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Kim et al. conducted single-cell RNA sequencing to determine the transcriptome profiles of human nail units using polydactyly specimens to demonstrate mesenchymal and epithelial cell populations, characterized by RSPO4 and SPINK6 respectively. RSPO4 + onychofibroblasts localized with LGR6 + nail matrix, leading to WNT/ β-catenin activation and suggesting a role for onychofibroblasts in onychomatricoma pathogenesis.

This study aimed to confirm the immunomodulatory effects of fermented Benincasa hispida extract (HR1901-BS) on RAW 264.7 macrophages. B. hispida was fermented for 72 h using Bacillus subtilis CJH 101. To evaluate the efficacy of HR1901-BS in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in HR1901-BS-stimulated RAW 264.7 cells. We evaluated the effects on nitric oxide (NO) production and the release of pro-inflammatory cytokines (interleukin IL-1β, IL-6, and tumor necrosis factor TNF-β) in the RAW 264.7 cell line. We confirmed that HR1901-BS affected macrophage activation by inducing a significantly high dose-dependent NO production and increasing the release of pro-inflammatory cytokines in RAW 264.7 macrophages. It also suggested that the immunomodulatory effect by HR1901-BS occurred mainly as a result of the activation of cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathways. Our results indicate that HR1901-BS is a promising candidate as a functional material that enhances immune responses through macrophage activation.

Although tumor immunotherapy has emerged as a promising therapeutic method for oncology, it encounters several limitations, especially concerning low response rates and potential off-targets that elicit side effects. Furthermore, tumor immunogenicity is the critical factor that predicts the success rate of immunotherapy, which can be boosted by the application of nanotechnology. Herein, we introduce the current approach of cancer immunotherapy and its challenges and the general methods to enhance tumor immunogenicity. Importantly, this review highlights the integration of anticancer chemo/immuno-based drugs with multifunctional nanomedicines that possess imaging modality to determine tumor location and can respond to stimuli, such as light, pH, magnetic field, or metabolic changes, to trigger chemotherapy, phototherapy, radiotherapy, or catalytic therapy to upregulate tumor immunogenicity. This promotion rouses immunological memory, such as enhanced immunogenic cell death, promoted maturation of dendritic cells, and activation of tumor-specific T cells against cancer. Finally, we express the related challenges and personal perspectives of bioengineered nanomaterials for future cancer immunotherapy.

Abstract Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

Background/Aims Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Chronic kidney disease (CKD) is a common and progressive disease that has become a major public health problem on a global scale. Renal fibrosis is a common feature in the pathogenesis of CKD, which is mainly related to the excessive accumulation and deposition of extracellular matrix caused by various inflammatory factors. No ideal treatment has yet been established. In recent years, based on the traditional Chinese medicine (TCM) theory of CKD and its molecular mechanism, clinical evidence or experimental studies have confirmed that a variety of Chinese materia medica (CMM) and their effective components can delay the progress of CKD. TCM believes that the pathogenesis of CKD is the deficiency in the root and excess in the branch, and the deficiency and excess are always accompanied by the disease. The strategies of TCM in treating CKD are mainly based on invigorating Qi, tonifying the kidneys, promoting blood circulation, removing stasis, eliminating heat and dampness, removing turbidity, and eliminating edema, and these effects are multitargeted and multifunctional. This review attempts to summarize the theories and treatment strategies of TCM in the treatment of CKD and presents the efficacy and mechanisms of several CMMs supported by clinical evidence or experimental studies. In addition, the relationship between the macroscopic of TCM and the microscopic of modern medicine and the problems faced in further research were also discussed.

