Analysis of Influencing Factors and Strategies for Premature Breast Development in Female Children based on Logistic Regression Analysis: A Randomized Double-blind Controlled Clinical Trial.

Objective: To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the time point of transformation in order to detect and prevent the occurrence of transformation in advance and reduce the incidence of idiopathic central precocious puberty. Ensure children's physical and mental health and normal growth and development. Methods: A total of 50 children with PT admitted to our hospital from April 2019 to December 2020 were included in the study group, and 50 children with physical examination during the same period were selected as the control group. All children were tested for vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., and IGFBp-3 at 3, 6, 9 and 12 months after the diagnosis of PT. Results: Vitamin D levels decreased in the child, indicating that vitamin D deficiency was closely related to the age of breast development in ICPP girls and may be related to serum P-FSH, P-LH and E2 levels. Increased levels of IGFBp-3 indicate that these indicators are involved in the onset of ICPP. Children have a higher BMI, watch idol dramas or play mobile games longer, often eat snacks containing preservatives, have a fishy diet, are more irritable and sensitive, and dry stools are also risk factors affecting the early development of simple breasts in girls. Conclusion: The influencing factors leading to simple, early breast development in girls include vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., IGFBp-3, and should be combined with the progression of breast Tanner staging (complete regression, recurrent, and persistent), height growth rate, bone age, Uterine and ovarian B ultrasound, sex hormones, etc., warn of the conversion of PT to ICPP, and ensure children's physical and mental health and normal growth and development.

Quantification of hetero-cyclic amines from different categories of braised beef by optimized UPLC-TQ-XS/ESI method.

This research work has developed and optimized a sensitive analytical method for separation and quantification of heterocyclic amines (HCAs) mainly including PhIP, Harman, Norharman, IQ, MeIQ, AαC, MeAαC and Trp-P-2 by optimizing UPLC-TQ-XS using electrospray ionization source (ESI+) on ACQUITY UPLC® BEH C18 column in <7 min, from braised beef sample matrix. Meanwhile, modified HCAs extraction by modifying QuEChERS (quick, easy, cheap, efficient, rugged and safe) technique and revisited with solid phase extraction (SPE) for HCAs purification, instead using traditional QuEChERS salts. Moreover, optimized pH conditions of HCA extracts before purification, for better extraction recoveries. Furthermore, this method was validated in terms of method validation parameters. Lastly, simulation of real braised beef model provided the minimum formation of HCAs by optimizing cooking parameters and precursors in a cooking system. Therefore, this method could be applied simultaneously on braised beef matrix either marketed or home cooked for HCAs analysis.

The impact of vaccination on patients with COVID-19 during the wave of Omicron in Shanghai.

Background: The global health has been affected by the COVID-19 pandemic persistently, of which Omicron is currently the predominant variant. However, the impact of vaccination on Omicron remained uncertain. Objective: This study sought to explore the effect of vaccination on patients infected with Omicron. Methods: A retrospective observational cohort was conducted in the largest Fangcang shelter hospital in Shanghai from April 1 to May 30, 2022. The demographics, length of hospital stay, clinical symptoms, the comorbidities and vaccination status were recorded. Clinical outcomes of the vaccinated and non-vaccinated groups were compared and analyzed. Results: Of the 3,119 patients who fulfilled the eligibility criteria and were enrolled in the study, 2,226 (71.4%) patients had received nCoV-19 vaccine while 893 (28.6%) patients had not received it before admission. Patients in the vaccinated group had significantly shorter length of hospital stay than those in the unvaccinated group (15.48 ± 2.708 vs. 15.85 ± 3.102, p < 0.001). More asymptomatic patients were observed in the vaccinated group than the non-vaccinated (70.4 vs. 64.5%, p < 0.001). Further subgroup analysis demonstrated that the older the age, the more significant the difference was (p < 0.005). Conclusions: Vaccination was associated with a significant reduction in the severity of Omicron infection compared with no vaccination. Vaccination appears to make Omicron-infected people with milder symptoms than unvaccinated people. This suggests the potential effectiveness of current vaccines against Omicron.

Compassion satisfaction and compassion fatigue in frontline nurses during the COVID-19 pandemic in Wuhan, China.

