Genome-wide association study of multiyear dynamic growth traits in hybrid Liriodendron identifies robust genetic loci associated with growth trajectories.

The genetic factors underlying growth traits differ over time points or stages. However, most current studies of phenotypes at single time points do not capture all loci or explain the genetic differences underlying growth trajectories. Hybrid Liriodendron exhibits obvious heterosis and is widely cultivated, although its complex genetic mechanism underlying growth traits remains unknown. A genome-wide association study (GWAS) is an effective method for elucidating the genetic architecture by identifying genetic loci underlying complex quantitative traits. In the present study, using a GWAS, we identified robust loci associated with growth trajectories in hybrid Liriodendron populations. We selected 233 hybrid progenies derived from 25 crosses for resequencing, and measured their tree height (H) and diameter at breast height (DBH) for 11 consecutive years; 192 972 high-quality single nucleotide polymorphisms (SNPs) were obtained. The dynamics of the multiyear single-trait GWAS showed that year-specific SNPs predominated, and only five robust SNPs for DBH were identified in at least three different years. Multitrait GWAS analysis with model parameters as latent variables also revealed 62 SNPs for H and 52 for DBH associated with the growth trajectory, displaying different biomass accumulation patterns, among which four SNPs exerted pleiotropic effects. All identified SNPs also exhibited temporal variations in effect sizes and inheritance patterns potentially related to different growth and developmental stages. The haplotypes resulting from these significant SNPs might pyramid favorable loci, benefitting the selection of superior genotypes. The present study provides insights into the genetic architecture of dynamic growth traits and lays a basis for future molecular-assisted breeding.

Identification and characterization of RAC1-related immune and prognostic subtypes of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with significant variability in prognosis among patients. Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key focus in the area of cancer research. However, the molecular mechanisms of RAC1 in HCC remain incompletely elucidated. MATERIALS AND METHODS: In this study, bioinformatics analysis was used, and public databases were used to obtain information about HCC cases. The samples were categorized into two groups of high and low expression based on the expression level of RAC1 gene. The limma package was used to calculate the differentially expressed genes between the two groups, and univariate Cox regression analysis was used to screen the prognostic related factors. Consensus clustering analysis was performed using the ConsensusClusterPlus package to identify molecular subtypes of HCC patients. Immune cell infiltration and ESTIMATE scores were assessed using the single sample gene set enrichment analysis and ESTIMATE algorithms. The sensitivity of different isoforms to chemotherapeutic agents was predicted by the oncoPredict package. Finally, we also performed cell function experiments to validate the biological role of RAC1 in vitro. Initially, we classified patients into high and low expression groups based on RAC1 gene expression levels and identified 195 up-regulated genes and 107 down-regulated genes. Through univariate Cox regression analysis, we screened out 169 prognosis-related factors. Furthermore, HCC patients were categorized into two subtypes. Subsequently, Kaplan-Meier survival curves showed that there was a significant difference in prognosis between the two molecular subtypes. Further analysis indicated substantial differences in gene expression levels and TIDE scores between two molecular subtypes. Moreover, these two subtypes exhibited varying sensitivity to chemotherapy drugs, as evidenced by differences in IC50 values. In addition, we found that the silence of RAC1 could effectively inhibit the migration and invasion of HCC cells in vitro. CONCLUSION: This study sheds light on the molecular intricacies of RAC1 in HCC and identifies patient populations that may benefit from immunotherapeutic interventions, with potential implications for tailored treatment strategies.

Comprehensive deciphering the alternative splicing patterns involved in leaf morphogenesis of Liriodendron chinense.

