We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases ...highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.
Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we ...mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.
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► Promoter-centered interactions are complex and widespread ► Higher-order chromatin architectures facilitate active and coordinated transcription ► Interacting promoters possess combinatorial regulatory functions ► Large enhancer-promoter repertoire allows functional annotation of noncoding elements
Higher order chromatin interactions between promoters synergistically promote transcription of clustered genes. These interactions indicate a topological, combinatorial mechanism of transcriptional and also suggest functions for noncoding elements, including those associated with disease, by connecting them to target genes.
Duchenne muscular dystrophy (DMD) is the most common debilitating muscular disorder. Developing a noninvasive measure for monitoring the progression of this disease is critical. The present study ...tested the effectiveness of using ultrasound Nakagami imaging to evaluate the severity of the dystrophic process. A total of 47 participants (40 with DMD and 7 healthy controls) were recruited. Patients were classified into stage 1 (presymptomatic and ambulatory), stage 2 (early nonambulatory), and stage 3 (late nonambulatory). All participants underwent ultrasound examinations on the rectus femoris, tibialis anterior, and gastrocnemius. The results revealed that the ultrasound Nakagami parameter correlated positively with functional severity in the patients with DMD. The median Nakagami parameter of the gastrocnemius muscle increased from 0.50 to 0.85, corresponding to the largest dynamic range between normal and stage 3. The accuracy, sensitivity, and specificity of diagnosing walking function were 85.52%, 76.31%, and 94.73%, respectively. The Nakagami parameter of the rectus femoris and gastrocnemius muscles correlated negatively with the 6-minute walking distance in the ambulatory patients. Therefore, changes in the Nakagami parameter for the gastrocnemius muscle are suitable for monitoring disease progression in ambulatory patients and for predicting ambulation loss. Ultrasound Nakagami imaging shows potential for evaluating patients with DMD.
Calcium sulfate, an injectable and biodegradable bone‐void filler, is widely used in orthopedic surgery. Based on clinical experience, bone‐defect substitutes can also serve as vehicles for the ...delivery of drugs, for example, antibiotics, to prevent or to treat infections such as osteomyelitis. However, antibiotic additions change the characteristics of calcium sulfate cement. Moreover, high‐dose antibiotics may also be toxic to bony tissues. Accordingly, cefazolin at varying weight ratios was added to calcium sulfate samples and characterized in vitro. The results revealed that cefazolin changed the hydration reaction and prolonged the initial setting times of calcium sulfate bone cement. For the crystalline structure identification, X‐ray diffractometer revealed that cefazolin additive resulted in the decrease of peak intensity corresponding to calcium sulfate dihydrate which implying incomplete phase conversion of calcium sulfate hemihydrate. In addition, scanning electron microscope inspection exhibited cefazolin changed the morphology and size of the crystals greatly. A relatively higher amount of cefazolin additive caused a faster degradation and a lower compressive strength of calcium sulfate compared with those of uploaded samples. Furthermore, the extract of cefazolin‐impregnated calcium sulfate impaired cell viability, and caused the death of osteoblast‐like cells. The results of this study revealed that the cefazolin additives prolonged setting time, impaired mechanical strength, accelerated degradation, and caused cytotoxicity of the calcium sulfate bone‐void filler. The aforementioned concerns should be considered during intra‐operative applications.
Lin et al. proposed a mediated semi‐quantum key distribution protocol in 2019. This study shows that Lin et al.'s protocol has a security loophole that could mount to the collective attack to reveal ...some information about the secret key without being detected. To overcome this problem, an improved protocol is proposed and its security is proven.
This study finds a security loophole of the mediated semi‐quantum key distribution (MSQKD) protocol proposed by Lin et al. An improved MSQKD protocol is proposed and its security is proven.
Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation ...signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B
:89A3B
:27A3B
), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.
The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown ...histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human–machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion’s location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.
We report a general copper‐catalyzed cross‐coupling of thiols with aryl halides by using N‐aryl‐N′‐alkyl oxalic diamide (L3) or N,N′‐dialkyl oxalic diamide (L5) as the ligand. Both aryl and alkyl ...thiols can be coupled with unactivated aryl bromides and chlorides to give the desired products in good yields. Furthermore, this system features a broad substrate scope and good tolerance of functional groups. Importantly, the oxalic diamides are stable and can be prepared easily from commercially available and cheap starting materials.
A practical synthetic method for diversified thioethers using oxalic diamides as highly air‐stable ligands through copper catalysis is demonstrated. A variety of aryl‐ and alkyl thiols can be coupled with aryl bromides and chlorides to afford the corresponding thioethers in good yields. This work is the first general method for copper‐catalyzed thioetherification of unactivated aryl chlorides.
Diabetes mellitus complicates pregnancies, leading to diseases in adult life in the offspring. Asymmetric dimethylarginine (ADMA) is increased in diabetes mellitus, kidney disease, and hypertension. ...We tested whether maternal diabetes causes increased ADMA in rats, resulting in kidney disease and hypertension in the adult offspring, and whether these can be prevented by maternal citrulline supplementation. Newborn female and pregnant Sprague-Dawley rats were injected with streptozotocin (STZ), which made up the nSTZ and STZ models, respectively. For the STZ model, 4 groups of male offspring were killed at age 3 months: the control, STZ, and Cit and STZ+Cit (control and STZ rats treated with 0.25% l-citrulline solution, respectively) groups. The nSTZ rats had lower nephron numbers. The renal level of ADMA was higher in the nSTZ rats than in controls. The STZ group developed kidney injury, renal hypertrophy, and elevated blood pressure at the age of 12 weeks. These conditions were found to be associated with increased ADMA levels, decreased nitric oxide (NO) production, and decreased dimethylarginine dimethylaminohydrolase (DDAH) activity in the kidney. In addition, ADMA caused a nephron deficit in cultured rat metanephroi. Maternal citrulline supplementation prevented hypertension and kidney injury, increased the renal DDAH-2 protein level, and restored the levels of ADMA and NO in the STZ+Cit group. Reduced nephron number and increased ADMA contribute to adult kidney disease and hypertension in offspring of mothers with STZ-induced diabetes. Manipulation of the ADMA-NO pathway by citrulline supplementation may be a potential approach to prevent these conditions.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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