Microtia, Branchial Cleft Fistula, and Tetralogy of Fallot: A Possible Association.

When searching over associations between congenital ear abnormalities, especially microtia and affiliated deformities like cleft lip or palate and congenital heart diseases, some clinical analysis and genetic theories are found. A 10-year-old boy sent to the plastic surgery hospital was puzzled by a congenital anterior auricular fistula with fluid trace for more than 9 years. The preoperative diagnoses were branchial cleft fistula and congenital left ear deformity with postoperation of TOF. By browsing over studies on genetic concerns and clinical performance, it may be attributed to a possible association between microtia, branchial cleft fistula, and tetralogy of Fallot, though whose fundamental mechanisms remain concerned.

Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer.

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.

Preparation of pH-Responsive Alginate-Chitosan Microspheres for L-Valine Loading and Their Effects on the A40926 Production.

The glycopeptide A40926 biosynthesized by Nonomuraea gerenzanensis is a precursor of the second generation glycopeptide antibiotic dalbavancin. The skeleton of this glycopeptide consists of seven amino acids and is biosynthesized by the NRPS gene module. L-valine, a branched amino acid, is also a significant precursor for A40926 production. This study details the use of pH-responsive alginate-chitosan microspheres loaded with L-valine prepared by internal emulsification gelation. The effects of process and formulation variables on microsphere size, loading capacity, and encapsulation efficiency were investigated. Then, effects on A40926 production by the pH-responsive microspheres were evaluated in a 10-L fermenter. Results demonstrated that use of the pH-responsive microspheres could improve A40926 yield from 465 to 602 mg L-1 in a 10-L scale fermenter.

Highly efficient genome editing in N. gerenzanensis using an inducible CRISPR/Cas9-RecA system.

OBJECTIVE: To develop an inducible CRISPR/Cas9-Recombinase A (RecA) system to manipulate genes in Nonomuraea gerenzanensis effectively. RESULTS: Compared with traditional homologous recombination, the inducible CRISPR/Cas9 system achieved 68.8% editing efficiency, whereas, with both the inducible Cas9 and the overexpressed RecA, the efficiency of the combined genome editing system reached 100%. The dbv23-deleted mutant obtained by the inducible CRISPR/Cas9-RecA system was confirmed to produce more A40926 with an approximate yield of 200 mg L-1 than that of around 150 mg L-1 produced by the wild-type strain. CONCLUSIONS: This inducible CRISPR/Cas9-RecA system was successfully constructed and can be utilized as an efficient genome editing tool for Actinomyces able to shorten editing time simultaneously.

Comparing public and private emergency departments in China: Early evidence from a national healthcare quality survey.

The number of private healthcare facilities has rapidly increased since the progressive open market policies, which began in the 1980s; however, little is known about the development of private emergency departments (EDs). This cross-sectional study was part of the National Control Information System (NCIS) project, which collects data annually from hospitals across China. Emergency services data were extracted and included location, infrastructure, human resources, beds, and number of patients; 4529 hospitals across 31 provinces in mainland China were eventually included, consisting of 988 private and 3541 public EDs. Evidence shows that most private EDs are located in central China, where local economies are relatively developed. Most private EDs (91.6%) are found in secondary hospitals but have significantly fewer beds and smaller workforces compared with public EDs. An imbalance of emergency medical resources was observed across China, and this disparity becomes even more profound in rural hospitals. These findings may initiate collaborative, public-private partnerships in emergency health services provision and suggest there is a need to offer tax breaks to incentivize investors, but further research is required. We may also need to rethink health insurance policies, which could enable more equitable access to private emergency care. Future planning and health policies must be based upon the strongest available evidence, if we are to address imbalanced health services distribution and growing demand.

Overweight and Obesity in Young Adulthood and the Risk of Stroke: a Meta-analysis.

