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1.
Anal Bioanal Chem ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558309

RESUMO

Since RNA is an important biomarker of many infectious pathogens, RNA detection of pathogenic organisms is crucial for disease diagnosis and environmental and food safety. By simulating the base mismatch during DNA replication, this study presents a novel three-way junction structure-mediated reverse transcription-free exponential amplification reaction (3WJ-RTF-EXPAR) for the rapid and sensitive detection of pathogen RNA. The target RNA served as a switch to initiate the reaction by forming a three-way junction (3WJ) structure with the ex-trigger strand and the ex-primer strand. The generated trigger strand could be significantly amplified through EXPAR to open the stem-loop structure of the molecular beacon to emit fluorescence signal. The proofreading activity of Vent DNA polymerase, in combination with the unique structure of 2+1 bases at the 3'-end of the ex-primer strand, could enhance the role of target RNA as a reaction switch to reduce non-specific amplification and ensure excellent specificity to differentiate target pathogen from those causing similar symptoms. Furthermore, detection of target RNA showed a detection limit of 1.0×104 copies/mL, while the time consumption was only 20 min, outperforming qRT-LAMP and qRT-PCR, the most commonly used RNA detection methods in clinical practice. All those indicates the great application prospects of this method in clinical diagnostic.

2.
Cell Rep ; 43(4): 114078, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38598334

RESUMO

The vaginal microbiome's composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

3.
Biomed Pharmacother ; 174: 116553, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38593703

RESUMO

This study is to investigate the effect of SPS on the UC model. An animal model of UC induced by DSS was developed using C57BL/6 mice. The body weight was recorded every day, and the symptoms related to UC were detected. H&E staining, AB-PAS staining and PSR staining were used to evaluate the histopathological changes of the colon. Inflammation and mucosal barrier indicators were detected by qRT-PCR, and the 16 S rRNA sequence was used to detect the intestinal flora. SPS can significantly prevent and treat DSS-induced ulcerative colitis in animals. SPS significantly improved clinical symptoms, alleviated pathological damage, inhibited the infiltration of intestinal inflammatory cells. SPS treatment can protect goblet cells, enhance the expression of tight junction proteins and mucins, inhibit the expression of antimicrobial peptides, thereby improving intestinal barrier integrity. The prevention and treatment mechanism of SPS may be related to the inhibition of STAT3/NF-κB signaling pathway to regulate intestinal barrier function. In particular, SPS also significantly adjusted the structure of intestinal flora, significantly increasing the abundance of Akkermansia and Limosilactobacillus and inhibiting the abundance of Bacteroides. Overall, SPS has a significant therapeutic effect on ulcerative colitis mice, and is expected to play its value effectively in clinical treatment.

4.
Circ Res ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557119

RESUMO

BACKGROUND: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown. METHODS: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events. RESULTS: Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3, which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase. CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

5.
Zhongguo Zhong Yao Za Zhi ; 49(4): 942-950, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621901

RESUMO

Scorpio, a commonly used animal medicine in China, is derived from Buthus martensii as recorded in the Chinese Pharmacopoeia. China harbors rich species of Scorpionida and adulterants exist in the raw medicinal material and deep-processed products of Scorpio. The microscopic characteristics of the deep-processed products may be incomplete or lost during processing, which makes the identification difficult. In this study, the maximum likelihood(ML) tree was constructed based on the morphology and cytochrome C oxidase subunit I(COⅠ) to identify the species of Scorpio products. The results showed that the main adulterant of Scorpio was Lychas mucronatus. According to the specific SNP sites in the COⅠ sequence of B. martensii, the stable primers were designed for the identification of the medicinal material and formula granules of Scorpio. The polymerase chain reaction(PCR) at the annealing temperature of 61 ℃ and 30 cycles produced bright specific bands at about 150 bp for both B. martensii and its formula particles and no band for adulterants. The adaptability of the method was investigated, which showed that the bands at about 150 bp were produced for Scorpio medicinal material, lyophilized powder, and formula granules, and commercially available formula granules. The results showed that the established method could be used to identify the adulterants of Scorpio and its formula granules, which could help to improve the quality control system and ensure the safe clinical application of Scorpio formula granules.


