Bone Mineral Density Around the Knee Joint: Correlation With Central Bone Mineral Density and Associated Factors.

INTRODUCTION: The aims of this study were to (1) assess the bone mineral density (BMD) around the knee joint, (2) determine the correlation between central and knee BMDs, and (3) investigate the factors associated with BMD around the knee joint in patients with knee osteoarthritis (OA). METHODOLOGY: This cross-sectional study included 122 patients who underwent total knee arthroplasty. Central and knee dual-energy X-ray absorptiometry was performed preoperatively. BMD at 6 regions of interest (ROIs) around the knee joint were measured, and their correlations with central BMD were determined using Spearman's correlation analysis. Lower limb alignment, severity of OA, body mass index (BMI), preoperative functional and pain scores were assessed to elucidate the factors associated with knee BMD using linear regression analysis. RESULTS: Around the knee joint, BMD was the lowest at the distal femoral metaphysis and lateral tibial condyle. Knee BMD was significantly correlated with central BMD. However, the correlation coefficients varied by the ROI. Additionally, multivariate analysis revealed different associations with respect to the regions around the knee joint. Varus alignment of the lower limb was associated with increased BMD of the medial condyles and decreased BMD of lateral condyles. High grade OA was a protective factor; it was associated with increased BMD at the lateral condyles of the femur and tibia. Higher BMI was an independent protective factor in all ROIs around the knee joint except the lateral femoral condyles. Lower functional level was not associated with decreased BMD, whereas a higher pain score was significantly associated with lower BMD at the proximal tibial metaphysis. CONCLUSIONS: Knee BMD was significantly correlated with central BMD. However, the correlations varied with the regions around the knee joint probably due to their independent association with the alignment of the lower limb, severity of OA, BMI, and preoperative pain level.

Two-stage approach to total knee arthroplasty using colistin-loaded articulating cement spacer for vancomycin-resistant Pseudomonas aeruginosa infection in an arthritic knee.

BACKGROUND: A two-stage approach to total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement spacer is an option for an infected arthritic knee. Vancomycin combined with broad-spectrum antibiotics can be used to make an antibiotic-impregnated articulating cement spacer. Causative organisms are sometimes not confirmed before surgery. Joint infections of multidrug-resistant organisms are increasing. Therefore, routine combinations of antibiotics may not be effective. METHODS AND RESULTS: We present a case of a patient who developed vancomycin-resistant Pseudomonas aeruginosa infection in an arthritic knee. A 71-year-old man was initially diagnosed with pyogenic arthritis caused by Staphylococcus aureus. He underwent arthroscopic debridement elsewhere. However, the infection persisted. He was referred to our hospital, and we performed a two-stage TKA using a vancomycin-based antibiotic-impregnated articulating cement spacer. Vancomycin-resistant P. aeruginosa was identified after surgery. Intravenous colistin was added. However, this failed, either because vancomycin was not effective against P. aeruginosa, or because insufficient systemic colistin due to colistin-induced acute kidney injury. Therefore, debridement was repeated, and colistin-loaded cement spacer was inserted. The spacer delivered high concentrations of colistin to the infected joint with decreased systemic effects. Thus, less systemic colistin was used. The infection was controlled without recurrent acute kidney injury. One year after surgery, conversion to TKA was successfully performed. CONCLUSION: A two-stage approach to TKA using a colistin-loaded articulating cement spacer can be used for an arthritic knee infected by vancomycin-resistant P. aeruginosa. Furthermore, local administration of colistin using a cement spacer can reduce the systemic side effects of colistin.

Incidence of deep vein thrombosis before and after total knee arthroplasty without pharmacologic prophylaxis: a 128-row multidetector CT indirect venography study.

