BACKGROUND: With the accumulating omics data, an efficient and time-saving transient assay to express target genes is desired. Mesophyll protoplasts, maintaining most stress-physiological responses and cellular activities as intact plants, offer an alternative transient assay to study target genes' effects on heat and oxidative stress responses. RESULTS: In this study, a perennial ryegrass (Lolium perenne L.) mesophyll protoplast-based assay was established to effectively over- or down-regulate target genes. The relative expression levels of the target genes could be quantified using RT-qPCR, and the effects of heat and H2O2-induced oxidative stress on protoplasts' viability could be quantitatively measured. The practicality of the assay was demonstrated by identifying the potential thermos-sensor genes LpTT3.1/LpTT3.2 in ryegrass that over-expressing these genes significantly altered protoplasts' viability rates after heat stress. CONCLUSION: This protoplast-based rapid stress regulatory gene identification assay was briefed as 'PRIDA' that will complement the stable genetic transformation studies to rapidly identify candidate stress-regulatory genes in perennial ryegrass and other grass species.
Methionine adenosyltransferase 2 A (MAT2A) mediates the synthesis of methyl donor S-Adenosylmethionine (SAM), providing raw materials for methylation reactions in cells. MAT2A inhibitors are currently used for the treatment of tumors with methylthioadenosine phosphorylase (MTAP) deficiency in clinical research. Methyltransferase like 3 (METTL3) catalyzes N6-methyladenosine (m6A) modification of mRNA in mammalian cells using SAM as the substrate which has been shown to affect the tumorigenesis of non-small cell lung cancer (NSCLC) from multiple perspectives. MAT2A-induced SAM depletion may have the potential to inhibit the methyl transfer function of METTL3. Therefore, in order to expand the applicability of inhibitors, improve anti-tumor effects and reduce toxicity, the combinational effect of MAT2A inhibitor AG-270 and METTL3 inhibitor STM2457 was evaluated in NSCLC. The results showed that this combination induced cell apoptosis rather than cell cycle arrest, which was non-tissue-specific and was independent of MTAP expression status, resulting in a significant synergistic anti-tumor effect. We further elucidated that the combination-induced enhanced apoptosis was associated with the decreased m6A level, leading to downregulation of PI3K/AKT protein, ultimately activating the apoptosis-related proteins. Unexpectedly, although combination therapy resulted in metabolic recombination, no significant change in methionine metabolic metabolites was found. More importantly, the combination also exerted synergistic effects in vivo. In summary, the combination of MAT2A inhibitor and METTL3 inhibitor showed synergistic effects both in vivo and in vitro, which laid a theoretical foundation for expanding the clinical application research of the two types of drugs.
Zero-dimensional (0D) hybrid metal halides (HMHs) have emerged as a promising platform for exploring excitation-dependent multicolor luminescent materials owing to their diverse crystal structures and chemical compositions. Nevertheless, understanding the mechanism behind excitation-dependent emissions (EDEs) in 0D HMHs and achieving precise modulation remains challenging. In this work, the delicate regulations on the EDE of 0D (DMEDABr)4SnBr3I3 (DMEDA: N, N'-dimethylethylenediamine) with mixed halogens are achieved under low temperature and high pressure, respectively. The inhomogeneous halogen occupation at the atomic scale leads to the formation of Br-rich and I-rich SnX6 (X = Br, I) octahedra, which act as distinct luminescent centers upon photoexcitation. At low temperatures, the narrowed photoluminescence spectra could distinguish the individual emissions from different luminescent centers, resulting in a pronounced EDE of (DMEDABr)4SnBr3I3. In addition, the contraction and distortion of the luminescent SnX6 (X = Br, I) centers at high pressure further result in different degrees of emission shifts, giving rise to the gradual emergence and disappearance of EDE. This work elucidates the underlying mechanism of EDE in 0D HMHs and highlights the crucial role of halogens in determining the optical properties of metal halides.