Assuntos
Animais Venenosos , Medicamentos de Ervas Chinesas , Escorpiões , Animais , Reação em Cadeia da Polimerase/métodos
6.
Cancer Lett ; 589: 216831, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574882

RESUMO

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.


Assuntos
Adenoma , Neoplasias do Colo , Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Lesões Pré-Cancerosas/genética , Mutação , Adenoma/genética , Adenoma/prevenção & controle , Adenoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/patologia
7.
Emerg Microbes Infect ; 13(1): 2339944, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38584592

RESUMO

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Adulto , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , DNA Viral , Estudos Retrospectivos , Vírus da Hepatite B/genética , Cirrose Hepática , Resultado do Tratamento , Antivirais/uso terapêutico
8.
medRxiv ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38562868

RESUMO

Humans experience many influenza infections over their lives, resulting in complex and varied immunological histories. Although experimental and quantitative analyses have improved our understanding of the immunological processes defining an individual's antibody repertoire, how these within-host processes are linked to population-level influenza epidemiology remains unclear. Here, we used a multi-level mathematical model to jointly infer antibody dynamics and individual-level lifetime influenza A/H3N2 infection histories for 1,130 individuals in Guangzhou, China, using 67,683 haemagglutination inhibition (HI) assay measurements against 20 A/H3N2 strains from repeat serum samples collected between 2009 and 2015. These estimated infection histories allowed us to reconstruct historical seasonal influenza patterns and to investigate how influenza incidence varies over time, space and age in this population. We estimated median annual influenza infection rates to be approximately 18% from 1968 to 2015, but with substantial variation between years. 88% of individuals were estimated to have been infected at least once during the study period (2009-2015), and 20% were estimated to have three or more infections in that time. We inferred decreasing infection rates with increasing age, and found that annual attack rates were highly correlated across all locations, regardless of their distance, suggesting that age has a stronger impact than fine-scale spatial effects in determining an individual's antibody profile. Finally, we reconstructed each individual's expected antibody profile over their lifetime and inferred an age-stratified relationship between probability of infection and HI titre. Our analyses show how multi-strain serological panels provide rich information on long term, epidemiological trends, within-host processes and immunity when analyzed using appropriate inference methods, and adds to our understanding of the life course epidemiology of influenza A/H3N2.

9.
Comput Biol Med ; 174: 108400, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38613888

RESUMO

Accurate liver tumor segmentation is crucial for aiding radiologists in hepatocellular carcinoma evaluation and surgical planning. While convolutional neural networks (CNNs) have been successful in medical image segmentation, they face challenges in capturing long-term dependencies among pixels. On the other hand, Transformer-based models demand a high number of parameters and involve significant computational costs. To address these issues, we propose the Spatial and Spectral-learning Double-branched Aggregation Network (S2DA-Net) for liver tumor segmentation. S2DA-Net consists of a double-branched encoder and a decoder with a Group Multi-Head Cross-Attention Aggregation (GMCA) module, Two branches in the encoder consist of a Fourier Spectral-learning Multi-scale Fusion (FSMF) branch and a Multi-axis Aggregation Hadamard Attention (MAHA) branch. The FSMF branch employs a Fourier-based network to learn amplitude and phase information, capturing richer features and detailed information without introducing an excessive number of parameters. The FSMF branch utilizes a Fourier-based network to capture amplitude and phase information, enriching features without introducing excessive parameters. The MAHA branch incorporates spatial information, enhancing discriminative features while minimizing computational costs. In the decoding path, a GMCA module extracts local information and establishes long-term dependencies, improving localization capabilities by amalgamating features from diverse branches. Experimental results on the public LiTS2017 liver tumor datasets show that the proposed segmentation model achieves significant improvements compared to the state-of-the-art methods, obtaining dice per case (DPC) 69.4 % and global dice (DG) 80.0 % for liver tumor segmentation on the LiTS2017 dataset. Meanwhile, the pre-trained model based on the LiTS2017 datasets obtain, DPC 73.4 % and an DG 82.2 % on the 3DIRCADb dataset.