BACKGROUND: We sought to document the incidences of deep vein thrombosis (DVT) before and after total knee arthroplasty (TKA). In addition, we aimed to explor whether routine preoperative DVT evaluation was useful to establish DVT treatment strategies after TKA. Finally, we wanted to evaluate whether the incidences of DVT differed between patients undergoing unilateral and staged bilateral TKA within the same hospitalization period. METHODS: The retrospective study included 153 consecutive patients (253 knees) with osteoarthritis who underwent primary TKA. After surgery, mechanical compression devices (only) were used for DVT prophylaxis. DVT status before and after TKA was determined via 128-row, multidetector, computed tomography/indirect venography. RESULTS: Overall, the preoperative DVT incidence was 2.6% per patient and 1.6% per knee. All preoperative DVTs were distal in nature and asymptomatic. After TKA, newly developed thrombi were evident in various calf veins, without propagation of any pre-existing thrombi. Postoperatively, the overall incidences of DVT were 69.9% per patient and 58.5% per knee. The DVT incidences were 66% per patient and 69.8% per knee in the unilateral TKA group. In contrast, the incidences were 72% per patient and 55.5% per knee in the staged bilateral TKA group. There was one case of symptomatic distal (unilateral TKA; 0.65% per patient and 0.4% per knee) and proximal DVT (bilateral TKA; 0.65% per patient and 0.4% per knee), respectively. CONCLUSIONS: The incidence of symptomatic DVT was low in Asian patients treated with mechanical compression devices alone, although substantial portion of patients had DVT after surgery. Routine preoperative DVT evaluation is probably not necessary; preoperative DVT was rare and of limited clinical relevance. Furthermore, staged bilateral TKA during a single period of hospitalization does not increase the incidence of DVT.

Medial Tibial Periprosthetic Bone Resorption and Its Effect on Clinical Outcomes After Total Knee Arthroplasty: Cobalt-Chromium vs Titanium Implants.

BACKGROUND: Recently, concerns arose over the medial tibial bone resorption of a novel cobalt-chromium implant. This study aimed at investigating the effects of tibial component material, design, and patient factors on periprosthetic bone resorption and at determining its association with clinical outcomes after total knee arthroplasty (TKA). METHODS: A total of 462 primary TKAs using 5 types of implants were included. To evaluate tibial periprosthetic bone resorption, we assessed radiolucent lines and change in bone mineral density at the medial tibial condyle (BMDMT). Factors related to bone resorption were assessed using regression analysis. Clinical outcomes were also evaluated with respect to periprosthetic bone resorption. RESULTS: Compared to titanium implants, cobalt-chromium implants showed a higher incidence of complete radiolucent lines (23.1% vs 7.9% at 2 years post-TKA) and a greater degree of BMDMT reduction. However, there was no significant difference between the implants made of the same material. Increased medial tibial bone resorption was associated with male sex, osteoporosis, larger preoperative varus deformity, longer follow-up period, and lower body mass index. The periprosthetic bone resorption was not associated with clinical outcomes including changes in range of motion and Western Ontario and McMaster Universities Osteoarthritis Index score. Furthermore, no cases warranted additional surgery. CONCLUSION: Periprosthetic bone resorption was associated with implant material but not with implant design. Moreover, patient factors were related to the medial tibial bone resorption post-TKA. However, the periprosthetic bone resorption was not associated with short-term clinical outcomes. We contend that researchers should incorporate integrative considerations when developing and assessing novel implants.

Subacute inhalation toxicity study of synthetic amorphous silica nanoparticles in Sprague-Dawley rats.

