Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up.

Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Clinical utility of keratin 14 expression measurement in reflecting the tumor properties and prognosis in patients with renal cell carcinoma: a study with long-term follow-up.

PURPOSE: Keratin 14 (KRT14) is hypothesized to be involved in the pathogenesis of renal cell carcinoma (RCC) based on its tumorigenic role in various cancers and its relationship with the prognosis of other urinary system malignancies. This study aimed to evaluate the correlation of KRT14 with tumor properties and prognosis in RCC patients. METHODS: Data from 180 RCC patients who received tumor resection were retrospectively reviewed. The KRT14 was assessed by immunohistochemistry (IHC) staining in tumor tissues and non-tumor tissues. RESULTS: KRT14 was insufficiently expressed in both tumor and non-tumor tissues, with median (interquartile range) IHC score of 2.0 (0.0-3.4) and 1.0 (0.0-2.0), respectively. While it was relatively higher in tumor versus non-tumor tissues (P < 0.001). Besides, tumor KRT14 was positively correlated with the pathological grade (P = 0.038), tumor size (P = 0.012), T stage (P = 0.006), and TNM stage (P = 0.018). Interestingly, tumor KRT14 high predicted shorter accumulating recurrence-free survival (RFS) (P = 0.003) and accumulating overall survival (OS) (P = 0.001), which was further verified by the multivariate Cox's regression analysis (both P < 0.05). Furthermore, tumor KRT14 high estimated shorter RFS and OS from the Gene Expression Profiling Interactive Analysis and Human Protein ATLAS databases (all P < 0.05). Subgroup analyses indicated that the correlation of tumor KRT14 with accumulating RFS and accumulating OS was more pronounced in RCC patients with better physical status (such as age < 65 years and better eastern cooperative oncology group performance status) and higher tumor stages (such as higher pathological grade). CONCLUSION: High KRT14 in tumor tissue could reflect an advanced tumor features and unsatisfying survival in RCC patients.

Homogeneous Vacancies-Enhanced Orbital Hybridization for Selective and Efficient CO2-to-CO Electrocatalysis.

Crafting vacancies offers an efficient route to upgrade the selectivity and productivity of nanomaterials for CO2 electroreduction. However, defective nanoelectrocatalysts bear catalytically active vacancies mostly on their surface, with the rest of the interior atoms adiaphorous for CO2-to-product conversion. Herein, taking nanosilver as a prototype, we arouse the catalytic ability of internal atoms by creating homogeneous vacancies realized via electrochemical reconstruction of silver halides. The homogeneous vacancies-rich nanosilver, compared to the surface vacancies-dominated counterpart, features a more positive d-band center to trigger an intensified hybridization of the Ag_d orbital with the C_P orbital of the *COOH intermediate, leading to an accelerated CO2-to-CO transformation. These structural and electronic merits allow a large-area (9 cm-2) electrode to generate nearly pure CO with a CO/H2 Faradaic efficiency ratio of 6932 at an applied current of 7.5 A. These findings highlight the potential of designing new-type defects in realizing the industrialization of electrocatalytic CO2 reduction.

N-nitrosamines in Qingdao dried aquatic products and dietary risk assessment.

N-nitrosamines are human carcinogens commonly present in dried aquatic products. A method of gas chromatography - mass spectrometry combined with steam distillation was developed for the determination of 9 N-nitrosamines in dried aquatic products in Qingdao, China, with which 300 samples of fish, squid, shrimp and sea cucumber collected from Qingdao were analysed. A health risk assessment was conducted based on determined levels of N-nitrosamines by using estimated daily intake and slope factors. Results showed that fish products was the category with the highest content of N-nitrosamines, whereas squid and shrimp products were the categories with the highest frequency of presence of N-nitrosamines. The average estimated cancer risk of N-nitrosamines in dried aquatic products in Qingdao ranged from 3.57 × 10-8 to 3.53 × 10-5. Nitrosodimethylamine, N-Nitrosodiethylamine and N-Nitrosodibutylamine could be considered to pose a potential cancer risk to residents in Qingdao.

Machine learning-based optimal design of groundwater pollution monitoring network.

It is an important task of environmental management to design groundwater pollution monitoring network (GPMN) to find out the occurrence of pollution events and carry out remediation in time. However, there are many uncertain factors in the process of designing GPMN, which affect the GPMN design result. In the process of applying the Monte Carlo method for uncertainty analysis, groundwater numerical simulation model may be utilized thousands of times, which results in a huge computational load. In order to overcome this disadvantage, a machine learning (ML)-based surrogate model is constructed with Kriging method, to replace the computational simulation model under uncertainty of pollution sources and parameters. The 0-1 integer programming optimization model is constructed to maximally cover serious polluted area to detect the occurrence of groundwater pollution in time. The optimal design framework of GPMN based on proposed ML algorithm was applied in a domestic landfill in Baicheng City, China. The results showed that the ML-based surrogate model has a great fitness with the groundwater solute transport simulation model. The optimal results of GPMN indicated that monitoring wells should be mainly placed at the downstream of the leachate equalization basin. If more wells are allowed to be placed, part of wells could be placed at the downstream of the landfill. Moreover, the area where the pollution plumes of landfill site meet that of leachate equalization basin should be set as the key monitoring objective. Verification and comparison showed that the pollutant detection rate of the optimal layout scheme is far higher than random layout schemes, which proves the reliability of the ML-based optimal design scheme of GPMN.