AIM: The aim of this study is to investigate the compassion satisfaction and compassion fatigue among Chinese frontline nurses during the COVID-19 pandemic in Wuhan, China and to explore the related factors. BACKGROUND: Frontline nurses undertake a huge nursing workload with a risk of infection, causing great pressure on them and making them face a risk of compassion fatigue during the pandemic. METHODS: A cross-sectional online survey was conducted from 9 March to 15 March 2020. A total of 1582 nurses caring for critical patients with COVID-19 participated. Compassion satisfaction and compassion fatigue (comprising burnout and secondary traumatic stress) were assessed with the Professional Quality of Life Scale, and resilience was measured with the Chinese 10-item Connor-Davidson Resilience Scale. RESULTS: Moderate levels of compassion satisfaction (36.99 ± 6.71), burnout (24.14 ± 5.33) and secondary traumatic stress (24.53 ± 5.24) were experienced by frontline nurses. Resilience and perceived work pressure were the main predictors. CONCLUSIONS: Frontline nurses demonstrated a moderate level of compassion satisfaction and compassion fatigue. IMPLICATIONS FOR NURSING MANAGEMENT: The compassion fatigue of frontline nurses should be considered. Strategies aiming to reduce stress and enhance resilience, such as training about psychological adjustment, developing professional skills and creating a supportive workplace environment, are several options. The trial is not registered. This study is a cross-sectional study, and according to China's clinical trial registration standards, such studies are not required to be registered. So the trial is not registered. However, oral consent was obtained from the ethics committee of the hospital before this study was conducted.

Facile synthesis of N-aryl phenothiazines and phenoxazines via Brønsted acid catalyzed C-H amination of arenes.

N-Aryl phenothiazines and phenoxazines are of significant importance in various disciplines throughout academia and industry. The conventional synthetic strategy for the construction of these structures centers on the transition-metal-catalyzed cross-coupling of aryl halides with phenothiazines or phenoxazines. Here we present an organocatalytic approach to access N-naphthyl phenothiazine and phenoxazine scaffolds through a straightforward C-H amination of arenes as enabled by an azo group. This reaction features operational simplicity, adequate substrate generality and excellent functional group compatibility. Notably, the efficiency of the catalyst could be perfectly preserved after 5 catalytic cycles.

Nitrosobenzene-Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric N-Arylbenzimidazoles.

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2-naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo- and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C-N bond formation while the resulting amine performs the nucleophilic addition to form the second C-N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.

DNase I improves blood-milk barrier integrity and alleviates inflammation induced by Staphylococcus aureus during mastitis.

Mastitis is an inflammation of mammary gland, which directly affects the milk production performance and causes huge economic losses in the dairy industry. During mastitis, the blood-milk barrier (BMB) loses its integrity and aggravates the severity of mastitis. Exogenous DNase I has been exerted protective effects in different model of tissue injury. Here, we designed a study to investigate the effects of DNase I on inflammation and BMB in a mice model of Staphylococcus aureus-induced mastitis. In the model, we found that DNase I treatment significantly alleviated the inflammatory response through decrease of inflammatory cells in mammary alveoli, MPO activity and cytokines in mammary gland. Furthermore, immunofluorescent staining and western blotting demonstrated that exogenous DNase I obviously reduced BMB permeability and changed the expression of tight junction proteins to support the re-establishment of the barrier integrity. Mechanismly, DNase I treatment inhibited NF-κB and enhanced AKT signaling pathways. Therefore, our results indicate that DNase I may be an effective treatment for attenuating mastitis.

Complete mitogenomes document substantial genetic contribution from the Eurasian Steppe into northern Pakistani Indo-Iranian speakers.

To elucidate whether Bronze Age population dispersals from the Eurasian Steppe to South Asia contributed to the gene pool of Indo-Iranian-speaking groups, we analyzed 19,568 mitochondrial DNA (mtDNA) sequences from northern Pakistani and surrounding populations, including 213 newly generated mitochondrial genomes (mitogenomes) from Iranian and Dardic groups, both speakers from the ancient Indo-Iranian branch in northern Pakistan. Our results showed that 23% of mtDNA lineages with west Eurasian origin arose in situ in northern Pakistan since ~5000 years ago (kya), a time depth very close to the documented Indo-European dispersals into South Asia during the Bronze Age. Together with ancient mitogenomes from western Eurasia since the Neolithic, we identified five haplogroups (~8.4% of maternal gene pool) with roots in the Steppe region and subbranches arising (age ~5-2 kya old) in northern Pakistan as genetic legacies of Indo-Iranian speakers. Some of these haplogroups, such as W3a1b that have been found in the ancient samples from the late Bronze Age to the Iron Age period individuals of Swat Valley northern Pakistan, even have sub-lineages (age ~4 kya old) in the southern subcontinent, consistent with the southward spread of Indo-Iranian languages. By showing that substantial genetic components of Indo-Iranian speakers in northern Pakistan can be traced to Bronze Age in the Steppe region, our study suggests a demographic link with the spread of Indo-Iranian languages, and further highlights the corridor role of northern Pakistan in the southward dispersal of Indo-Iranian-speaking groups.