Synthetic amorphous silica nanoparticles (SiNPs) are one of the most applied nanomaterials and are widely used in a broad variety of industrial and biomedical fields. However, no recent long-term inhalation studies evaluating the toxicity of SiNPs are available and results of acute studies are limited. Thus, we conducted a subacute inhalation toxicity study of SiNPs in Sprague-Dawley rats using a nose-only inhalation system. Rats were separated into four groups and target concentrations selected in this study were as follows: control (fresh air), low- (0.407 ± 0.066 mg/m3), middle- (1.439 ± 0.177 mg/m3) and high-concentration group (5.386 ± 0.729 mg/m3), respectively. The rats were exposed to SiNPs for four consecutive weeks (6 hr/day, 5 days/week) except for control group of rats which received filtered fresh air. After 28-days of inhalation exposure to SiNPs, rats were sacrificed after recovery periods of one, seven and 28 days. Although there were minimal toxic changes such as temporary decrease of body weight after exposure, increased levels of red blood cells (RBCs) and hemoglobin (Hb) concentration, the lung histopathological findings and inflammatory markers in bronchoalveolar lavage (BAL) fluid including polymorphonuclear (PMN) leukocyte, lactate dehydrogenase (LDH), albumin and protein did not show significant changes at any recovery period. The results of this study suggest that the subacute inhalation of SiNPs had no toxic effects on the lung of rats at the concentrations and selected time points used in this study.

Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons.

Hes6 is a member of the hairy-enhancer of split homolog (Hes) family of transcription factors and interacts with other Hes family genes. During development, Hes genes are expressed in neural stem cells and progenitor cells. However, the role of Hes6 in adult hippocampal neurogenesis remains unclear. We therefore investigated the effects of Hes6 on adult hippocampal neurogenesis, by comparing Hes6 knockout and wild-type mice. To this end, we immunostained for markers of neural stem cells and progenitor cells (nestin), proliferating cells (Ki67), post-mitotic neuroblasts and immature neurons (doublecortin, DCX), mature neuronal cells (NeuN), and astrocyte (S100ß). We also injected 5-bromo-2'-deoxyuridine (BrdU) to trace the fate of mitotic cells. Nestin- and Ki67-positive proliferating cells did now show any significant differences between wild and knockout groups. Hes6 knockout negatively affects neuroblast differentiation based on DCX immunohistochemistry. On the contrary, the ratio of the BrdU and NeuN double-positive cells did not show any significance, even though it was slightly higher in the knockout group. These results suggest that Hes6 is involved in the regulation of neuroblast differentiation during adult neurogenesis, but does not influence integration into mature neurons.

Increased Cell Proliferations and Neurogenesis in the Hippocampal Dentate Gyrus of Ahnak Deficient Mice.

Expression of the giant protein Ahnak has been reported in endothelial cells of the blood brain barrier and in non-neuronal cells including myelinating Schwann cells. However, the function of Ahnak in neurogenesis has not been determined. In the present study, we report for the first time the effects of Ahnak on adult hippocampal neurogenesis using Ahnak(-/-) mice. Proliferating cells were labeled with BrdU for a 30-day period before sacrifice. In Ahnak(-/-) mice, the incorporation of BrdU with NeuN (Neuronal Nuclei) increased significantly in both the subgranular zone and the granular cell layer of the dentate gyrus. In addition, Ahnak(-/-) mice displayed increased Doublecortin-immunoreactive neuroblasts compared with wild-type controls. Taken together, Ahnak deficiency plays a positive role for hippocampal neurogenesis in adult mice because proliferating cells were increased in Ahnak(-/-) mice and advanced to mature neurons. These findings suggest that Ahnak might be involved in modulating the differentiation of newly generated cells into neuronal or non-neuronal cells.

Size-dependent clearance of gold nanoparticles from lungs of Sprague-Dawley rats after short-term inhalation exposure.

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.8 ± 2.42 µg/m(3), and to large gold nanoparticles (105 nm in diameter on average) at an exposure concentration of 13.7 ± 1.32 µg/m(3). The experimental animals were exposed to the gold nanoparticles and the control animals to fresh air for 5 days (6 h/day), followed by a recovery period of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any toxic response to the gold nanoparticles. Despite the difference in size, both small and large gold nanoparticles deposited mainly in rat lungs. Their biodistribution from the lungs to secondary target organs was significantly higher with the small compared to the large gold nanoparticles. While the large gold nanoparticles were only found in the blood, the small gold nanoparticles were detected in the liver, spleen, brain, testes, and blood. In addition, the elimination half-life of the small gold nanoparticles from the lungs was significantly shorter than that of the large gold nanoparticles. The present data may, therefore, suggest that the smaller gold nanoparticles are able to translocate from the lungs, the primary exposure organ to extrapulmonary organs at a faster rate than the larger gold nanoparticles and thus confirming previous observations reported in the literature.