Atypical magnetic resonance imaging features and differential diagnosis of hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. We aimed to summarize and analyze the atypical magnetic resonance imaging (MRI) features of HCC to improve its diagnostic accuracy. METHODS: We retrospectively analyzed MRI data for 66 patients with HCC with atypical MRI features confirmed by operation and pathology. RESULTS: Twelve patients had high signals and 18 patients had significant decreases in opposed phase signals in T1WI plain scans. Nine patients had high signals and six patients had large cystic lesions in apparent diffusion coefficient images. Dynamic enhancement showed progressive enhancement in 15 patients, ring enhancement in three, irregular patchy enhancement in three, 'nodule-in-nodule' enhancement in six, delayed central patchy enhancement in six, delayed central 'star-like aristate scars' (T2WI revealed high signal intensity) in 21, and poor blood supply in three patients. CONCLUSIONS: MRI can make a clear diagnosis of typical HCC, and atypical cases can also be distinguished from other tumors or tumor-like lesions by MRI. The analysis of atypical signs may improve the diagnostic accuracy of MRI for HCC.

Threonine ADP-Ribosylation of Ubiquitin by a Bacterial Effector Family Blocks Host Ubiquitination.

Ubiquitination is essential for numerous eukaryotic cellular processes. Here, we show that the type III effector CteC from Chromobacterium violaceum functions as an adenosine diphosphate (ADP)-ribosyltransferase that specifically modifies ubiquitin via threonine ADP-ribosylation on residue T66. The covalent modification prevents the transfer of ubiquitin from ubiquitin-activating enzyme E1 to ubiquitin-conjugating enzyme E2, which inhibits subsequent ubiquitin activation by E2 and E3 enzymes in the ubiquitination cascade and leads to the shutdown of polyubiquitin synthesis in host cells. This unique modification also causes dysfunction of polyubiquitin chains in cells, thereby blocking host ubiquitin signaling. The disruption of host ubiquitination by CteC plays a crucial role in C. violaceum colonization in mice during infection. CteC represents a family of effector proteins in pathogens of hosts from different kingdoms. All the members of this family specifically ADP-ribosylate ubiquitin. The action of CteC reveals a new mechanism for interfering with host ubiquitination by pathogens.

Approach to Cushing's syndrome in pregnancy: two cases of Cushing's syndrome in pregnancy and a review of the literature.

Cushing's syndrome (CS) rarely occurs during pregnancy. The primary aim of this article is to propose a therapeutic approach to CS in pregnancy. Here, we present two cases of CS in pregnancy and a literature review. This article proposes the early diagnostic points, especially the clinical approach to this medical condition, mainly for pregnant women without a previous diagnosis of CS. More importantly, we present therapeutic strategies for CS during pregnancy, especially glucocorticoid replacement for perioperative, postoperative, and perinatal periods in pregnant women with CS in order to minimize complications for both mother and fetus. At the same time, we also assess the anxiety status of patients. This article summarizes the approach to CS in pregnancy, not only with a physiological assessment but with a psychological assessment as well.

Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.

It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.

[Role of calcineurin-nuclear factor of activated T cells signaling pathway in myoblast apoptosis induced by cyclic tensile strain].

OBJECTIVE: This study investigated the role and mechanism of calcineurin (CaN)-nuclear factor of activated T cells (NFAT) pathway in the myoblast apoptosis induced by cyclic tensile strain. METHODS: Myoblasts were cultured using an in vitro-mechanical stimulation model and imposed with tension for different hours with a multi-channel cell stress loading system. Cyclosporine (CsA) was used as CaN inhibitor to clarify the role of CaN in the apoptosis induced by cyclic stress. Hochest 33258 staining and flow cytometry detection were performed to detect the apoptotic cells. Real-time polymerase chain reaction was conducted to detect the mRNA expression of CaN and NFAT. Protein levels of NFAT3 were evaluated by Western blot. RESULTS: The apoptosis rate increased with the extension of loading time. The mRNA expression of the CaN subunits, CnA and CnB, and the protein levels of NFAT3 also increased. When the myoblasts were incubated with CsA, the apoptosis rate decreased, the mRNA expression of CnA and NFAT3 significantly decreased, and the NFAT3 protein expression levels became significantly lower than those of the groups without CsA. CONCLUSION: Continuous cyclic tensile stress can induce myoblast apoptosis. The CaN-NFAT signaling pathway may be involved in the cyclic stretch-induced apoptosis of myoblasts.