Search

Protein content in food is an important indicator of the nutritional value of food, and it is also related to food safety and many other issues, therefore it is significant to accurately determine the protein content for the valuation of food nutrition and safety. The main elements in food include carbon, nitrogen, hydrogen and sulphur, of which nitrogen mainly comes from protein. The average nitrogen content in protein is 16%, so the conversion factor for “nitrogen-to-protein” is 6.25. Therefore, the protein content in food can be obtained by measuring the nitrogen content of food combined with “nitrogen-to-protein” conversion factor. The traditional methods of protein detection are Kjeldahl method, spectrophotometry, and Dumas combustion. The Kjeldahl method is time-consuming and consumes a large amount of reagents, which can cause environmental pollution. Spectrophotometry is susceptible to interference and the quantitative curve is not easy to draw. Dumas combustion is expensive in terms of consumables. In this paper, a platform of tube furnace-quadrupole mass spectrometer was set up to analyze the protein content in food. Food samples were heated at high temperatures in a tube furnace and combusted in an oxygen-rich environment. After the gas products were ionized, they were directly introduced into a quadrupole mass analyzer for detection, which eliminated the need for processes such as oxidation-reduction, adsorption-desorption by using the selection ion scan function of the mass spectrometer. Five kinds of food samples with different protein contents were selected as research object. Each food sample was weighed at 1 g. The food samples were fully combusted in tube furnace at high temperature (1 300 ℃). The gas products were infused through a drying and filtering tube to remove water and smoke, and then entered the EI ion source through a capillary for ionization. By electronic ionization, nitrogen element characteristic ions, N+, NO+, and NO2+ are generated. The peak intensity of the NO2+ ions were detected by the selection ion scan function of the quadrupole mass analyzer. A standard curve for nitrogen quantification is plotted to be y=115.64x+1 896.9 with the correlation coefficient (R2) of 0.99992 and the relative standard deviation (RSD) of 2.1%-6.1%. The nitrogen content can be calculated by using the peak intensity of NO2+ ions according to the standard curve. The experimental platform of tube furnace-mass spectrometer provides a green, rapid, accurate, and low-cost detection method for quantitative analysis of protein content in food.

Background: The objective of this study was to investigate the correlation between the 7-joint ultrasound score (US7) and disease activity in patients with rheumatoid arthritis (RA). Methods: Forty-four patients with active RA were assessed, and the correlation between US7 and disease activity indicators such as the disease activity score (DAS28), rheumatoid factor (RF), the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was analyzed. In addition, the proportions of US7 points accounted for by different joint regions and joint surfaces were analyzed. Results: RF, CRP, and ESR were significantly increased in the RA group compared with the control group (P < 0.05). In the RA group, DAS28 (r = 0.0.561, P < 0.01), RF (r = 0.635, P < 0.01), ESR (r = 0.585, P < 0.01), and CRP (r = 0.492, P < 0.01) were positively correlated with US7. In terms of contributions to US7, the most susceptible joint surface is the dorsal surface, and the most susceptible joint area is the dorsal wrist. Conclusion: US7 is positively correlated with disease activity indicators of RA, which can objectively reflect disease activity in RA patients and provide a reference for clinical diagnosis and efficacy evaluation.

The surrounding rock of underground space is always affected by external dynamic disturbance from the side position, such as blasting vibration from a stope at the same level or seismic waves from adjacent strata. A series of laboratory tests, numerical simulations and theoretical analyses were carried out in this study to disclose the sliding mechanism of roof rock blocks under lateral disturbance. Firstly, the experiments on trapezoidal key block under various clamping loads and disturbance were conducted, followed by numerical simulations using the fast Lagrangian analysis of continua (FLAC3D). Then, based on the conventional wave propagation model and the classical shear-slip constitutive model, a theoretical model was proposed to capture the relative displacement between blocks and the sliding displacement of the key block. The results indicate that the sliding displacement of the key block increased linearly with the disturbance energy and decreased exponentially with the clamping load when the key block was disturbed to slide (without instability). Meanwhile, when the key block was disturbed to fall, two types of instability process may appear as immediate type or delayed type. In addition, the propagation of stress waves in the block system exhibited obvious low-velocity and low-frequency characteristics, resulting in the friction reduction effect appearing at the contact interface, which is the essential reason for the sliding of rock blocks. The results can be applied to practical underground engineering and provide valuable guidance for the early detection and prevention of rock-falling disasters.

Abstract Background Reperfusion is the most effective strategy for myocardial infarct, but induces additional injury. WD repeat and SOCS box containing protein 1 (WSB1) plays a protective role in ischemic cells. This study aims to investigate the effects of WSB1 on myocardial ischemia–reperfusion (IR) injury. Methods The myocardial IR was induced by left anterior descending (LAD) ligation for 45 min and subsequent reperfusion. The overexpression of WSB1 was mediated by tail vein injection of AAV9 loaded with WSB1 encoding sequence two weeks before IR surgery. H9c2 myocardial cells underwent oxygen-sugar deprivation/reperfusion (OGD/R) to mimic IR, and transfected with WSB1 overexpression or silencing plasmid to alter the expression of WSB1. Results WSB1 was found highly expressed in penumbra of myocardial IR rats, and the WSB1 overexpression relieved IR-induced cardio dysfunction, myocardial infarct and pathological damage, and cardiomyocyte death in penumbra. The ectopic expression of WSB1 in H9c2 myocardial cells mitigated OGD/R-caused apoptosis, and silencing of WSB1 exacerbated the apoptosis. In addition, WSB1 activated β-catenin signaling, which was deactivated under the ischemic condition. The co-immunoprecipitation results revealed that WSB1 mediated ubiquitination and degradation of glycogen synthase kinase 3 beta (GSK3β) as an E3 ligase in myocardial cells. The effects of WSB1 on myocardial cells under ischemic conditions were abolished by an inhibitor of β-catenin signaling. Conclusion WSB1 activated β-catenin pathway by promoting the ubiquitination of GSK3β, and restrained IR-induced myocardial injury. These findings might provide novel insights for clinical treatment of myocardial ischemic patients.

Abstract Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore‐forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin, thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non‐viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics.

Abstract Background Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.

Abstract Background It is widely acknowledged that hypoxia and m6A/m5C/m1A RNA modifications promote the occurrence and development of tumors by regulating the tumor microenvironment. This study aimed to establish a novel liver cancer risk signature based on hypoxia and m6A/m5C/m1A modifications. Methods We collected data from The Cancer Genome Atlas (TCGA-LIHC), the National Omics Data Encyclopedia (NODE-HCC), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO) databases for our study (GSE59729, GSE41666). Using Cox regression and least absolute shrinkage and selection operator (LASSO) method, we developed a risk signature for liver cancer based on differentially expressed genes related to hypoxia and genes regulated by m6A/m5C/m1A modifications. We stratified patients into high- and low-risk groups and assessed differences between these groups in terms of gene mutations, copy number variations, pathway enrichment, stemness scores, immune infiltration, and predictive capabilities of the model for immunotherapy and chemotherapy efficacy. Results Our analysis revealed a significantly correlated between hypoxia and methylation as well as m6A/m5C/m1A RNA methylation. The three-gene prognosis signature (CEP55, DPH2, SMS) combining hypoxia and m6A/m5C/m1A regulated genes exhibited strong predictive performance in TCGA-LIHC, NODE-HCC, and ICGC-LIHC-JP cohorts. The low-risk group demonstrated a significantly better overall survival compared to the high-risk group (p

Abstract Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through diverse machine-learning algorithms. The reliability and robustness of the MET score were validated using various in vitro assays and in vivo models. Our findings revealed a distinct molecular landscape in metastatic melanoma characterized by the enrichment of metastasis-related pathways, intricate cell–cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients in the high MET score group exhibited poorer prognoses and an immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients with low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 therapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies.