Serum levels of IL-8 and ICAM-1 as biomarkers for progressive massive fibrosis in coal workers' pneumoconiosis.

Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-α), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.

In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- ß, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.

Liraglutide impacts iron homeostasis in a murine model of hereditary hemochromatosis.

Classic hereditary hemochromatosis (HH) is an autosomal recessive iron-overload disorder resulting from loss-of-function mutations of the HFE gene. HH patients exhibit excessive hepatic iron accumulation that predisposes these patients to liver disease, including the risk for developing liver cancer. Chronic iron overload also poses a risk for the development of metabolic disorders such as obesity, type 2 diabetes and insulin resistance. We hypothesized that liraglutide, GLP1 Receptor agonist (GLP1RA), alters iron metabolism while also reducing body weight and glucose tolerance in a mouse model of HH (global HFE knockout, HFE KO) and diet-induced obesity and glucose intolerance. The total body HFE KO and WT control mice were fed high-fat diet for 8 weeks. Mice were subdivided into liraglutide and vehicle-treated groups and received daily subcutaneous administration of the respective treatment once daily for 18 weeks. Liraglutide improved glucose tolerance, hepatic lipid markers and reduced body weight in a mouse model of HH, the HFE KO mouse, similar to WT controls. Importantly, our data shows that liraglutide alters iron metabolism in HFE KO mice, leading to decreased circulating and stored iron levels in HFE KO mice. These observations highlight the potential that GLP1RA could be utilized to reduce iron overload in addition to reducing body weight and improving glucose regulation in HH patients.

Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.

Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction-associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis-inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.

Reg3γ: current understanding and future therapeutic opportunities in metabolic disease.

Regenerating family member gamma, Reg3γ (the mouse homolog of human REG3A), belonging to the antimicrobial peptides (AMPs), functions as a part of the host immune system to maintain spatial segregation between the gut bacteria and the host in the intestine via bactericidal activity. There is emerging evidence that gut manipulations such as bariatric surgery, dietary supplementation or drug treatment to produce metabolic benefits alter the gut microbiome. In addition to changes in a wide range of gut hormones, these gut manipulations also induce the expression of Reg3γ in the intestine. Studies over the past decades have revealed that Reg3γ not only plays a role in the gut lumen but can also contribute to host physiology through interaction with the gut microbiota. Herein, we discuss the current knowledge regarding the biology of Reg3γ, its role in various metabolic functions, and new opportunities for therapeutic strategies to treat metabolic disorders.

Comparison of failure rates and functional outcomes between hamstring autografts and hybrid grafts in anterior cruciate ligament reconstruction: A systematic review and meta-analysis.

BACKGROUND: The viability of augmenting small-diameter hamstring autografts with allografts remains unclear. Recent studies have reported different clinical results after allograft augmentation. Hence, we sought to determine whether hamstring autografts and hybrid grafts differed in terms of failure rates and functional outcomes after anterior cruciate ligament (ACL) reconstruction. We also evaluated whether the results of the comparisons differed based on allograft sterilization methods. PATIENTS AND METHODS: This systematic review and meta-analysis were performed by searching the PubMed, Cochrane Library, and EMBASE databases to identify prospective or retrospective studies (evidence levels 1, 2, or 3) that compared the failure rates and functional outcomes of ACL reconstruction using autografts and hybrid grafts. RESULTS: We identified 15 relevant studies, including 1,521 patients, with 798 and 723 treated using autografts and hybrid grafts, respectively. Fourteen studies were retrospective comparative studies, and one was a prospective randomized controlled trial. Of these, three studies used non-irradiated allografts. In the analysis of all participants, no significant differences in failure rates and subjective International Knee Documentation Committee (IKDC) scores were observed between the autograft and hybrid graft groups. Comparing the autograft and hybrid graft groups that used non-irradiated allografts, no differences in the failure rates and subjective IKDC scores were also noted. Meanwhile, in the groups that used irradiated allograft, the autograft group demonstrated higher Lysholm knee scores and reduced anterior laxity than the hybrid graft group. DISCUSSION: Overall, ACL reconstruction using hybrid grafts may not reduce failure rates compared to reconstructions using hamstring autografts, although hybrid grafts with irradiation may decrease functional outcomes. LEVEL OF EVIDENCE: III; systematic review of level II and III studies.

