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Laparoscopic surgery for pheochromocytoma is difficult because of the potential release of catecholamines, which may lead to severe intraoperative hemodynamic changes. In particular, extra-adrenal pheochromocytoma imposes special demands on the laparoscopic surgical skills of the operator because of changes in anatomic disposition. In this paper, we report a case of extra-adrenal pheochromocytoma, located in the vulnerable anatomic structures, taking place in tiny areas that were difficult to access and that was resected by using the da Vinci® robotic system. We found that the da Vinci robotic system gave us improved visual quality to surrounding structures. After our initial experience, we suggest the robot-assisted laparoscopic resection for extra-adrenal pheochromocytoma. [ABSTRACT FROM AUTHOR]

Marine organisms' lipid metabolism contributes to marine ecosystems by producing a variety of lipid molecules. Historically, research focused on the lipid metabolism of the organisms themselves. Recent microbiome studies, however, have revealed that gut microbial communities influence the amount and type of lipids absorbed by organisms, thereby altering the organism's lipid metabolism. This has highlighted the growing importance of research on gut microbiota. This review highlights mechanisms by which gut microbiota facilitate lipid digestion and diversify the lipid pool in aquatic animals through the accelerated degradation of exogenous lipids and the transformation of lipid molecules. We also assess how environmental factors and pollutants, along with the innovative use of probiotics, interact with the gut microbiome to influence lipid metabolism within the host. We aim to elucidate the complex interactions between lipid metabolism and gut microbiota in aquatic animals by synthesizing current research and identifying knowledge gaps, providing a foundation for future explorations., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA 1 Ca 2.2 (PO 4 ) 1.3 OH 2.1 , has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone., (© 2024 Wiley‐VCH GmbH.)

The marine medaka Oryzias melastigma is a useful fish model for marine and estuarine ecotoxicology studies and can be applied to field-based population genomics because of its distribution in Asian estuaries and other coastal areas. We identified 769 full-length G protein-coupled receptor genes in the O. melastigma genome and classified them into five distinct classes. A phylogenetic comparison of GPCR genes in O. melastigma to humans and two other small fish species revealed a high-level orthological relationship. Purinergic and chemokine receptors were highly differentiated in humans whereas significant differentiation of chemosensory receptors was evident in fish species. Our results suggest that the GPCR gene families among the species used in this study exhibit evidence of sporadic evolutionary processes. These results may help improve our understanding of the advanced repertoires of GPCR and expand our knowledge of physiological mechanisms of fish in response to various environmental stimuli., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3 H -1,2,4-triazole-3-thione (compound 20 ) and 4-phenyl-4 H -1,2,4-triazole (compound 15 ). Notably, hindered rotation caused by steric interaction between the 3-thione and ortho -trifluoromethyl group of compounds 20 , 21 induced formation of thermodynamically stable atropisomers. Distinct X-ray cocrystal structures of 20 and 21 were obtained, which clearly demonstrated that the configuration of 21 proscribes a key halogen bonding σ-hole interaction of 3-chloro with carbonyl oxygen of Gly182, thereby leading to significant loss in potency. Ultimately, 20 and 15 were evaluated in mouse pharmacokinetic studies, and both compounds exhibited oral exposures suitable for further in vivo assessment.