IntroductionPlant bacterial wilt is an important worldwide disease caused by Ralstonia solanacearum which is a complex of species.MethodsIn this study, we identified and sequenced the genome of R. solanacearum strain gd-2 isolated from tobacco.ResultsStrain gd-2 was identified as R. solanacearum species complex (RSSC) phylotype I sequevar 15 and exhibited strong pathogenicity to tobacco. The genome size of gd-2 was 5.93 Mb, including the chromosomes (3.83 Mb) and the megaplasmid (2.10 Mb). Gene prediction results showed that 3,434 and 1,640 genes were identified in the chromosomes and plasmids, respectively. Comparative genomic analysis showed that gd-2 exhibited high conservation with ten highly similar strain genomes and the differences between gd-2 and other genomes were mainly located at positions GI12-GI14. 72 type III effectors (T3Es) were identified and RipAZ2 was a T3E specific to gd-2 compared with other eight sequenced strain.DiscussionOur study provides a new basis and evidence for studying the pathogenic mechanism of R. solanacearum.

Sub-group 4 R2R3-type MYB transcription factors (TFs) are involved in repression of the phenylpropanoid pathway. In this study, we identified and characterized three MYB transcriptional repressors in common tobacco, named NtMYB1, NtMYB2, and NtMYB4, which belong to sub-group 4 members. Tissue expression properties and specificity of stress-induced expression indicated that the NtMYB1, NtMYB2, and NtMYB4 may perform different functions in tobacco. Overexpression of NtMYB1, NtMYB2, and NtMYB4 reduced phenylpropanoids and flaonoid compounds, such as caffeic acid, chlorogenic acid, neochlorogenic acid, and rutin, respectively. Meanwhile, the expression of the most structural genes involved in phenylpropanoids and flavonoids were reduced in the overexpression transgenic lines. In addition, results based on co-expression and expression analyses revealed possible interactions between NtMYB1, NtMYB2, and NtMYB4 and multiple bHLH TFs. Our results showed that the three sub-group 4 R2R3 members exhibited different expression pattern in various tissues and under abiotic stress conditions. Meanwhile, we hypothesized that the three of them involved in the inhibition of phenylpropanoid and flavonoid biosynthesis might be interaction with bHLH TFs.

Introduction: In REFLECT, lenvatinib was noninferior to sorafenib in terms of overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC; median 13.6 vs 12.3 months; HR 0.92, 95% CI 0.79-1.06). The objective response rate (ORR) with lenvatinib was 18.8% by blinded independent imaging review (IIR) per Response Evaluation Criteria in Solid tumors version 1.1 (RECIST v1.1); per modified RECIST (mRECIST), the ORR was 40.6%. We sought to further characterize these tumor responses and explore ORR’s importance among outcomes for patients with HCC. Methods: Efficacy assessments included all patients randomized to receive lenvatinib treatment (body weight ≥60 kg, 12 mg/day;

Abstract Background Melanoma is the deadliest form of skin tumor, and G protein-coupled receptors (GPCRs) play crucial roles in its carcinogenesis. Furthermore, the tumor microenvironment (TME) affects the overall survival (OS) and the response to immunotherapy. The combination of GPCRs and TME from a multi-omics perspective may help to predict the survival of the melanoma patients and their response to immunotherapy. Methods Bulk-seq, single-cell RNA sequencing (scRNA-seq), gene mutations, immunotherapy responses, and clinicopathologic feature data were downloaded from public databases, and prognostic GPCRs and immune cells were screened using multiple machine learning algorithms. The expression levels of GPCRs were detected using real-time quantitative polymerase chain reaction (qPCR) in A375 and HaCaT cell lines. The GPCR–TME classifier was constructed and verified using different cohorts and multi-omics. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and tracking tumor immunophenotype (TIP) were used to identify the key biological pathways among the GPCR–TME subgroups. Then, tumor mutational burden (TMB), vital mutant genes, antigen presentation genes, and immune checkpoints were compared among the subgroups. Finally, the differences in immunotherapy response rates among the GPCR–TME subgroups were investigated. Results A total of 12 GPCRs and five immune cell types were screened to establish the GPCR–TME classifier. No significant differences in the expression levels of the 12 GPCRs were found in the two cell lines. Patients with high GPCR score or low TME score had a poor OS; thus, the GPCRlow/TMEhigh subgroup had the most favorable OS. The scRNA-seq result revealed that immune cells had a higher GPCR score than tumor and stromal cells. The GPCR–TME classifier acted as an independent prognostic factor for melanoma. GSEA, WGCNA, and TIP demonstrated that the GPCRlow/TMEhigh subgroup was related to the activation and recruitment of anti-tumor immune cells and the positive regulation of the immune response. From a genomic perspective, the GPCRlow/TMEhigh subgroup had higher TMB, and different mutant genes. Ultimately, higher expression levels of antigen presentation genes and immune checkpoints were observed in the GPCRlow/TMEhigh subgroup, and the melanoma immunotherapy cohorts confirmed that the response rate was highest in the GPCRlow/TMEhigh cohort. Conclusions We have developed a GPCR–TME classifier that could predict the OS and immunotherapy response of patients with melanoma highly effectively based on multi-omics analysis.

Abstract Background Currently, there is lack of marker to accurately assess the prognosis of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). This study aims to establish a hypoxia-related risk scoring model that can effectively predict the prognosis and chemotherapy outcomes of PDAC patients. Methods Using unsupervised consensus clustering algorithms, we comprehensively analyzed The Cancer Genome Atlas (TCGA) data to identify two distinct hypoxia clusters and used the weighted gene co-expression network analysis (WGCNA) to examine gene sets significantly associated with these hypoxia clusters. Then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used to construct a signature and its efficacy was evaluated using the International Cancer Genome Consortium (ICGC) PDAC cohort. Further, the correlation between the risk scores obtained from the signature and carious clinical, pathological, immunophenotype, and immunoinfiltration factors as well as the differences in immunotherapy potential and response to common chemotherapy drugs between high-risk and low-risk groups were evaluated. Results From a total of 8 significantly related modules and 4423 genes, 5 hypoxia-related signature genes were identified to construct a risk model. Further analysis revealed that the overall survival rate (OS) of patients in the low-risk group was significantly higher than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk scoring signature was an independent factor for prognosis prediction. Analysis of immunocyte infiltration and immunophenotype showed that the immune score and the anticancer immune response in the high-risk were significantly lower than that in the low-risk group. Conclusion The constructed hypoxia-associated prognostic signature demonstrated could be used as a potential risk classifier for PDAC.

Abstract Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups.