Lab on a chip for detecting Clara cell protein 16 (CC16) for potential screening of the workers exposed to respirable silica aerosol.

Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625-20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol.

Multicomponent Covalent Organic Framework Solid Electrolyte Allowing Effective Li-Ion Dissociation and Diffusion for All-Solid-State Batteries.

Organic solid electrolytes compatible with all-solid-state Li metal batteries (LMBs) are essential to ensuring battery safety, high energy density, and long-term cycling performance. However, it remains a challenge to develop an approach to provide organic solid electrolytes with capabilities for the facile dissociation of strong Li-ion pairs and fast transport of ionic components. Herein, a diethylene glycol-modified pyridinium covalent organic framework (DEG-PMCOF) with a well-defined periodic structure is prepared as a multicomponent solid electrolyte with a cationic moiety of high polarity, an additional flexible ion-transporter, and an ordered ionic channel for all-solid-state LMBs. The DEG-containing pyridinium groups of DEG-PMCOF allow a lower dissociation energy of Li salts and a smaller energy barrier of Li-ion transport, leading to high ion conductivity (1.71 × 10-4 S cm-1) and a large Li-ion transfer number (0.61) at room temperature in the solid electrolyte. The DEG-PMCOF solid electrolyte exhibits a wide electrochemical stability window and effectively suppresses the formation of Li dendrites and dead Li in all-solid-state LMBs. Molecular dynamics and density functional theory simulations provide insights into the mechanisms for the enhanced Li-ion transport driven by the integrated diffusion process based on hopping motion, vehicle motion, and free diffusion of DEG-PMCOF. The all-solid-state LMB assembled with a DEG-PMCOF solid electrolyte displays a high specific capacity with a retention of 99% and an outstanding Coulombic efficiency of 99% at various C-rates during long-term cycling. This DEG-PMCOF approach can offer an effective route to design various solid-state Li batteries.

An Ion-Channel-Restructured Zwitterionic Covalent Organic Framework Solid Electrolyte for All-Solid-State Lithium-Metal Batteries.

Organic solid electrolytes offer an effective route for safe and high-energy-density all-solid-state Li metal batteries. However, it remains a challenge to devise a new strategy to promote the dissociation of strong ion pairs and the transport of ionic components in organic solid electrolytes. Herein, a zwitterionic covalent organic framework (Zwitt-COF) with well-defined chemical and pore structures is prepared as a solid electrolyte capable of accelerating the dissociation and transport of Li ions. The Zwitt-COF solid electrolyte exhibits a high room-temperature ionic conductivity of 1.65 × 10-4  S cm-1 with a wide electrochemical stability window. Besides, the Zwitt-COF solid electrolyte displays stable Li plating/stripping behavior via effective inhibition of the formation of Li dendrites and dead Li, leading to superior long-term cycle performance with retention of 99% discharge capacity and 98% Coulombic efficiency in an all-solid-state Li-metal battery. Theoretical simulations reveal that the incorporation of zwitterionic groups into COF can facilitate the dissociation of strong ion pairs and reconstruct the AA-stacking configuration by dissociative adsorption of Li+ ions on Zwitt-COF producing linear hexagonal ion channels in the Zwitt-COF solid electrolyte. This strategy based on Zwitt-COF can provide an alternative way to construct various solid-state Li batteries.