10.
Surg Endosc ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632118

RESUMO

BACKGROUND: We aimed to study the impact of operative time on textbook outcome (TO), especially postoperative complications and length of postoperative stay in minimally invasive esophagectomy. METHODS: Patients undergoing esophagectomy for curative intent within a prospectively maintained database from 2016 to 2022 were retrieved. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with medical teams random effects. A restricted cubic spline (RCS) plotting was used to characterize correlation between operative time and the odds for achieving TO. RESULTS: Data of 2210 patients were examined. Median operative time was 270 mins (interquartile range, 233-313) for all cases. Overall, 902 patients (40.8%) achieved TO. Among non-TO patients, 226 patients (10.2%) had a major complication (grade ≥ III), 433 patients (19.6%) stayed postoperatively longer than 14 days. Multivariable analysis revealed operative time was associated with higher odds of major complications (odds ratio 1.005, P < 0.001) and prolonged postoperative stay (≥ 14 days) (odds ratio 1.003, P = 0.006). The relationship between operative time and TO exhibited an inverse-U shape, with 298 mins identified as the tipping point for the highest odds of achieving TO. CONCLUSIONS: Longer operative time displayed an adverse influence on postoperative morbidity and increased lengths of postoperative stay. In the present study, the TO displayed an inverse U-shaped correlation with operative time, with a significant peak at 298 mins. Potential factors contributing to prolonged operative time may potentiate targets for quality metrics and risk-adjustment process.

11.
Food Funct ; 15(8): 4538-4551, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38578200

RESUMO

Background: Evidence about the associations between Cantonese dietary patterns and mortality is scarce. We examined the prospective association of the dietary pattern with all-cause, cancer and cardiovascular disease (CVD) mortality in older Chinese. Methods: We included 19 598 participants of a Guangzhou Biobank cohort study aged 50+ years, who were recruited from 2003 to 2006 and followed up until July, 2022. The diet was assessed by using a 300-item validated food frequency questionnaire. The food items were collapsed into 27 food groups. Factor analysis (FA) was used to identify dietary patterns. Multivariable Cox regression produced hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: During 305 410 person-years, 4966 deaths including 1971 CVD, 1565 cancer and 1436 other-causes occurred. Four dietary patterns were identified by FA. No association of the vegetable-based dietary pattern with all-cause, CVD and cancer mortality was found. Compared with the lowest quartile of the healthy Cantonese dietary pattern score, the highest quartile showed lower risks of all-cause (HR 0.86, 95% CI 0.80-0.94) and CVD mortality (HR 0.84, 95% CI 0.72-0.97). The highest quartile of the nut and fruit dietary pattern showed lower risks of all-cause (HR 0.92, 95% CI 0.85-0.99) and CVD mortality (HR 0.82, 95% CI 0.72-0.93), while the unhealthy western dietary pattern was associated with a higher risk of all-cause (HR 1.10, 95% CI 1.01-1.19) and cerebrovascular disease mortality (HR 1.28, 95% CI 1.03-1.58). Conclusion: We have first identified four dietary patterns based on the Cantonese cuisine and found that healthy Cantonese and nut and fruit dietary patterns were associated with lower risks of all-cause and CVD mortality, whereas the unhealthy western dietary pattern was associated with a higher risk of all-cause and cerebrovascular disease mortality.