Alternative splicing (AS), a pivotal post-transcriptional regulatory mechanism, profoundly amplifies diversity and complexity of transcriptome and proteome. Liriodendron chinense (Hemsl.) Sarg., an excellent ornamental tree species renowned for its distinctive leaf shape, which resembles the mandarin jacket. Despite the documented potential genes related to leaf development of L. chinense, the underlying post-transcriptional regulatory mechanisms remain veiled. Here, we conducted a comprehensive analysis of the transcriptome to clarify the genome-wide landscape of the AS pattern and the spectrum of spliced isoforms during leaf developmental stages in L. chinense. Our investigation unveiled 50,259 AS events, involving 10,685 genes (32.9%), with intron retention as the most prevalent events. Notably, the initial stage of leaf development witnessed the detection of 804 differentially AS events affiliated with 548 genes. Although both differentially alternative splicing genes (DASGs) and differentially expressed genes (DEGs) were enriched into morphogenetic related pathways during the transition from fishhook (P2) to lobed (P7) leaves, there was only a modest degree of overlap between DASGs and DEGs. Furthermore, we conducted a comprehensively AS analysis on homologous genes involved in leaf morphogenesis, and most of which are subject to post-transcriptional regulation of AS. Among them, the AINTEGUMENTA-LIKE transcript factor LcAIL5 was characterization in detailed, which experiences skipping exon (SE), and two transcripts displayed disparate expression patterns across multiple stages. Overall, these findings yield a comprehensive understanding of leaf development regulation via AS, offering a novel perspective for further deciphering the mechanism of plant leaf morphogenesis.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

Diagnostic efficacy of an optimized nucleotide MALDI-TOF-MS assay for anti-tuberculosis drug resistance detection.

PURPOSE: We aimed at evaluating the diagnostic efficacy of a nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay to detect drug resistance of Mycobacterium tuberculosis. METHODS: Overall, 263 M. tuberculosis clinical isolates were selected to evaluate the performance of nucleic MALDI-TOF-MS for rifampin (RIF), isoniazid (INH), ethambutol (EMB), moxifloxacin (MXF), streptomycin (SM), and pyrazinamide (PZA) resistance detection. The results for RIF, INH, EMB, and MXF were compared with phenotypic microbroth dilution drug susceptibility testing (DST) and whole-genome sequencing (WGS), and the results for SM and PZA were compared with those obtained by WGS. RESULTS: Using DST as the gold standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 98.2%, 98.7%, and 0.97 for RIF; 92.8%, 99%, and 0.90 for INH; 82.4%, 98.0%, and 0.82 for EMB; and 92.6%, 99.5%, and 0.94 for MXF, respectively. Compared with WGS as the reference standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 97.4%, 100.0%, and 0.98 for RIF; 98.7%, 92.9%, and 0.92 for INH; 96.3%, 100.0%, and 0.98 for EMB; 98.1%, 100.0%, and 0.99 for MXF; 98.0%, 100.0%, and 0.98 for SM; and 50.0%, 100.0%, and 0.65 for PZA. CONCLUSION: The nucleotide MALDI-TOF-MS assay yielded highly consistent results compared to DST and WGS, suggesting that it is a promising tool for the rapid detection of sensitivity to RIF, INH, EMB, and MXF.

Earthworm gut digestion drives the transfer behavior of antibiotic resistance genes in layers of extracellular polymeric substances during vermicomposting of dewatered sludge.

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS.

Association between socio-demographic factors, lifestyle, eating habits and hypertension risk among middle-aged and older rural Chinese adults.

BACKGROUND AND AIMS: Hypertension is a global health issue with increasing prevalence. This study aimed to understand the epidemiological characteristics and influencing factors of hypertension in rural Chinese populations and help develop effective prevention and control strategies. METHODS AND RESULTS: This cross-sectional study used database from the Early Diagnosis and Early Treatment Project of Esophageal Cancer conducted in a rural population from September 2012 to December 2017. A total of 10,111 subjects aged 35-75 years residing in Huai'an District, Huai'an City, Jiangsu Province for at least three years were included. Unconditional univariate and multivariate logistic regression models were performed to evaluate the association between socio-demographic information, lifestyle habits, dietary characteristics and the risk of hypertension. The prevalence of hypertension was 34.32 % in this rural population. Men and older individuals are more likely to have hypertension when compared with women and young individuals, respectively. Factors associated with an increased risk of hypertension included: fast eating speed, a high-salt diet (both currently and ten years ago), a high-spicy diet ten years ago, high BMI, poor educational attainment, preference for fatty meats, hot diet, green tea drinking, intake of pickled potherb mustard and corn flour, family smoking and alcohol consumption. Light smoking in males, consumption of fruits, adzuki bean, and pork liver were associated with reduced risk of hypertension. CONCLUSIONS: The study identified some factors, including eat habits and lifestyle, associated with hypertension risk, and highlighted the need for targeted policies and interventions in rural China to address potential risk factors for hypertension.