Non-small cell lung cancer (NSCLC) is a fatal malignancy all over the world. Emerging studies have shown that curcumin might repress NSCLC progression by regulating ferroptosis, but the underlying mechanism remains unclear. 16HBE, LK-2, and H1650 cell viability was detected using Cell Counting Kit-8 assay. LK-2 and H1650 cell proliferation, apoptosis, and angiopoiesis were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, and tube formation assay. Superoxide dismutase, Malondialdehyde, Glutathione, and lactate dehydrogenase levels in LK-2 and H1650 cells were examined using special assay kits. Fe+ level was assessed using an iron assay kit. Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) and solute carrier family 7 member 11 (SLC7A11) protein levels were detected using western in NSCLC tissues, adjacent matched normal tissues, 16HBE cells, LK-2 cells, H1650 cells, and xenograft tumor tissues. Glutathione peroxidase 4, Acyl-CoA Synthetase Long Chain Family Member 4, and transferrin receptor 1 protein levels in LK-2 and H1650 cells were examined by western blot assay. DMRT3 and SLC7A11 levels were determined using real-time quantitative polymerase chain reaction. After JASPAR prediction, binding between DMRT3 and SLC7A11 promoter was verified using Chromatin immunoprecipitation and dual-luciferase reporter assays in LK-2 and H1650 cells. Role of curcumin on NSCLC tumor growth was assessed using the xenograft tumor model in vivo. Curcumin blocked NSCLC cell proliferation and angiopoiesis, and induced apoptosis and ferroptosis. DMRT3 or SLC7A11 upregulation partly abolished the suppressive role of curcumin on NSCLC development. In mechanism, DMRT3 was a transcription factor of SLC7A11 and increased the transcription of SLC7A11 via binding to its promoter region. Curcumin inhibited NSCLC growth in vivo by modulating DMRT3. Curcumin might constrain NSCLC cell malignant phenotypes partly through the DMRT3/SLC7A11 axis, providing a promising therapeutic strategy for NSCLC.
BACKGROUND: Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted. METHODS: We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination. RESULTS: Our mIHC results revealed a more substantial presence of Foxp3+Tregs in HCC samples than in adjacent normal tissue samples (P < .001). An increased presence of Foxp3+Tregs in HCC samples correlated with unfavorable patient outcomes (HR = 1.722, 95% CI:1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes (HR = 3.84, 95% CI:2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4+T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions. CONCLUSION: An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues.
Carcinoma, Hepatocellular , Liver Neoplasms , T-Lymphocytes, Regulatory , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , T-Lymphocytes, Regulatory/immunology , Prognosis , Forkhead Transcription Factors/metabolism , Male , Female
BACKGROUND: The effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear. METHODS: The training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker- preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index. RESULTS: Patients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort. CONCLUSION: TMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.
BACKGROUND: Erectile dysfunction (ED) seriously affects men's normal life, and obstructive sleep apnoea (OSA) has been diagnosed as a causative factor. Currently, exosomes secreted by adipose mesenchymal stem cells (ADSC) have been used in the non-clinical experimental treatment of ED disease with prominent efficacy due to the advantages of high stability and no immune exclusion. METHODS: In this study, chronic intermittent hypoxia (CIH) exposure was used to induce ED-corresponding phenotypes in Sprague Dawley (SD) rats as well as in cavernous smooth muscle cells (CCSMCs). ED symptoms were treated using exosomes secreted by ADSCs overexpressing circPIP5K1C (EXO-circ) injected into the rat corpus cavernosum. RESULTS: EXO-circ has the effect of ameliorating ED induced by CIH exposure in rats, the mechanism of which is to promote the expression of the downstream target gene SMURF1 after adsorption of miR-153-3p through the sponge so that SMURF1 and PFKFB3 occur protein-protein binding and ubiquitination degradation of PFKFB3 appears to inhibit the occurrence of spongiotic smooth muscle cells glycolysis, and to restore the function of the smooth muscle. CONCLUSIONS: These findings show that EXO-circ have a promising therapeutic potential in OSA-induced ED.
In the post-genomic era, virus-induced gene silencing (VIGS) has played an important role in research on reverse genetics in plants. Commonly used Agrobacterium-mediated VIGS inoculation methods include stem scratching, leaf infiltration, use of agrodrench, and air-brush spraying. In this study, we developed a root wounding-immersion method in which 1/3 of the plant root (length) was cut and immersed in a tobacco rattle virus (TRV)1:TRV2 mixed solution for 30 min. We optimized the procedure in Nicotiana benthamiana and successfully silenced N. benthamiana, tomato (Solanum lycopersicum), pepper (Capsicum annuum L.), eggplant (Solanum melongena), and Arabidopsis thaliana phytoene desaturase (PDS), and we observed the movement of green fluorescent protein (GFP) from the roots to the stem and leaves. The silencing rate of PDS in N. benthamiana and tomato was 95-100%. In addition, we successfully silenced two disease-resistance genes, SITL5 and SITL6, to decrease disease resistance in tomatoes (CLN2037E). The root wounding-immersion method can be used to inoculate large batches of plants in a short time and with high efficiency, and fresh bacterial infusions can be reused several times. The most important aspect of the root wounding-immersion method is its application to plant species susceptible to root inoculation, as well as its ability to inoculate seedlings from early growth stages. This method offers a means to conduct large-scale functional genome screening in plants.