BACKGROUND: A systematic review assessing the association between overweight and obesity in young adulthood and stroke risk is lacking. Therefore, we conducted a meta-analysis to evaluate the association between overweight and obesity in young adulthood and stroke risk. METHODS: We systematically searched PubMed and Embase databases for related studies of human subjects in the English language. Two investigators independently selected original studies in a 2-step process. Fixed- and random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Subgroup analyses were also performed. RESULTS: Eight studies met the inclusion criteria. The pooled adjusted RR of stroke was 1.36 (95% CI: 1.28-1.44) for overweight in young adulthood and 1.81 (95% CI: 1.45-2.25) for obesity in young adulthood. In subgroup analyses, overweight and obesity in young adulthood increased the risk of stroke in most groups, except for the group of stroke subtype. For ischemic stroke, the adjusted RR was 1.40 (95% CI: 1.24-1.58) for overweight in young adulthood and 1.78 (95% CI: 1.003-3.16) for obesity in young adulthood, whereas adjusted RR for hemorrhagic stroke was 1.25 (95% CI: .83-1.90) for overweight in young adulthood and 1.80 (95% CI: .97-3.35) for obesity in young adulthood. CONCLUSIONS: Overweight and obesity in young adulthood are associated with an increased risk of stroke, probably, independent of other cardiovascular risk factors. The risk effect gradually increases with increasing body weight.

[Application of ultrasound counter currentextraction in patent of traditional Chinese medicine].

The patent information of ultrasound countercurrent extraction used in traditional Chinese medicine was analyzed in this paper by the samples from Derwent World Patent Database (DWPI) and the Chinese Patent Abstracts Database (CNABS). The application of ultrasound countercurrent was discussed with the patent applicant,the amount of the annual distribution, and the pharmaceutical raw materials and other aspects. While the technical parameters published in the patent was deeply analyzed, such as material crushing, extraction solvent, extraction time and temperature, extraction equipment and ultrasonic frequency. Thought above research, various technical parameters of ultrasound countercurrent extraction used in traditional Chinese was summarize. The analysis conclusion of the paper can be used in discovering the technical advantages, optimizing extraction conditions, and providing a reference to extraction technological innovation of traditional Chinese medicine.

Stem cell factor combined with matrix proteins regulates the attachment and migration of melanocyte precursors of human hair follicles in vitro.

In conjunction with matrix proteins, stem cell factor (SCF) plays an important role in the migration of melanocyte precursors (MPs) derived from the mouse embryo. However, no studies have demonstrated an effect of SCF on human follicular MPs migration in vitro. In this report, first we demonstrate the immature state of the follicular MPs. Then cell attachment rate was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Standard 48-well chemotaxis chambers were used for a transfilter migration assay. F-actin was labeled by rhodamine-conjugated phalloidin, and then organization of the actin cytoskeleton was observed by confocal microscope. In the results, we directly show that MPs adhere more strongly to fibronectin (FN), laminin (LN) and type IV collagen (CIV) than to the negative control. SCF decreased the adhesion of MPs to FN and CIV. A chemotaxis analysis showed that FN and CIV have chemotactic effects on MPs. FN showed an obvious increase in chemotactic effects on MPs with SCF treatment comparing with the control group, but there were no significant changes in the levels of chemotaxis with CIV and LN when the cells were treated with SCF. SCF was chemotactic to MPs, and the presence of FN caused a statistically significant increase in MPs migration at various concentrations of SCF. Furthermore, we showed that SCF, in combination with FN, could induce an apparent increase in actin stress fiber formation in MPs. Our results indicate that SCF, in combination with matrix proteins and in particular with FN, regulates the movement of MPs by both altering cell attachment and increasing cell chemotaxis.

Diagnostic value of BinaxNOW antigen card for Severe Acute Respiratory Syndrome Coronavirus 2.

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.

Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing.

The interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ. The labelled adenines and the endogenous methylated CpG sites are simultaneously detected on individual nanopore reads using a hidden Markov model, which is implemented in the nanoHiMe software package. We demonstrate the utility, robustness and sensitivity of nanoHiMe-seq by jointly profiling DNA methylation and histone modifications at low coverage depths, concurrently determining phased patterns of DNA methylation and histone modifications, and probing the intrinsic connectivity between these epigenetic marks across the genome.

[Corrigendum] Transforming growth factor­ß1 induces fibrosis in rat meningeal mesothelial cells via the p38 signaling pathway.

Subsequently to the publication of this paper, while performing a careful re­examination of the scientific integrity of the data included in their publications, the authors have realized that they inadvertently used the incorrect western blotting images in Fig. 2B of this article, However, still having access to their original data, the authors were able to reassemble Fig. 2 correctly, and the corrected version of this figure is shown below. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors thank the Editor of Molecular Medicine Reports for granting them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published on Molecular Medicine Reports 14: 1709­1713, 2016; DOI: 10.3892/mmr.2016.5411].

Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro.