There has been a long-standing expectation that the optical-resolution embodiment of photoacoustic tomography could have a substantial impact on gastrointestinal endoscopy by enabling microscopic visualization of the vasculature based on the endogenous contrast mechanism. Although multiple studies have demonstrated the in vivo imaging capability of a developed imaging device over the last decade, the implementation of such an endoscopic system that can be applied immediately when necessary via the instrument channel of a video endoscope has been a challenge. In this study, we developed a 3.38-mm diameter catheter-based, integrated optical-resolution photoacoustic and ultrasonic mini-probe system and successfully demonstrated its intra-instrument channel workability for the standard 3.7-mm diameter instrument channel of a clinical video endoscope based on a swine model. Through the instrument channel, we acquired the first in vivo dual-mode photoacoustic and ultrasonic endoscopic images from the esophagogastric junction of a swine. Further, in a rat colorectum in vivo imaging experiment, we visualized hierarchically developed mesh-like capillary networks with a hole size as small as ~50 µm, which suggests the potential level of image details that could be photoacoustically provided in clinical settings in the future.

Abstract Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic‐based methods require complex infrastructure and expensive equipment, which are not suitable for low‐resource settings. Over the past years, smartphone‐based point‐of‐care testing (POCT) has rapidly emerged as a potential alternative to laboratory‐based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory‐based and POCT‐based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone‐based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone‐based POCT diagnostics for various viruses including COVID‐19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone‐based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease‐causing viruses worldwide.

The primary purpose of this study is to examine the relationship between the dynamic capabilities (DCs) embedded in ESG management, which are being pursued by global companies, and corporate performance amid increasing uncertainty. Furthermore, the secondary purpose is to examine the function of environmental uncertainty moderating the DCs-performance relationship. Concerning the analysis tool, this study employs topic modeling with Word2Vec embedding that analyzes unstructured data. This was employed as an alternative method beyond the limitations of the traditional approach, i.e., survey or interview. A DCs dictionary was constructed by redesigning the 12 detailed dimensions of Teece’s DCs into 10 dimensions, and then time series scores of individual global companies were extracted by applying this dictionary to the sustainability reports of 97 companies. Sustainability reports of 153 companies among Fortune Global 500 companies announced in 2020 were originally collected, but in the process of collecting additional financial data about these companies from OSIRIS, a total of only 97 companies was selected in the end due to omission of data. A fixed effect panel analysis was conducted, and the main findings are as follows: First, the DCs embedded in ESG management have a positive or negative direct effect on corporate performance. In particular, a statistically significant relationship was not observed in the innovation (technology) oriented capabilities, whereas a statistically significant positive relationship was observed in the customer (market) oriented capabilities. Second, uncertainty moderates the relationship between DCs and corporate performance positively or negatively. Interestingly, the moderating effect of uncertainty only appears in the function of the sensing and reconfiguring capabilities. From this, it can be seen that the function of DCs, which is embedded in the ESG management of global companies, is limited due to the imbalance between the sensing-seizing-reconfiguring capabilities. These findings imply that, despite the positive function of DCs embedded in ESG management, costs and benefits occur at the same time, and DCs can improve performance only if there is an organizational adaptation strategy suitable for uncertainty. Accordingly, business managers need to recognize the importance of pursuing sensing-seizing-reconfiguring capabilities in a balanced way to improve corporate performance through ESG management under uncertainty.

BackgroundPreoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias.MethodsWe analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia.ResultsThe unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206–2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178–2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481–5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597–11.395), p = 0.004] were predictors of postoperative severe complications.ConclusionPreoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Abstract For valence change memory (VCM)‐type synapses, a large number of vacancies help to achieve very linearly changed dynamic range, and also, the low activation energy of vacancies enables low‐voltage operation. However, a large number of vacancies increases the current of artificial synapses by acting like dopants, which aggravates low‐energy operation and device scalability. Here, mixed‐dimensional formamidinium bismuth iodides featuring in‐situ formed type‐I band structure are reported for the VCM‐type synapse. As compared to the pure 2D and 0D phases, the mixed phase increases defect density, which induces a better dynamic range and higher linearity. In addition, the mixed phase decreases conductivity for non‐paths despite a large number of defects providing lots of conducting paths. Thus, the mixed phase‐based memristor devices exhibit excellent potentiation/depression characteristics with asymmetricity of 3.15, 500 conductance states, a dynamic range of 15, pico ampere‐scale current level, and energy consumption per spike of 61.08 aJ. A convolutional neural network (CNN) simulation with the Canadian Institute for Advanced Research‐10 (CIFAR‐10) dataset is also performed, confirming a maximum recognition rate of approximately 87%. This study is expected to lay the groundwork for future research on organic bismuth halide‐based memristor synapses usable for a neuromorphic computing system.

