d -Glucosamine has been studied for C–N and C–S bond formations via cross-coupling reactions of nitrogen and sulfur nucleophiles with both aryl iodides and bromides. Imidazoles, benzimidazole, ...indole, pyrrolidine and diphenyl disulfide undergo reactions with aryl halides in the presence of 10 mol% d -glucosamine, 10 mol% CuI, and 2 equiv. of Cs 2 CO 3 in DMSO–H 2 O at moderate temperature to give the corresponding products in good to excellent yields. Substrates bearing halides, free amino groups, trifluoromethyl and heterocycles were well tolerated. The high water solubility of the ligand enables easy catalyst removal. In addition, the application of this catalytic system for the synthesis of nilotinib intermediate was also successfully demonstrated using commercially available substrates.
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IJS, KILJ, NUK, UL, UM, UPUK
Increased data rates and very low-latency requirements place strict constraints on the computational complexity of channel decoders in the new 5G communications standard. Practical low-density ...parity-check (LDPC) decoder implementations use message-passing decoding with finite precision, which becomes coarse as complexity is more severely constrained. In turn, performance degrades as the precision becomes more coarse. Recently, the information bottleneck (IB) method was used to design mutual-information-maximizing mappings that replace conventional finite-precision node computations. As a result, the exchanged messages in the IB approach can be represented with a very small number of bits. 5G LDPC codes have the so-called protograph-based raptor-like (PBRL) structure which offers inherent rate-compatibility and excellent performance. This paper extends the IB principle to the flexible class of PBRL LDPC codes as standardized in 5G. The extensions include IB decoder design for puncturing and rate-compatibility. In contrast to existing IB decoder design techniques, the proposed decoder can be used for a large range of code rates with a static set of optimized mappings. The proposed construction approach is evaluated for a typical range of code rates and bit resolutions ranging from 3 bit to 5 bit. Frame error rate simulations show that the proposed scheme always outperforms min-sum decoding algorithms and operates close to double-precision sum-product belief propagation decoding. Furthermore, alternatives to the lookup table implementations of the mutual-information-maximizing mappings are investigated.
MicroRNA （miRNA） biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins （RBPs）. Here, we show that an RBP, QKI5, activates the processing ...of primary miR-124- 1 （pri-124-1） during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCRS. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation. When erythropoiesis proceeds, the concomitant decrease of QKI5 releases Mi- croprocessor from pri-124-1 and reduces mature miR-124 levels to facilitate erythrocyte maturation. Mechanistically, miR-124 targets TALl and c-MYB, two transcription factors involved in normal erythropoiesis. Importantly, this QKI5-mediated regulation also gives rise to a unique miRNA signature, which is required for erythroid differentiation. Taken together, these results demonstrate the pivotal role of QKI5 in primary miRNA processing during erythropoiesis and provide new insights into how a distal element on primary transcripts affects miRNA biogenesis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The new 5G communications standard increases data rates and supports low-latency communication that places constraints on the computational complexity of channel decoders. 5G low-density parity-check ...(LDPC) codes have the so-called protograph-based raptor-like (PBRL) structure which offers inherent rate-compatibility and excellent performance. Practical LDPC decoder implementations use message-passing decoding with finite precision, which becomes coarse as complexity is more severely constrained. Performance degrades as the precision becomes more coarse. Recently, the information bottleneck (IB) method was used to design mutual-information-maximizing lookup tables that replace conventional finite-precision node computations. The IB approach exchanges messages represented by integers with very small bit width. This paper extends the IB principle to the flexible class of PBRL LDPC codes as standardized in 5G. The extensions include puncturing and rate-compatible IB decoder design. As an example of the new approach, a 4-bit information bottleneck decoder is evaluated for PBRL LDPC codes over a typical range of rates. Frame error rate simulations show that the proposed scheme outperforms offset min-sum decoding algorithms and operates very close to double-precision sum-product belief propagation decoding.
In adult mammals, spermatogenesis embodies the complex developmental process from spermatogonial stem cells (SSCs) to spermatozoa. At the top of this developmental hierarchy lie a series of SSC ...subpopulations. Their individual identities as well as the relationships with each other, however, remain largely elusive. Using single-cell analysis and lineage tracing, we discovered both in mice and humans the quiescent adult SSC subpopulation marked specifically by forkhead box protein C2 (FOXC2). All spermatogenic progenies can be derived from FOXC2
+
SSCs and the ablation of FOXC2
+
SSCs led to the depletion of the undifferentiated spermatogonia pool. During germline regeneration, FOXC2
+
SSCs were activated and able to completely restore the process. Germ cell-specific
Foxc2
knockout resulted in an accelerated exhaustion of SSCs and eventually led to male infertility. Furthermore, FOXC2 prompts the expressions of negative regulators of cell cycle thereby ensures the SSCs reside in quiescence. Thus, this work proposes that the quiescent FOXC2
+
SSCs are essential for maintaining the homeostasis and regeneration of spermatogenesis in adult mammals.
Left ventricular (LV) diastolic dysfunction has been demonstrated to be an independent predictor of the future heart failure. Heart failure is one of the severe complications caused by overt ...hyperthyroidism. However, the effects of overt hyperthyroidism on diastolic dysfunction are conflicting, and little is known about the prevalence and risk factors of the diastolic dysfunction in patients with overt hyperthyroidism.
A total of 388 patients with overt hyperthyroidism were included and compared with 388 age- and gender- matched euthyroid control subjects. LV diastolic function was evaluated by traditional and tissue-Doppler echocardiography. Routine clinical medical data and echocardiographic parameters were recorded for analysis.