A potential role for inflammatory cytokines in a rare late-onset capsular block syndrome: a case report.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

Sex differences and dietary patterns in the association of air pollutants and hypertension.

BACKGROUND: Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM2.5), ozone(O3) and hypertension in adults residing in Jiangsu Province of China. METHODS: A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM2.5 and O3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk. RESULTS: After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females. CONCLUSIONS: Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM2.5 exposure-induced hypertension in males.

Rethinking 'family': A call for conceptual amelioration.

The modern concept of 'family' in the United States recognizes many types of social groups as families, a conceptual shift which was largely helped along by advancements in assisted reproductive technologies enabling those formerly unable to biologically reproduce to have children, as well as by social movements aimed at garnering recognition for these emergent nonbiologically related social groups spearheaded by LGBTQ+ and adoption activists. That these social groups are now recognized as types of families is unquestionably an improvement to the concept, though there are still defects in the concept that preclude these nonnuclear families from achieving the same social-ontological status as nuclear families. Drawing from the nascent philosophical field of conceptual engineering, I analyze our current conception of 'family' and argue that it is tacitly exclusionary of nonnuclear families, which can be attributed to a combination of widespread genetic essentialism and linguistic practices that unduly cast the nuclear family as a more desirable type of family by emphasizing genetic relatedness as a valuable quality. I then offer proposals to ameliorate these defects, such as educational interventions to reduce genetic essentialism and the introduction of new terminology that does not connote one type of family as being superior to another. In doing so, my hope is to reveal and begin to resolve an overlooked defect in the concept of 'family' in order to bolster the movement to view all families as equal.

Detecting of Barely Visible Impact Damage on Carbon Fiber Reinforced Polymer Using Diffusion Ultrasonic Improved by Time-Frequency Domain Disturbance Sensitive Zone.

Based on the decorrelation calculation of diffusion ultrasound in time-frequency domain, this paper discusses the repeatability and potential significance of Disturbance Sensitive Zone (DSZ) in time-frequency domain. The experimental study of Barely Visible Impact Damage (BVID) on Carbon Fiber Reinforced Polymer (CFRP) is carried out. The decorrelation coefficients of time, frequency, and time-frequency domains and DSZ are calculated and compared. It has been observed that the sensitivity of the scattered wave disturbance caused by impact damage is non-uniformly distributed in both the time and frequency domains. This is evident from the non-uniform distribution of the decorrelation coefficient in time-domain and frequency-domain decorrelation calculations. Further, the decorrelation calculation in the time-frequency domain can show the distribution of the sensitivity of the scattered wave disturbance in the time domain and frequency domain. The decorrelation coefficients in time, frequency, and time-frequency domains increase monotonically with the number of impacts. In addition, in the time-frequency domain decorrelation calculation results, stable and repetitive DSZ are observed, which means that the specific frequency component of the scattered wave is extremely sensitive to the damage evolution of the impact region at a specific time. Finally, the DSZ obtained from the first 15 impacts is used to improve the decorrelation calculation in the 16-th to 20-th impact. The results show that the increment rate of the improved decorrelation coefficient is 10.22%. This study reveals that the diffusion ultrasonic decorrelation calculation improved by DSZ makes it feasible to evaluate early-stage damage caused by BVID.

