Global prevalence of congenital hypothyroidism among neonates from 1969 to 2020: a systematic review and meta-analysis.

Little is known about the global prevalence of congenital hypothyroidism (CH), though it is known to vary across countries and time periods. This meta-analysis aims to estimate the global and regional prevalence of CH among births between 1969 and 2020. PubMed, Web of Sciences, and Embase databases were searched for relevant studies between January 1, 1975, and March 2, 2020. Pooled prevalence was calculated using a generalized linear mixed model, and expressed as a rate per 10,000 neonates. The meta-analysis involved 116 studies, which analyzed 330,210,785 neonates, among whom 174,543 were diagnosed with CH. The pooled global prevalence of CH from 1969 to 2020 was 4.25 (95% confidence interval (CI) 3.96-4.57). The geographic region with highest prevalence was the Eastern Mediterranean (7.91, 95% CI 6.09-10.26), where the prevalence was 2.48-fold (95% CI 2.04-3.01) that in Europe. The national income level with the highest prevalence was upper-middle (6.76, 95% CI 5.66-8.06), which was 1.91-fold (95% CI 1.65-2.22) that in high-income countries. Global prevalence of CH was 52% (95% CI 4-122%) higher in 2011-2020 than in 1969-1980, after adjusting for geographic region, national income level, and screening strategy.  Conclusion: The global prevalence of CH increased from 1969 to 2020, which may reflect the implementation of national neonatal screening, neonatal testing for thyroid-stimulating hormone, and a lowering of the diagnostic level of this hormone. Additional factors are likely to be driving the increase, which should be identified in future research. What is Known: • Cumulated evidence had suggested that the occurrences of congenital hypothyroidism (CH) among newborns were varied in different countries.. • Up-trends of the birth prevalence of CH were observed in many European and American countries. What is New: • This is the first meta-analysis to estimate global and regional prevalence of CH among newborns. • The global prevalence of CH has increased by 127% since 1969. The Eastern Mediterranean has the highest prevalence and stands out with the most pronounced escalation in the prevalence of CH.

Identification of Key Aromatic Compounds in Basil (Ocimum L.) Using Sensory Evaluation, Metabolomics and Volatilomics Analysis.

Basil (Ocimum L.) is widely used as a flavor ingredient, however research on basil flavor is limited. In the current study, nine basil species were selected, including Ocimum basilicum L.var. pilosum (Willd.) Benth., Ocimum sanctum, Ocimum basilicum cinnamon, Ocimum gratissimum var. suave, Ocimum tashiroi, Ocimum basilicum, Ocimum americanum, Ocimum basilicum ct linalool, and Ocimum basilicum var. basilicum, and their fragrance and flavor characteristics were assessed by sensory evaluation. The results indicated that Ocimum basilicum var. basilicum and Ocimum gratissimum var. suave have a strong clove smell and exhibited a piquant taste. Metabolomics and volatilomics analyses measured 100 nonvolatile metabolites and 134 volatiles. Differential analysis showed that eugenol, γ-terpinene, germacrene D and malic acid were among the most varied metabolites in basil species. Combined with sensory evaluation results, correlation analysis revealed that ß-pinene and γ-cadinene contributed to the piquant smell, while eugenol and germacrene D contributed to the clove smell, and malic acid and L-(−)-arabitol contributed to the sweet flavor in basil. This study provided comprehensive flavor chemistry profiles of basil species and could be used as a guide for basil flavor improvement. The better understanding of objective sensory attributes and chemical composition of fresh basil could introduce the improved cultivars with preponderant traits, which is also in accordance with the various demands of breeders and growers, food producers, and consumers.

Government Environmental Regulation and Corporate ESG Performance: Evidence from Natural Resource Accountability Audits in China.

With the increasing global concern for the ecological environment and sustainable development, all countries have proposed environmental regulatory policies to improve the quality of their ecological environments. China has also proposed an environmental regulation policy: Leading an officials' accountability audit of natural resources (AANR). As the main subject of consuming resources, the sustainability of enterprises has become a focus of all parties. The Environmental, Social, and Governance (ESG) metric measures corporate sustainability. As a result, companies' ESG performance has gained the community's attention. Based on data from Chinese A-share listed companies in Shanghai and Shenzhen from 2011 to 2019, this study investigates the role of AANR on the ESG performance of companies via the difference-in-differences (DID) method. This study found that implementing the AANR pilot significantly negatively impacted corporate ESG performance. This result was found to remain robust after passing parallel trend and robustness tests. Further research found that the AANR differed significantly across corporate ownership and regions in corporate ESG performance. First, pilot implementation had a more significant impact on the ESG performance of non-state enterprises. Second, the differences across regions showed that the central region had the most significant impact, followed by the western region, while the eastern region had the most negligible impact. This study will help government departments improve the AANR system and enable companies to focus on their ESG performance.