Assuntos
Doenças Cardiovasculares , Dieta , Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Seguimentos , Neoplasias/mortalidade , Estudos Prospectivos , Fatores de Risco , Estudos de Coortes , Bancos de Espécimes Biológicos , Frutas , Modelos de Riscos Proporcionais , Comportamento Alimentar , 60408 , População do Leste Asiático
12.
Phys Rev Lett ; 132(10): 106502, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518342

RESUMO

Computing thermal transport from first-principles in UO_{2} is complicated due to the challenges associated with Mott physics. Here, we use irreducible derivative approaches to compute the cubic and quartic phonon interactions in UO_{2} from first principles, and we perform enhanced thermal transport computations by evaluating the phonon Green's function via self-consistent diagrammatic perturbation theory. Our predicted phonon lifetimes at T=600 K agree well with our inelastic neutron scattering measurements across the entire Brillouin zone, and our thermal conductivity predictions agree well with previous measurements. Both the changes due to thermal expansion and self-consistent contributions are nontrivial at high temperatures, though the effects tend to cancel, and interband transitions yield a substantial contribution.

13.
Asia Pac J Clin Nutr ; 33(1): 1-10, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494682

RESUMO

BACKGROUND AND OBJECTIVES: Recent controversy over the bone benefits of calcium and vitamin D supplementation, and the potential detrimental effects of excess calcium supplementation, has confused clinicians. To systematically evaluate the effectiveness and safety of vitamin D combined with calcium in preventing and treating osteoporotic symptoms in the elderly. METHODS AND STUDY DESIGN: Databases were searched to collect randomized controlled trials (RCTs) on vitamin D combined with calcium in the prevention and treatment of osteoporotic fractures in the elderly. After screening the literature, extracting data, and assessing the risk of bias in the included studies, the Meta-analysis was performed. RESULTS: 19 RCTs were included, including 69,234 patients. Meta-analysis results showed that the mortality rate of the vitamin D combined with calcium group was not statistically significant compared with the control group; the calcium combined with vitamin D significantly reduced the incidence of fractures compared with the control group,Density and serum 25-hydroxyl concentration, adverse reactions of calcium combined with vitamin D were higher than those in the control group. CONCLUSIONS: The combination of vitamin D and calcium has no difference in mortality rate, and it can prevent fractures in the elderly, and enhance bone density and serum 25-hydroxyvitamin D concentration, but still need to pay attention to adverse reactions in the gastrointestinal tract.


Assuntos
Cálcio , Fraturas Ósseas , Humanos , Idoso , Suplementos Nutricionais , Vitamina D/efeitos adversos , Vitaminas , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/prevenção & controle , Cálcio da Dieta/efeitos adversos
14.
J Agric Food Chem ; 72(12): 6414-6423, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501560

RESUMO

Previous research has demonstrated that in pregnant mice deficient in l-methionine (Met), the mixture of the dipeptide l-methionyl-l-methionine (Met-Met) with Met was more effective than Met alone in promoting mammogenesis and lactogenesis. This study aimed to investigate the role of a novel long noncoding RNA (lncRNA), named mammary gland proliferation-associated lncRNA (MGPNCR), in these processes. Transcriptomic analysis of mammary tissues from Met-deficient mice, supplemented either with a Met-Met/Met mixture or with Met alone, revealed significantly higher MGPNCR expression in the Met group compared to the mixture group, a finding recapitulated in a mammary epithelial cell model. Our findings suggested that MGPNCR hindered mammogenesis and milk protein synthesis by binding to eukaryotic initiation factor 4B (eIF4B). This interaction promoted the dephosphorylation of eIF4B at serine-422 by enhancing its association with protein phosphatase 2A (PP2A). Our study sheds light on the regulatory mechanisms of lncRNA-mediated dipeptide effects on mammary cell proliferation and milk protein synthesis. These insights underscore the potential benefits of utilizing dipeptides to improve milk protein in animals and potentially in humans.