Although deep deterministic policy gradient (DDPG) algorithm gets widespread attention as a result of its powerful functionality and applicability for large-scale continuous control, it cannot be denied that DDPG has problems such as low sample utilization efficiency and insufficient exploration. Therefore, an improved DDPG is presented to overcome these challenges in this article. Firstly, an optimizer based on fractional gradient is introduced into the algorithm network, which is conductive to increase the speed and accuracy of training convergence. On this basis, high-value experience replay based on weight-changed priority is proposed to improve sample utilization efficiency, and aiming to have a stronger exploration of the environment, an optimized exploration strategy for boundary action space is adopted. Finally, our proposed method is tested through the experiments of gym and pybullet platform. According to the results, our method speeds up the learning process, obtains higher average rewards in comparison with other algorithms.
Bisphenol A (BPA) is a typical endocrine disruptor, which can be used as an industrial raw material for the synthesis of polycarbonate and epoxy resins, etc. Recently, BPA has appeared on the list of priority new pollutants for control in various countries and regions. In this study, phenolic resin waste was utilized as a multi-carbon precursor for the electrocatalytic cathode and loaded with cobalt/nitrogen (Co/N) on its surface to form qualitative two-dimensional carbon nano-flakes (Co/NC). The onset potentials, half-wave potentials, and limiting current densities of the nitrogen-doped composite carbon material Co/NC in oxygen saturated 0.5 mol H2SO4 were -0.08 V, -0.61 V, and -0.41 mA cm-2; and those of alkaline conditions were -0.65 V, -2.51 V, and -0.38 mA cm-2, and the corresponding indexes were improved compared with those of blank titanium electrodes, which indicated that the constructed nitrogen-doped composite carbon material Co/NC was superior in oxygen reduction ability. The catalysis by metallic cobalt as well as the N-hybridized active sites significantly improved the efficiency of electrocatalytic degradation of BPA. In the electro-Fenton system, the yield of hydrogen peroxide generated by cathodic reduction of oxygen was 4.012 mg L-1, which effectively promoted the activation of hydroxyl radicals. The removal rate of BPA was above 95% within 180 min. This work provides a new insight for the design and development of novel catalyst to degrade organic pollutants.
BACKGROUND AND AIM: Head and neck nuclear protein of testis carcinoma (HN-NUT) is a rare form of carcinoma diagnosed by NUT immunohistochemistry positivity and/or NUTM1 translocation. Although the prototype of HN-NUT is a primitive undifferentiated round cell tumour (URC) with immunopositivity for squamous markers, it is our observation that it may assume variant histology or immunoprofile. METHODS: We conducted a detailed clinicopathological review of a large retrospective cohort of 30 HN-NUT, aiming to expand its histological and immunohistochemical spectrum. RESULTS: The median age of patients with HN-NUT was 39 years (range = 17-86). It affected the sinonasal tract (43%), major salivary glands (20%), thyroid (13%), oral cavity (7%), larynx (7%), neck (7%) and nasopharynx (3%). Although most cases of HN-NUT (63%) contained a component of primitive URC tumour, 53% showed other histological features and 37% lacked a URC component altogether. Variant histological features included basaloid (33%), differentiated squamous/squamoid (37%), clear cell changes (13%), glandular differentiation (7%) and papillary architecture (10%), which could co-exist. While most HN-NUT were positive for keratins, p63 and p40, occasional cases (5-9%) were entirely negative. Immunopositivity for neuroendocrine markers and thyroid transcription factor-1 was observed in 33 and 36% of cases, respectively. The outcome of HN-NUT was dismal, with a 3-year disease specific survival of 38%. CONCLUSIONS: HN-NUT can affect individuals across a wide age range and arise from various head and neck sites. It exhibits a diverse spectrum of histological features and may be positive for neuroendocrine markers, potentially leading to underdiagnosis. A low threshold to perform NUT-specific tests is necessary to accurately diagnose HN-NUT.
