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AimWe aimed to systematically assess whether the level of body roundness index (BRI) is associated with the risk of developing chronic kidney disease (CKD) in US adults.MethodsThe studied data was extracted from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. A total of 29,062 participants aged ≥20 years with complete information about BRI and CKD were included in this study. Logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve, stratified analysis and receiver operating characteristic (ROC) curve were performed to investigate the association between BRI and CKD.ResultsA total of 29,062 patients were included, involving 4,623 individuals with CKD and 24,439 individuals without CKD. A higher BRI level was substantially related to an increased prevalence of CKD in US adults. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. However, in the subgroup analysis stratified by race and body mass index (BMI), no significant associations between BRI and CKD were observed among Mexican participants (OR: 1.10; 95% CI: 0.98–1.23) and those with underweight or normal weight (OR: 0.95; 95% CI: 0.81–1.05). Moreover, a non-linear relationship was found between BRI and the prevalence of CKD. In ROC analysis, BRI demonstrated higher discriminating for CKD (area under the curve: 0.6247; 95% CI: 0.6161–0.6333; optimal cutoff value: 5.161) compared with other indices.ConclusionIn summary, BRI was independently associated with a higher prevalence of CKD in overweight and obese US adults, excluding Mexican. This may be an important therapeutic target and predictor of CKD. Physicians should advise patients with high BRI scores, especially overweight and obese patients, to embrace healthy lifestyle changes, such as maintaining a balanced diet and engaging in regular physical activity. These changes can help them control their body weight and reduce abdominal fat, ultimately lowering the risk of CKD.

BackgroundPredicting intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) can aid early treatment and prevent coronary artery lesions. A clinically consistent predictive model was developed for IVIG resistance in KD.MethodsIn this retrospective cohort study of children diagnosed with KD from January 1, 2016 to December 31, 2021, a scoring system was constructed. A prospective model validation was performed using the dataset of children with KD diagnosed from January 1 to June 2022. The least absolute shrinkage and selection operator (LASSO) regression analysis optimally selected baseline variables. Multivariate logistic regression incorporated predictors from the LASSO regression analysis to construct the model. Using selected variables, a nomogram was developed. The calibration plot, area under the receiver operating characteristic curve (AUC), and clinical impact curve (CIC) were used to evaluate model performance.ResultsOf 1975, 1,259 children (1,177 IVIG-sensitive and 82 IVIG-resistant KD) were included in the training set. Lymphocyte percentage; C-reactive protein/albumin ratio (CAR); and aspartate aminotransferase, sodium, and total bilirubin levels, were risk factors for IVIG resistance. The training set AUC was 0.825 (sensitivity, 0.723; specificity, 0.744). CIC indicated good clinical application of the nomogram.ConclusionThe nomogram can well predict IVIG resistance in KD. CAR was an important marker in predicting IVIG resistance in Kawasaki disease.

IntroductionBlueberries have a high antioxidant content and are produced as healthy food worldwide. Long non-coding RNAs (lncRNAs) are a type of regulatory RNAs that play a variety of roles in plants. Nonetheless, information on lncRNAs and their functions during blueberry fruit development is scarce in public databases.MethodsIn the present study, we performed genome-wide identification of lncRNAs in a southern highbush blueberry using strand-specific RNA sequencing (ssRNA-Seq). Differentially expressed lncRNAs (DE-lncRNAs) and their potential target genes were analyzed at four stages of fruit development. Cis-regulatory DE-lncRNAs were predicted using co-localization analysis.ResultsThese findings included a total of 25,036 lncRNAs from 17,801 loci. Blueberry lncRNAs had shorter transcript lengths, smaller open reading frame (ORF) sizes, fewer exons, and fewer isoforms than protein-coding RNAs, as well as lower expression levels and higher stage-specificity during fruit development. A total of 105 DE-lncRNAs were identified among the comparison group of PAD vs. CUP, 443 DE-lncRNAs were detected when comparing CUP with PINK fruits, and 285 DE-lncRNAs were revealed when comparing PINK and BLUE fruits. According to Kyoto Encyclopedia of Genes and Genomes annotation, target genes of DE-lncRNAs were primarily enriched in the “Autophagy-other”, “DNA replication”, “Endocytosis”, ‘photosynthesis’ and ‘chlorophyll metabolism’ pathways, suggesting that lncRNAs may pay potential roles in fruit expansion and ripening. Moreover, several lncRNAs have been proposed as cis-regulators of the key genes involved in flavonoid biosynthesis. MSTRG.107242.6, and its putative target gene, BTB/POZ and TAZ domain-containing protein, might play critical roles in anthocyanin accumulation in blueberries.DiscussionThese findings highlight the regulatory function of lncRNAs and aid in elucidating the molecular mechanism underlying blueberry fruit growth.