To study multigenerational resilience to high temperature (HT) conditions, we exposed Brachionus plicatilis marine rotifers to HT, high salinity (HS), and nanoplastics (NPs), and measured reproductive and life-cycle endpoints. After exposure to HT, rotifer lifespans were reduced, but daily production of offspring increased. However, both combined HT/HS and HT/HS/NP exposure led to additional decreases in longevity and reproductive ability; the antioxidant defense mechanisms of the rotifers were also notably upregulated as measured by reactive oxygen species levels. Fatty-acid profiles were reduced in all conditions. In multigenerational experiments, the negative effects of HT dissipated rapidly; however, the effects of HT/HS and HT/HS/NPs required four generations to disappear completely. The findings indicated that B. plicatilis were able to recover from these environmental stressors. This study demonstrated the resilience of aquatic organisms in response to changing environmental conditions and provides insights into the complex interactions of different abiotic stressors., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study reports the effects of bisphenol A (BPA) on the rotifer Brachionus plicatilis, focusing on growth performance, reproductive output, oxidative stress responses, and lipid metabolism genes. High BPA levels disrupted peak daily offspring production and led to oxidative stress and increased superoxide dismutase and catalase activity. The research identified distinctive monoacylglycerol O-acyltransferase (MGAT) and diacylglycerol O-acyltransferase (DGAT) genes in B. plicatilis, B. rotundiformis, and B. koreanus, enhancing understanding of lipid metabolism in these species. BPA exposure significantly altered MGAT and DGAT expression, and feeding status affected these regulatory patterns. When food was unavailable, BPA reduced DGAT2 and MGAT2a expression. However, under feeding conditions, DGAT2 and MGAT1 levels increased, indicating that nutritional status and BPA exposure interact to affect gene expression., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aging-related bone loss is driven by various biological factors, such as imbalanced bone metabolism from decreased osteoblast and increased osteoclast activities. Various transcriptional and post-transcriptional factors increase osteoclast activity with aging; however, studies regarding the post-translational regulators of osteoclast activity are still limited. The ubiquitin E3 ligase Pellino-1 is a well-known post-translational regulator of inflammation. However, how Pellino-1 expression regulation affects osteoclast differentiation remains unclear. This study determined that Pellino-1 levels are reduced in bone marrow monocytes (BMMs) from 40-week-old mice compared to 4-week-old mice. Interestingly, conditional Knockout (cKO) of Pellino-1 in 6-week-old mice resulted in decreased bone mass, reduced body size, and lower weight than in Pellino-1 floxed mice; however, these differences are not observed in 20-week-old mice. The increased number of tartrate-resistant acid phosphatase (TRAP)-positive cells and serum levels of C-terminal telopeptides of type I collagen, a marker of bone resorption, in 6-week-old Pellino-1 cKO mice implied a connection between Pellino-1 and the osteoclast population. Enhanced TRAP activity and upregulation of osteoclast genes in BMMs from the cKO mice indicate that Pellino-1 deletion affects osteoclast differentiation, leading to decreased bone mass and heightened osteoclast activity. Thus, targeting Pellino-1 could be a potential gene therapy for managing and preventing osteoporosis., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Background: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer., Methods: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes., Results: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%., Conclusions: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

In this study, the effects of electrode porosity on nerve regeneration and functional recovery after sciatic nerve transection in rats was investigated. A sieve-type neural electrode with 70% porosity was designed and compared with an electrode with 30% porosity. Electrodes were fabricated from photosensitive polyimide and implanted into the transected sciatic nerves. Motor function recovery was evaluated using the Sciatic Function Index. The number of active channels and their signal quality were recorded and analyzed to assess the sensory neural signal acquisition. Electrical impedance spectroscopy was used to evaluate the electrode performance. The group implanted with the 70% porosity electrode demonstrated significantly enhanced nerve regeneration and motor function recovery, approaching control group levels by the fifth week. In contrast, the group with the 30% porosity electrode exhibited limited improvement. Immunohistochemical analysis confirmed extensive nerve fiber growth within the 70% porous structure. Moreover, the 70% porosity electrode consistently acquired neural signals from more channels compared to the 30% porosity electrode, demonstrating its superior performance in sensory signal detection. These findings emphasize the importance of optimizing electrode porosity in the development of advanced neural interfaces, with the potential to enhance clinical outcomes in peripheral nerve repair and neuroprosthetic applications.