A new technique known as dough crumb-sheet composite rolling (DC-SCR) was used to improve the quality of fresh noodles. However, there is a dearth of theoretical investigations into the optimal selection of specific parameters for this technology, and the underlying mechanisms are not fully understood. Therefore, the effects of dough crumb addition times in DC-SCR on the texture, cooking, and eating quality of fresh noodles were first studied. Then, the underlying regulation mechanism of DC-SCR technology on fresh noodles was analyzed in terms of moisture distribution and microstructure. The study demonstrated that the most significant enhancement in the quality of fresh noodles was achieved by adding dough crumbs six times. Compared with fresh noodles made without the addition of dough crumbs, the initial hardness and chewiness of fresh noodles made by adding six times of dough crumbs increased by 25.32% and 46.82%, respectively. In contrast, the cooking time and cooking loss were reduced by 28.45% and 29.69%, respectively. This quality improvement in fresh noodles made by DC-SCR came from the microstructural differences of the gluten network between the inner and outer layers of the dough sheet. A dense structure on the outside and a loose structure on the inside could endow the fresh noodles made by DC-SCR with higher hardness, a shortened cooking time, and less cooking loss. This study would provide a theoretical and experimental basis for creating high-quality fresh noodles.
Bread , Cooking , Flour , Food Handling , Water , Cooking/methods , Flour/analysis , Food Handling/methods , Bread/analysis , Hardness , Glutens/analysis , Food Quality , Triticum/chemistry , Humans
Background/Purpose: Cutaneous lupus erythematosus (CLE) affects up to 70% of patients with systemic lupus erythematosus (SLE), and type I interferons (IFNs) are important promoters of SLE and CLE. Our previous work identified IFN-kappa (IFN-κ), a keratinocyte-produced type I IFN, as upregulated in non-lesional and lesional lupus skin and as a critical regulator for enhanced UVB-mediated cell death in SLE keratinocytes. Importantly, the molecular mechanisms governing regulation of IFN-κ expression have been relatively unexplored. Thus, this study sought to identify critical regulators of IFN-κ and identified a novel role for IFN-beta (IFN-ß). Methods: Human N/TERT keratinocytes were treated with the RNA mimic poly (I:C) or 50 mJ/cm2 ultraviolet B (UVB), followed by mRNA expression quantification by RT-qPCR in the presence or absence neutralizing antibody to the type I IFN receptor (IFNAR). IFNB and STAT1 knockout (KO) keratinocytes were generated using CRISPR/Cas9. Results: Time courses of poly(I:C) and UVB treatment revealed a differential expression of IFNB, which was upregulated between 3-6 hours and IFNK, which was upregulated 24 hours after stimulation. Intriguingly, only IFNK expression was substantially abrogated by neutralizing antibodies to IFNAR, suggesting that IFNK upregulation required type I IFN signaling for induction. Indeed, deletion of IFNB abrogated IFNK expression. Further exploration confirmed a role for type I IFN-triggered STAT1 activation. Conclusion: Collectively, our work describes a novel mechanistic paradigm in keratinocytes in which initial IFN-κ induction in response to poly(I:C) and UVB is IFNß1-dependent, thus describing IFNK as both an IFN gene and an interferon-stimulated gene.
Importance: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. Objective: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. Design, Setting, and Participants: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Interventions: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. Main Outcomes and Measures: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. Results: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). Conclusions: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.
BACKGROUND: In bypass surgery for moyamoya disease (MMD), the superficial temporal artery's (STA) pressure needs to surpass that of the cortical M4 recipient of the middle cerebral artery (MCA), boosting cerebral blood flow into the MCA and enhancing cerebral circulation. This study investigates the STA-MCA arterial pressure parameters and gradients during bypass surgery, aiming to deepen our understanding of hemodynamic shifts pre- and post-operation. METHODS: DSA imaging data were prospectively collected from patients diagnosed with bilateral MMD who underwent STA-MCA bypass surgery between 2022 and 2023 and stratified according to the Suzuki stage. The mean arterial pressure (MAP) of the donor and recipient arteries was directly measured during the STA-MCA bypass procedure, and these data were statistically analyzed and evaluated. RESULTS: Among 48 MMD patients, Suzuki grading revealed that 43.8% were in early stages (II and III), while 56.2% were in advanced stages (IV, V, and VI). Predominantly, 77.1% presented with ischemic-type MMD and 22.9% with hemorrhagic type. Pre-bypass assessments showed that 62.5% exhibited antegrade blood flow direction, and 37.5% had retrograde. The mean recipient artery pressure was 35.0 ± 2.3 mmHg, with a mean donor-recipient pressure gradient (δP) of 46.4 ± 2.5 mmHg between donor and recipient arteries. Post-bypass, mean recipient artery pressure increased to 73.3 ± 1.6 mmHg. No significant correlation (r = 0.18, P = 0.21) was noted between δP and Suzuki staging. CONCLUSION: Our study elucidated that cerebral blood pressure significantly decreases beyond the moyamoya network at the distal M4 segment. Furthermore, we observed bidirectional flow in MCA territories and a significant positive pressure gradient between the STA and M4 segments. The lack of correlation between Suzuki stages and M4 pressures indicates that angiographic severity may not reflect hemodynamic conditions before surgery, highlighting the need for customized surgical approaches.