With the excavation of underground opening, the roof rock block may fall under external dynamic disturbance. In this paper, the roof rock mass was simplified as a rock block system composed of trapezoidal rock blocks. A series of experiments and numerical simulations were performed to study the sliding process of the key block under the horizontal static clamping load and vertical impact disturbance. The propagation of stress wave in the block system were captured and analyzed by using high-speed camera and digital image correlation technique. The results reveal that a pendulum-type wave was generated due to the propagation and superposition of stress waves in the block system. Therefore, the governing mechanism of the sliding displacement of the key block was clarified based on the propagation of incident stress waves or pendulum-type waves. Meanwhile, it is found that the sliding distance of the key block decreases in a power function with the increasing friction coefficient, or decreases in a parabolic function with the increasing trapezoid internal angle. Finally, a case study on the roof block sliding of the roadway at a gold mine was conducted, and it is concluded that the sliding of the key block resulted from the coupled effects of “shear driving” and “low friction” driven by stress wave propagation, regardless of a single or multi-layer rock block system. These results may provide technical guideline for preventing rock-falling accidents caused by blasting disturbances in underground mining.

Abstract Background Uridine disphosphate (UDP) glycosyltransferases (UGTs) act upon a huge variety of highly diverse and complex substrates, such as phytohormones and specialized metabolites, to regulate plant growth, development, disease resistance, and environmental interactions. However, a comprehensive investigation of UGT genes in tobacco has not been conducted. Results In this study, we carried out a genome-wide analysis of family-1 UDP glycosyltransferases in Nicotiana tabacum. We predicted 276 NtUGT genes, which were classified into 18 major phylogenetic subgroups. The NtUGT genes were invariably distributed among all the 24 chromosomes with structural diversity in exon/intron structure, conserved motifs, and cis-acting elements of promoters. Three groups of proteins which involved in flavonoid biosynthesis, plant growth and development, transportation and modification were identified that interact with NtUGT proteins using the PPI analysis. Expression analysis of NtUGT genes in cold stress, drought stress and different flower color using both online RNA-Seq data and the realtime PCR analysis, suggested the distinct role of NtUGT genes in resistance of cold, drought and in flavonoid biosynthesis. The enzymatic activities of seven NtUGT proteins that potentially involved in flavonoid glycosylation were analyzed, and found that all seven exhibited activity on myricetin; six (NtUGT108, NtUGT123, NtUGT141, NtUGT155, NtUGT179, and NtUGT195) showed activity on cyanidin; and three (NtUGT108, NtUGT195, and NtUGT217) were active on the flavonol aglycones kaempferol and quercetin, which catalyzing the substrates (myricetin, cyanidin or flavonol) to form new products. We further investigated the enzymatic products and enzymatic properties of NtUGT108, NtUGT195, and NtUGT217, suggested their diverse enzymatic activity toward flavonol, and NtUGT217 showed the highest catalyzed efficient toward quercetin. Overexpression of NtUGT217 significantly increase the content levels of the quercetin-3-O-glucoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside in transgenic tobacco leaves. Conclusion We identified 276 UGT genes in Nicotiana tabacum. Our study uncovered valuable information about the phylogenetic structure, distribution, genomic characters, expression patterns and enzymatic activity of NtUGT genes in tobacco. We further identified three NtUGT genes involved in flavonoid biosynthesis, and overexpressed NtUGT217 to validate its function in catalyze quercetin. The results provide key candidate NtUGT genes for future breeding of cold and drought resistance and for potential metabolic engineering of flavonoid compounds.

The probabilistic hesitant fuzzy sets (P-HFSs) allow experts to express their preferences regarding different membership degrees with probabilistic information. Fuzzy entropy is an important concept to measure the uncertainty of probabilistic hesitant fuzzy information. In this paper, we propose a novel fuzzy entropy named as the exponential probabilistic hesitant fuzzy entropy for the P-HFEs. This novel fuzzy entropy not only observes the basic property of fuzzy entropy, but also has the same characteristics and change tends with the existing fuzzy entropy proposed and studied by other scholars. Then, based on the cardinal reconciliation method and TODIM(Tomada de decisao interativa multicriterio) method, we propose a multi-criteria decision-making (MCDM) problem, where the attribute weight is determined by the exponential probabilistic hesitant fuzzy entropy of the integration results. Finally, a application case in green building is given for the sake of illustrating the efficiency of the MCDM problem. Numerical and theoretical results show that a MCDM problem based on the proposed novel fuzzy entropy and the TODIM method have a wide range of application.

IntroductionBreast cancer (BC) is now the most common type of cancer in women. Disulfidptosis is a new regulation of cell death (RCD). RCD dysregulation is causally linked to cancer. However, the comprehensive relationship between disulfidptosis and BC remains unknown. This study aimed to explore the predictive value of disulfidptosis-related genes (DRGs) in BC and their relationship with the TME.MethodsThis study obtained 11 disulfidptosis genes (DGs) from previous research by Gan et al. RNA sequencing data of BC were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) databases. First, we examined the effect of DG gene mutations and copy number changes on the overall survival of breast cancer samples. We then used the expression profile data of 11 DGs and survival data for consensus clustering, and BC patients were divided into two clusters. Survival analysis, gene set variation analysis (GSVA) and ss GSEA were used to compare the differences between them. Subsequently, DRGs were identified between the clusters used to perform Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a prognosis model. Finally, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. CCK-8 and a colony assay obtained by knocking down genes and gene sequencing were used to validate the model.ResultTwo DG clusters were identified based on the expression of 11DGs. Then, 225 DRGs were identified between them. RS, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-RS shows a better prognosis and higher immunotherapy response than high-RS. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. CCK-8 and colony assay obtained by knocking down genes have demonstrated that the knockdown of high-risk genes in the RS model significantly inhibited cell proliferation.DiscussionThis study elucidates the potential relationship between disulfidptosis-related genes and breast cancer and provides new guidance for treating breast cancer.

Acute respiratory tract infections (ARTI) are caused by respiratory pathogens and range from asymptomatic infections to severe respiratory diseases. These diseases can be life threatening with high morbidity and mortality worldwide. Under the pandemic of coronavirus disease 2019 (COVID-19), little has been reported about the pathogen etiologies and epidemiology of patients suffering from ARTI of all age in Xiamen. Region-specific surveillance in individuals with ARTI of all ages was performed in Xiamen from January 2020 to October 2022. Here, we observed the epidemiological characteristics of thirteen pathogens within ARTI patients and further revealed the difference of that between upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In total 56.36 % (2358/4184) of the ARTI patients were positive for at least one respiratory pathogen. Rhinovirus (RVs, 29.22 %), influenza A (FluA, 19.59 %), respiratory syncytial virus (RSV, 18.36 %), metapneumovirus (MPV, 13.91 %), and adenovirus (ADV, 10.31 %) were the five leading respiratory pathogens. Respiratory pathogens displayed age- and season-specific patterns, even between URTI and LRTI. Compared with other groups, a higher proportion of FluA (52.17 % and 68.75 %, respectively) infection was found in the adult group and the elder group, while the lower proportion of RVs (14.11 % and 11.11 %) infection was also observed in them. Although ARTI cases circulated throughout the year, RVs, FluB, and BoV peaked in autumn, and FluA circulated more in summer. Besides, the co-infectious rate was 8.7 % with the most common for RVs. Logistic regression analyses revealed the correlations between respiratory pathogens and disease types. These results are essential for replenishing epidemiological characteristics of common respiratory pathogens that caused ARTI in Xiamen during the epidemic of COVID-19, and a better understanding of it might optimize the local prevention and clinical control.