Introduction: Despite its efficacy, conventional center-based cardiac rehabilitation has several limitations which have led to the emergence of home-based programs and intensive cardiac rehabilitation as alternative methods for overcoming these limitations. Alternative methods for primary prevention have been recommended for similar reasons. Lifestyle modification is considered key to success in both primary and secondary prevention. Therefore, this primary prevention study aimed to investigate the efficiency of intensive lifestyle education and home-based programs involving unstructured exercise in urban forests to prevent coronary artery disease (CAD). The availability of urban forests as preventive exercise environments was also examined., Methods: Patients with risk factors for CAD participated in primary prevention using either FBEG (forest-based exercise group (FBEG, n = 11) or CBEG (center-based exercise group (CBEG, n = 17) for 12 weeks. The FBEG was provided with intensive residential lifestyle education and followed a home program that included performing exercise in an urban forest. The CBEG followed a conventional supervised exercise program at a fitness facility. Changes in body composition, cardiometabolic variables, and functional capacity were tested using a 2-way repeated ANOVA measurement. An independent t -test was used to examine the differences in weekly energy expenditure between the two groups., Results: Significant within-group differences were identified in body composition, cardiometabolic variables, and the 10-yr probability of CAD in both groups. However, the functional capacity, weekly energy expenditure, and attendance rate showed between-group differences, with superiority in the FBEG., Conclusion: Intensive lifestyle education and subsequent home-based programs with unstructured exercise in the forest were as effective as a conventional center-based program, with superiority in terms of the change of some variables. Intensive education on experiencing and habituating a healthy lifestyle seemed to play an important role in improving motivation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: We compared the osteoblastogenesis by serially administrating recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc)., Methods: The MC3T3-E1 preosteoblast cell line was differentiated for 1, 3, and 7 days with a treatment of OPG-Fc in 10~200 ng/mL concentration and the cell viability was evaluated by Cell Counting Kit-8 analysis. The level of differentiation from MC3T3-E1 cells to osteoblasts was determined by alkaline phosphatase activity. The level of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) manifestation, involved in osteoblast differentiation, was examined by real-time polymerase chain reaction and western blotting., Results: During MC3T3-E1 cell differentiation, the differentiation level was high with 1-day treatment using 100 ng/mL OPG-Fc. The treatment with 50 ng/mL rhBMP-2 for 7 days, followed by 1-day treatment with 100 ng/mL OPG-Fc produced the highest differentiation level, which was approximately 5.3 times that of the control group (p<0.05). The expression of Runx2 mRNA significantly increased, reaching 2.5 times the level of the control group under the condition of 7-day treatment with rhBMP-2 and 1-day treatment with OPG-Fc (p<0.001). The expression of Runx2 protein significantly increased to approximately 5.7 times that of the control group under the condition of 7-day treatment with rhBMP-2, followed by 1-day treatment with OPG-Fc (p<0.01). The expression of OPN protein showed no change from that of the control group under various conditions of rhBMP-2 and OPG-Fc combinations., Conclusion: These results imply that the treating preosteoblasts with rhBMP-2 first and then with OPG-Fc increased osteoblast differentiation efficacy., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (M pro ) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo M pro -inhibitor screening platform to evaluate the efficacies of M pro inhibitors based on M pro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and M pro -cleavage sequence, mimicking in vivo viral replication process mediated by M pro . By measuring the proteolytic activity of M pro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of M pro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering M pro inhibitors and may accelerate the development of therapeutics against COVID-19., (© 2024. The Author(s).)

Objective. This study aims to develop and validate a sophisticated fork-shaped neural interface (FNI) designed for peripheral nerves, focusing on achieving high spatial resolution, functional selectivity, and improved charge storage capacities. The objective is to create a neurointerface capable of precise neuroanatomical analysis, neural signal recording, and stimulation. Approach. Our approach involves the design and implementation of the FNI, which integrates 32 multichannel working electrodes featuring enhanced charge storage capacities and low impedance. An insertion guide holder is incorporated to refine neuronal selectivity. The study employs meticulous electrode placement, bipolar electrical stimulation, and comprehensive analysis of induced neural responses to verify the FNI's capabilities. Stability over an eight-week period is a crucial aspect, ensuring the reliability and durability of the neural interface. Main results. The FNI demonstrated remarkable efficacy in neuroanatomical analysis, exhibiting accurate positioning of motor nerves and successfully inducing various movements. Stable impedance values were maintained over the eight-week period, affirming the durability of the FNI. Additionally, the neural interface proved effective in recording sensory signals from different hind limb areas. The advanced charge storage capacities and low impedance contribute to the FNI's robust performance, establishing its potential for prolonged use. Significance. This research represents a significant advancement in neural interface technology, offering a versatile tool with broad applications in neuroscience and neuroengineering. The FNI's ability to capture both motor and sensory neural activity positions it as a comprehensive solution for neuroanatomical studies. Moreover, the precise neuromodulation potential of the FNI holds promise for applications in advanced bionic prosthetic control and therapeutic interventions. The study's findings contribute to the evolving field of neuroengineering, paving the way for enhanced understanding and manipulation of peripheral neural functions., (© 2024 IOP Publishing Ltd.)