Aniline is a toxic organic pollutant and raw material in industries. In this study, the start-up of sequencing batch reactor for treating aniline wastewater was assessed and functional microbial clusters were analyzed after enrichment of denitrifying phosphate-accumulating organisms (DNPAOs). The aniline degradation and subsequent removal of NH4+-N mainly happened in aerobic condition, and denitrification was conducted in both anaerobic and anoxic conditions. Besides aerobic phosphorus uptake, phosphorus accumulation also occurred via DNPAOs in anoxic condition utilizing nitrate as electron acceptor. The removal efficiencies of COD, NH4+-N, TN, and TP was over 91.6, 67.1, 65.0, and 79.9% respectively. Proteobacteria, Bacteroidetes, and Firmicutes were found to be predominant at phylum level treating aniline wastewater. Blastocatella, Ferruginibacter and Clostridium were predominant strains involved in aniline degradation and Pseudomonas was enriched in the presence of aniline. Aeromonas, Acinetobacter, and Comamonas may play key roles in nitrogen removal and phosphorus accumulation with tolerance of aniline.

Abstract Background It is widely assumed that all mutant microorganisms present in a culture are able to grow and form colonies, provided that they express the features required for selection. Unlike wild-type Escherichia coli, PHO-constitutive mutants overexpress alkaline phosphatase and hence can hydrolyze glycerol-2-phosphate (G2P) to glycerol and form colonies on plates having G2P as the sole carbon source. These mutations mostly occur in the pst operon. However, the frequency of PHO-constitutive colonies on the G2P selective plate is exceptionally low. Results We show that the rate in which spontaneous PHO-constitutive mutations emerge is about 8.0 × 10−6/generation, a relatively high rate, but the growth of most existing mutants is inhibited by their neighboring wild-type cells. This inhibition is elicited only by non-mutant viable bacteria that can take up and metabolize glycerol formed by the mutants. Evidence indicates that the few mutants that do form colonies derive from microclusters of mutants on the selective plate. A mathematical model that describes the fate of the wild-type and mutant populations under these circumstances supports these results. Conclusion This scenario in which neither the wild-type nor the majority of the mutants are able to grow resembles an unavoidable “tragedy of the commons” case which results in the collapse of the majority of the population. Cooperation between rare adjacent mutants enables them to overcome the competition and eventually form mutant colonies. The inhibition of PHO-constitutive mutants provides an example of mutant frequency masked by orders of magnitude due to a competition between mutants and their ancestral wild-type cells. Similar “tragedy of the commons-like” cases may occur in other settings and should be taken into consideration while estimating true mutant frequencies and mutation rates.

An anastomosis stricture with a total obstruction is rare and treatment options are variable. We describe our experience with a combination of a single port transanal laparoscopic approach and intraoperative colonoscopic balloon dilatation. The patient was a 48-year-old man with rectal cancer. A laparoscopic single port lower anterior resection and diverting ileostomy were performed followed by a colon study and ileostomy takedown. The colon study and sigmoidoscopy revealed total obstruction of the rectum at the anastomosis level. We employed a transanal approach using a single port to correct this. We located the anastomosis stricture site and generated a lumen using a dissector and electocautery method to insert the balloon device. Colonoscopic balloon dilatation was subsequently successful. The patient was discharged with no postoperative complications. A laparoscopic single port transanal approach with an intraoperative colonoscopic balloon dilatation is a viable alternative approach to treating an anastomosis stricture of the rectum.