The prevalence of LV diastolic dysfunction was 35.1% among hyperthyroid patients and significantly higher than control subjects whose prevalence was 25.5% (
= 0.003), and it increased with age and body mass index (BMI) in patients with overt hyperthyroidism. The possible risk factors for LV diastolic dysfunction, such as hypertension, diabetes, decreased estimated glomerular filtration rate (eGFR), and increased level of thyroid hormones weren't associated with LV diastolic dysfunction. However, overweight or obese were significantly associated with LV diastolic dysfunction (OR = 3.024, 95% CI = 1.517-6.027,
= 0.002) compared with normal BMI. When compared with age <40 years old group, 40-50 years old group, 50-60 years old group and age ≥60 years old group were significantly associated with LV diastolic dysfunction, with ORs of 2.976 (95% CI = 1.744-5.019), 12.424 (95% CI = 4.934-31.283), 24.966 (95% CI = 5.975-104.321), respectively.
LV diastolic dysfunction was very common, in particular, in older and overweight or obese patients with overt hyperthyroidism. Additionally, age and BMI were independent risk factors for LV diastolic dysfunction, while the level of thyroid hormones was not. Therefore, besides the LV systolic function, we also need focus on the diastolic function in patients with overt hyperthyroidism in clinical work, especially the older and overweight or obese patients.
The relationships between land use types, water and sediment parameters, and macrobenthos community structures in the upper and middle reaches of the Fenhe River and urbanization intensity were ...studied. Samples were collected from 23 sampling sites. Spearman rank correlation analyses were performed to assess the relationships between the percentages of impervious area or the proportions of four land uses and the water and sediment physicochemical properties, heavy metal and polycyclic aromatic hydrocarbon concentrations in water and sediment, and biological indicators of the macrobenthos communities. Some water parameters (temperature, oxidation-reduction potential, electrical conductivity, total N concentration, total P concentration, ammonia-N concentration, and nitrate-N concentration), some sediment parameters (total N concentration, total P concentration, organic matter content, percentage of particles with diameters <2 mm, and polycyclic aromatic hydrocarbon, Cd, Cr, Cu, Ni Pb, and Zn concentrations), and some macrobenthos parameters (Berger–Parker index and percentages of collectors, tolerant taxa, and Oligochaeta) significantly positively correlated with the percentage of impervious area. Some water parameters (pH and dissolved oxygen concentration), some sediment parameters (percentage of particles with diameters >2 mm), and some macrobenthos parameters (total biomass, total number of taxa, Shannon’s index, N diversity index, and percentages of Ephemeroptera, Plecoptera, Trichoptera, filterers, scrapers, and sensitive taxa) significantly negatively correlated with the percentage of impervious area. The results indicate that intensification of urbanization has strongly affected the water, sediment, and macrobenthos in the Fenhe River watershed.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We have previously reported that rhomboid domain containing 1 (RHBDD1), a mammalian rhomboid protease highly expressed in the testis, can cleave the Bcl-2 protein Bik. In this study, we identified a ...multi-pass transmembrane protein, tumor suppressor activated pathway-6 (TSAP6) as a potential substrate of RHBDD1. RHBDD1 was found to induce the proteolysis of TSAP6 in a dose- and activity-dependent manner. The cleavage of TSAP6 was not restricted to its glycosylated form and occurred in three different regions. In addition, mass spectrometry and mutagenesis analyses both indicated that the major cleavage site laid in the C-terminal of the third transmembrane domain of TSAP6. A somatic cell knock-in approach was used to genetically inactivate the endogenous RHBDD1 in HCT116 and RKO colon cancer cells. Exosome secretion was significantly elevated when RHBDD1 was inactivated in the two cells lines. The increased exosome secretion was verfied through the detection of certain exosomal components, including Tsg101, Tf-R, FasL and Trail. In addition, the elevation of exosome secretion by RHBDD1 inactivation was reduced when TSAP6 was knocked down, indicating that the role of RHBDD1 in regulating exosomal trafficking is very likely to be TSAP6-dependent. We found that the increase in FasL and Trail increased exosome-induced apoptosis in Jurkat cells. Taken together, our findings suggest that RHBDD1 is involved in the regulation of a nonclassical exosomal secretion pathway through the restriction of TSAP6.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is one of the most common malignancies, and it's expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and ...associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism.
Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway.
Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN.
These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Open hemorrhoidectomy is one of the standard procedures for grade IV hemorrhoids. Postsurgical pain is a common problem for patients. We aim to prospectively evaluate potential factors affecting ...postoperative pain among hemorrhoidectomy patients.
An observational study was conducted on 360 patients who had undergone Milligan-Morgan open hemorrhoidectomy. Details of the surgery and baseline information were recorded. Preoperative anxiety and depression were analyzed via the self-rating anxiety scale 20 (SAS-20) and self-rating depression scales 20 (SDS-20), respectively. Postoperative pain score was performed daily after surgery until the patient was discharged. The numerical pain score was evaluated by the visual analogue scale (VAS). The association between preoperative psychological states (anxiety or depression) and postoperative pain was analyzed using a generalized additive mixed model.
A total of 340 patients eventually provided complete data and were included in our study. The average age was 43.3 ± 14.4 years, and 62.1% of patients were women. In total, 14.9% of patients had presurgical anxiety and 47.1% had presurgical depression. Postsurgical pain reached a peak point 1-2 days after surgery and went down to a very low level around 4-5 days after surgery. More excision of hemorrhoids could lead to more pain experience after surgery. Presurgical depression was associated with postsurgical pain. Patients who had presurgical depression had higher pain scores after surgery (2.3 ± 1.9 vs. 3.3 ± 1.9,
= 0.025).
Preoperative depression and the amount of excisional hemorrhoids are positively related to postsurgical pain.
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