The global threat posed by the COVID-19 pandemic has catalyzed the development of point-of-care (POC) molecular diagnostics. While loop-mediated isothermal amplification (LAMP) stands out as a promising technique among FDA-approved methods, it is occasionally susceptible to a high risk of false positives due to nonspecific amplification of a primer dimer. In this work, we report an enhancing LAMP technique in terms of assay sensitivity and reliability through streamlined integration with a nonpowered nanoelectric preconcentration (NPP). The NPP, serving as a sample preparation tool, enriched the virus concentration in samples prior to the subsequent LAMP assay. This enrichment enabled not only to achieve more sensitive assay but also to shorten the assay time for all tested clinical samples by ∼10 min compared to the conventional LAMP. The shortened assay time suppresses the occurrence of nonspecific amplification by not providing the necessary incubation time, effectively suppressing misidentification by false positives. Utilizing this technique, we also developed a prototype of the POC NPP-LAMP kit. This kit offers a streamlined diagnostic process for nontrained individuals, from the sample enrichment, transfer of the enriched sample to LAMP assays, which facilitates on-site/on-demand diagnosis of SARS-CoV-2. This development holds the potential to contribute toward preventing not only the current outbreak but also future occurrences of pandemic viruses.

Prominent techniques such as real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and rapid kits are currently being explored to both enhance sensitivity and reduce assay time for diagnostic tests. Existing commercial molecular methods typically take several hours, while immunoassays can range from several hours to tens of minutes. Rapid diagnostics are crucial in Point-of-Care Testing (POCT). We propose an approach that integrates a time-series deep learning architecture and AI-based verification, for the enhanced result analysis of lateral flow assays. This approach is applicable to both infectious diseases and non-infectious biomarkers. In blind tests using clinical samples, our method achieved diagnostic times as short as 2 minutes, exceeding the accuracy of human analysis at 15 minutes. Furthermore, our technique significantly reduces assay time to just 1-2 minutes in the POCT setting. This advancement has the potential to greatly enhance POCT diagnostics, enabling both healthcare professionals and non-experts to make rapid, accurate decisions., (© 2024. The Author(s).)

Background: Pure laparoscopic donor hepatectomy (PLDH) is an increasingly performed procedure despite its technical difficulties. This study introduced a selective liver parenchymal hanging maneuver and rubber band retraction technique for PLDH., Methods: We retrospectively reviewed perioperative data from 58 patients who underwent donor right hepatectomy (including right extended) between March 2009 and February 2021. Eighteen patients underwent open donor right hepatectomy (ODRH) and 38 patients underwent pure laparoscopic donor right hepatectomy (PLDRH)., Results: All PLDRH donors underwent the procedure without the need for open conversion. The median PLDRH operative time was 396.84 ± 72.459 min, the median PLDRH intraoperative bleeding amount was 496.05 ± 272.591 ml, and the warm ischemic time was 8.77 ± 3.062 min. Compared to ODRH, laparoscopic surgery showed further advantages in terms of postoperative hospital stay (10.94 ± 4.036 days vs. 8.03 ± 2.646 days, respectively, P = 0.01) and estimated blood loss (676.67 ± 321.046 ml vs. 496.05 ± 272.591 ml, respectively, P = 0.033)., Conclusions: The selective liver parenchymal hanging maneuver and rubber band retraction technique is a simple and effective pure laparoscopic procedure for donor hepatectomy. Our results demonstrate the safety and feasibility of this technique., Competing Interests: Declaration of competing interest The authors (Ju Man Ki, Sung Hwan Yoo, Gi Hong Choi, Dong Sub Yoon, Jin Hong Lim) declare no competing interests., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The safety of single-incision laparoscopic cholecystectomy (SILC) for acute cholecystitis (AC) has not yet been confirmed., Methods: This single-center retrospective study included patients who underwent laparoscopic cholecystectomy (LC) for AC between April 2010 and December 2020. Propensity scores were used to match patients who underwent SILC with those who underwent conventional multiport LC (CMLC) in the entire cohort and in the two subgroups., Results: A total of 1,876 patients underwent LC for AC, and 427 (22.8%) underwent SILC. In the propensity score-matched analysis of the entire cohort (404 patients in each group), the length of hospital stay (2.9 days vs. 3.5 days, p = 0.029) was shorter in the SILC group than in the CMLC group. No significant differences were observed in other surgical outcomes. In grade I AC (336 patients in each group), the SILC group showed poorer surgical outcomes than the CMLC group, regarding operation time (57.6 minutes vs. 52.4 minutes, p = 0.001) and estimated blood loss (22.9 mL vs. 13.1 mL, p = 0.006). In grade II/III AC (58 patients in each group), there were no significant differences in surgical outcomes between the two groups. Postoperative pain outcomes were also not significantly different in the two groups, regardless of severity., Conclusion: This study demonstrated that SILC had similar surgical and pain outcomes to CMLC in patients with AC; however, subgroup analysis showed that SILC was associated with poor surgical outcomes than CMLC in grade I AC. Therefore, SILC should be carefully performed in patients with AC by experienced hepatobiliary surgeons.

