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•A composite electrode of Li and Ag-coated Cu powder (Li/Cu@Ag) is prepared.•Ag is coated via galvanic replacement and Li/Cu@Ag has a free-standing form.•Li plating occurs ...preferentially on Ag-coated Cu powder due to the lithiophilic Ag.•Li-dendrite growth and dead Li formation are greatly inhibited on Li/Cu@Ag.•As a result, Li/Cu@Ag shows low nucleation overpotential and stable cycling.
In this study, we fabricate a composite electrode of lithium metal powder (LMP) and Ag-coated Cu powder (Li/Cu@Ag) for lithium metal battery simply by Ag-coating on Cu powder through galvanic replacement and pelletizing their mixture. Due to the structure of the composite electrode and high surface area of LMP, local current density can be reduced. The lithiophilic Ag particles on the Cu powder lower lithium nucleation overpotential and enable uniform lithium plating. The Li/Cu@Ag electrode shows superior electrochemical performance with this synergetic effect and the reason for the improvement has been investigated. Specifically, a long lifespan of 400 h at a current density of 1 mA/cm2 is achieved with a Li||Li symmetric cell when using the Li/Cu@Ag electrode in a corrosive carbonate electrolyte. In addition, LiFePO4||Li/Cu@Ag cell shows excellent cycling stability and high-capacity retention (over 74 % after 400 cycles at 3C).
Background
Since its introduction, robotic surgery has been applied actively in several fields of minimally invasive surgery, and its use in the field of colorectal surgery is also increasing. In the ...studies to date, feasibility and safety have been the main focus, but the economics involved are important to examine. We compared the economics of robotic surgery with those of laparoscopic surgery for rectal cancer.
Material and methods
We analyzed the clinical characteristics, total hospital charges, payments, operating room costs, and hospital profits for patients who underwent robotic and laparoscopic resection of rectal cancer at Korea University Anam Hospital between July 2007 and August 2010.
Results
From July 2007 and August 2010, 154 robot-assisted and 150 laparoscopic rectal surgeries were performed. The patient demographics were similar in the two groups with the exception of tumor location (6.7 vs 8.7 cm distal to the anal verge;
p
= 0.043), preoperative chemoradiotherapy (22.7 vs 8 %;
p
= 0.001), and operative time (285.2 vs 219.7 min;
p
= 0.018). Postoperative course and complications were also similar in the two groups. The total hospital charges in U.S. dollars ($14,647 vs $9,978;
p
= 0.001) and payments made by patients ($11,540 vs $3,956;
p
< 0.001) were significantly higher in the robotic group. Hospital profit was significantly lower in the robotic group than in the laparoscopic group ($689 vs $1,671;
p
< 0.001).
Conclusions
Robot-assisted surgery is more expensive than laparoscopic surgery for rectal cancer. Considering that robotic surgery can be applied more easily for low-lying cancers, the cost-effectiveness of robotic rectal cancer surgery should be assessed based on oncologic outcomes and functional results from future studies.
T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which ...suggests that inhibiting the exhaustion progress will improve the efficacy of immunotherapy. Thus, regulatory factors promoting T cell exhaustion could serve as potential targets for delaying the process and improving ICI efficacy.
We analyzed the single-cell transcriptome data derived from human melanoma and non-small cell lung cancer (NSCLC) samples and classified the tumor-infiltrating (TI) CD8
T cell population based on PDCD1 (PD-1) levels, i.e., PDCD1-high and PDCD1-low cells. Additionally, we identified differentially expressed genes as candidate factors regulating intra-tumoral T cell exhaustion. The co-expression of candidate genes with immune checkpoint (IC) molecules in the TI CD8
T cells was confirmed by single-cell trajectory and flow cytometry analyses. The loss-of-function effect of the candidate regulator was examined by a cell-based knockdown assay. The clinical effect of the candidate regulator was evaluated based on the overall survival and anti-PD-1 responses.
We retrieved many known factors for regulating T cell exhaustion among the differentially expressed genes between PDCD1-high and PDCD1-low subsets of the TI CD8
T cells in human melanoma and NSCLC. TOX was the only transcription factor (TF) predicted in both tumor types. TOX levels tend to increase as CD8
T cells become more exhausted. Flow cytometry analysis revealed a correlation between TOX expression and severity of intra-tumoral T cell exhaustion. TOX knockdown in the human TI CD8
T cells resulted in downregulation of PD-1, TIM-3, TIGIT, and CTLA-4, which suggests that TOX promotes intra-tumoral T cell exhaustion by upregulating IC proteins in cancer. Finally, the TOX level in the TI T cells was found to be highly predictive of overall survival and anti-PD-1 efficacy in melanoma and NSCLC.
We predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8
T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally, TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.
Background Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular ...hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. Methods Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. Results Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e′ ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e′ ratio and LVMI after adjustment for multiple confounding factors. Conclusions Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical ...conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary ...neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl
to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl
caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl
. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.
Insects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we ...comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (± 97.7) OTUs per sample. The insect gut microbiota were dominated by Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences) and Firmicutes (20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities.
Donor death is the most serious complication of living liver donation but is reported rarely. We investigated the actual mortality of living liver donors (LLDs) compared with matched control groups ...based on analysis of the Korean National Health Insurance Services (NHIS) database.
This cohort study included 12,372 LLDs who donated a liver graft between 2002 and 2018, and were registered in the Korean Network for Organ Sharing. They were compared to 3 matched control groups selected from the Korean NHIS and comprising a total of 123,710 individuals: healthy population (Group I); general population without comorbidities (Group II); and general population with comorbidities (Group III).
In this population, 78.5% of living liver donors were 20-39 years old, and 64.7% of all donors were male. Eighty-nine donors (0.7%) in the LLD group died (68 males and 21 females), a mortality rate (/1,000 person-years) of 0.91 (0.74-1.12). Mortality rate ratio and the adjusted hazard ratio of the LLD group was 2.03 (1.61-2.55) and 1.71 (1.31-2.25) compared to Control Group I, 0.75 (0.60-0.93) and 0.63 (0.49-0.82) compared to Control Group II, and 0.58 (0.46-0.71) and 0.49 (0.39-0.60) compared to Control Group III. LLD group, depression, and lower income were risk factors for adjusted mortality. The incidence of liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the LLD group was significantly higher than in Control Group I.
Outcomes of the LLD group were worse than those of the matched healthy control group despite the small number of deaths and medical morbidities in this group. LLDs should receive careful medical attention for an extended period after donation.
The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation.
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•The incidence of mortality and mortality rate (1,000 person/year) of the LLD group was 0.7% and 0.91.•LLDs had twice the all-cause mortality of matched healthy controls despite there being few deaths.•LLD group, depression, and lower income were risk factors for adjusted mortality.•Incidence of diseases affecting multiple organ systems was significantly higher in the LLD group compared to healthy controls.•LLDs should receive careful medical and psychiatric attention for an extended period after donation.
An attempt was made to control the surface charge of colloidal silica nanoparticles with 20 nm and 100 nm diameters. Untreated silica nanoparticles were determined to be highly negatively charged and ...have stable hydrodynamic sizes in a wide pH range. To change the surface to a positively charged form, various coating agents, such as amine containing molecules, multivalent metal cation, or amino acids, were used to treat the colloidal silica nanoparticles. Molecules with chelating amine sites were determined to have high affinity with the silica surface to make agglomerations or gel-like networks. Amino acid coatings resulted in relatively stable silica colloids with a modified surface charge. Three amino acid moiety coatings (L-serine, L-histidine, and L-arginine) exhibited surface charge modifying efficacy of L-histidine > L-arginine > L-serine and hydrodynamic size preservation efficacy of L-serine > L-arginine > L-histidine. The time dependent change in L-arginine coated colloidal silica was investigated by measuring the pattern of the backscattered light in a Turbiscan™. The results indicated that both the 20 nm and 100 nm L-arginine coated silica samples were fairly stable in terms of colloidal homogeneity, showing only slight coalescence and sedimentation.
We set out to determine the usability of serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and retinal parameters by using optical coherence tomography (OCT) as ...reliable biomarkers of the progression of oxaliplatin-induced peripheral neuropathy (OIPN). Forty-three patients scheduled to undergo oxaliplatin-based chemotherapy at the National Cancer Center of Korea between June 2018 and October 2019 were prospectively assessed at baseline, 3 months, and 6 months of chemotherapy. Patients were assessed on clinical scales and underwent OCT, sNfL, and sGFAP level measurement at each follow-up visit. By applying the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), OIPN was classified as grade 1 in 12 (28%) patients, grade 2 in 25 (58%), and grade 3 in 5 (12%) at 6 months of chemotherapy. sNfL levels increased during oxaliplatin administration, while serial sGFAP levels or retinal parameters did not change. Patients with grade-3 OIPN showed significantly higher mean sNfL levels than patients with grade 0-2 OIPN at 6 months of treatment. At 4-6 months after completion of chemotherapy, sNfL levels were significantly reduced compared to the levels at 6 months of chemotherapy. Monitoring of sNfL during chemotherapy can indicate ongoing neuroaxonal injury and the severity of OIPN.
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