The developmental potential of oocytes decreases with time after ovulation in vivo or in vitro. Epitalon is a synthetic short peptide made of four amino acids (alanine, glutamic acid, aspartic acid, and glycine), based on a natural peptide called epithalamion extracted from the pineal gland. It is a potent antioxidant, comparable to melatonin, that may confer longevity benefits. The current study aims to test the protective effects of Epitalon on the quality of post-ovulatory aging oocytes. Epitalon at 0.1mM was added to the culture medium, and the quality of oocytes was evaluated at 6h, 12h, and 24h of culture. We found that 0.1mM Epitalon reduced intracellular reactive oxygen species. Epitalon treatment significantly decreased frequency of spindle defects and abnormal distribution of cortical granules during aging for 12h and 24h, while increased mitochondrial membrane potential and DNA copy number of mitochondria, thus decreasing apoptosis of oocytes by 24h of in vitro aging. Our results suggest that Epitalon can delay the aging process of oocytes in vitro via modulating mitochondrial activity and ROS levels.

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

Rare leptin in non-alcoholic fatty liver cirrhosis: A case report.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)-related cirrhosis is mainly caused by NAFLD by causing inflammation which leads to fibrosis. The role of leptin in NAFLD-related cirrhosis has been rarely reported. CASE SUMMARY: This study presents the case of a 65-year-old male patient who was referred to The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China, for diagnosis and treatment for liver cirrhosis. Initially, the cause of liver cirrhosis was unknown. After radiology, laboratory examination, pathological results and analysis of the patient's signs and symptoms, the case was finally diagnosed with final NAFLD-related cirrhosis. Although this study reports a single case, the findings might expand the understanding of leptin's role in NAFLD-related cirrhosis and might provide a basis for the clinical diagnostic criteria, pathological features and treatment of NAFLD-related cirrhosis. CONCLUSION: Although the occurrence of marasmus NAFLD-related cirrhosis is rare, it needs to be distinguished from other liver diseases, including viral hepatitis, drug-induced liver disease, Wilson's disease and autoimmune liver disease. Aggressive treatment is needed to prevent the progression of NAFLD-related cirrhosis.

Improved A40926 production from Nonomuraea gerenzanensis using the promoter engineering and the co-expression of crucial genes.

The semi-synthetic antibiotic dalbavancin is clinically used in the treatment of severe infections caused by multidrug resistant Gram-positive pathogens. So far, fermentation has still been the only approach for the production of A40926 in the industrial scale, which is used as the precursor of dalbavancin and biosynthesized by the rare actinomycete Nonomuraea gerenzanensis (N. gerenzanensis). Therefore, it is particularly essential and necessary to enhance the yield of A40926 continually. In this paper, we firstly assessed the activity of 6 heterologous promoters using the enhanced green fluorescence protein (EGFP) reporter system in N. gerenzanensis. Furthermore, the strongest constitutive promoter gapdh confirmed in this study was applied to separately overexpress the total of ten dbv genes involved in the A40926 biosynthesis. PCR and RT-qPCR were successively carried out to verify the mutant and the overexpression of dbv genes. As a consequence, the overexpression of dbv3 and dbv20 genes both increased the A40926 production remarkably. Based on the above consequences, a mutant strain named N320 laboring the co-expression of dbv3 and dbv20 was constructed. The results of fermentation showed that the N320 strain enhanced the yield of A40926 from 163 mg/L to 272 mg/L.

Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24.

AIM: The aim of this study was to creatively implement a novel chemo-gene-virotherapeutic strategy and further strengthen the antitumor effect in cancer cells by the combined use of ZD55-IL-24 and cisplatin. METHODS: ZD55-IL-24 is an oncolytic adenovirus that harbors interleukin 24 (IL-24), which has a strong antitumor effect and was identified and evaluated by PCR, RT-PCR, and Western blot analysis. Enhancement of cancer cell death using a combination of ZD55-IL-24 and cisplatin was assessed in several cancer cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cytopathic effect (CPE) assay. Apoptosis induction by treatment with ZD55-IL-24 and/or cisplatin was detected in BEL7404 and SMMC7721 by morphological evaluation, apoptotic cell staining, and flow cytometry analysis. In addition, negative effects on normal cells were evaluated in the L-02 cell line using the MTT assay, the CPE assay, morphological evaluation, apoptotic cell staining, and flow cytometry analysis. RESULTS: The combination of ZD55-IL-24 and cisplatin, which is superior to ZD55-IL-24, cisplatin, and ZD55-EGFP, as well as ZD55-EGFP plus cisplatin, resulted in a significantly increased effect. Most importantly, conjugation of ZD55-IL-24 with cisplatin had toxic effects equal to that of cisplatin and did not have overlapping toxicities in normal cells. CONCLUSION: This study showed that ZD55-IL-24 conjugated with cisplatin exhibited a remarkably increased cytotoxic and apoptosis-inducing effect in cancer cells and significantly reduced the toxicity in normal cells through the use of a reduced dose.