IntroductionBlueberry (Vaccinium corymbosum L.) is a popular fruit with an abundance of anthocyanins in its leaves and fruits. Light is one of the pivotal environmental elements that affects plant growth and development, but the regulatory mechanism between light quality and anthocyanin formation is poorly understood.MethodsAn integrated transcriptome and metabolome analysis was performed to investigate the effects of white (control), blue (B), red (R), and red/blue (60R/40B) light on blueberry growth and reveal the potential pathway controlling anthocyanin biosynthesis in blueberry leaves.ResultsThe anthocyanin content was significantly improved by the blue and red/blue light when compared with white light, whereas there was a significant reduction in the photosynthesis under the blue light, showing an inverse trend to that of anthocyanin accumulation. Transcriptomic analysis resulted in the assembly of 134,709 unigenes. Of these, 22 were differentially expressed genes (DEGs) that participate in the anthocyanin biosynthesis pathway, with the majority being significantly up-regulated under the blue light. Most of the photosynthesis-related genes that were down-regulated were expressed during anthocyanin accumulation. Targeted metabolome profiling identified 44 metabolites associated with anthocyanin biosynthesis. The contents of most of these metabolites were higher under blue light than the other light conditions, which was consistent with the transcriptome results. The integrated transcriptome and metabolome analysis suggested that, under blue light, leucoanthocyanidin dioxygenase (LDOX), O-methyltransferase (OMT), and UDP-glucose flavonoid glucosyltransferase (UFGT) were the most significantly expressed, and they promoted the synthesis of cyanidin (Cy), malvidin (Mv), and pelargonidin (Pg) anthocyanidins, respectively. The expression levels of dihydroflavonol 4-reductase (DFR) and OMT, as well as the accumulation of delphinidin (Dp), peonidin (Pn), and petunidin (Pt), were significantly increased by the red/blue light.DiscussionThe blue and red/blue lights promoted anthocyanin biosynthesis via inducing the expression of key structural genes and accumulation of metabolites involved in anthocyanin synthesis pathway. Moreover, there was a possible feedback regulating correlation between anthocyanin biosynthesis and photosynthesis under different light qualities in blueberry leaves. This study would provide a theoretical basis for elucidating the underlying regulatory mechanism of anthocyanin biosynthesis of V. corymbosum.

Few studies have explored the trajectories of Chinese early adolescent depressive symptoms or comprehensively considered the factors of family and peers. The present study aimed to identify the trajectories of depressive symptoms in early adolescence using a school-based sample assessed in three waves. The study also examined whether family and peer factors were significant predictors. A total of 586 Chinese primary and middle school students participated in the survey. A growth mixture model was used to find the trajectories of depressive symptoms, and multinominal logistic regression was used to identify the predictors. Three trajectories were identified, including a stable-low class, an increasing class, and a high-decreasing class. Results indicated that gender, parental psychological aggression and neglect, parental psychological control, traditional bullying/cyberbullying victimization, and friendship quality were significant predictors. However, witnessing intimate partner violence, parental behavior control, and traditional bullying/cyberbullying perpetration could not significantly predict the trajectories. The findings of this study can provide an empirical basis for teachers and clinical interveners to determine different development trajectories of depressive symptoms and carry out prevention and intervention.