Aim: To explore the potential categories and characteristic differences of maternal postpartum depression literacy. Design: Cross-sectional survey. Methods: From February 2023 to April 2023, convenience sampling was used to survey 278 women attending postnatal visits to three tertiary level A hospitals. The study included general demographic characteristics, postpartum depression literacy scale, and family caring index scale. Latent profile analysis was performed to identify the categories of maternal postpartum depression literacy, and multiple disordered logistic regression was used to analyze the influencing factors of different categories. Results: Maternal postpartum depression literacy was divided into three categories: low literacy (41.0 %), moderate literacy (32.4 %), and high literacy (26.6 %). The results showed that work status, education level, whether the pregnancy was planned, whether or not they had participated in mental health-related courses, and family functioning status were factors influencing the category of maternal postpartum depression literacy (P

As an essential technology in the evolution towards full duplex, the subband full duplex (SBFD) operation has attracted significant attention from both the academic and industrial communities, as well as global standardization bodies for its capability to increase the user perceived throughput (UPT) and the uplink coverage, reduce the transmission latency and support various traffics with different requirements in the same cell in time division duplexing (TDD) bands. In this paper, the model of a SBFD based communication system is clearly presented, along with the interference. To facilitate the early deployment of SBFD in 5G-Advanced and 6G networks, comprehensive performance evaluations on UPT, latency and coverage under different scenarios, different SBFD patterns and different traffics are conducted to explore the potential of the SBFD operation. Furthermore, a field test is carried out to verify the practical performance of SBFD in a typical outdoor scenario. Results obtained from both the simulations and field tests demonstrate significant performance gain for SBFD compared with traditional division duplexing schemes, especially for uplink transmissions.

Objective: The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodul es by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods: A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors wer e analyzed, and the diagnostic efficacy was evaluated. Results: Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA–RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sens itivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions: Our study revealed the distinct molecular profile of thyroid tu mors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

Bacterial wilt, caused by the Ralstonia solanacearum species complex, is one of the most damaging bacterial diseases in tobacco and other Solanaceae crops. In this study, we conducted an analysis and comparison of transcriptome landscape changes in seedling roots of three tobacco BC4F5 lines, C244, C010, and C035, with different resistance to bacterial wilt at 3, 9, 24, and 48 h after R. solanacearum infection. A number of biological processes were highlighted for their differential enrichment between C244, C010, and C035, especially those associated with cell wall development, protein quality control, and stress response. Hence, we performed a genome-wide identification of seven cell wall development-related gene families and six heat shock protein (Hsp) families and proposed that genes induced by R. solanacearum and showing distinct expression patterns in C244, C010, and C035 could serve as a potential gene resource for enhancing bacterial wilt resistance. Additionally, a comparative transcriptome analysis of R. solanacearum-inoculated root samples from C244 and C035, as well as C010 and C035, resulted in the identification of a further 33 candidate genes, of which Nitab4.5_0007488g0040, a member of the pathogenesis-related protein 1 (PR-1) family, was found to positively regulate bacterial wilt resistance, supported by real-time quantitative PCR (qRT-PCR) and virus-induced gene silencing (VIGS) assays. Our results contribute to a better understanding of molecular mechanisms underlying bacterial wilt resistance and provide novel alternative genes for resistance improvement.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by destruction of synovial joints, abnormal immune responses and chronic inflammatory manifestations, which seriously affects patients’ well-being. We explored this study to ascertain the effect and mechanism of silent information regulator 6 (SIRT6) on RA. Methods: Genes of RA patients and normal volunteers were analyzed using Gene Expression Omnibus (GEO), Kyoto-Encyclopedia of Genes and Genomes (KEGG) and Disconet databases. Serum samples of RA patients and normal subjects were collected before detection of myeloid differentiation factor-88 (MyD88)-extracellular signal-regulated kinase (ERK) pathway proteins expression with Western blot. In vitro RA fibroblast-like synoviocytes (FLS) cell model (RA-FLS) was established by treating RSC-364 with recombinant rat IL-1β (10 ng/mL) after which SIRT6 and MyD88 adenoviruses treatment was carried out. The enzyme linked immunoassay (ELISA), real time polymerase chain reaction (RT-PCR) and Western blot were respectively used to measure inflammatory factors, related messenger ribonucleic acid (mRNA) and protein expressions. Also, we constructed RA rat model with bovine type II collagen (BIIC) and complete Freund’s adjuvant, before treatment with SIRT6 and MyD88 adenoviruses. Results: Low expression of SIRT6 gene were detected in RA patients. Also, levels of MyD88, ERK and phosphorylated extracellular signal-regulated protein kinase (p-ERK) protein expressions in RA patients were increased, whilst that of SIRT6 protein decreased. Compared to FLS cells in Control group, inflammatory factors levels of rats in Model batch increased significantly. SIRT6 adenovirus treatment potentially and significantly inhibited inflammation including suppression of increased inflammatory factors induced by MyD88. In comparison with FLS cells in Control group, Model batch cells’ MyD88, interleukin (IL)-1β, IL-21, IL-22, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) mRNA expressions increased but SIRT6 gene treatment could reduce mRNA expression of the aforesaid factors, even after MyD88 adenovirus treatment. Besides, overpressed SIRT6 negatively regulated levels of MyD88, ERK and p-ERK proteins expressions. SIRT6 demonstrated anti-RA effect by regulating MyD88-ERK pathway and inhibiting inflammatory response in RA rats. Conclusions: SIRT6 could potentially inhibit the inflammatory response of RA via a regulatory mechanism mainly relating to MyD88-ERK signal pathway. Thus, SIRT6 and its agonists may serve as new targets for developing drugs that can potentially treat RA.

Follicular dendritic cell sarcoma (FDCS) is an uncommon low-grade malignant sarcoma. For localized FDCS, surgery is the most commonly recommended therapy option. However, there is no standard treatment protocol for metastatic FDCS. Here, we present a 68-year-old female with primary spleen FDCS who had multiple peritoneal metastases. She was treated with sintilimab (PD-1 inhibitor) plus chemotherapy (epirubicin plus ifosfamide) as first-line treatment achieving partial response (PR) and a relatively long progression-free survival (PFS) of 17 months. This case suggests that PD-1 inhibitor plus chemotherapy as first-line therapy seem to be a promising treatment option for metastatic FDCS.