Lateral flow assays (LFAs) have emerged as indispensable tools for point-of-care testing during the pandemic era. However, the interpretation of results through unassisted visual inspection by untrained individuals poses inherent limitations. In our study, we propose a novel approach that combines computer vision (CV) and lightweight machine learning (ML) to overcome these limitations and significantly enhance the performance of LFAs. By incorporating CV-assisted analysis into the LFA assay, we achieved a remarkable three-fold improvement in analytical sensitivity for detecting Influenza A and for SARS-CoV-2 detection. The obtained R 2 values reached approximately 0.95, respectively, demonstrating the effectiveness of our approach. Moreover, the integration of CV techniques with LFAs resulted in a substantial amplification of the colorimetric signal specifically for COVID-19 positive patient samples. Our proposed approach, which incorporates a simple machine learning algorithm, provides substantial enhancements in assay sensitivity, improving diagnostic efficacy and accessibility of point-of-care testing without requiring significant additional resources. Moreover, the simplicity of the machine learning algorithm enables its standalone use on a mobile phone, further enhancing its practicality for point-of-care testing.

Background: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established., Methods: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis., Results: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3., Conclusion: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Regeneration of pathological wounds, such as diabetic ulcers, poses a significant challenge in clinical settings, despite the widespread use of drugs. To overcome clinical side effects and complications, drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events. This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass (namely, CoNZ), which exhibits high enzymatic/catalytic activity while releasing therapeutic ions. Cobalt oxide "Co 3 O 4 " tiny crystallites produced in situ through a chemical reaction with H 2 O 2 within CoNZ nanoparticles play a crucial role in scavenging ROS. Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process, promoting neovascularization, matrix deposition, and epithelial lining while reducing pro-inflammatory signs. Notably, CoNZ was highly effective in treating pathological wounds (streptozotocin-induced diabetic wounds). Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events. In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ. CoNZ-promoted angiogenesis was attributed to the release of cobalt ions, as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α. Finally, we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine. Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound, indicating the potential of CoNZ as a novel drug-free therapeutic approach., Competing Interests: HW Kim is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2023 The Authors.)

