Lithium metal is the “holy grail” anode for next‐generation high‐energy rechargeable batteries due to its high capacity and lowest redox potential among all reported anodes. However, the practical ...application of lithium metal batteries (LMBs) is hindered by safety concerns arising from uncontrollable Li dendrite growth and infinite volume change during the lithium plating and stripping process. The formation of stable solid electrolyte interphase (SEI) and the construction of robust 3D porous current collectors are effective approaches to overcoming the challenges of Li metal anode and promoting the practical application of LMBs. In this review, four strategies in structure and electrolyte design for high‐performance Li metal anode, including surface coating, porous current collector, liquid electrolyte, and solid‐state electrolyte are summarized. The challenges, opportunities, perspectives on future directions, and outlook for practical applications of Li metal anode, are also discussed.
This review summarizes recent advances in stabilizing Li metal anodes via four effective strategies, including surface coating, porous current collector, liquid electrolyte, and solid‐state electrolyte. The aim is to provide a thorough and comprehensive overview of the recent development and applications of Li metal anodes to guide the future study of high‐safety, high‐stability, and high‐energy Li metal batteries.
Background
Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are ...reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity.
Objectives
This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model.
Methods
The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 μg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 μg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days.
Results
The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 μg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC.
Conclusion
APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.
Solid malignancies are associated with the development of Pneumocystis jirovecii pneumonia (PJP). This study aimed to evaluate the risk factors for PJP among patients with lung cancer. This ...retrospective case-control study compared patients who had lung cancer with PJP (n = 112) or without PJP (n = 336) matched according to age, sex, histopathology, and stage. PJP definition was based on (i) positive PCR or direct immunofluorescence results for pneumocystis, (ii) clinical symptoms and radiological abnormalities that were consistent with a pneumonic process, and (iii) received targeted PJP treatment. The development of PJP was associated with radiotherapy (RTx), concurrent chemoradiotherapy (CCRTx), lymphopenia, and prolonged high-dose steroid therapy (20 mg of prednisolone equivalent per day for ≥3 weeks). Multivariate analysis revealed independent associations with prolonged high-dose steroid therapy (odds ratio OR: 1.96, 95% confidence interval CI: 1.06-3.63; p = 0.032) and CCRTx (OR: 2.09, 95% CI: 1.27-3.43; p = 0.004). Steroid use was frequently related to RTx pneumonitis or esophagitis (29 patients, 43.3%). Prolonged high-dose steroid therapy and CCRTx were risk factors for PJP development among patients with lung cancer. As these patients had a poor prognosis, clinicians should consider PJP prophylaxis for high-risk patients with lung cancer.
The role of the gut microbiome in the development of renal stone diseases has not been well characterized. This study focused on the taxonomic and functional profiles of gut microbiomes according to ...the prevalence and incidence of nephrolithiasis. Stool samples from 915 Korean adults were collected at baseline. Participants were followed for a median of 4.0 years. We evaluated the biodiversity of the gut microbiota and taxonomic profiles associated with nephrolithiasis status, using 16S rRNA gene sequencing. Nephrolithiasis status was categorized into three groups: control (no-stone at both baseline and follow-up visits), incidental nephrolithiasis, and prevalent nephrolithiasis. Compared to the control and incidental nephrolithiasis, the prevalent nephrolithiasis showed a reduced evenness in alpha diversity. Nephrolithiasis was associated with a reduced abundance of some key taxa involved in short-chain fatty acid production. Moreover, the abundance of Bifidobacterium, which possess oxalate-degrading ability, was higher in the control. Conversely, there was no significant difference in the bacterial composition between the incidental and prevalent nephrolithiasis. In our study with repeated nephrolithiasis measurements, prevalent renal stones were associated with an altered gut microbiota composition compared to the control. Besides the known oxalate degradation pathway, other functional pathways inferred in this study require further investigation.
Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor ...cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C‐X‐C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti‐PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.
Cellular senescence can either support or inhibit cancer progression. In colorectal cancer, senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12 and enhanced M2 macrophage differentiation by CSF1. Neutralization of CXCL12/CSF1 increases the effect of anti‐PD1 antibody. These findings suggest that senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack.
Sepsis, including severe sepsis and septic shock, is a major cause of morbidity and mortality. Albumin and C-reactive protein (CRP) are considered as good diagnostic markers for sepsis. Thus, initial ...CRP and albumin levels were combined to ascertain their value as an independent predictor of 180-day mortality in patients with severe sepsis and septic shock.
We conducted a retrospective cohort study involving 670 patients (>18 years old) who were admitted to the emergency department and who had received a standardized resuscitation algorithm (early goal-directed therapy) for severe sepsis and septic shock, from November 2007 to February 2013, at a tertiary hospital in Seoul, Korea. The outcome measured was 180-day all-cause mortality. A multivariate Cox proportional hazard model was used to identify the independent risk factors for mortality. A receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the CRP/albumin ratio at admission.