Effects of Potassium-Containing Fertilizers on Sugar and Organic Acid Metabolism in Grape Fruits.

To identify suitable potassium fertilizers for grape (Vitis vinifera L.) production and study their mechanism of action, the effects of four potassium-containing fertilizers (complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate) on sugar and organic acid metabolism in grape fruits were investigated. Potassium-containing fertilizers increased the activity of sugar and organic acid metabolism-related enzymes at all stages of grape fruit development. During the later stages of fruit development, potassium-containing fertilizers increased the total soluble solid content and the sugar content of the different sugar fractions and decreased the titratable acid content and organic acid content of the different organic acid fractions. At the ripening stage of grape fruit, compared with the control, complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate increased the total soluble solid content by 1.5, 1.2, 3.5, and 3.4 percentage points, decreased the titratable acid content by 0.09, 0.06, 0.18, and 0.17 percentage points, respectively, and also increased the total potassium content in grape fruits to a certain degree. Transcriptome analysis of the differentially expressed genes (DEGs) in the berries showed that applying potassium-containing fertilizers enriched the genes in pathways involved in fruit quality, namely, carbon metabolism, carbon fixation in photosynthetic organisms, glycolysis and gluconeogenesis, and fructose and mannose metabolism. Potassium-containing fertilizers affected the expression levels of genes regulating sugar metabolism and potassium ion uptake and transport. Overall, potassium-containing fertilizers can promote sugar accumulation and reduce acid accumulation in grape fruits, and potassium sulfate and potassium dihydrogen phosphate had the best effects among the fertilizers tested.

Clinical application and nursing experience of the plan-do-check-act cycle in daytime varicocelectomy.

BACKGROUND: Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy. METHODS: Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction. RESULTS: The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P < 0.05).No significant difference was observed in the incidence of postoperative complications between the two groups during hospitalization (P > 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy. CONCLUSION: In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches. TRIAL REGISTRATION: The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.

Natural variation of Alfin-like family affects seed size and drought tolerance in rice.

The Alfin-like (AL) family is a group of small plant-specific transcriptional factors involved in abiotic stresses in dicotyledon. In an early study, we found an AL gene in rice that was associated with grain yield under drought stress. However, little information is known about the AL family in rice. In this study, AL genes in the rice genome were identified, and the OsAL proteins were found to locate in the nucleus and have no transcriptional self-activation activity. The expression of the OsALs was regulated by different environmental stimulations and plant hormones. Association and domestication analysis revealed that natural variation of most OsALs was significantly associated with yield traits, drought resistance and divergence in grain size in indica and japonica rice varieties. Hap1 of OsAL7.1 and Hap7 of OsAL11 were favorable haplotypes of seed weight and germination under osmotic stress. Furthermore, osal7.1 and osal11 mutants have larger seeds and are more sensitive to abscisic acid and mannitol during germination stage. Overexpressing of OsAL7.1 and OsAL11 in rice weakened the tolerance to drought in the adult stage. Thus, our work provides informative knowledge for exploring and harnessing haplotype diversity of OsALs to improve yield stability under drought stress.

Differentiation of malignant from benign pleural effusions based on artificial intelligence.

INTRODUCTION: This study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE). METHODS: A total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs. RESULTS: The average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns. CONCLUSIONS: We applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Coordination of growth and drought responses by GA-ABA signaling in rice.

The drought caused by global warming seriously affects the crop growth and agricultural production. Plants have evolved distinct strategies to cope with the drought environment. Under drought stress, energy and resources should be diverted from growth toward stress management. However, the molecular mechanism underlying coordination of growth and drought response remains largely elusive. Here, we discovered that most of the gibberellin (GA) metabolic genes were regulated by water scarcity in rice, leading to the lower GA contents and hence inhibited plant growth. Low GA contents resulted in the accumulation of more GA signaling negative regulator SLENDER RICE 1, which inhibited the degradation of abscisic acid (ABA) receptor PYL10 by competitively binding to the co-activator of anaphase-promoting complex TAD1, resulting in the enhanced ABA response and drought tolerance. These results elucidate the synergistic regulation of crop growth inhibition and promotion of drought tolerance and survival, and provide useful genetic resource in breeding improvement of crop drought resistance.