Research on the evolution of spatial network structure of tourism eco-efficiency and its influencing factors in China's provinces based on carbon emission accounting.

In the context of global warming, although the coordinated development of tourism has led to regional economic growth, the high energy consumption-driven effects of such development have also led to environmental degradation. This research combines the undesired output of the Super-SBM model and social network analysis methods to determine the eco-efficiency of provincial tourism in China from 2010-2019 and analyzes its spatial correlation characteristics as well as its influencing factors. The aim of the project is to improve China's regional tourism eco-efficiency and promote cross-regional tourism correlation. The results show that (1) the mean value of provincial tourism eco-efficiency in China is maintained at 0.405~0.612, with an overall fluctuating upward trend. The tourism eco-efficiency of eastern China is higher than that of central, western and northeastern China, but the latter three regions have not formed a stable spatial distribution pattern. (2) The spatial network of provincial tourism eco-efficiency in China is multithreaded, dense and diversified. Throughout the network, affiliations are becoming closer, and network structure robustness is gradually improving, although the "hierarchical" spatial network structure remains. In individual networks, Jiangsu, Guangdong and Shandong provinces in eastern China have higher centrality degrees, closeness centrality and betweenness centrality than other provinces, which means they are dominant in the network. Hainan Province, also located in eastern China, has not yet built a "bridge" for tourism factor circulation. In the core-periphery model, the core-periphery areas of China's provincial tourism eco-efficiency are distributed in clusters, and the number of "core members" has increased. (3) The economic development level, information technology development level, and tourism technology level collectively drive the development and evolution of China's provincial tourism eco-efficiency spatial network.

Bioinformatics analysis identifies diagnostic biomarkers and their correlation with immune infiltration in diabetic nephropathy.

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Currently, microalbuminuria is mainly used as a diagnostic indicator of DN, but there are still limitations and lack of immune-related diagnostic markers. In this study, we aimed to explore diagnostic biomarkers associated with immune infiltration of DN. Methods: Immune-related differentially expressed genes (DEGs) were derived from those at the intersection of the ImmPort database and DEGs identified from 3 datasets, which were based on the Gene Expression Omnibus (GEO). Functional enrichment analyses were performed; a protein-protein interaction (PPI) network was constructed; and hub genes were identified by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). After screening the key genes using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), a prediction model for DN was constructed. The predictive performance of the model was quantified by receiver-operating characteristic curve, decision curve analysis, and nomogram. Next, infiltration of 22 types of immune cells in DN kidney tissue was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Expression of diagnostic markers was analyzed in DN and control patient groups to determine the genes with the maximum diagnostic potential. Finally, we explored the correlation between diagnostic markers and immune cells. Results: Overall, 191 immune-related DEGs were identified, that primarily positively regulated with cell adhesion, T cell activation, leukocyte proliferation and migration, urogenital system development, lymphocyte differentiation and proliferation, and mononuclear cell proliferation. Gene sets were related to the PI3K-Akt, MAPK, Rap1, and WNT signaling pathways. Finally, CCL19, CD1C, and IL33 were identified as diagnostic markers of DN and recognized in the 3 datasets [area under the curve (AUC) =0.921]. Immune cell infiltration analysis demonstrated that CCL19 was positively correlated with macrophages M1 (R=0.47, P<0.001) and macrophages M2 (R=0.75, P<0.001). CD1C was positively correlated with macrophages M1 (R=0.47, P<0.05), macrophages M2 (R=0.75, P<0.01), and monocytes (R=0.42, P<0.01). IL33 was positively correlated with macrophages M1 (R=0.45, P<0.05), macrophages M2 (R=0.74, P<0.01), and monocytes (R=0.41, P<0.01). Conclusions: Our results provide evidence that CCL19, CD1C, and IL33, which are associated with immune infiltration, are the potential diagnostic biomarkers for DN candidates.

Effects of chronic kidney disease on cognitive function and α-klotho expression in hippocampus.