Lysine-specific demethylase 1 (LSD1) serves as an potential epigenetic determinant to regulate inflammatory responses in mastitis.

It is well-established that lysine-specific demethylase 1 (LSD1) is the first identified histone demethylase. Based on its demethylase enzymatic activity, LSD1 plays a pivotal role in vast range of cellular processes and cancers, but the understanding of its effects on inflammation is relatively limited. Using in vivo models of lipopolysaccharide (LPS)-induced inflammation and in vitro assays in mouse mammary epithelial cells, we identified the novel regulatory roles and underlying mechanisms of LSD1 on LPS-induced mastitis. Mammary gland and cells were collected for the following experiments after treatment. Histological changes were determined by H&E. Western blot analysis was used to detect the protein expression. ELISA and real-time PCR were used to evaluate protein and mRNA expression of inflammatory genes. Our results showed that LPS treatment resulted in a significant increase in LSD1 protein expression. GSK-LSD1 is a selective inhibitor of LSD1 enzyme activity. Treatment of mice with GSK-LSD1 inhibited LSD1 activity, reduced inflammatory cells recruitment to tissues and attenuated LPS-induced damage in mammary gland. Mechanistic investigations suggested that LSD1 inhibition led to the increase of histone H3K4me2 and H3K9me2. Furthermore, GSK-LSD1 inhibition of LSD1 further inhibited nuclear factor κ-B (NF-κB) signaling cascades, and subsequently inhibited the production of cytokines (TNF-α, IL-6 and IL-1ß) in mammary gland. Taken together, our data reveal LSD1 as a potential regulator of inflammation and improve our understanding of epigenetic control on inflammation.

High-continuity genome assembly of the jellyfish Chrysaora quinquecirrha.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

[Systematic review of efficacy and safety of Xinmailong Injection in treatment of coronary heart disease complicated with heart failure].

To systematically evaluate the efficacy and safety of Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. Seven databases,namely CNKI, VIP,WanFang,SinoMed,PubMed,EMbase,Cochrane Library, were retrieved by computer for collecting the randomized controlled trials about Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. The literatures were screened out, data was extracted, and the methodological quality evaluation was conducted by 2 researchers independently according to inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis and corresponding description analysis. A total of 19 studies involving 1 922 patients were included, including 967 cases in the trial group and 955 cases in the control group. All the clinical studies showed a low quality. Meta-analysis results showed that Xinmailong Injection combined with conventional treatment could better reduce the BNP level(SMD=-3.34, 95%CI[-4.06,-2.63]) in patients of coronary heart disease complicated with heart failure or NT-proBNP level, improve the cardiac function(RR=1.23,95%CI[1.18,1.29]) and LVEF(MD=6.85,95%CI[4.93,8.76]),increase 6 MWT(MD=24.34, 95%CI[16.05, 32.64]) and VEGF(MD=26.39,95%CI[24.30,28.49]),and decreased LVEDD(MD=-4.06, 95%CI[-6.33,-1.80]). And subgroup analysis suggested that the course of treatment may be related to the increase of LVEF. This study found that Xinmailong Injection for coronary heart disease complicated with heart failure can further alleviate clinical symptoms and relevant indicators, with no serious adverse reaction. However, it still needs the support of well-designed multicenter, double-blind and high-quality clinical trials.

Pd-catalyzed asymmetric Suzuki-Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position.

Pd-catalyzed asymmetric Suzuki-Miyaura couplings of 3-methyl-2-bromophenylamides, 3-methyl-2-bromo-1-nitrobenzene and 1-naphthaleneboronic acids have been successfully developed and the corresponding axially chiral biaryl compounds were obtained in very high yields (up to 99%) with good enantioselectivities (up to 88% ee) under mild conditions. The chiral-bridged biphenyl monophosphine ligands developed by our group exhibit significant superiority to the naphthyl counterpart MOP in both reactivity and enantioselectivity control. The large steric hindrance from π-conjugated ortho-substituents of the bromobenzene substrates and the Pd···O interaction between carbonyl and palladium seem essential to achieve high enantioselectivity.

Xenobiotic transcription factors CncC and maf regulate expression of CYP321A16 and CYP332A1 that mediate chlorpyrifos resistance in Spodoptera exigua.