Assuntos
Fatores de Iniciação em Eucariotos , Metionina , RNA Longo não Codificante , Gravidez , Humanos , Feminino , Animais , Camundongos , Metionina/metabolismo , RNA Longo não Codificante/metabolismo , Dipeptídeos/metabolismo , Racemetionina/metabolismo , Proteínas do Leite/metabolismo , Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo
15.
J Stroke Cerebrovasc Dis ; 33(6): 107680, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38508478

RESUMO

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

16.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38546324

RESUMO

Enrichment analysis contextualizes biological features in pathways to facilitate a systematic understanding of high-dimensional data and is widely used in biomedical research. The emerging reporter score-based analysis (RSA) method shows more promising sensitivity, as it relies on P-values instead of raw values of features. However, RSA cannot be directly applied to multi-group and longitudinal experimental designs and is often misused due to the lack of a proper tool. Here, we propose the Generalized Reporter Score-based Analysis (GRSA) method for multi-group and longitudinal omics data. A comparison with other popular enrichment analysis methods demonstrated that GRSA had increased sensitivity across multiple benchmark datasets. We applied GRSA to microbiome, transcriptome and metabolome data and discovered new biological insights in omics studies. Finally, we demonstrated the application of GRSA beyond functional enrichment using a taxonomy database. We implemented GRSA in an R package, ReporterScore, integrating with a powerful visualization module and updatable pathway databases, which is available on the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/ReporterScore). We believe that the ReporterScore package will be a valuable asset for broad biomedical research fields.


Assuntos
Pesquisa Biomédica , Microbiota , Benchmarking , Bases de Dados Factuais , Metaboloma
17.
Front Pharmacol ; 15: 1332574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455963

RESUMO

Background: Breast squamous cell carcinoma (SCC) is an uncommon and highly aggressive variant of metaplastic breast cancer. Despite its rarity, there is currently no consensus on treatment guidelines for this specific subtype. Previous studies have demonstrated that chemotherapy alone has limited efficacy in treating breast SCC. However, the potential for targeted therapy in combination with chemotherapy holds promise for future treatment options. Case presentation: In this case report, we present a patient with advanced HER2-positive breast SCC, exhibiting a prominent breast mass, localized ulcers, and metastases in the lungs and brain. Our treatment approach involved the administration of HER2-targeted drugs in conjunction with paclitaxel, resulting in a sustained control of tumor growth. Conclusion: This case represents a rare occurrence of HER2-positive breast SCC, with limited available data on the efficacy of previous HER2-targeted drugs in treating such patients. Our study presents the first application of HER2-targeted drugs in this particular case, offering novel therapeutic insights for future considerations. Additionally, it is imperative to conduct further investigations to assess the feasibility of treatment options in a larger cohort of patients.

18.
Micromachines (Basel) ; 15(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38542571

RESUMO

Because the conventional Temperature Drift Error (TDE) estimation model for Capacitive MEMS Gyros (CMGs) has inadequate Temperature Correlated Quantities (TCQs) and inaccurate parameter identification to improve their bias stability, its novel model based on thermal stress deformation analysis is presented. Firstly, the TDE of the CMG is traced precisely by analyzing its structural deformation under thermal stress, and more key decisive TCQs are explored, including ambient temperature variation ∆T and its square ∆T2, as well its square root ∆T1/2; then, a novel TDE estimation model is established. Secondly, a Radial Basis Function Neural Network (RBFNN) is applied to identify its parameter accurately, which eliminates local optimums of the conventional model based on a Back-Propagation Neural Network (BPNN) to improve bias stability. By analyzing heat conduction between CMGs and the thermal chamber with heat flux analysis, proper temperature control intervals and reasonable temperature control periods are obtained to form a TDE precise test method to avoid time-consuming and expensive experiments. The novel model is implemented with an adequate TCQ and RBFNN, and the Mean Square Deviation (MSD) is introduced to evaluate its performance. Finally, the conventional model and novel model are compared with bias stability. Compared with the conventional model, the novel one improves CMG's bias stability by 15% evenly. It estimates TDE more precisely to decouple Si-based materials' temperature dependence effectively, and CMG's environmental adaptability is enhanced to widen its application under complex conditions.