Background/Aims This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. Methods This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. Results Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P

Abstract Chitinase and chitin-oligosaccaride can be used in multiple field, so it is important to develop a high-yield chitinase producing strain. Here, a recombinant Pichia pastoris with 4 copies of ChiA gene from Bacillus licheniformis and co-expression of molecular chaperon HAC1 was constructed. The amount of recombinant ChiA in the supernatant of high-cell-density fermentation reaches a maximum of 12.7 mg/mL, which is 24-fold higher than that reported in the previous study. The recombinant ChiA can hydrolyze 30% collodidal chitin with 74% conversion ratio, and GlcNAc is the most abundant hydrolysis product, followed by N, N′-diacetylchitobiose. Combined with BsNagZ, the hydrolysate of ChiA can be further transformed into GlcNAc with 88% conversion ratio. Additionally, the hydrolysate of ChiA can obviously accelerate the germination growth of rice and wheat, increasing the seedling height and root length by at least 1.6 folds within 10 days.

In general, turfgrass grows well and forms high quality turf under full sun exposure. It is very difficult, however, to grow a warm season turfgrass under shaded condition. Zoysia grass is a popular warm season grass that commonly grow under full sun exposure condition. There are limited information regarding the growth response and turf quality of zoysia grass when grown under shaded condition. This study aims to observe the growth and quality of various zoysia grass local cultivars at different shading intensities and different mowing. This research was carried out using 10 zoysia grass cultivars planted in the rice fields’ vertisol clay with randomized complete block design. The shading used were control, shade-nets with 25% and 65% hole densities. Zoysia grass was fertilized using NPK; 4:1:3 and mowed three times. The results showed that plants without shade, 25% and 65% received on average solar irradiance of 25,141; 12,456 and 3,727 lux. The increase in shade level decreased the shoot fresh weight, dry weight, root dry weight and the plant height. Shading and frequent mowing effected the plant height. Mowing has more effect on plant height in 25% shading than in 65% shading. The increase in shading, in mowed grass showed increased plant height and decreased plant dry weight. Mowing three times can reduce plant height in all shades. The grasses under 25% shading resulted the highest plant dry weight; whereas and shading 65% resulted the lowest. Plant dry weight and uniformity of turf were affected by the cultivars.

Abstract Exosomes are secreted by cells and are widely present in body fluids. Exosomes contain various molecular constituents of their cells of origin such as proteins, mRNA, miRNAs, DNA, lipid and glycans which are very similar as the content in tumor cells. These contents play an important role in various stages of tumor development, and make the tumor-derived exosome as a hot and emerging biomarker for various cancers diagnosis and management in non-invasive manner. The present problems of exosome isolation and detection hinder the application of exosomes. With the development of exosome isolation and detection technology, the contents of exosomes can be exploited for early cancer diagnosis. This review summarizes the recent progress on exosome-associated tumor biomarkers and some new technologies for exosome isolation and detection. Furthermore, we have also discussed the future development direction in exosome analysis methods.

Abstract Background The human placenta (HP) is a complex organ used to alleviate tiredness and promote wound healing. Previous research showed the hair growth-promoting effect of HP. However, no reports have addressed the effects of HP on hair regrowth in chemotherapy-induced alopecia. In this study, we investigated the effects of HP on the apoptosis and proliferation of hair follicles in chemotherapy-induced alopecia. Methods Male C57BL/6 mice in telogen were depilated to enter anagen. After 9 days, dystrophic catagen was induced by the intraperitoneal injection of 150 mg/kg cyclophosphamide. During 9 to 16 days, 0.1 and 1 mg/mL HP were topically applied to depilated dorsal skin. Results Dystrophic hair follicles by cyclophosphamide were recovered by HP treatment. New hair shafts containing hair fibers appeared to be straight after HP treatment. Immunohistological staining revealed a significant increase of Ki67-positive cells in hair follicles treated with 1 mg/mL HP. Topical HP treatment increased the ratio of Bcl-2/Bax, while it attenuated the expression of pro-apoptotic Bax, p53, and cytochrome c with caspase-9 and -3. In addition, the expression of KGF and the phosphorylation of AKT were upregulated by HP treatment. Conclusion These results suggest that HP treatment induced hair growth by inhibiting apoptosis and promoting the proliferation of hair follicles. HP may be useful for treating chemotherapy-induced alopecia.