Decreased angiogenesis contributes to delayed wound healing in diabetic patients. Recombinant human bone morphogenetic protein-2 (rhBMP2) has also been demonstrated to promote angiogenesis. However, the short half-lives of soluble growth factors, including rhBMP2, limit their use in wound-healing applications. To address this limitation, we propose a novel delivery model using a protein transduction domain (PTD) formulated in a lipid nanoparticle (LNP). We aimed to determine whether a gelatin hydrogel dressing loaded with LNP-formulated PTD-BMP2 (LNP-PTD-BMP2) could enhance the angiogenic function of BMP2 and improve diabetic wound healing. In vitro, compared to the control and rhBMP2, LNP-PTD-BMP2 induced greater tube formation in human umbilical vein endothelial cells and increased the cell recruitment capacity of HaCaT cells. We inflicted large, full-thickness back skin wounds on streptozotocin-induced diabetic mice and applied gelatin hydrogel (GH) cross-linked by microbial transglutaminase containing rhBMP2, LNP-PTD-BMP2, or a control to these wounds. Wounds treated with LNP-PTD-BMP2-loaded GH exhibited enhanced wound closure, increased re-epithelialization rates, and higher collagen deposition than those with other treatments. Moreover, LNP-PTD-BMP2-loaded GH treatment resulted in more CD31- and α-SMA-positive cells, indicating greater neovascularization capacity than rhBMP2-loaded GH or GH treatments alone. Furthermore, in vivo near-infrared fluorescence revealed that LNP-PTD-BMP2 has a longer half-life than rhBMP2 and that BMP2 localizes around wounds. In conclusion, LNP-PTD-BMP2-loaded GH is a viable treatment option for diabetic wounds., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.I.Y. is an inventor of the patent related to this work filed by MET Life Sciences Co., Ltd. (Korean Patent Number: 10-2227966, PCT Application Number: PCT/KR2020/007011). N.H.K., H.S.K., and J.I.Y. are the founders of MET Life Sciences Co., Ltd. and shareholders. All other authors declare that they have no competing interests., (© The Author(s) 2023.)

Using biosensor to screen for Alzheimer's disease (AD) facilitates early detection of AD with high sensitivity and accuracy. This approach overcomes the limitations of conventional AD diagnostic methods, such as neuropsychological assessment and neuroimaging analysis. Here, we propose a simultaneous analysis of signal combinations generated by four crucial AD biomarkers (Amyloid beta 1-40 (Aβ 40 ), Aβ 42 , total tau 441 (tTau 441 ), and phosphorylated tau 181 (pTau 181 )) by inducing a dielectrophoretic (DEP) force on fabricated interdigitated microelectrode (IME) sensor. By applying an optimal DEP force, our biosensor selectively concentrates and filters the plasma-based AD biomarkers, exhibiting high sensitivity (limit of detection <100 fM) and selectivity in the plasma-based AD biomarkers detection (p < 0.0001). Consequently, it is demonstrated that a complex combined signal comprising four AD-specific biomarker signals (Aβ 40 - Aβ 42 + tTau 441 - pTau 181 ) can differentiate between patients with AD and healthy subjects with high accuracy (78.85%) and precision (80.95%) (p < 0.0001)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since many lateral flow assays (LFA) are tested daily, the improvement in accuracy can greatly impact individual patient care and public health. However, current self-testing for COVID-19 detection suffers from low accuracy, mainly due to the LFA sensitivity and reading ambiguities. Here, we present deep learning-assisted smartphone-based LFA (SMART AI -LFA) diagnostics to provide accurate decisions with higher sensitivity. Combining clinical data learning and two-step algorithms enables a cradle-free on-site assay with higher accuracy than the untrained individuals and human experts via blind tests of clinical data (n = 1500). We acquired 98% accuracy across 135 smartphone application-based clinical tests with different users/smartphones. Furthermore, with more low-titer tests, we observed that the accuracy of SMART AI -LFA was maintained at over 99% while there was a significant decrease in human accuracy, indicating the reliable performance of SMART AI -LFA. We envision a smartphone-based SMART AI -LFA that allows continuously enhanced performance by adding clinical tests and satisfies the new criterion for digitalized real-time diagnostics., (© 2023. The Author(s).)

