate beam hardening artifacts and metal artifacts effectively as energy spectra estimation is considered in PDD. However, noise amplification occurs during the decomposition process, which significantly impacts the accuracy of effective atomic number and electron density. Therefore, effective noise reduction techniques are required in PDD. OBJECTIVE: This study aims to develop a new algorithm capable of minimizing noise while simultaneously preserving edges and fine details. METHODS: In this study, a denoising algorithm based on low rank and similarity-based regularization (LRSBR) is presented. This algorithm incorporates the low-rank characteristic of tensors into similarity-based regularization (SBR) framework. This method effectively addresses the issue of instability in edge pixels within the SBR algorithm and enhances the structural consistency of dual-energy images. RESULTS: A series of simulation and practical experiments were conducted on a dual-layer dual-energy CT system. Experiments demonstrate that the proposed method outperforms exiting noise removal methods in Peak Signal-to-noise Ratio (PSNR), Root Mean Square Error (RMSE), and Structural Similarity (SSIM). Meanwhile, there has been a notable enhancement in the visual quality of CT images. CONCLUSIONS: The proposed algorithm has a significantly improved noise reduction compared to other competing approach in dual-energy CT. Meanwhile, the LRSBR method exhibits outstanding performance in preserving edges and fine structures, making it practical for PDD applications.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Phantoms, Imaging , Signal-To-Noise Ratio , Tomography, X-Ray Computed , Image Processing, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Artifacts , Computer Simulation
19.
J Appl Psychol ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619473

ABSTRACT

Salary comparison has well-established implications for employees' attitudes and behaviors at work. Yet how employees process information about simultaneous comparisons, particularly when internal and external comparison information is incongruent, remains controversial. In this article, we draw from the model of dispositional attribution and equity theory to predict how the incongruence of internal and external salary comparisons affects perceptions of distributive justice and subsequent employee withdrawal behavior. We hypothesized that the effect of salary comparisons on perceived distributive justice follows a hierarchically restrictive schema in which a lower salary in comparison to a referent has a greater effect than a higher salary. This further affects employee withdrawal (neglect, turnover intention, and voluntary turnover). We also propose that the effects of salary comparisons are bounded by employees' zero-sum construal of success. Three studies were conducted to test our hypotheses: a quasi-experimental study and two time-lagged field studies. Consistent with our hypotheses, we observed that, when comparison information was incongruent, underpayment compared with others more strongly affected perceived distributive justice than overpayment did. The subsequent impact on perceived distributive justice was negatively related to employee withdrawal. As expected, the effect of incongruent salary comparison information was stronger for employees with lower zero-sum construal of success. The theoretical and practical implications of these findings are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

20.
BMC Genomics ; 25(Suppl 1): 401, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658824

ABSTRACT

BACKGROUND: Most of the important biological mechanisms and functions of transmembrane proteins (TMPs) are realized through their interactions with non-transmembrane proteins(nonTMPs). The interactions between TMPs and nonTMPs in cells play vital roles in intracellular signaling, energy metabolism, investigating membrane-crossing mechanisms, correlations between disease and drugs. RESULTS: Despite the importance of TMP-nonTMP interactions, the study of them remains in the wet experimental stage, lacking specific and comprehensive studies in the field of bioinformatics. To fill this gap, we performed a comprehensive statistical analysis of known TMP-nonTMP interactions and constructed a deep learning-based predictor to identify potential interactions. The statistical analysis describes known TMP-nonTMP interactions from various perspectives, such as distributions of species and protein families, enrichment of GO and KEGG pathways, as well as hub proteins and subnetwork modules in the PPI network. The predictor implemented by an end-to-end deep learning model can identify potential interactions from protein primary sequence information. The experimental results over the independent validation demonstrated considerable prediction performance with an MCC of 0.541. CONCLUSIONS: To our knowledge, we were the first to focus on TMP-nonTMP interactions. We comprehensively analyzed them using bioinformatics methods and predicted them via deep learning-based solely on their sequence. This research completes a key link in the protein network, benefits the understanding of protein functions, and helps in pathogenesis studies of diseases and associated drug development.


Subject(s)
Computational Biology , Membrane Proteins , Membrane Proteins/metabolism , Membrane Proteins/genetics , Computational Biology/methods , Deep Learning , Humans , Protein Interaction Maps
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