Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to ...evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.
Summary
The Orchidaceae is a diverse and ecologically important plant family. Approximately 69% of all orchid species are epiphytes, which provide diverse microhabitats for many small animals and ...fungi in the canopy of tropical rainforests. Moreover, many orchids are of economic importance as food flavourings or ornamental plants. Phalaenopsis aphrodite, an epiphytic orchid, is a major breeding parent of many commercial orchid hybrids. We provide a high‐quality chromosome‐scale assembly of the P. aphrodite genome. The total length of all scaffolds is 1025.1 Mb, with N50 scaffold size of 19.7 Mb. A total of 28 902 protein‐coding genes were identified. We constructed an orchid genetic linkage map, and then anchored and ordered the genomic scaffolds along the linkage groups. We also established a high‐resolution pachytene karyotype of P. aphrodite and completed the assignment of linkage groups to the 19 chromosomes using fluorescence in situ hybridization. We identified an expansion in the epiphytic orchid lineage of FRS5‐like subclade associated with adaptations to the life in the canopy. Phylogenetic analysis further provides new insights into the orchid lineage‐specific duplications of MADS‐box genes, which might have contributed to the variation in labellum and pollinium morphology and its accessory structure. To our knowledge, this is the first orchid genome to be integrated with a SNP‐based genetic linkage map and validated by physical mapping. The genome and genetic map not only offer unprecedented resources for increasing breeding efficiency in horticultural orchids but also provide an important foundation for future studies in adaptation genomics of epiphytes.
Precision positioning is very important for automatic assembly and inspection in the electronic manufacturing process. In this paper, we propose a fast image alignment method using the ...expectation-maximization (E-M) technique. The proposed algorithm is especially applied to positioning and defect inspection of printed circuit boards (PCBs). It can well handle deformed or incomplete object shapes with translation, rotation, and scale changes. The Canny edge detector is used to generate the edge maps of images. The E-step of the E-M procedure finds mutual edge points in both compared images by assigning weights to individual edge points. The mutual edge points give larger weights, while the foreign edge points in two images have smaller weights. The M-step then calculates the geometric transformation parameters using the weighted edge points in individual images. For an edge point in one image, a fast spiral search is proposed to find its corresponding edge point with the shortest distance in the other image. The spiral search is carried out by a predetermined lookup table, and no computation is involved in the search process. The weight of each edge point is inversely proportional to the neighboring distance. Experimental results indicate that the proposed E-M positioning method can achieve a translation error less than 1 pixel and a rotation error smaller than 1° for PCB positioning.
Background
Laparoscopic cholecystectomy (LC) with associated procedures and endoscopic retrograde cholangiopancreatography (ERCP) have been the standard treatments for both common and rare biliary ...diseases. Mirizzi syndrome (MS) is a rare and complex biliary condition. We report our experience with MS treatment and investigate the value of laparoscopic procedures and ERCP in patient management.
Methods
From 2004 to 2017, 100 consecutive patients with MS were diagnosed by ERCP and underwent surgery in a referral center. Sixty patients were treated with intended LC, and 40 patients were treated with open cholecystectomy (OC). The clinical manifestations, ERCP and associated procedures, surgical procedures, and postoperative outcomes were investigated.
Results
The surgical mortality rate was 1%, while the surgical morbidity rate was 15%. The patients treated with intended LC suffered from less morbidity (5%). The percentage of postoperative residual biliary stones was 32% (n = 32), and only three patients underwent re‐operation (laparotomy) for stone removal. The laparotomy conversion rate in the intended LC group was 16.7% (10/60). The length of hospitalization for the patients with successful LC was significantly shorter than that for the patients with conversion and intended OC. Csendes classification was a risk factor for conversion from LC to OC (type I vs types II to V, P < .0001).
Conclusions
A combination of a laparoscopic procedure and ERCP may provide therapeutic benefits for patients with MS.
Highlight
Yeh and colleagues report that a combination of perioperative endoscopic retrograde cholangiopancreatography and laparoscopic surgery can provide clinical benefits for patients with Mirizzi syndrome with significantly less surgical morbidity and shorter hospital stay. Both preoperative diagnosis and postoperative residual biliary stones can be managed by endoscopic retrograde cholangiopancreatography with satisfactory outcomes.
Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis. Compared to spatial signals, little is known about temporal signals and the mechanisms integrating the ...two. In the Caenorhabditis elegans hermaphrodite, the stereotyped migration pattern of two somatic distal tip cells (DTCs) is responsible for shaping the gonad. Guidance receptor UNC-5 is necessary for the dorsalward migration of DTCs. We found that BLMP-1, similar to the mammalian zinc finger transcription repressor Blimp-1/PRDI-BF1, prevents precocious dorsalward turning by inhibiting precocious unc-5 transcription and is only expressed in DTCs before they make the dorsalward turn. Constitutive expression of blmp-1 when BLMP-1 would normally disappear delays unc-5 transcription and causes turn retardation, demonstrating the functional significance of blmp-1 down-regulation. Correct timing of BLMP-1 down-regulation is redundantly regulated by heterochronic genes daf-12, lin-29, and dre-1, which regulate the temporal fates of various tissues. DAF-12, a steroid hormone receptor, and LIN-29, a zinc finger transcription factor, repress blmp-1 transcription, while DRE-1, the F-Box protein of an SCF ubiquitin ligase complex, binds to BLMP-1 and promotes its degradation. We have therefore identified a gene circuit that integrates the temporal and spatial signals and coordinates with overall development of the organism to direct cell migration during organogenesis. The tumor suppressor gene product FBXO11 (human DRE-1 ortholog) also binds to PRDI-BF1 in human cell cultures. Our data suggest evolutionary conservation of these interactions and underscore the importance of DRE-1/FBXO11-mediated BLMP-1/PRDI-BF1 degradation in cellular state transitions during metazoan development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy ...of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection.
A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated.
Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI 45-74%) and 78% (95% CI 69-86%). The diagnostic odds ratio was estimated at 5.47 (95% CI 2.86-10.46). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI 26-83%) and 75% (95% CI 68-82%), and those for CRP were 67% (95% CI 35-88%) and 73% (95% CI 69-77%). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93).
While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Modification of proteins with polyubiquitin chains is a key regulatory mechanism to control cellular behavior and alterations in the ubiquitin system are linked to many diseases. Linear (M1-linked) ...polyubiquitin chains play pivotal roles in several cellular signaling pathways mediating immune and inflammatory responses and apoptotic cell death. These chains are formed by the linear ubiquitin chain assembly complex (LUBAC), a multiprotein E3 ligase that consists of 3 subunits, HOIP, HOIL-1L, and SHARPIN. Herein, we describe the discovery of inhibitors targeting the active site cysteine of the catalytic subunit HOIP using fragment-based covalent ligand screening. We report the synthesis of a diverse library of electrophilic fragments and demonstrate an integrated use of protein LC–MS, biochemical ubiquitination assays, chemical synthesis, and protein crystallography to enable the first structure-based development of covalent inhibitors for an RBR E3 ligase. Furthermore, using cell-based assays and chemoproteomics, we demonstrate that these compounds effectively penetrate mammalian cells to label and inhibit HOIP and NF-κB activation, making them suitable hits for the development of selective probes to study LUBAC biology. Our results illustrate the power of fragment-based covalent ligand screening to discover lead compounds for challenging targets, which holds promise to be a general approach for the development of cell-permeable inhibitors of thioester-forming E3 ubiquitin ligases.
Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of ...patients who had received curative-intent liver resection.
A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed.
Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients.
Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the ...relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.
The eight stacked Ge 0.9 Sn 0.1 ultrathin bodies down to 3 nm with high <inline-formula> <tex-math notation="LaTeX">{I}_{\text {ON}}/I_{\text {OFF}} </tex-math></inline-formula> and eight stacked Ge ...0.9 Sn 0.1 thick nanosheets with high <inline-formula> <tex-math notation="LaTeX">{I}_{\text {ON}} </tex-math></inline-formula> per stack are demonstrated. For the eight stacked Ge 0.9 Sn 0.1 ultrathin bodies, the 50 epilayers, including Ge 0.9 Sn 0.1 channels, double Ge 0.97 Sn 0.03 /Ge (8 nm/3 nm) caps, heavily B-doped (~2E21 cm −3 ) Ge sacrificial layers (SLs), and undoped Ge buffer were epitaxially grown to reach high inter-channel uniformity with the co-optimization of epitaxy and radical-based highly selective isotropic dry etching (HiSIDE). The thin double Ge 0.97 Sn 0.03 caps can provide sufficient etching selectivity and stabilize the channel to prevent the channels from bending and buckling. The neutral radicals can isotropically etch the Ge 0.97 Sn 0.03 /Ge caps, Ge:B SLs, and Ge buffer to form the highly uniform eight stacked Ge 0.9 Sn 0.1 ultrathin bodies. The record <inline-formula> <tex-math notation="LaTeX">{I}_{\text {ON}}/{I}_{\text {OFF}} </tex-math></inline-formula> of 1.4 <inline-formula> <tex-math notation="LaTeX">\times 10^{{7}} </tex-math></inline-formula> at <inline-formula> <tex-math notation="LaTeX">{V}_{\text {DS}} \,\,=\,\,-0.05 </tex-math></inline-formula> V is achieved among GeSn 3-D pFETs due to the quantum confinement. For the eight stacked Ge 0.9 Sn 0.1 thick nanosheets, the record <inline-formula> <tex-math notation="LaTeX">{I}_{\text {ON}} </tex-math></inline-formula> of 92 <inline-formula> <tex-math notation="LaTeX">\mu \text{A} </tex-math></inline-formula> per stack at <inline-formula> <tex-math notation="LaTeX">{V}_{\text {OV}} = {V}_{\text {DS}} = -0.5 </tex-math></inline-formula> V is achieved among GeSn 3-D pFETs. Thick nanosheets can provide higher mobility than ultrathin bodies due to the reduced surface roughness scattering.
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