Prognosis prediction of icotinib as targeted therapy for advanced EGFR-positive non-small cell lung cancer patients.

Clinical trials on icotinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), have shown promising results as targeted therapy for non-small cell lung cancer (NSCLC). This study aimed to establish an effective scoring system to predict the one-year progression-free survival (PFS) of advanced NSCLC patients with EGFR mutations treated with icotinib as targeted therapy. A total of 208 consecutive patients with advanced EGFR-positive NSCLC treated with icotinib were enrolled in this study. Baseline characteristics were collected within 30 days before icotinib treatment. PFS was taken as the primary endpoint and the response rate as the secondary endpoint. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox proportional hazards regression analysis were used to select the optimal predictors. We evaluated the scoring system using a five-fold cross-validation. PFS events occurred in 175 patients, with a median PFS of 9.9 months (interquartile range, 6.8-14.5). The objective response rate (ORR) was 36.1%, and the disease control rate (DCR) was 67.3%. The final ABC-Score consisted of three predictors: age, bone metastases and carbohydrate antigen 19-9 (CA19-9). Upon comparison of all three factors, the combined ABC-score (area under the curve (AUC)= 0.660) showed a better predictive accuracy than age (AUC = 0.573), bone metastases (AUC = 0.615), and CA19-9 (AUC = 0.608) individually. A five-fold cross-validation showed good discrimination with AUC = 0.623. The ABC-score developed in this study was significantly effective as a prognostic tool for icotinib in advanced NSCLC patients with EGFR mutations.

Six immune-related promising biomarkers may promote hepatocellular carcinoma prognosis: a bioinformatics analysis and experimental validation.

BACKGROUND: Abnormal miRNA and mRNA expression and dysregulated immune microenvironment have been found to frequently induce the progression of hepatocellular carcinoma (HCC) in recent reports. In particular, the immune-related competing endogenous RNAs (ceRNA) mechanism plays a crucial role in HCC progression. However, the underlying mechanisms remain unclear. METHODS: Differentially expressed immune-related genes were obtained from the Immport, GEO, and TCGA databases. The mRNA and protein expression levels in HCC tissues and adjacent normal tissues were confirmed, and we further investigated the methylation levels of these biomarkers to explore their function. Then, the TIMER and TISCH databases were used to assess the relationship between immune infiltration and hub genes. Survival analysis and univariate and multivariate Cox models were used to evaluate the association between hub genes and HCC diagnosis. Hub gene expression was experimentally validated in six HCC cell lines and 15 HCC samples using qRT-PCR and immunohistochemistry. The hub genes were uploaded to DSigDB for drug prediction enrichment analysis. RESULTS: We identified that patients with abnormal miRNAs (hsa-miR-125b-5p and hsa-miR-21-5p) and their targeted genes (NTF3, PSMD14, CD320, and SORT1) had a worse prognosis. Methylation analysis of miRNA-targeted genes suggested that alteration of methylation levels is also a factor in the induction of tumorigenesis. We also found that the development of HCC progression caused by miRNA-mRNA interactions may be closely correlated with the infiltration of immunocytes. Moreover, the GSEA, GO, and KEGG analysis suggested that several common immune-related biological processes and pathways were related to miRNA-targeted genes. The results of qRT-PCR, immunohistochemistry, and western blotting were consistent with our bioinformatics results, suggesting that abnormal miRNAs and their targeted genes may affect HCC progression. CONCLUSIONS: Briefly, our study systematically describes the mechanisms of miRNA-mRNA interactions in HCC and predicts promising biomarkers that are associated with immune filtration for HCC progression.

Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.