Purpose The purpose of this study was to describe the ultrasonographic findings of testicular atrophy after mumps orchitis. Methods We retrospectively reviewed the case files of eight patients (14 to 24 years old; mean, 17 years) with mumps orchitis and testicular atrophy who were treated between January 2011 and September 2017. On gray-scale and color Doppler, the ultrasonographic features of volume, shape, echogenicity, and degree of blood flow in the testes were analyzed as part of both initial and follow-up ultrasonography. The duration between the initial diagnosis of mumps orchitis and the ultrasonographic diagnosis of testicular atrophy after mumps orchitis ranged from 25 to 230 days (mean, 95.9 days). Results Of the eight patients with testicular atrophy after mumps orchitis, the testes were affected unilaterally in seven patients (6 right-sided and 1 left-sided) and bilaterally in one patient. The affected testes (n=9) were 23%-55% (mean, 44.7%) smaller in volume (mean, 6.3±2.0 mL) than the contralateral normal testes (n=7) (mean, 10.8±2.3 mL) on follow-up ultrasonography (P=0.001). The shape of the atrophic testes was oblong in seven cases and elliptical in two cases. The atrophic testes were either heterogeneously hypoechoic with multiple hyperechoic islands (n=7) or heterogeneously hyperechoic (n=2). On follow-up color Doppler ultrasonography, the degree of vascularity of the atrophic testis was either similar to (n=3) or lower than (n=6) that of the contralateral testis. Conclusion On ultrasonography, atrophic testes after mumps orchitis tended to exhibit an oblong shape, heterogeneous low echogenicity with multiple hyperechoic islands, and decreased vascularity.

Objective: The coronavirus disease (COVID-19) epidemic occurred suddenly, and had a severe impact on the whole society, especially the health care system. The purpose of this article is to share the experience of infection control management in the ultrasound department of China-Japan Friendship Hospital in response to the epidemic.Methods: In accordance with relevant academic guidance and consensus guidelines, the ultrasound department followed principles of prevention and control which were promulgated by the hospital, combined management measures with the characteristics of ultrasound diagnosis and treatment, to control infection during the epidemic period. These measures included reducing the number of patients and doctors, using targeted protection standards in different work areas, and strengthening the training of staff in the department.Results: During the epidemic in February to March 2020, the ultrasound department completed a total of 10,719 cases in the outpatient area (a decrease of 68.3% compared with the same period last year) and 1,583 cases from emergency (including 53 cases from the fever clinic). While the clinical needs were met, there was zero infection with COVID-19 of all health care staff in the ultrasound department during the epidemic.Conclusions: We hope the valuable experience of infection control management in our ultrasound department in response to the epidemic can help global ultrasound doctors be prepared for the pandemic. The teams of ultrasound departments should also work closely with local infection control colleagues to implement measures that are appropriate for their own clinical settings to overcome the pandemic.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and it is thus critical to identify novel molecular biomarkers of HCC prognosis and elucidate the molecular mechanisms underlying HCC progression. Here, we show that G-protein-coupled receptor 50 (GPR50) in HCC is overexpressed and that GPR50 knockdown may downregulate cancer cell progression through attenuation of the Notch signaling pathway. GPR50 knockdown was found to reduce HCC progression by inactivating Notch signaling in a ligand-independent manner through a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), a proteolytic enzyme that cleaves the Notch receptor, which was corroborated by GPR50 overexpression in hepatocytes. GPR50 silencing also downregulated transcription and translation of ADAM17 through the AKT/specificity protein-1 (SP1) signaling axis. Notably, GPR50 was found to directly interact with ADAM17. Overall, we demonstrate a novel GPR50-mediated regulation of the ADAM17-Notch signaling pathway, which can provide insights into HCC progression and prognosis and development of Notch-based HCC treatment strategies.

Groin lesions can be classified as neoplastic or non-neoplastic. Neoplastic lesions include lipoma, epidermoid cyst, angiomyofibroblastoma-like tumor, liposarcoma, and synovial sarcoma, as well as metastases from lymphoma, neuroendocrine carcinoma, and carcinomas of the lung, breast, urinary bladder, ovary, vulva, and colon. Non-neoplastic lesions include hernias, round ligament varices, endometriosis, Kimura disease, Castleman disease, hematoma, and inflammation. Because the clinical implications and therapeutic strategies for groin lesions vary depending on the cause, the ability to noninvasively differentiate among etiologies is very important. Although there is substantial overlap in ultrasonographic findings across various groin lesions, some ultrasonographic features, along with clinical characteristics, may suggest a specific diagnosis. Familiarity with the ultrasonographic and clinical features of various groin lesions facilitates accurate diagnosis and treatment.