Background: Alpha-klotho (α-KL) is not only related to the regulation of calcium-phosphorus metabolism, and fibrosis in chronic kidney disease (CKD), it is also involved in the regulation of many cognitive disorders. We conducted this study to investigate the effects of CKD on cognitive dysfunction and α-KL. Methods: Doxorubicin was used to induce a CKD model, which was validated by weight, 24-hour urine protein quantification, serum creatinine (Cr), blood urea nitrogen (BUN), and kidney hematoxylin-eosin (HE) staining. The Morris water maze (MWM) paradigm was used to assess the effects of CKD on cognitive behavior. The expression of α-KL in the hippocampus was detected using real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry (IHC). Results: (I) In the CKD group, the weight of the rats increased slowly (P<0.001), 24-hour urine protein increased (P<0.05), and Cr (P=0.026) and BUN levels (P=0.003) increased; (II) HE staining showed that in the CKD group there were changes in the structure, fibrosis, and inflammatory infiltration of the renal tissues, and changes in the structure, cell necrosis, and neuronal degeneration of the hippocampus; (III) in the MWM experiment, the escape latency of the CKD group was prolonged compared to that of the control group (P=0.043, 0.023), and the number of crossing the platform was reduced (P=0.003); (IV) in the CKD group, the expressions of α-KL messenger ribonucleic acid (P=0.0005) and α-KL protein (P=0.0005) in the hippocampus were downregulated. The IHC results showed that the expression of α-KL protein in the hippocampal region III cornus ammonis (CA3) of the CKD group region was also downregulated, and the α-KL-positive cells (P=0.019) and mean optical density (P=0.015) were decreased. Conclusions: The expression of α-KL appears to effect the cognitive function of CKD rats; thus, it may be a valuable target in the treatment of CKD with cognitive impairment.

Development of a widely targeted volatilomics method for profiling volatilomes in plants.

Volatile organic compounds play essential roles in plant environment interactions as well as determining the fragrance of plants. Although gas chromatography-mass spectrometry-based untargeted metabolomics is commonly used to assess plant volatiles, it suffers from high spectral convolution, low detection sensitivity, a limited number of annotated metabolites, and relatively poor reproducibility. Here, we report a widely targeted volatilomics (WTV) method that involves using a "targeted spectra extraction" algorithm to address spectral convolution, constructing a high-coverage MS2 spectral tag library to expand volatile annotation, adapting a multiple reaction monitoring mode to improve sensitivity, and using regression models to adjust for signal drift. The newly developed method was used to profile the volatilome of rice grains. Compared with the untargeted method, the newly developed WTV method shows higher sensitivity (for example, the signal-to-noise ratio of guaicol increased from 4.1 to 18.8), high annotation coverage (the number of annotated volatiles increased from 43 to 132), and better reproducibility (the number of volatiles in quality control samples with relative standard deviation value below 30.0% increased from 14 to 92 after normalization). Using the WTV method, we studied the metabolic responses of tomato to environmental stimuli and profiled the volatilomes of different rice accessions. The results identified benzothiazole as a potential airborne signal priming tomato plants for enhanced defense and 2-nonanone and 2-heptanone as novel aromatic compounds contributing to rice fragrance. These case studies suggest that the widely targeted volatilomics method is more efficient than those currently used and may considerably promote plant volatilomics studies.

Clinical significance and biological function of transcriptional repressor GATA binding 1 in gastric cancer: a study based on data mining, RT-qPCR, immunochemistry, and vitro experiment.

Transcriptional repressor GATA binding 1 (TRPS1) is a newly discovered transcription factor, which has been reported in many tumors, except for gastric cancer (GC). In this study, we aimed to grope for clinical significance and biological function of TRPS1 in GC. TRPS1 expression in GC and its relationship with clinicopathological features were analyzed based on public databases, and verified by immunohistochemistry and RT-qPCR. Kaplan-Meier survival curve and Cox regression model were used to estimate the influence of TRPS1 on the univariate prognosis and multivariate survival risk factors of GC. The effects of TRPS1 on malignant biological behaviors of GC cells were studied by CCK8 cell proliferation, scratch test, and Transwell assay. The function of TRPS1 was further analyzed by signaling pathway analysis. TRPS1 mRNA expression in GC tissues was up-regulated and was of great significance in some prognostic factors. Protein expression of TRPS1 in tumor tissues was significantly higher than that in paracancerous tissues. Over-expression of TRPS1 was a poor prognostic indicator for GC patients. TRPS1 knockdown could inhibit the proliferation, migration, and invasion of GC cells. The important role of TRPS1 was in the extracellular matrix, and it was involved in actin binding and proteoglycan in cancer. The hub genes of TRPS1 (FN1, ITGB1) were defined. TRPS1 may be a tumor promoter and promote the development of GC by influencing the malignant biological behaviors of GC. TRPS1 is expected to be a key diagnostic and prognostic indicator for GC patients.

Primary thyroid Burkitt lymphoma in a 15-year-old boy.