Insect cytochrome P450 s (P450 s) are associated with the metabolic detoxification of toxic xenobiotics and their constitutive upregulation is often associated with resistance to natural and synthetic toxicants. The P450 s CYP321A16 and CYP332A1 are constitutively overexpressed in an insecticide-resistant strain of beet armyworm, Spodoptera exigua. However, the function and upstream regulation of these two P450 s remain unknown. Here, we investigated the function of CYP321A16 and CYP332A1 in resistance to the organophosphate insecticide, chlorpyrifos and their regulation by the transcription factors CncC and Maf. Transgenic strains of Drosophila melanogaster expressing CYP321A16 or CYP332A1 showed higher levels of tolerance to chlorpyrifos than the control flies with the same genetic background. Furthermore, recombinant CYP321A16 and CYP332A1 proteins metabolized chlorpyrifos. Analysis of the putative promoter sequences of the genes coding for CYP321A16 and CYP332A1 revealed conserved CncC/Maf binding sites. Transfection of luciferase reporter plasmids containing the promoter of CYP450 gene together with CncC and Maf expression plasmids significantly enhanced the activity of the reporter. Promoter truncation identified a site in the promoter of CYP321A16 that is critical for the CncC/Maf binding. These data demonstrate that resistance to chlorpyrifos in S. exigua is conferred by the combined action of CYP321A16 and CYP332A1 and uncovered their regulation by the transcription factors CncC and Maf.

Michael Reaction Inspired Atroposelective Construction of Axially Chiral Biaryls.

The first copper-catalyzed atroposelective Michael-type addition between azonaphthalenes and arylboronic acids for the construction of biaryl atropisomers was established using a novel BINOL-derived phosphoramidite as a chiral ligand. A broad range of atropisomeric biaryls were obtained with good efficiency, and the practicality of this approach was verified by versatile transformations toward axially chiral ligands, catalysts, and other functional atropisomers. This set of catalytic systems successfully inhibited the routine 1,2-addition and promoted the formation of an aryl-aryl chiral axis. Meanwhile, this strategy bypassed the use of an oxidant as well as the harsh conditions normally necessary for transition-metal-mediated arene C-H coupling with arylboronic acids as an arylation counterpart, offering a straightforward alternative to access optically active biaryls.

Chiral Phosphoric Acid Catalyzed Atroposelective C-H Amination of Arenes.

N-arylcarbazole structures are important because of their prevalence in natural products and functional OLED materials. C-H amination of arenes has been widely recognized as the most efficient approach to access these structures. Conventional strategies involving transition-metal catalysts suffer from confined substrate generality and the requirement of exogenous oxidants. Organocatalytic enantioselective C-N chiral axis construction remains elusive. Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N-arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N-arylcarbazoles in good yields with excellent enantiocontrol. This approach not only offers an alternative to metal-catalyzed C-N cross-coupling, but also brings about opportunities for the exploitation of structurally diverse N-aryl atropisomers and OLED materials.

Glycerophosphodiester phosphodiesterase 1 (GDE1) acts as a potential tumor suppressor and is a novel therapeutic target for non-mucin-producing colon adenocarcinoma.

Colon adenocarcinoma (COAD) represents a major public health issue due to its high incidence and mortality. As different histological subtypes of COAD are related to various survival outcomes and different therapies, finding specific targets and treatments for different subtypes is one of the major demands of individual disease therapy. Interestingly, as these different subtypes show distinct metabolic profiles, it may be possible to find specific targets related to histological typing by targeting COAD metabolism. In this study, the differential expression patterns of metabolism-related genes between COAD (n = 289) and adjacent normal tissue (n = 41) were analyzed by one-way ANOVA. We then used weighted gene co-expression network analysis (WGCNA) to further identify metabolism-related gene connections. To determine the critical genes related to COAD metabolism, we obtained 2,114 significantly differentially expressed genes (DEGs) and 12 modules. Among them, we found the hub module to be significantly associated with histological typing, including non-mucin-producing colon adenocarcinoma and mucin-producing colon adenocarcinoma. Combining survival analysis, we identified glycerophosphodiester phosphodiesterase 1 (GDE1) as the most significant gene associated with histological typing and prognosis. This gene displayed significantly lower expression in COAD compared with normal tissues and was significantly correlated with the prognosis of non-mucin-producing colon adenocarcinoma (p = 0.0017). Taken together, our study showed that GDE1 exhibits considerable potential as a novel therapeutic target for non-mucin-producing colon adenocarcinoma.

Weighted Gene Co-Expression Network Analysis Reveals Six Hub Genes Involved in and Tight Junction Function in Pancreatic Adenocarcinoma and their Potential Use in Prognosis.