Abstract Background This study aimed to compare the diagnostic accuracy of high-frequency ultrasound (HFUS) and fiberoptic ductoscopy (FDS) for pathologic nipple discharge (PND). Methods HFUS and FDS were conducted in 210 patients with PND (248 lesions) treated at our hospital. The diagnostic accuracy of these two methods was compared using pathological diagnosis as the standard. Results Among 248 lesions, 16 and 15 of 16 malignant lesions were accurately diagnosed by HFUS and FDS, respectively. Of 232 benign lesions, 183 and 196 cases were accurately diagnosed by HFUS and FDS, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HFUS in diagnosis of intraductal lesions were 84.36% (95% CI 79.26–88.39%), 60% (95% CI 23.07–92.89%), 96.03% (95% CI 96.55–99.83%), and 7.31% (95% CI 2.52–19.4%) respectively. The sensitivity, specificity, PPV, and NPV of FDS in diagnosis of intraductal lesions were 86.83% (95% CI 82.00–90.52%), 100% (95% CI 56.55–100%), 100% (95% CI 98.21–100%), and 13.51% (95% CI 5.91–27.98%) respectively. Diagnostic accuracy rates of HFUS and FDS were 83.87% (208/248) and 85.08% (211/248), respectively, exhibiting no statistically differences (χ2 = 0.80, P > 0.05). The accuracy of HFUS combined with FDS was 93.14% (231/248), showing statistically differences (χ2 = 10.91, P

For multi-attribute decision-making problems with interval numbers whose attribute weights are completely unknown, it is difficult to compare the value of interval numbers. So this paper proposes a method based on TOPSIS and the weighted parameter to deal with it. Firstly, this paper transforms the interval number matrix into two exact number matrices which reduces sorting complexity. Secondly, a parameter is given when determining the weights with entropy weight in order to reflect all the information of the interval numbers. Then TOPSIS is used to determine the order of each scheme. In addition, the average value of the ranking number is used to reflect the actual situation better. Finally, the analysis of the car purchase case shows the proposed method is feasible and practical. And the comparative analysis with the other method based on practical application dataset demonstrates the proposed method is stable and effective.

Abstract Background Clinical neurology is difficult for young residents. To familiarize with neurological emergencies as soon as possible for young doctors, the urgent inpatient neurologic consultations were analyzed. Methods A retrospective study was conducted on the urgent inpatient neurologic consultations in a large tertiary hospital for 4 consecutive years. Results A total of 1437 cases were included, and the annual consultation cases gradually decreased from 573 to 257, involving 29 clinical departments. The disorders of urgent inpatient neurologic consultations were divided into three categories: neurological disorders (77.8%), non‐neurological disorders (10.4%), and undiagnosed disorders (11.8%), common causes in consultation were disturbance of consciousness (36.0%), convulsions/stiffness (13.6%), limb weakness (8%), and mental disorder (5.6%). Common neurological disorders included acute cerebrovascular disease (33.6%), epilepsy/status epilepticus (15.8%), and metabolic or infectious toxic encephalopathy (14.9%). Conclusion Urgent inpatient neurologic consultations involve multidisciplinary critical diseases, mainly neurological diseases. The standardized training of residents may help to rapidly improve the comprehensive diagnosis and treatment ability of young residents and is suitable for use in hospitals at all levels.

BackgroundAn inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor with a prevalence ranging from 0.04% to 0.7% worldwide, in which the lung is the most common predilection site, accounting for 33% of cases, followed by the abdomen, pelvis, mesentery, and uterus. Approximately 50% of uterine IMTs present as anaplastic lymphoma kinase (ALK) positive along with ALK gene fusion, which lays a solid foundation for the development of ALK-based target therapy to optimize treatment strategies.Case presentationHerein we describe a 57-year-old woman who presented with a slow-growing mass in the uterus for over 10 years and then received surgical resection because of significant progressive enlargement of the mass during follow-up. She was diagnosed with uterine leiomyosarcoma (LMS) with no further interventions until recurrence. We revised the diagnosis to uterine IMT based on diffuse ALK expression, ALK-IGFBP5 gene fusion, and the morphologic features of the tumors by pathology consultation. Based on these, we recommended an ALK tyrosine kinase inhibitor (TKI) treatment, crizotinib (250 mg bid), and she achieved a complete response (CR) with at least 18 months of progression-free survival (PFS). We monitored the dynamics of target lesions and peripheral blood cells at regular intervals through CT scans and routine blood tests during the treatment process. We present patient responses to ALK inhibitor-based targeted therapy with uterine IMT harboring ALK-IGFBP5 fusion, and the neutrophil-to-lymphocyte ratio (NLR) may be an effective indicator to predict prognosis.

ObjectiveThis stydy aims to assess the value of monitoring of postoperative neutrophil-to-lymphocyte ratio (NLR), D-dimer, and carbohydrate antigen 153 (CA153) for diagnosis of breast cancer (BC) recurrence and metastasis.Materials/MethodsA cohort of 252 BC patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between August 2008 and August 2018 were enrolled in this retrospective study. All patients were examined during outpatient follow-ups every 3 months for 5 years postoperation and every 6 months thereafter. Recurrence or metastasis was recorded for 131 patients but not for the remaining 121. Retrospective analysis of hematological parameters and clinicopathological characteristics allowed comparison between the two groups and evaluation of these parameters for the recurrent and metastatic patients.ResultsLymph node metastasis, higher tumor node metastasis (TNM) staging, and higher histological grade correlated with BC recurrence and metastasis (p

Accurate predictions of the surface deformation caused by underground mining are crucial for the safe development of underground resources. Although surface deformation has been predicted by artificial intelligence (AI) methods, most AI models are established based on the relationships between surface deformation and influential factors. The lack of consideration of the deformation state transition often leads to errors in the prediction results of catastrophic deformation by conventional AI methods. In this respect, this study introduces a surface deformation prediction model based on spatio-temporal association rule mining (STARM). Surface deformation is classified as excessive deformation zone (EDZ) and hysteretic deformation zone (HDZ), representing different surface deformation stage or state. The spatio-temporal association rules between the monitored EDZ and HDZ data are then mined. A surface deformation prediction model is established according to the spatio-temporal relationship between monitored EDZ and HDZ data. The proposed model is verified based on a practical case study of the Chengchao Iron Mine in China. The data collection of the influential factors is not requisite for the proposed model. It can achieve accurate prediction of the catastrophic deformation that was characterized by deformation state transition.

Abstract To investigate the effect of radiation therapy (RT) after endometrial cancer (EC) diagnosis on the risk of occurring secondary bladder cancer (SBC) as well as on the survival outcome of those patients who suffered with SBC. Data was extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. Chi-squared test was utilized to compare clinicopathological characteristics among different groups. The Fine and Gray’s competing risk model was utilized to assess cumulative incidence and risk of occurring SBC in EC survivors. The Kaplan–Meier method and the Cox regression model were used for survival analysis. As a result, a total of 108,060 EC patients were included, among which 37,118 (34.3%) patients received RT while others did not. The incidence of SBC was 1.31%, 1.76% and 0.96% among patients who received prior brachytherapy, external-beam radiotherapy (EBRT) and others, respectively. Both of the EBRT (standardized incidence ratio (SIR) = 2.24, 95% CI [1.94–2.58]) and brachytherapy (SIR = 1.76, 95% CI [1.44–2.13]) group had a higher incidence of SBC than the general population in USA. The competing risk analysis demonstrated that receiving EBRT (HR = 1.97, 95% CI [1.64–2.36]) or brachytherapy (HR = 1.46, 95% CI [1.14–1.87]) were all independent risk factors for developing SBC. A survival detriment was only observed in SBC patients who received prior EBRT after EC diagnosis, but not for brachytherapy, when compared with those who did not undergo RT. Additionally, there were no significant survival differences between primary bladder cancer and SBC with or without prior RT history. Patients who underwent RT after EC had an increased risk of developing bladder cancer as secondary primary cancer. The prognosis of these SBC patients varied depending on types of RT that received after EC diagnosis.