Hepatokines are proteins secreted by the liver that can regulate whole body metabolism. Here the authors identify apolipoprotein J as a hepatokine that regulates muscle glucose metabolism and insulin resistance through a low-density lipoprotein receptor-related protein−2 mediated mechanism in mice.

Abstract This study presents the shear capacity of eco-friendly high-strength concrete (HSC) beams reinforced by 0.75% (by volume) of hooked steel fibers or shear stirrups with various spacings. Five large-scale HSC beams with steel fibers or stirrups were tested and investigated with respect to shear capacity, failure mode, and crack patterns. The test results indicate that all five tested beams finally failed by a shear-critical failure mode and that the use of 0.75 vol% of steel fibers significantly improved the shear strength although it decreased the diagonal crack angle of HSC beam in the case of without stirrups. There are some different properties compared with ACI 318-19 recommendation, but the use of 0.75 vol% steel fibers exhibited approximately 13.2% higher shear strength when compared with that of minimum shear reinforcement for the HSC beam. Furthermore, the shear capacity of steel fibers calculated by experimental data, and it was compared with several prediction equations. The prediction models containing fiber factor were more closely agreeable with test results with a minimum of 10.9% difference.

Background and ObjectiveIt is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis.MethodsKawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis.ResultsTanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties.ConclusionTanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.

BackgroundSystemic inflammatory response syndrome (SIRS) is a systemic insult that has been described with many interventional cardiac procedures. The outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) are thought to be influenced by this syndrome not only on short-term, but also on long-term.ObjectiveWe assessed the association of SIRS to different clinical, echocardiographic, and computed tomographic (CT) outcomes after TAVI.MethodsTwo hundred and twenty-four consecutive patients undergoing TAVI were enrolled in this study. They were assessed for the occurrence of SIRS within the first 48 h after TAVI. Patients were followed-up for short- and long-term clinical outcomes. Serial echocardiographic follow-ups were conducted at 1-week, 6-months, and 1-year. CT follow-up at 1 year was recorded.ResultsEighty patients (36%) developed SIRS. Among different parameters, only pre-TAVI total leucocytic count (TLC), pre-TAVI heart rate, and post-TAVI systolic blood pressure independently predicted the occurrence of SIRS. The incidence of HALT was not significantly different between both groups, albeit higher among SIRS patients (p = 0.1) at 1-year CT follow-up. Both groups had similar patterns of LV recovery on serial echocardiography. Long-term follow-up showed that all-cause death, cardiac death, and re-admission for heart failure (HF) or acute coronary syndrome (ACS) were significantly more frequent among SIRS patients. Early safety and clinical efficacy outcomes were more frequently encountered in the SIRS group, while device-related events and time-related valve safety were comparable.ConclusionAlthough SIRS implies an early acute inflammatory status post-TAVI, yet its clinical sequelae seem to extend to long-term clinical outcomes.

In the published publication [...]