Background: Pancreatic adenocarcinoma (PAAD) is an aggressive and invasive tumor with poor prognosis. Identifying prognostic biomarkers of PAAD will provide crucial information for developing treatment plans. Methods: In this analysis, a gene-expression dataset, containing RNA-sequencing data recalculated into transcripts per million, was obtained from the UCSC Xena platform. Three thousand nine hundred and seventy six differentially expressed genes were obtained with analysis of variance. Using these data a co-expression network was constructed using weighted gene co-expression network analysis, from which we obtained eight modules. Results: The blue module included 497 genes and demonstrated significant negative correlation with overall survival. Furthermore, pathway analyses demonstrated the involvement of many of these genes in the tight junction pathway, which plays a critical role in PAAD. In addition, we identified six genes in common (i.e., ANXA2 [annexin A2], EPHA2 [erythropoietin-producing hepatocellular class A2], ITGB4 [integrin beta 4], KRT19 [keratin type I cytoskeletal 19], LGALS3 [galectin-3], and S100A14 [S100 calcium binding protein A14]) between the protein-protein interaction and gene co-expression networks that may have critical functions in PAAD. These hub genes were not only highly expressed at the RNA level but also exhibited high expression in the immunohistological data in the Human Protein Atlas Database. Conclusion: Thus, this research clarified the framework of co-expressed gene modules in PAAD and highlighted potential prognostic biomarkers for the clinical diagnosis of PAAD.

Long non-coding RNAs and their potential functions in Ligon-lintless-1 mutant cotton during fiber development.

BACKGROUND: Long non-coding RNAs (LncRNAs) are part of genes, which are not translated into proteins and play a vital role in plant growth and development. Nevertheless, the presence of LncRNAs and how they functions in Ligon-lintless-1 mutant during the early cessation of cotton fiber development are still not well understood. In order to investigate the function of LncRNAs in cotton fiber development, it is necessary and important to identify LncRNAs and their potential roles in fiber cell development. RESULTS: In this work, we identified 18,333 LncRNAs, with the proportion of long intergenic noncoding RNAs (LincRNAs) (91.5%) and anti-sense LncRNAs (8.5%), all transcribed from Ligon-lintless-1 (Li1) and wild-type (WT). Expression differences were detected between Ligon-lintless-1 and wild-type at 0 and 8 DPA (day post anthesis). Pathway analysis and Gene Ontology based on differentially expressed LncRNAs on target genes, indicated fatty acid biosynthesis and fatty acid elongation being integral to lack of fiber in mutant cotton. The result of RNA-seq and RT-qPCR clearly singles out two potential LncRNAs, LNC_001237 and LNC_017085, to be highly down-regulated in the mutant cotton. The two LncRNAs were found to be destabilized or repressed by ghr-miR2950. Both RNA-seq analysis and RT-qPCR results in Ligon-lintless-1 mutant and wild-type may provide strong evidence of LNC_001237, LNC_017085 and ghr-miR2950 being integral molecular elements participating in various pathways of cotton fiber development. CONCLUSION: The results of this study provide fundamental evidence for the better understanding of LncRNAs regulatory role in the molecular pathways governing cotton fiber development. Further research on designing and transforming LncRNAs will help not only in the understanding of their functions but will also in the improvement of fiber quality.

Identification of four hub genes associated with adrenocortical carcinoma progression by WGCNA.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignant cancer in the adrenal cortex with poor prognosis. Though previous research has attempted to elucidate the progression of ACC, its molecular mechanism remains poorly understood. METHODS: Gene transcripts per million (TPM) data were downloaded from the UCSC Xena database, which included ACC (The Cancer Genome Atlas, n = 77) and normal samples (Genotype Tissue Expression, n = 128). We used weighted gene co-expression network analysis to identify gene connections. Overall survival (OS) was determined using the univariate Cox model. A protein-protein interaction (PPI) network was constructed by the search tool for the retrieval of interacting genes. RESULTS: To determine the critical genes involved in ACC progression, we obtained 2,953 significantly differentially expressed genes and nine modules. Among them, the blue module demonstrated significant correlation with the "Stage" of ACC. Enrichment analysis revealed that genes in the blue module were mainly enriched in cell division, cell cycle, and DNA replication. Combined with the PPI and co-expression networks, we identified four hub genes (i.e., TOP2A, TTK, CHEK1, and CENPA) that were highly expressed in ACC and negatively correlated with OS. Thus, these identified genes may play important roles in the progression of ACC and serve as potential biomarkers for future diagnosis.