Background: Although mRNA dysregulation can induce changes in mesenchymal stem cell (MSC) homeostasis, the mechanisms by which post-transcriptional regulation influences MSC differentiation potential remain understudied. PUMILIO2 (PUM2) represses translation by binding target mRNAs in a sequence-specific manner., Methods: In vitro osteogenic differentiation assays were conducted using human bone marrow-derived MSCs. Alkaline phosphatase and alizarin red S staining were used to evaluate the osteogenic potential of MSCs. A rat xenograft model featuring a calvarial defect to examine effects of MSC-driven bone regeneration. RNA-immunoprecipitation (RNA-IP) assay was used to determine the interaction between PUM2 protein and Distal-Less Homeobox 5 (DLX5) mRNA. Ovariectomized (OVX) mice were employed to evaluate the effect of gene therapy for postmenopausal osteoporosis., Results: Here, we elucidated the molecular mechanism of PUM2 in MSC osteogenesis and evaluated the applicability of PUM2 knockdown (KD) as a potential cell-based or gene therapy. PUM2 level was downregulated during MSC osteogenic differentiation, and PUM2 KD enhanced MSC osteogenic potential. Following PUM2 KD, MSCs were transplanted onto calvarial defects in 12-week-old rats; after 8 weeks, transplanted MSCs promoted bone regeneration. PUM2 KD upregulated the expression of DLX5 mRNA and protein and the reporter activity of its 3'-untranslated region. RNA-IP revealed direct binding of PUM2 to DLX5 mRNA. We then evaluated the potential of adeno-associated virus serotype 9 (AAV9)-siPum2 as a gene therapy for osteoporosis in OVX mice., Conclusion: Our findings suggest a novel role for PUM2 in MSC osteogenesis and highlight the potential of PUM2 KD-MSCs in bone regeneration. Additionally, we showed that AAV9-siPum2 is a potential gene therapy for osteoporosis., (© 2023. The Author(s).)

Cholera is a highly contagious and lethal waterborne disease induced by an infection with Vibrio cholerae (V. cholerae) secreting cholera toxin (CTx). Cholera toxin subunit B (CTxB) from the CTx specifically binds with monosialo-tetra-hexosyl-ganglioside (GM1) found on the exterior cell membrane of an enterocyte. Bioinspired by the pathological process of CTx, we developed an electrochemical biosensor with GM1-expressing Caco-2 cell membrane (CCM) on the electrode surface. Briefly, the electrode surface was functionalized with CCM using the vesicle fusion method. We determined the CTxB detection performances of Caco-2 cell membrane-coated biosensor (CCB) using electrochemical impedance spectroscopy (EIS). the CCB had an excellent limit of detection of ∼11.46 nM and a detection range spanning 100 ng/mL - 1 mg/mL. In addition, the CCB showed high selectivity against various interfering molecules, including abundant constituents of intestinal fluid and various bacterial toxins. The long-term stability of the CCBs was also verified for 3 weeks using EIS. Overall, the CCB has excellent potential for practical use such as point-of-care and cost-effective testing for CTxB detection in developing countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Highly sensitive rapid testing for COVID-19 is essential for minimizing virus transmission, especially before the onset of symptoms and in asymptomatic cases. Here, we report bioengineered enrichment tools for lateral flow assays (LFAs) with enhanced sensitivity and specificity (BEETLES 2 ), achieving enrichment of SARS-CoV-2 viruses, nucleocapsid (N) proteins and immunoglobulin G (IgG) with 3-minute operation. The limit of detection is improved up to 20-fold. We apply this method to clinical samples, including 83% with either intermediate (35%) or low viral loads (48%), collected from 62 individuals (n = 42 for positive and n = 20 for healthy controls). We observe diagnostic sensitivity, specificity, and accuracy of 88.1%, 100%, and 91.9%, respectively, compared with commercial LFAs alone achieving 14.29%, 100%, and 41.94%, respectively. BEETLES 2 , with permselectivity and tunability, can enrich the SARS-CoV-2 virus, N proteins, and IgG in the nasopharyngeal/oropharyngeal swab, saliva, and blood serum, enabling reliable and sensitive point-of-care testing, facilitating fast early diagnosis., (© 2023. The Author(s).)