The 180-day mortality was 28.35% (190/670). Based on the multivariate Cox proportional hazard analysis, age, the CRP/albumin ratio at admission (adjusted HR 1.06, 95% CI 1.03-1.10, p<0.001), lactate level at admission (adjusted HR 1.10, 95% CI 1.05-1.14, p<0.001), and the Sequential Organ Failure Assessment (SOFA) score at admission (adjusted HR 1.12, 95% CI 1.07-1.18, p<0.001) were independent predictors of 180-day mortality. The area under the curve of CRP alone and the CRP/albumin ratio at admission for 180-day mortality were 0.5620 (P<0.001) and 0.6211 (P<0.001), respectively.
The CRP/albumin ratio was an independent predictor of mortality in patients with severe sepsis or septic shock.
Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This ...study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.
Very-long-chain fatty acids (VLCFAs) are essential precursors of cuticular waxes and aliphatic suberins in roots. The first committed step in VLCFA biosynthesis is condensation of C₂ units to an acyl ...CoA by 3-ketoacyl CoA synthase (KCS). In this study, two KCS genes, KCS20 and KCS2/DAISY, that showed higher expression in stem epidermal peels than in stems were isolated. The relative expression of KCS20 and KCS2/DAISY transcripts was compared among various Arabidopsis organs or tissues and under various stress conditions, including osmotic stress. Although the cuticular waxes were not significantly altered in the kcs20 and kcs2/daisy-1 single mutants, the kcs20 kcs2/daisy-1 double mutant had a glossy green appearance due to a significant reduction of the amount of epicuticular wax crystals on the stems and siliques. Complete loss of KCS20 and KCS2/DAISY decreased the total wax content in stems and leaves by 20% and 15%, respectively, and an increase of 10-34% was observed in transgenic leaves that over-expressed KCS20 or KCS2/DAISY. The stem wax phenotype of the double mutant was rescued by expression of KSC20. In addition, the kcs20 kcs2/daisy-1 roots exhibited growth retardation and abnormal lamellation of the suberin layer in the endodermis. When compared with the single mutants, the roots of kcs20 kcs2/daisy-1 double mutantss exhibited significant reduction of C₂₂ and C₂₄ VLCFA derivatives but accumulation of C₂₀ VLCFA derivatives in aliphatic suberin. Taken together, these findings indicate that KCS20 and KCS2/DAISY are functionally redundant in the two-carbon elongation to C₂₂ VLCFA that is required for cuticular wax and root suberin biosynthesis. However, their expression is differentially controlled under osmotic stress conditions.
We report the construction and analysis of 4,836 heterozygous diploid deletion mutants covering 98.4% of the fission yeast genome providing a tool for studying eukaryotic biology. Comprehensive gene ...dispensability comparisons with budding yeast--the only other eukaryote for which a comprehensive knockout library exists--revealed that 83% of single-copy orthologs in the two yeasts had conserved dispensability. Gene dispensability differed for certain pathways between the two yeasts, including mitochondrial translation and cell cycle checkpoint control. We show that fission yeast has more essential genes than budding yeast and that essential genes are more likely than nonessential genes to be present in a single copy, to be broadly conserved and to contain introns. Growth fitness analyses determined sets of haploinsufficient and haploproficient genes for fission yeast, and comparisons with budding yeast identified specific ribosomal proteins and RNA polymerase subunits, which may act more generally to regulate eukaryotic cell growth.
Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia‐induced autophagy in human dental pulp cells (HDPCs) is unclear. The present ...study aimed to investigate the role of autophagy in hypoxia‐induced apoptosis of HDPCs. Cobalt chloride (CoCl2) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis‐related signal molecules, cleaved caspase‐3 and PARP levels, were enhanced in CoCl2‐treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule‐associated protein 1 light chain 3 (LC3)‐II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles. Autophagy inhibition by 3 methyladenine (3MA) or RNA interference of LC3B resulted in increased levels of cleaved PARP and caspase‐3, and the release of cytochrome c from mitochondria into cytosol in the CoCl2‐treated HDPCs. However, autophagy activation by rapamycin enhanced the p62 and LC3‐II levels, whereas it reduced PARP and caspase‐3 cleavage induced by CoCl2. These results revealed that CoCl2‐activated autophagy showed survival effects against CoCl2‐induced apoptosis in the HDPCs. CoCl2 upregulated HIF‐1α and decreased the phosphorylation of mTOR/p70S6K. HIF‐1α inhibitor, YC‐1 decreased p62 and LC3‐II levels, whereas it augmented PARP and caspase‐3 cleavage in response to CoCl2. Also, YC‐1 enhanced the phosphorylation of mTOR and p70S6K suppressed by CoCl2, demonstrating that CoCl2‐induced autophagy via mTOR/p70S6K is mediated by HIF‐1α. Taken together, these finding suggest that CoCl2‐induced autophagy mediated by the mTOR/p70S6K pathway plays a protective role against hypoxic stress in HDPCs.
CoCl2‐induced autophagy plays a protective role against cytotoxicity under hypoxic stress. In addition, Autophagy process is mediated by the suppression of the mTOR/p70S6K pathway regulating by HIF1 in CoCl2‐treated HDPCs.
PDF