As the largest artificial ecosystem on Earth, croplands not only secure the basic living materials for people but also provide ecological service values for human society. For croplands, ecosystem services have proven to be of great value and are closely linked to human activities and climate change. However, spatiotemporal patterns of cropland ecosystem services and their drivers still need to be further assessed quantitatively. In this study, we provided a comprehensive evaluation of ecosystem services across China's cropland ecosystems over the past two decades using gross ecosystem product (GEP) as a single metric of the monetary evaluation of final ecosystem services. The values of material services, regulating services, and cultural services were calculated to summarize the GEP value of cropland ecosystems in China. Our results showed that the multiyear mean value of GEP was 4.35 × 107 million CNY. The value of regulating services reached 3.86 × 107 million CNY, followed by material services of 4.76 × 106 million CNY and cultural services of 1.16 × 105 million CNY. GEP value was different among provinces, leading to a heterogeneous spatial pattern associated with population and cultivated area. Moreover, we analyzed the trends in the GEP value at the provincial and national scales. The results showed that the GEP value of China's cropland ecosystems has increased over the period. The values of the material, regulating, and cultural services have increased at a rate of (0.35 ± 0.01) × 106 million CNY a−1, (1.12 ± 0.10) × 106 million CNY a−1, and (0.002 ± 0.0002) × 106 million CNY a−1, respectively (P < 0.05). The majority of provinces had an increasing trend in GEP, yet some developed provinces, e.g., Beijing and Shanghai, showed a decreasing trend. Furthermore, we evaluated the impacts of social-economic and natural factors on changes in GEP. We found that rising prices for agricultural products and services boosted an increase in GEP. Meanwhile, the spatiotemporal patterns of GEP were also associated with the adjustments of planting area in each province. Overall, our findings highlight the importance of assessing spatiotemporal patterns of cropland ecosystem services for decision-makers.

Loquat (Eriobotrya japonica Lindl. ) is one of the most economically important evergreen fruit crops in China, while it often suffered the injury of cold stress in winter and earlier spring, and the annual yield loss of loquat fruits caused by cold or freezing stress was immeasurable. However, knowledge about the physiological response and molecular mechanism under cold stress is still limited. To investigate the potential regulation mechanism pre- and post-cold stress in loquat and the changes in physiological indicators, a comparative transcriptome analysis was performed against a cold-resistant cv. “Huoju” and a cold-sensitive cv. “Ninghaibai”. The results of physiological indicators related to cold resistance indicated that rachis was most sensitive to cold stress and was considered as the representative organ to directly evaluate cold resistance of loquat based on subordinate function analysis. Here, we compared the transcriptome profiles of rachis pre- and under cold stress in “Huoju” and “Ninghaibai”. A total of 4,347 and 3,513 differentially expressed genes (DEGs) were detected in “Ninghaibai” and “Huoju”, among which 223 and 166 were newly identified genes, respectively, most of them were functionally enriched in plant hormone signal transduction (Huoju: 142; Ninghaibai: 200), and there were higher plant hormone content and related DEG expression levels in “Huoju” than that of “Ninghaibai”. Moreover, a total of 3,309 differentially expressed transcription factors (DETFs) were identified, and some DEGs and DETFs were screened to be subjected to co-expression network analysis based on the gene expression profile data. Some candidate DEGs, including UDP-glycosyltransferase (UGT), glycosyltransferase (GT), sugar phosphate/phosphate translocator (SPT), sugar transport protein (STP), proline-rich receptor-like protein kinase (PERK), and peroxidise (POD), were significantly affected by cold stress, and the expression level of these genes obtained from real-time quantitative RT-PCR was consistent with the pattern of transcriptome profile, which suggested that these genes might play the vital roles in cold resistance of loquat. Our results provide an invaluable resource for the identification of specific genes and TFs and help to clarify gene transcription during the cold stress response of loquat.

Liver cirrhosis (LC) is a fibrotic lesion of liver tissue caused by the repeated progression of chronic hepatitis. The traditional Chinese medicine Gexia-Zhuyu formula (GXZY) has a therapeutic effect on LC. However, its pharmacological mechanisms on LC remain elucidated. Here, we used the network pharmacology approach to explore the action mechanisms of GXZY on LC. The compounds of GXZY were from the traditional Chinese medicine systems pharmacology (TCMSP) database, and their potential targets were from SwissTargetPrediction and STITCH databases. The disease targets of LC came from GeneCards, DisGeNET, NCBI gene, and OMIM databases. Then we constructed the protein-protein interaction (PPI) network to obtain the key target genes. And the gene ontology (GO), pathway enrichment, and expression analysis of the key genes were also performed. Subsequently, the potential action mechanisms of GXZY on LC predicted by the network pharmacology analyses were experimentally validated in LC rats and LX2 cells. A total of 150 components in GXZY were obtained, among which 111 were chosen as key compounds. The PPI network included 525 targets, and the key targets were obtained by network topological parameters analysis, whereas the predicted key genes of GXZY on LC were AR, JUN, MYC, CASP3, MMP9, GAPDH, and RELA. Furthermore, these key genes were related to pathways in cancer, hepatitis B, TNF signaling pathway, and MAPK signaling pathway. The in vitro and in vivo experiments validated that GXZY inhibited the process of LC mainly via the regulation of cells proliferation and migration through reducing the expression of MMP9. In conclusion, through the combination of network pharmacology and experimental verification, this study offered more insight molecular mechanisms of GXZY on LC.

Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with 68Ga-DOTA-DiPSMA in prostate cancer (PCa) patients.Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan and whole-body PET were performed with 2 min per bed position in 40 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake were measured. A lesion-by-lesion analysis was performed.Results: 68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 μSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 μSv/MBq) in accordance with the expected Prostate-Specific Membrane Antigen (PSMA) renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUVmax of 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases was 4.41 ± 2.72, 2.95 ± 1.11, and 3.26 ± 1.20, respectively.Conclusion: Injection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. 68Ga-DOTA-DiPSMA shows favorable kinetics and imaging characteristics in patients who warrant further head-to-head comparison to validate 68Ga-DOTA-DiPSMA as an alternative for gallium-68-labeled PSMA clinical PET. Low nonspecific uptake in normal organs of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.

Introduction: Given the ongoing coronavirus disease 2019 (COVID-19) pandemic and the consequent global healthcare crisis, there is an urgent need to better understand risk factors for symptom deterioration and mortality among patients with COVID-19. This systematic review aimed to meet the need by determining the predictive value of chronic diseases for COVID-19 severity and mortality.Methods: We searched PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Complete to identify studies published between December 1, 2019, and December 31, 2020. Two hundred and seventeen observational studies from 26 countries involving 624,986 patients were included. We assessed the risk of bias of the included studies and performed a cumulative meta-analysis.Results: We found that among COVID-19 patients, hypertension was a very common condition and was associated with higher severity, intensive care unit (ICU) admission, acute respiratory distress syndrome, and mortality. Chronic obstructive pulmonary disease was the strongest predictor for COVID-19 severity, admission to ICU, and mortality, while asthma was associated with a reduced risk of COVID-19 mortality. Patients with obesity were at a higher risk of experiencing severe symptoms of COVID-19 rather than mortality. Patients with cerebrovascular disease, chronic liver disease, chronic renal disease, or cancer were more likely to become severe COVID-19 cases and had a greater probability of mortality.Conclusions: COVID-19 patients with chronic diseases were more likely to experience severe symptoms and ICU admission and faced a higher risk of mortality. Aggressive strategies to combat the COVID-19 pandemic should target patients with chronic diseases as a priority.

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of the coronavirus disease 2019 (COVID-19), which elicits a wide variety of symptoms, ranging from mild to severe, with the potential to lead to death. Although used as the standard method to screen patients for SARS-CoV-2 infection, real-time PCR has challenges in dealing with asymptomatic patients and those with an undetectable viral load. Serological tests are therefore considered potent diagnostic tools to complement real-time PCR-based diagnosis and are used for surveillance of seroprevalence in populations. However, the dynamics of the antibody response against SARS-CoV-2 currently remain to be investigated. Here, through analysis of plasma samples from 84 patients with COVID-19, we observed that the response of virus-specific antibodies against three important antigens, RBD, N and S, dynamically changed over time and reached a peak 5–8 weeks after the onset of symptoms. The antibody responses were irrespective of sex. Severe cases were found to have higher levels of antibody response, larger numbers of inflammatory cells and C-reactive protein levels. Within the mild/moderate cases, pairwise comparison indicated moderate association between anti-RBD vs. anti-N, anti-RBD vs. anti-S1S2, and anti-N vs. anti-S1S2. Furthermore, the majority of cases could achieve IgM and IgG seroconversion at 2 weeks since the disease onset. Analysis of neutralizing antibodies indicated that these responses were able to last for more than 112 days but decline significantly after the peak. In summary, our findings demonstrate the longitudinally dynamic changes in antibody responses against SARS-CoV-2, which can contribute to the knowledge of humoral immune response after SARS-CoV-2 infection and are informative for future development of vaccine and antibody-based therapies.