Objectives: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains. Methods: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies. Results: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus.Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13–18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P

Abstract Insulin resistance (IR) plays an important role in the development of hypertension. Triglyceride and glucose index (TyG index), and triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL‐c) as effective IR surrogate indexes have been verified in numerous studies. Therefore, the authors conducted a large cross‐sectional study to explore the association of TyG index and TG/HDL‐c with prehypertension and hypertension in the same normoglycemic subjects from Tianjin, China. A total of 32 124 adults were eligible for this study. According to the level of blood pressure, the enrolled individuals were divided into three groups, which were normotension, prehypertension, and hypertension. In multiple logistic regression analysis, there was associated with prehypertension and hypertension when comparing the highest TyG index to the lowest TyG index and corresponding ORs were 1.795 (1.638, 1.968) and 2.439 (2.205, 2.698), respectively. For TG/HDL‐c, the corresponding ORs were 1.514 (1.382, 1.658) and 1.934 (1.751, 2.137), respectively. Furthermore, when comparing the fourth quartile to the first quartile of TyG index and TG/HDL‐c, respectively, both corresponding ORs of hypertension were higher than prehypertension. Elevated TyG index and TG/HDL‐c levels were associated with prehypertension and hypertension in normoglycemic individuals. Moreover, the TyG index was more significant than TG/HDL‐c in distinguishing hypertension. They have the potential to become cost‐effective monitors in the hierarchical management of prehypertension and hypertension.

Introduction: Baseline liver function among patients starting treatment for unresectable hepatocellular carcinoma (uHCC) impacts survival and could impact efficacy outcomes and safety profiles of treatments. This post hoc analysis of the phase 3 REFLECT study examined the efficacy and safety outcomes for lenvatinib and for sorafenib in patients with uHCC, assessed by Child-Pugh score (CPS) and albumin-bilirubin (ALBI) grade. Methods: Efficacy and safety were assessed in patient cohorts from REFLECT according to study entry baseline ALBI grade and CPS. Results: Lenvatinib treatment generally provided survival benefits in all groups. Median overall survival (OS) among patients with an ALBI grade of 1 was consistently higher than among patients with an ALBI grade of 2 for both the lenvatinib and sorafenib arms (lenvatinib: 17.4 vs. 8.6 months; sorafenib: 14.6 vs. 7.7 months, respectively). Median OS among patients with a CPS of 5 was consistently higher than among patients with a CPS of 6 (lenvatinib: 15.3 vs. 9.4 months; sorafenib: 14.2 vs. 7.9 months, respectively). Progression-free survival and objective response rates for these ALBI grades and CPS demonstrated similar patterns. Among patients who received lenvatinib and experienced a treatment-related treatment-emergent adverse event leading to withdrawal, 6.6% had an ALBI grade of 1, while 13.3% had an ALBI grade of 2, and 7.9% had a CPS of 5, while 12.1% had a CPS of 6. Conclusions: Better liver function at baseline, as measured by ALBI grade or CPS, may be prognostic for better survival outcomes in patients with uHCC undergoing treatment with lenvatinib or sorafenib.

BackgroundDiastolic wall shear stress (WSS), assessed by using vector flow mapping (VFM), is the result of the interaction between the blood flow and the ventricular wall. This study aimed to evaluate the trend of left ventricular (LV) WSS in normal subjects.Methods and resultsA total of 371 healthy volunteers were recruited and divided into four age groups (group I: 18–30 years; group II: 31–43 years; group III: 44–56 years; group IV: 57–70 years). LV WSS of different age groups was measured at each diastolic phase (P1: isovolumic diastolic period, P2: rapid filling period, P3: slow filling period, and P4:atrial contraction period) to evaluate the change trend of LV WSS. In each age group, LV WSS coincided with a trend of increasing-decreasing-increasing during P1–P4 (P < 0.05). Besides, among groups I, II, III, and IV, WSS of anterolateral, inferoseptal, and anteroseptal in P1 and WSS of inferolateral, inferoseptal, and anteroseptal in P4 all showed an increasing trend with age (P < 0.05). Regarding sex differences, women had greater diastolic WSS compared to men (P < 0.05).ConclusionLV WSS showed a regular variation and had specific age- and sex-related patterns in different diastolic phases.

BackgroundPathological complete response (pCR) is considered a surrogate for favorable survival in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NACT), which is the goal of NACT. This study aimed to develop and validate a nomogram for predicting the pCR probability of BC patients after NACT based on the clinicopathological features.MethodsA retrospective analysis of 527 BC patients treated with NACT between January 2018 and December 2021 from two institutions was conducted. Univariate and multivariate logistic regression analyses were performed to select the most useful predictors from the training cohort (n = 225), and then a nomogram model was developed. The performance of the nomogram was evaluated with respect to its discrimination, calibration, and clinical usefulness. Internal validation and external validation were performed in an independent validation cohort of 96 and 205 consecutive BC patients, respectively.ResultsAmong the 18 clinicopathological features, five variables were selected to develop the prediction model, including age, American Joint Committee on Cancer (AJCC) T stage, Ki67 index before NACT, human epidermal growth factor receptor 2 (HER2), and hormone receptor (HR) status. The model showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.825 (95% CI, 0.772 to 0.878) in the training cohort, and 0.755 (95% CI, 0.658 to 0.851) and 0.79 (95% CI, 0.724 to 0.856) in the internal and external validation cohorts, respectively. The calibration curve presented good agreement between prediction by nomogram and actual observation, and decision curve analysis (DCA) indicated that the nomogram had good net benefits in clinical scenarios.ConclusionThis study constructed a validated nomogram based on age, AJCC T stage, Ki67 index before NACT, HER2, and HR status, which could be non-invasively applied to personalize the prediction of pCR in BC patients treated with NACT.

Background: Lenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment. Methods: We retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8. Results: Patients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8–7.4] and 6.8 months (95% CI: 2.6–10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6–7.4) and 13.3 months (95% CI: 11.6–16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1–3.6) and 4.5 months (95% CI: 2.9–6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7–3.7) and 12.0 months (95% CI: 10.2–14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup). Conclusion: Results suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib. Trial registration: ClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266 .

ABSTRACT The genetic diversity of human papillomavirus (HPV) 16 within cervical cells and tissue is usually associated with persistent virus infection and precancerous lesions. To explore the HPV16 mutation patterns contributing to the cervical cancer (CC) progression, a total of 199 DNA samples from HPV16-positive cervical specimens were collected and divided into high‐grade squamous intraepithelial lesion (HSIL) and the non‐HSIL(NHSIL) groups. The HPV16 E6 region (nt 7125-7566) was sequenced using next-generation sequencing. Based on HPV16 E6 amino acid mutation features selected by Lasso algorithm, four machine learning approaches were used to establish HSIL prediction models. The receiver operating characteristic was used to evaluate the model performance in both training and validation cohorts. Western blot was used to detect the degradation of p53 by the E6 variants. Based on the 13 significant mutation features, the logistic regression (LR) model demonstrated the best predictive performance in the training cohort (AUC = 0.944, 95% CI: 0.913–0.976), and also achieved a high discriminative ability in the independent validation cohort (AUC = 0.802, 95% CI: 0.601–1.000). Among these features, the E6 D32E and H85Y variants have higher ability to degrade p53 compared to the E6 wildtype (P

This article focuses on the mining dilemma of block withholding attack between the mining pools in the bitcoin system. In order to obtain the higher revenue, the rational mining pool usually chooses an infiltration attack, that is, the pool will falls into the mining dilemma of the PoW consensus algorithm. Thus the article proposes to apply zero-determinant strategies for optimizing the behavior selection of the mining pool under PoW consensus mechanism to increase the total revenues of the system, so as to solve the mining dilemma. After theoretically studying the set and extortionate strategy of zero-determinant, the article devises an adaptive zero-determinant strategy that the pool can change the corporation probability of the next round based on its previous revenues. To verify the effectiveness of zero-determinant strategies, based on the actual revenue of the mining pool defined and deduced in the paper, it simulates 30 sets of game strategies to illustrate the revenue variation of the mining pools. The simulation results show that the three zero-determinant strategies can effectively improve the convergence rate of cooperation, mitigate block withholding attack and maximize the total revenues of the system. Compared with the set and extortionate strategy, the adaptive strategy can ensure more stability and more revenue.

BackgroundArtificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the diagnostic accuracy of the models based on deep learning or radiomics for lung cancer staging.MethodsStudies were systematically reviewed using literature searches from PubMed, EMBASE, Web of Science, and Wanfang Database, according to PRISMA guidelines. Studies about the diagnostic accuracy of radiomics and deep learning, including the identifications of lung cancer, tumor types, malignant lung nodules and lymph node metastase, were included. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist. We extracted the characteristic of each study; the sensitivity, specificity, and AUROC for lung cancer diagnosis were summarized for subgroup analysis.ResultsThe systematic review identified 19 eligible studies, of which 14 used radiomics models and 5 used deep learning models. The pooled AUROC of 7 studies to determine whether patients had lung cancer was 0.83 (95% CI 0.78–0.88). The pooled AUROC of 9 studies to determine whether patients had NSCLC was 0.78 (95% CI 0.73–0.83). The pooled AUROC of the 6 studies that determined patients had malignant lung nodules was 0.79 (95% CI 0.77–0.82). The pooled AUROC of the other 6 studies that determined whether patients had lymph node metastases was 0.74 (95% CI 0.66–0.82).ConclusionThe models based on deep learning or radiomics have the potential to improve diagnostic accuracy for lung cancer staging.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-3-0167/, identifier: INPLASY202230167.

Agronomic traits such as plant height (PH), leaf number (LN), leaf length (LL), and leaf width (LW), which are closely related to yield and quality, are important in tobacco (Nicotiana tabacum L.). To identify quantitative trait loci (QTLs) associated with agronomic traits in tobacco, 209 recombinant inbred lines (RILs) and 537 multiparent advanced generation intercross (MAGIC) lines were developed. The biparental RIL and MAGIC lines were genotyped using a 430 K single-nucleotide polymorphism (SNP) chip assay, and their agronomic traits were repeatedly evaluated under different conditions. A total of 43 QTLs associated with agronomic traits were identified through a combination of linkage mapping (LM) and association mapping (AM) methods. Among these 43 QTLs, three major QTLs, namely qPH13-3, qPH17-1, and qLW20-1, were repeatedly identified by the use of various genetically diverse populations across different environments. The candidate genes for these major QTLs were subsequently predicted. Validation and utilization of the major QTL qLW20-1 for the improvement of LW in tobacco were investigated. These results could be applied to molecular marker-assisted selection (MAS) for breeding important agronomic traits in tobacco.

Ralstonia solanacearum species complex (RSSC) is a diverse group of plant pathogens that attack a wide range of hosts and cause devastating losses worldwide. In this study, we conducted a comprehensive analysis of 131 RSSC strains to detect their genetic diversity, pathogenicity, and evolution dynamics. Average nucleotide identity analysis was performed to explore the genomic relatedness among these strains, and finally obtained an open pangenome with 32,961 gene families. To better understand the diverse evolution and pathogenicity, we also conducted a series of analyses of virulence factors (VFs) and horizontal gene transfer (HGT) in the pangenome and at the single genome level. The distribution of VFs and mobile genetic elements (MGEs) showed significant differences among different groups and strains, which were consistent with the new nomenclatures of the RSSC with three distinct species. Further functional analysis showed that most HGT events conferred from Burkholderiales and played a great role in shaping the genomic plasticity and genetic diversity of RSSC genomes. Our work provides insights into the genetic polymorphism, evolution dynamics, and pathogenetic variety of RSSC and provides strong supports for the new taxonomic classification, as well as abundant resources for studying host specificity and pathogen emergence.

Background Fibrillin (FBN) proteins are widely distributed in the photosynthetic organs. The members of FBN gene family play important roles in plant growth and development, and response to hormone and stresses. Tomato is a vegetable crop with significantly economic value and model plant commonly used in research. However, the FBN family has not been systematical studied in tomato. Methods In this study, 14 FBN genes were identified in tomato genome by Pfam and Hmmer 3.0 software. ExPASy, MEGA 6.0, MEME, GSDS, TBtools, PlantCARE and so on were used for physical and chemical properties analysis, phylogenetic analysis, gene structure and conserved motifs analysis, collinearity analysis and cis-acting element analysis of FBN family genes in tomato. Expression characteristics of SlFBNs in different tissues, fruit shape near isogenic lines (NILs), Pst DC3000 and ABA treatments were analyzed based on transcriptome data and quantitative Real-time qPCR (qRT-PCR) analysis. Results The SlFBN family was divided into 11 subgroups. There were 8 FBN homologous gene pairs between tomato and Arabidopsis. All the members of SlFBN family contained PAP conserved domain, but their gene structure and conserved motifs showed apparent differences. The cis-acting elements of light and hormone (especially ethylene, methyl jasmonate (MeJA) and abscisic acid (ABA)) were widely distributed in the SlFBN promoter regions. The expression analysis found that most of SlFBNs were predominantly expressed in leaves of Heinz and S. pimpinellifolium LA1589, and showed higher expressions in mature or senescent leaves than in young leaves. Expression analysis of different tissues and fruit shape NILs indicated SlFBN1, SlFBN2b and SlFBN7a might play important roles during tomato fruit differentiation. All of the SlFBNs responded to Pst DC3000 and ABA treatments. The results of this study contribute to exploring the functions and molecular mechanisms of SlFBNs in leaf development, fruit differentiation, stress and hormone responses.

Abstract As evidenced by the behavior of loss-of-function mutants of PTEN in the context of a gain-of-function mutation of AKT1, the PTEN-AKT1 signaling pathway plays a critical role in human cancers. In this study, we demonstrated that a deficiency in PTEN or activation of AKT1 potentiated the expression of platelet-derived growth factor receptor α (PDGFRα) based on studies on Pten−/− mouse embryonic fibroblasts, human cancer cell lines, the hepatic tissues of Pten conditional knockout mice, and human cancer tissues. Loss of PTEN enhanced PDGFRα expression via activation of the AKT1-CREB signaling cascade. CREB transactivated PDGFRα expression by direct binding of the promoter of the PDGFRα gene. Depletion of PDGFRα attenuated the tumorigenicity of Pten-null cells in nude mice. Moreover, the PI3K-AKT signaling pathway has been shown to positively correlate with PDGFRα expression in multiple cancers. Augmented PDGFRα was associated with poor survival of cancer patients. Lastly, combination treatment with the AKT inhibitor MK-2206 and the PDGFR inhibitor CP-673451 displayed synergistic anti-tumor effects. Therefore, activation of the AKT1-CREB-PDGFRα signaling pathway contributes to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment.