Abies holophylla is an evergreen coniferous species that has been widely used for treating pulmonary diseases and colds. Previous research has demonstrated the anti-inflammatory effect of Abies species and the anti-asthmatic activities of Abies holophylla leaf essential oil (AEO). As asthma and allergic rhinitis (AR) share pathophysiology and pharmacotherapeutic interventions, AEO inhalation can also ameliorate upper respiratory allergic diseases. This study explored the protective effects of AEO on AR with network pharmacological pathway prediction. The potential target pathways of AEO were analyzed by a network pharmacological approach. The BALB/c mice were sensitized by ovalbumin (OVA) and 10 μm particular matter (PM10) to induce allergic rhinitis. Aerosolized AEO 0.0003% and 0.03% were delivered by nebulizer for 5 min a day, 3 times a week for 7 weeks. Nasal symptoms (sneezing and rubbing), histopathological changes in nasal tissues, serum IgE, and zonula occludens-1 (ZO-1) expressions on nasal tissues were analyzed. After AR induction with OVA+PM10 and inhalation of AEO 0.0003% and 0.03% treatment, AEO significantly decreased allergic symptoms (sneezing and rubbing), hyperplasia of nasal epithelial thickness, goblet cell counts, and serum IgE level. The network analysis demonstrated that the possible molecular mechanism of AEO is highly associated with the IL-17 signaling pathway and tight junction. The target pathway of AEO was investigated in RPMI 2650 nasal epithelial cells. Treatment of AEO on PM10-treated nasal epithelial cells significantly reduced the production of inflammatory mediators related to the IL-17 signaling pathway, NF-κB, and the MAPK signaling pathway and prevented the reduction in TJ-related factors. When taken together, AEO inhalation may be considered as a potential treatment for AR by alleviating nasal inflammation and recovering the tight junction.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Bridges are key social overhead capital facilities with a direct impact on citizen safety and the socioeconomic development of a country. Many bridges in South Korea were completed during the nation’s period of rapid economic growth in the 1970s and 1980s, meaning that bridge aging is now accelerating and should be of real concern. Based on records of other highly developed countries not having adequate maintenance systems for old bridges and consequently experiencing a number of tragic bridge collapses, Korea is at risk of following suit. Being able to measure the efficiency of bridge management considering economic and social values is therefore critical. In this work, a qualitative bridge maintenance priority evaluation model using open-source bridge information was developed. The model was evaluated by applying it to eight actual bridges located in Daegu Metropolitan City, Korea. It is concluded that aging bridge maintenance and management can be performed more efficiently and reliably if the model proposed in this work is used.

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Background. The optimal duration of dual antiplatelet therapy (DAPT) after biodegradable-polymer (BP) everolimus-eluting stent (EES) implantation remains uncertain. Methods. This study analyzed 793 patients who underwent percutaneous coronary intervention (PCI) with BP-EES in 10 cardiovascular centers in Korea between July 2016 and January 2018. Using the prescription data at 6 months post-PCI, we divided these patients into two groups, namely, short-DAPT and prolonged-DAPT groups, which underwent DAPT for 6 and > 6 months of PCI, respectively. The primary endpoint, which included mortality, myocardial infarction, or target-vessel revascularization at 2 years, was compared by propensity score (PS) matching between the two groups. Results. Out of the 793 patients, 283 matched pairs were identified by PS matching. Out of this matched population, 405 (71.6%) patients had an acute coronary syndrome. The primary endpoint did not differ in 2 years between the short-DAPT and prolonged-DAPT groups (7.5% vs. 8.3%; hazard ratio, 0.87; 95% confidential interval, 0.47–1.60; P=0.648). Likewise, no difference was found regarding mortality, cardiac mortality, myocardial infarction, target-lesion failure, target-vessel failure, and bleeding events defined by the Bleeding Academic Research Consortium and Thrombolysis In the Myocardial Infarction classification. Meanwhile, one patient in the short-DAPT group had definite stent thrombosis at 364 days post-PCI. Subgroup analysis showed that several anatomical and procedural factors were not significantly related to DAPT duration. Most patients (77.4%) in both groups were prescribed clopidogrel at discharge. Conclusions. In real-world patients undergoing PCI with BP-EES, the ischemic and bleeding endpoints demonstrated no difference between 6-month and prolonged (>6 months) DAPT.