In children, primary thyroid Burkitt lymphoma (PTBL) is an extremely rare pathologic entity of thyroid malignant tumor. Here we describe a case of PTBL in a 15-year-old boy, who developed a rapidly enlarging neck mass that showed signs of compression. The color Doppler ultrasound revealed diffuse swelling of the thyroid gland, with a solid and irregular mass from the left to the isthmus, which was about 8 × 7 × 5 cm in size. Computed tomography showed Irregular masses were seen in the left thyroid with a range of about 7.1 × 5.4 × 8.0 cm, and a beaded slightly enlarged lymph node with a maximum of 1.6 × 0.8 cm was discovered in the left neck. Postoperative pathologic examination also found the specific starry-sky phenomenon of Burkitt lymphoma. Moreover, immunohistochemistry also indicated that the related cellular immunophenotypic expression was also positive or negative. In particular, the proliferation rate by ki67 was almost 100% and C-MYC was also positive. After thyroidectomy, patient underwent four cycles of CHOP regimen chemotherapy. Unfortunately, the patient died as a result of the deterioration of his condition. This report provides an opportunity to review an uncommon type of PTBL in children.

Hepatic fibrosarcoma in a middle-aged man.

Hepatic fibrosarcoma (HF) is a rare sarcoma with a high malignancy and a poor prognosis. Moreover, it is hard to diagnose before completing a pathological examination, for HF has almost no features of clinical or imaging manifestations. Here we report a case of HF in a 42-year-old male who complained of pain in the right upper abdomen. Computed tomography (CT) and ultrasonography confirmed a large mass was occupying the right lobe of his liver. The patient was finally diagnosed with HF based on the morphology and immunohistochemistry of the tumor after resection. This case indicates that a diagnosis of HF should be considered, especially when the results of imaging examinations and tumor markers do not support the common hepatic diseases.

Diagnostic significance and potential function of miR-338-5p in hepatocellular carcinoma: A bioinformatics study with microarray and RNA sequencing data.

MicroRNA (miR)-338-5p has been studied in hepatocellular carcinoma (HCC); however, the diagnostic value and molecular mechanism underlying its actions remains to be elucidated. The present study aimed to validate the diagnostic ability of miR­338­5p and further explore the underlying molecular mechanism. Data from eligible studies, Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) datasets were gathered in the data mining and the integrated meta­analysis, to evaluate the significance of miR­338­5p in diagnosing HCC comprehensively. The potential target genes of miR­338­5p were achieved from the intersection of the deregulated targets of miR­338­5p from GEO and TCGA in addition to the predicted target genes from 12 online software. A protein­protein­interaction (PPI) network was drawn to illustrate the interaction between target genes and to define the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the function of the target genes. From the results, miR­338­5p exhibited favorable value in diagnosing HCC. Types of sample and experiment were defined as the possible sources of heterogeneity in meta­analysis. A total of 423 genes were selected as the potential target genes of miR­338­5p, and five genes were defined as the hub genes from the PPI network. The GO and KEGG analyses indicated that the target genes were significantly assembled in the pathways of metabolic process and cell cycle. miR­338­5p may function as a novel diagnostic target for HCC through regulating certain target genes and signaling pathways.

Potential targets and clinical value of miR-490-5p in hepatocellular carcinoma: a study based on TCGA, qRT-PCR and bioinformatics analyses.

OBJECTIVE: To explore potential targets and clinical value of miR-490-5p in the oncogenesis and progression of hepatocellular carcinoma (HCC). METHODS: Clinical value of miR-490-5p was accessed through The Cancer Genome Atlas (TCGA) and qRT-PCR analyses. Potential target mRNAs of miR-490-5p were predicted by bioinformatics methods and were annotated as Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and Protein-Protein Interaction (PPI) network analysis. RESULTS: miR-490 expression in HCC tissues was lower compared with normal control tissues based on TCGA and down regulation of miR-490-5p was verified by qRT-PCR (P<0.0001). Both miR-490 and miR-490-5p had moderate ability to diagnose HCC tissues from noncancerous tissues. Moreover, lower miR-490 level predicted poorer overall survival in patients with HCC (P=0.0063). One hundred and eighty-four mRNAs were selected as potential targets of miR-490-5p by overlap with 4,090 prediction genes and 1,478 differentially expressed genes (DEGs). Gene Ontology (GO) function analysis showed that the most significant terms were vasculature development, endoplasmic reticulum, and protein binding in biological process (BP), cellular component (CC), and molecular function (MF). In KEGG signaling pathway analysis, the statistically significant terms were lysosome, focal adhesion, glioma. In PPI network analysis, SRC, SRP9, PDGFRB, RPL28, and RPS23 were identified as the hub genes. CONCLUSION: miR-490-5p is down-regulated in HCC and may be a prospectively diagnostic and prognostic biomarker. Moreover, miR-490-5p might directly target SRC, SRP9, PDGFRB, RPL28, or RPS23 and play an important role in HCC.