19.
J Cancer Res Clin Oncol ; 150(3): 169, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546889

RESUMO

BACKGROUND: Based on liquid-based cytology, we performed an enzyme histochemical staining using acid phosphatase as a marker and termed it ELLBC. The aim of this study was to investigate the value of ELLBC in the diagnosis of bladder cancer. METHODS: Fifty patients who were initially diagnosed with suspected bladder cancers (hematuria or bladder irritation symptoms, urinary ultrasound suggestive of bladder mass) at the Second Affiliated Hospital of Anhui Medical University (Anhui, China) from January 2022 to December 2022 were selected as the study subjects, all of whom underwent ELLBC, CC, and histopathology Histopathology was used as the gold standard to calculate the diagnostic efficacy of ELLBC, CC and ELLBC combined with CC in bladder cancer. RESULTS: Histopathological examination revealed 35 positive cases in 50 patients, including 15 cases of high-grade uroepithelial carcinoma (HGUC) and 20 cases of low-grade uroepithelial carcinoma (LGUC.) The sensitivity of ELLBC was 82.86%, the specificity was 93.33%, the positive predictive value (PPV) was 96.67%, the negative predictive value (NPV) was 70.00%, and the accuracy was 86.00%; CC had a sensitivity of 37.14%, specificity of 80.00%, PPV of 81.25%, NPV of 35.29%, and accuracy of 50%; ELLBC combined with CC had a sensitivity of 88.57%, specificity of 73.33%, PPV of 88.57%, NPV of 73.33%, and accuracy of 84.00%. The sensitivity and specificity of ELLBC were higher than that of CC, and the difference was statistically significant (p < 0.05), ELLBC combined with CC achieved higher sensitivity, but the diagnostic accuracy decreased. For clinical staging, the diagnostic accuracy was 86.36% for ELLBC and 40.91% for CC in patients in Stage I, and 90.91% for ELLBC and 36.36% for CC in patients in Stage II. CONCLUSION: ELLBC has high clinical application value for the diagnosis of bladder cancer and can provide new options and methods for the early screening of bladder cancer.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Citologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Valor Preditivo dos Testes , Sensibilidade e Especificidade
20.
Environ Sci Technol ; 58(12): 5229-5243, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466915

RESUMO

Silicone-based passive samplers, commonly paired with gas chromatography-mass spectrometry (GC-MS) analysis, are increasingly utilized for personal exposure assessments. However, its compatibility with the biotic exposome remains underexplored. In this study, we introduce the wearable silicone-based AirPie passive sampler, coupled with nontargeted liquid chromatography with high-resolution tandem mass spectrometry (LC-HRMS/MS), GC-HRMS, and metagenomic shotgun sequencing methods, offering a comprehensive view of personalized airborne biotic and abiotic exposomes. We applied the AirPie samplers to 19 participants in a unique deep underwater confined environment, annotating 4,390 chemical and 2,955 microbial exposures, integrated with corresponding transcriptomic data. We observed significant shifts in environmental exposure and gene expression upon entering this unique environment. We noted increased exposure to pollutants, such as benzenoids, polycyclic aromatic hydrocarbons (PAHs), opportunistic pathogens, and associated antibiotic-resistance genes (ARGs). Transcriptomic analyses revealed the activation of neurodegenerative disease-related pathways, mostly related to chemical exposure, and the repression of immune-related pathways, linked to both biological and chemical exposures. In summary, we provided a comprehensive, longitudinal exposome map of the unique environment and underscored the intricate linkages between external exposures and human health. We believe that the AirPie sampler and associated analytical methods will have broad applications in exposome and precision medicine.


Assuntos
Expossoma , Doenças Neurodegenerativas , Hidrocarbonetos Policíclicos Aromáticos , Dispositivos Eletrônicos Vestíveis , Humanos , Espaços Confinados , Transcriptoma , Monitoramento Ambiental/métodos , Silicones
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