Abstract Anoxic–oxic process is also called anaerobic aerobic process and used widely with the membrane bioreactor (MBR) for wastewater treatment, particularly in China, thanks for their high efficiency, good-quality permeate and easy operation. However, because the content of the feed wastewater fluctuates in a large range and the operation condition of the system needs to be controlled accurately, it is very important to find an efficient way to constantly monitor the nodes of the system, and adjust the operation parameters, including the quantities used in the chemical treatment. Therefore, it is necessary to use Internet of things technology (IOT) sensing and control equipment to realize the dynamic monitoring of sewage treatment process parameters, so as to serve the drug delivery and equipment online control. This study introduces an application case based on IOT sensor control and supporting maintenance business. Through the practical application of this technology in an environmental protection sewage treatment enterprise in Wuxi, this study introduces a method of bringing the IOT into the MBR system of industrial wastewater treatment which can continuously and accurately monitoring the nodes of the system. Based on this study, an analysis and decision-making system based on real-time monitoring data can be realized to adjust operation parameters in time. In this method, the IOT is introduced into the MBR system of industrial wastewater treatment. The results show that with the support of IOT, the sewage treatment system runs stably and the treatment efficiency is significantly improved.

Abstract Background To analyze the risk factors for hypertension in different age groups of urban and rural residents in Tianjin. Methods A total of 33,997 people (35–75 years old) from 13 community health service centers and primary hospitals in Tianjin participated in this study. They were divided into the youth group (≤ 40 years old), middle-aged group (41–65 years old), and elderly group (> 65 years old). Then, a questionnaire survey was administered, followed by physical and blood biochemical examinations. The demographic characteristics and prevalence were recorded and counted. Subsequently, risk factors were analyzed using univariate and stepwise multivariate logistic regression analysis. Results In the youth, middle-aged, and elderly groups, the prevalence rate of hypertension was 18.65, 51.80, and 76.61%, respectively. Logistic regression analysis showed that obesity(OR: 3.263, 95% CI: 1.039–1.656), men (OR: 2.117, 95% CI: 1.691–2.651), diabetes (OR: 1.978, 95% CI: 1.398–2.799), high triglycerides(OR 1.968 95% CI: 1.590–2.434) and family history of stroke (OR: 1.936, 95% CI: 1.287–2.911) are the five factors in youth. In middle-aged group, the significantly associating factors were obesity (OR: 2.478, 95% CI: 2.330–2.636), diabetes (OR: 2.173, 95% CI: 1.398–2.799), family history of stroke (OR: 1.808, 95% CI: 1.619–2.020), maleness (OR: 1.507, 95% CI: 1.412–1.609),Hypertriglyceridemia (OR 1.490 95% CI: 1.409–1.577),family history of cardiovascular disease (OR: 1.484, 95% CI: 1.307–1.684),Hypercholesterolemia (OR 1.228 95% CI: 1.160–1.299). In the elderly group, obesity (OR: 2.104, 95% CI: 1.830–2.418), family history of strokes (OR: 1.688, 95% CI: 1.243–2.292), diabetes mellitus (OR: 1.544, 95% CI: 1.345–1.773), family history of cardiovascular disease (OR: 1.470, 95% CI: 1.061–2.036), hypertriglyceridemia (OR: 1.348, 95% CI: 1.192–1.524) increased the risk for hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) increased with age, and the value of these two measures for predicting hypertension was better than BMI in middle-aged group. Conclusion Obesity is the most important risk factor for hypertension in all age groups. Diabetes, family history of strokes and high triglyceride were also significant risk factors for all age groups. There was a gender difference between the young and middle-aged groups, with men more likely to hypertension. Waist circumference (WC) and waist-to-height ratio (WHtR) were better predictors of hypertension than BMI in middle-aged group.

Abstract Phytophthora nicotianae is highly pathogenic to Solanaceous crops and is a major problem in tobacco production. The tobacco cultivar Beihart1000-1 (BH) is resistant, whereas the Xiaohuangjin 1025 (XHJ) cultivar is susceptible to infection. Here, BH and XHJ were used as models to identify resistant and susceptible genes using RNA sequencing (RNA-seq). Roots were sampled at 0, 6, 12, 24, and 60 h post infection. In total, 23,753 and 25,187 differentially expressed genes (DEGs) were identified in BH and XHJ, respectively. By mapping upregulated DEGs to the KEGG database, changes of the rich factor of “plant pathogen interaction pathway” were corresponded to the infection process. Of all the DEGs in this pathway, 38 were specifically regulated in BH. These genes included 11 disease-resistance proteins, 3 pathogenesis-related proteins, 4 RLP/RLKs, 2 CNGCs, 7 calcium-dependent protein kinases, 4 calcium-binding proteins, 1 mitogen-activated protein kinase kinase, 1 protein EDS1L, 2 WRKY transcription factors, 1 mannosyltransferase, and 1 calmodulin-like protein. By combining the analysis of reported susceptible (S) gene homologs and DEGs in XHJ, 9 S gene homologs were identified, which included 1 calmodulin-binding transcription activator, 1 cyclic nucleotide-gated ion channel, 1 protein trichome birefringence-like protein, 1 plant UBX domain-containing protein, 1 ADP-ribosylation factor GTPase-activating protein, 2 callose synthases, and 2 cellulose synthase A catalytic subunits. qRT-PCR was used to validate the RNA-seq data. The comprehensive transcriptome dataset described here, including candidate resistant and susceptible genes, will provide a valuable resource for breeding tobacco plants resistant to P. nicotianae infections.

ObjectiveThe objective of this study is to investigate the therapeutic effect of surfactant replacement therapy (SRT) on respiratory distress syndrome (RDS) in premature infants in the Qinghai-Tibet Plateau.Materials and MethodsThis multi-center retrospective cohort study collected and screened reasonable clinical data of 337 premature infants with RDS from 10 hospitals in the Qinghai-Tibet Plateau from 2015 to 2017. We grouped the cases by rationally analyzing their baseline characteristics, using logistic analysis to evaluate each factor's effect on the prognosis of the infants, and comparing the short-term improvement in blood gas and mortality after SRT treatment at different altitudes, in high-altitude (1,500–3,500 m) and ultra-high-altitude (3,500–5,500 m) groups.ResultsIndependent of altitude, the mortality rate of children with RDS in the SRT group was significantly lower than that of children in the non-SRT group (both P < 0.05). The effect of SRT on preterm infants with RDS in the high-altitude group [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.22–0.87, P = 0.02] was better than that in the infants in the ultra-high-altitude group (OR = 0.26, 95% CI = 0.13–0.58, P < 0.01), with death rates of 34.34 and 49.71%, respectively. Similarly, after SRT, the improvement of PaO2/FiO2 and pH of children at high altitude was significantly better than those of children at ultra-high altitude (all P < 0.01).ConclusionsSRT plays a prominent role in curing infants with RDS in both high- and ultra-high-altitude regions, although with better effects at high rather than ultra-high altitude. This study provides a basis for further large-scale studies on SRT for RDS treatment at high altitudes.