Тhe most pressing issue in generating induced pluripotent stem cells (iPSCs) in clinical practice is the cell source. Compared to human dermal fibroblasts (HDFs), which have been widely used, human peripheral blood could be a more easily obtainable alternative. However, iPSCs generated from fresh peripheral blood require inconvenient specific methods including isolation. Recently, we succeeded in isolating and culturing human heart-derived circulating cells called circulating multipotent stem (CiMS) cells. Here, we investigated the generation efficiency of CiMS-derived iPSCs (CiMS-iPSCs) and tested their differentiation potential into mesodermal lineages and cardiovascular cells. We isolated and cultured CiMS cells from peripheral mononuclear cells with a high efficiency. Moreover, our method succeeded in reprogramming the CiMS cells and generating iPSCs with higher efficiency compared to when HDFs were used. Compared to HDF-iPSCs or human embryonic stem cells (hESCs), CiMS-iPSCs showed high differentiation potential into mesodermal lineage cells and subsequently into endothelial cells, vascular smooth muscle cells, and cardiomyocytes. Further, we checked the epigenetic status of each cell type. While methylation of the CpG site of the brachyury T promoter did not differ between cell types, the histone H3 lysine 4 trimethylation level in the brachyury T promoter region was enhanced in CiMS-iPSCs, compared to that in other cell types. In contrast, histone H3 lysine 9 acetylation was downregulated during the differentiation process of the CiMS-iPSCs. In the myocardial infarction model, the CiMS-iPSCs group showed more therapeutic potential in regenerating the myocardium than other cell types. Our study showed a new method to isolate human heart-derived stem cells from human peripheral blood and to generate iPSCs efficiently. Due to epigenetic memory, these CiMS-iPSCs easily differentiated into cardiovascular lineage cells, resulting in improved efficiency in vivo. These results suggest that our new method using CiMS cells has therapeutic potential in regenerative medicine using cell therapy.

Abstract Increasing evidence has demonstrated that lactate and adenosine triphosphate (ATP) both play important roles in regulating abnormal metabolism in the tumor microenvironment. Herein, an O2 self‐supplying catalytic nanoagent, based on tannic acid (TA)–Fe(III) coordination complexes‐coated perfluorooctyl bromide (PFOB) nanodroplets with lactate oxidases (LOX) loading (PFOB@TA–Fe(III)–LOX, PTFL), is designed for cascade metabolic‐chemodynamic therapy (CDT) by dual‐depletion of lactate and ATP with hydroxyl •OH radicals generation. Benefiting from the catalytic property of loaded LOX and O2 self‐supplying of PFOB nanodroplets, PTFL nanoparticles (NPs) efficiently deplete tumoral lactate for down‐regulation of vascular endothelial growth factor expression and supplement the insufficient endogenous H2O2 . Simultaneously, TA–Fe(III) complexes release Fe(III) ions and TA in response to intracellular up‐regulated ATP in tumor cells followed by TA‐mediated Fe(III)/Fe(II) conversion, leading to the depletion of energy source ATP and the generation of cytotoxic •OH radicals from H2O2. Moreover, TA–Fe(III) complexes provide photoacoustic contrast as imaging guidance to enhance therapeutic accuracy. As a result, PTFL NPs efficiently accumulate in tumors for suppression of tumor growth and show evidence of anti‐angiogenesis and anti‐metastasis effects. This multifunctional nanoagent may provide new insight for targeting abnormal tumor metabolism with the combination of CDT to achieve a synergistic therapeutic effect.

With the increase in bone metabolic diseases owing to the aging of the global population, interest in functional food ingredients for improving bone health is increasing. This study aimed to determine the anti-osteoporosis effect of Benincasa hispida extract (BHE, HR1901-W) and 2-furoic acid in ovariectomy (OVX)-induced osteoporosis in female ICR mice. Thirty-five female ICR mice underwent OVX or sham operation and were randomized into seven groups of five animals as follows: normal, sham, OVX, OVX with genistein (10 mg/kg), 2-furoic acid (20 mg/kg), LBHE (100 mg/kg), and HBHE (200 mg/kg). After an 8-week treatment period, femur and blood samples were collected from mice. Bone density and bone formation markers were significantly recovered in the 2-furoic acid and HBHE supplementation groups compared with those in the OVX group. In addition, bone resorption markers were increased in OVX mice, whereas they were significantly decreased in the OVX + 2-furoic acid and HBHE supplementation groups. This study suggests that BHE supplementation prevents bone resorption and promotes bone formation in OVX mice. These findings indicate that BHE could be used as a promising natural means to prevent OVX-induced osteoporosis and bone metabolic diseases.