Ahnak depletion accelerates liver regeneration by modulating the TGF-ß/Smad signaling pathway.

Ahnak, a large protein first identified as an inhibitor of TGF-ß signaling in human neuroblastoma, was recently shown to promote TGF-ß in some cancers. The TGF-ß signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-ß signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -ß/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-ß signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-ß expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-ß signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment. [BMB Reports 2022; 55(8): 401-406].

The T Category of Distal Extrahepatic Bile Duct Carcinoma: A Comparative Analysis With Invasive Tumor Thickness.

The T category of distal extrahepatic bile duct carcinoma (DBDC) is based on invasion depth from the basal lamina to the deepest infiltrating tumor cells. Recently, invasive tumor thickness (ITT) was proposed, defined as maximal vertical distance of invasive tumor components regardless of the basal lamina. We compared the predictive value of T category, and ITT grading in 424 surgically resected DBDCs. DBDCs were categorized as 6 Tis (1.4%), 134 T1 (<5 mm; 31.6%), 204 T2 (5 to 12 mm; 48.1%), and 80 T3 (>12 mm; 18.9%). With ITT, there were 6 G0 (no invasion; 1.4%), 3 G1 (<1 mm; 0.7%), 90 G2 (≥1 and <5 mm; 21.2%), 188 G3 (≥5 and <10 mm; 44.4%), and 137 G4 (≥10 mm; 32.3%). The 5-year survival rates of T1, T2, and T3 were 58.9%, 44.2%, and 18.2%, and those of ITT G1, G2, G3, and G4 were 33.3%, 54.1%, 51.6%, and 26.7%, respectively. The T category discriminated patient survival by overall (P<0.001) and pairwise (T1 vs. T2, P=0.007; T2 vs. T3, P<0.001) comparisons. ITT grading distinguished survival by overall and between G3-G4 (both P<0.001), with no survival differences observed between G1-G2 and G2-G3 comparisons. The T category more accurately discriminated patient survival than ITT grading. To determine the T category for DBDCs, (1) longitudinal sectioning on gross examination, especially for DBDCs with large papillary or nodular growth patterns; (2) evaluation of serial sections or alternative hematoxylin and eosin slides; (3) use of a straight or curved baseline depending on the shape of the peritumoral normal bile duct wall and/or the basal lamina of the peritumoral normal biliary epithelia/biliary intraepithelial neoplasias are recommended.

Modulating the electrocatalytic activity of N-doped carbon frameworks via coupling with dual metals for Zn-air batteries.

N-Doped carbon electrocatalysts are a promising alternative to precious metal catalysts to promote oxygen reduction reaction (ORR). However, it remains a challenge to design the desired active sites on carbon skeletons in a controllable manner for ORR. Herein, we developed a facile approach based on oxygen-mediated solvothermal radical reaction (OSRR) for preparation of N-doped carbon electrocatalysts with a pre-designed active site and modulated catalytic activity for ORR. In the OSRR, 2-methylimidazole reacted with Co and Mn salts to form an active site precursor (MnCo-MIm) in N-methyl-2-pyrrolidone (NMP) at room temperature. Then, the reaction temperature increased to 140 °C under an oxygen atmosphere to generate NMP radicals, followed by their polymerization with the pre-formed MnCo-MIm to produce Mn-coupled Co nanoparticle-embedded N-doped carbon framework (MnCo-NCF). The MnCo-NCF showed uniform dispersion of nitrogen atoms and Mn-doped Co nanoparticles on the carbon skeleton with micropores and mesopores. The MnCo-NCF exhibited higher electrocatalytic activity for ORR than did a Co nanoparticle only-incorporated carbon framework due to the improved charge transfer from the Mn-doped Co nanoparticles to the carbon skeleton. In addition, the Zn-air battery assembled with MnCo-NCF had superior performance and durability to the battery using commercial Pt/C. This facile approach can be extended for designing carbon electrocatalysts with desired active sites to promote specific reactions.