[Near-infrared reflectance spectroscopy analytic models established for the crude protein and crude fiber of alfalfa property].

Near-infrared reflectance spectroscopy (NIRS) calibrations of crude protein and crude fiber in 152 alfalfa samples were developed by means of partial least-squares (PLS) regression. Different interval wavelengths of 1, 2 and 5 nm and two kinds of samples (crude and fine) were set to collect spectral data and establish calibration respectively. The accuracy and repeatability of calibrations were verified so as to compare superiority and inferiority. Results showed that the best validation result is the calibration by 2 nm interval wavelength and fine sample, and the correlation coefficients of calibration (R2) were 0.97 and 0.94 for crude protein and crude fiber, and the SECV of these parameters were 0.42 and 0.78 respectively. The coefficients of determination for validation (R2(val)) were 0.96 and 0.92, and the SEP of these parameters were 0.43 and 0.79. The experiment showed that it is feasible to evaluate the major quality traits of alfalfa by NIRS. All together, it provided a new model to verify the crude protein and fiber compositions of alfalfa.

Activation of ß-adrenoceptor facilitates active avoidance learning through enhancement of glutamate levels in the hippocampal dentate gyrus.

Long-term potentiation (LTP) is widely accepted as the best studied model for neurophysiological mechanisms that could underlie learning and memory formation. Despite a number of studies indicating that ß-adrenoceptors in the hippocampal dentate gyrus (DG) is involved in the modulation of learning and memory as well as LTP, few studies have used glutamate release as a visual indicator in awake animals to explore the role of ß-adrenoceptors in learning-dependent LTP. Therefore, in the present study, the effects of propranolol (an antagonist of ß-adrenoceptor) and isoproterenol (an agonist of ß-adrenoceptor) on extracellular concentrations of glutamate and amplitudes of field excitatory postsynaptic potential were measured in the DG region during active avoidance learning in freely moving conscious rats. In the control group, the glutamate level in the DG was significantly increased during the acquisition of active avoidance behavior and returned to basal level following extinction training. In propranolol group, antagonism of ß-adrenoceptors in the DG significantly reduced the change in glutamate level, and the acquisition of the active avoidance behavior was significantly inhibited. In contrast, the change in glutamate level was significantly enhanced by isoproterenol, and the acquisition of the active avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in glutamate level were accompanied by corresponding changes in field excitatory postsynaptic potential amplitude and active avoidance behavior. Our results suggest that activation of ß-adrenoceptors in the hippocampal DG facilitates active avoidance learning by modulations of glutamate level and synaptic efficiency in rats.

Microplastics releasing from personal care and cosmetic products in China.

Microplastics (MPs) have become a major global issue; their release from various products affects the aquatic environment, especially marine ecosystems. As a primary source of MPs, personal care and cosmetics products (PCCPs) containing MPs contribute to this environmental risk. We visited several supermarket chains in Beijing, China to identify PCCPs containing MPs. Overall, 7.1% of facial cleansers contained MPs, with an average weight of 25.04±10.69mgMP/g and average size of 313±130µm; whereas, 2.2% of shower gel products contained an average weight of 17.80±7.50mgMPs/g with an average size of 422±185µm. The majority of MPs were made of polyethylene, based on Raman and Fourier transform-infrared spectra analyses, while only a few were made of walnut shells and carbon particles. Finally, estimated 39tons MPs were released into the environment based on PCCPs use in China based on available data.

A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3.

Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted and reticulate pigmentation of the flexures. The gene, or even the chromosomal location, for RPAF has not yet been identified. In this study, one Chinese family with RPAF was identified and subjected to a genomewide screen for linkage analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination fraction theta=0.00). Haplotype analyses indicated that the disease gene is located within the 6.8 cM region distal to D17S1798. It is the first locus identified for RPAF. This study provides a map location for isolation of a disease gene causing RPAF.