Background: The advantages of the dissecting the metastatic lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) remain a great deal of controversies in papillary thyroid carcinoma (PTC) patients without clinical evidence. The purpose of our retrospective research was to investigate the predictive factors of the LN-prRLN in cN0 PTC patients. Methods and Materials: Altogether 251 consecutive cN0 PTC participants accepted unilateral or bilateral thyroidectomy accompanied with LN-prRLN dissection between June 2020 and May 2023 were included in the research. Then, univariate and multivariate logical regression analysis were conducted to analyze the relationship between the LN-prRLN and these predictive factors, and a predictive model was also developed. Surgical complications of LN-prRLN dissection were also presented. Results: The rate of LN-prRLN was 17.9% (45/251) in cN0 PTC patients after the analysis of postoperative histology. The age <55 years, multifocality, microcalcification, and BRAFV600E mutation were identified to be predictive factors of LN-prRLN in cN0 PTC patients. The risk score for LN-prRLN was calculated: risk score = 1.192 × (if age <55 years) + 0.808 × (if multifocality) + 1.196 × (if microcalcification in nodule) + 0.918 × (if BRAFV600E mutation in nodule). The rates of the transient hypoparathyroidism and hoarseness were 1.2% (3/251) and 2.0% (5/251), respectively. Conclusion: The age <55 years, multifocality, microcalcification, and BRAFV600E mutation are independent predictors of the LN-prRLN in cN0 PTC patients. An effective predictive model was established for predicting the LN-prRLN in cN0 PTC patients, with the aim to better guide the surgical treatment of PTC. A thorough inspection of the lateral compartment is recommended in PTC patients with risk factors. The multicenter research with long-term follow-up should be carried out to ascertain the optimal surgical approach for patients with PTC.
What is already known about this topic?: Sierra Leone, with a gross domestic product (GDP) per capita below $300 and significant poverty, ranks among the world's least developed countries (LDCs). Despite its modest population of 8.6 million, the nation reports approximately 2.6 million malaria cases annually. Previously, there has been no reporting on the malaria genome data from this country. What is added by this report?: In this study, we present the first reported whole-genome sequence analysis of 19 high parasite-density Plasmodium falciparum isolates from Sierra Leone, providing insights into the genomic epidemiology of this high-prevalence area. We found a high degree of relatedness among infections and substantial genetic diversity, consistent with the gradual reduction in overall case numbers. Moreover, our whole-genome analysis revealed that, beyond drug-resistance genes, gene families related to blood cell invasion, immune evasion, and others are undergoing directional selection. This suggests that the population in Sierra Leone has developed a relatively strong acquired immunity. What are the implications for public health practice?: The genomic data not only facilitate the creation of single nucleotide polymorphism barcodes for case tracking but also enable the analysis of evolving transmission dynamics and selection pressures. Additionally, the samples from Sierra Leone exhibited higher selective pressures on resistance genes compared to those from Asia, a trend not commonly observed in other African samples. This suggests that less stringent healthcare systems and inconsistent treatment strategies can subject parasites to increased drug pressure, thereby accelerating the development of resistant strains.
BACKGROUND: Guillain-Barré Syndrome (GBS) is an autoimmune disease that typically develops after a previous gastrointestinal (GI) infection. However, the exact association between Gut Microbiota (GM) and GBS still remains unknown due to various challenges. This study aimed to investigate the potential causal association between GM and GBS by using a two-sample Mendelian Randomization (TSMR) analysis. METHODS: Utilizing the largest available genome-wide association study (GWAS) meta-analysis from the MiBioGen consortium (n = 13,266) as a foundation, we conducted a TSMR to decipher the causal relationship between GM and GBS. Various analytical methods were employed, including the inverse variance weighted (IVW), MR-PRESSO, MR-Egger, and weighted median. The heterogeneity of instrumental variables (IVs) was assessed using Cochran's Q statistics. RESULTS: The analysis identified three microbial taxa with a significantly increased risk association for GBS, including Ruminococcus gnavus group (OR = 1.40, 95 % CI: 1.07-1.83), Ruminococcus gauvreauii group (OR = 1.51, 95 % CI: 1.02-2.25), and Ruminococcaceae UCG009 (OR = 1.42, 95 % CI: 1.02-1.97), while Eubacterium brachy group (OR = 1.44, 95 % CI: 1.10-1.87) and Romboutsia (OR = 1.67, 95 % CI: 1.12-2.47) showed a suggestively causal association. On the other hand, Ruminococcaceae UCG004 (OR = 0.61, 95 % CI: 0.41-0.91) had a protective effect on GBS, while Bacilli (OR = 0.60, 95 % CI: 0.38-0.96), Gamma proteobacteria (OR = 0.63, 95 % CI: 0.41-0.98) and Lachnospiraceae UCG001 (OR = 0.69, 95 % CI: 0.49-0.96) showed a suggestively protective association for GBS. CONCLUSION: The MR analysis suggests a potential causal relationship between specific GM taxa and the risk of GBS. However, further extensive research involving diversified populations is imperative to validate these findings.
Gastrointestinal Microbiome , Genome-Wide Association Study , Guillain-Barre Syndrome , Mendelian Randomization Analysis , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/microbiology , Humans , Gastrointestinal Microbiome/genetics , Ruminococcus/genetics , Risk Factors
Globally, 50% of people consume rice (Oryza sativa), which is among the most abundant and extensively ingested cereal grains. Rice bran is a by-product of the cereal industry and is also considered a beneficial waste product of the rice processing industry. Rice bran oil (RBO) is created from rice bran (20-25 wt% in rice bran), which is the outermost layer of the rice kernel; has a lipid content of up to 25%; and is a considerable source of a plethora of bioactive components. The main components of RBO include high levels of fiber and phytochemicals, including vitamins, oryzanols, fatty acids, and phenolic compounds, which are beneficial to human health and well-being. This article summarizes the stabilization and extraction processes of rice bran oil from rice bran using different techniques (including solvent extraction, microwaving, ohmic heating, supercritical fluid extraction, and ultrasonication). Some studies have elaborated the various biological activities linked with RBO, such as antioxidant, anti-platelet, analgesic, anti-inflammatory, anti-thrombotic, anti-mutagenic, aphrodisiac, anti-depressant, anti-emetic, fibrinolytic, and cytotoxic activities. Due to the broad spectrum of biological activities and economic benefits of RBO, the current review article focuses on the extraction process of RBO, its bioactive components, and the potential health benefits of RBO. Furthermore, the limitations of existing studies are highlighted, and suggestions are provided for future applications of RBO as a functional food ingredient.
Accurate detection of endogenous miRNA modifications, such as N6-methyladenosine (m6A), 7-methylguanosine (m7G), and 5-methylcytidine (m5C), poses significant challenges, resulting in considerable uncertainty regarding their presence in mature miRNAs. In this study, we demonstrate for the first time that liquid chromatography coupled with a tandem mass spectrometry (LC-MS/MS) nucleoside analysis method is a practical tool for quantitatively analyzing human miRNA modifications. The newly designed liquid-solid two-step hybridization (LSTH) strategy enhances specificity for miRNA purification, while LC-MS/MS offers robust capability in recognizing modifications and sufficient sensitivity with detection limits ranging from attomoles to low femtomoles. Therefore, it provides a more reliable approach compared to existing techniques for revealing modifications in endogenous miRNAs. With this approach, we characterized m6A, m7G, and m5C modifications in miR-21-5p, Let-7a/e-5p, and miR-10a-5p isolated from cultured cells and observed unexpectedly low abundance (<1% at each site) of these modifications.
Adenosine/analogs & derivatives , Cytidine/analogs & derivatives , Guanosine/analogs & derivatives , MicroRNAs , Tandem Mass Spectrometry , MicroRNAs/analysis , Tandem Mass Spectrometry/methods , Humans , Chromatography, Liquid/methods , Adenosine/analysis , Nucleic Acid Hybridization , Guanosine/analysis , Liquid Chromatography-Mass Spectrometry