A simple, affordable point of care test (POCT) is necessary for on-site detection of coronavirus disease 2019 (COVID-19). The lateral flow assay (LFA) has great potential for use in POCT mainly because of factors such as low time consumption, low cost, and ease of use. However, it lacks sensitivity and limits of detection (LOD), which are essential for early diagnostics. In this study, we proposed a non-powered preconcentrator (NPP) based on nanoelectrokinetics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Antigen (Ag) lateral flow assay. The non-powered preconcentrator is composed of glass fiber-based composite paper and ion permselective material, and it can be simply operated by force balancing gravitational, capillary, and depletion-induced forces. The proposed approach helps enrich the SARS-CoV-2 viral nucleocapsid (N) proteins based on a 10-min operation, and it improved the LOD by up to 10-fold. The corresponding virus enrichment, which was evaluated using the reverse-transcriptase polymerase chain reaction (RT-PCR), revealed an improvement in ΔCt values > 3. We successfully demonstrated the enhancement of the NPP-assisted LFA, we extended to applying it to clinical samples. Further, we demonstrated an affordable, easy-to-implement form of LFA by simply designing NPP directly on the LFA buffer tube., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Proteolysis of amyloids is related to prevention and treatment of amyloidosis. What if the conditions for proteolysis were the same to those for amyloid formation? For example, pepsin, a gastric protease is activated in an acidic environment, which, interestingly, is also a condition that induces the amyloid formation. Here, we investigate the competition reactions between proteolysis and synthesis of amyloid under pepsin-activated conditions. The changes in the quantities and nanomechanical properties of amyloids after pepsin treatment were examined by fluorescence assay, circular dichroism and atomic force microscopy. We found that, in the case of pepsin-resistant amyloid, a secondary reaction can be accelerated, thereby proliferating amyloids. Moreover, after this reaction, the amyloid became 32.4 % thicker and 24.2 % stiffer than the original one. Our results suggest a new insight into the proteolysis-driven proliferation and rigidification of pepsin-resistant amyloids., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson's disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

Background: Chondrocyte hypertrophy has been implicated in endochondral ossification and osteoarthritis (OA). In OA, hypertrophic chondrocytes contribute to the destruction and focal calcification of the joint cartilage. Although studies in this field have remarkably developed the modulation of joint inflammation using gene therapy and regeneration of damaged articular cartilage using cell therapy, studies that can modulate or prevent hypertrophic changes in articular chondrocytes are still lacking. Methods: In vitro hypertrophic differentiation and inflammation assays were conducted using human normal chondrocyte cell lines, TC28a2 cells. Human cartilage tissues and primary articular chondrocytes were obtained from OA patients undergoing total knee arthroplasty. Long non-coding RNAs (lncRNAs), LINC02035 and LOC100130207, were selected through RNA-sequencing analysis using RNAs extracted from TC28a2 cells cultured in hypertrophic medium. The regulatory mechanism was evaluated using western blotting, real-time quantitative polymerase chain reaction, osteocalcin reporter assay, RNA-immunoprecipitation (RNA-IP), RNA- in situ hybridization, and IP. Results: LncRNAs are crucial regulators of various biological processes. In this study, we identified two important lncRNAs, LINC02035 and LOC100130207, which play important roles in hypertrophic changes in normal chondrocytes, through RNA sequencing. Interestingly, the expression level of RUNX2, a master regulator of chondrocyte hypertrophy, was regulated at the post-translational level during hypertrophic differentiation of the normal human chondrocyte cell line, TC28a2. RNA-immunoprecipitation proved the potential interaction between RUNX2 protein and both lncRNAs. Knockdown (KD) of LINC02035 or LOC100130207 promoted ubiquitin-mediated proteasomal degradation of RUNX2 and prevented hypertrophic differentiation of normal chondrocyte cell lines, whereas overexpression of both lncRNAs stabilized RUNX2 protein and generated hypertrophic changes. Furthermore, the KD of the two lncRNAs mitigated the destruction of important cartilage matrix proteins, COL2A1 and ACAN, by hypertrophic differentiation or inflammatory conditions. We also confirmed that the phenotypic changes raised by the two lncRNAs could be rescued by modulating RUNX2 expression. In addition, the KD of these two lncRNAs suppressed hypertrophic changes during chondrogenic differentiation of mesenchymal stem cells. Conclusion: Therefore, this study suggests that LINC02035 and LOC100130207 contribute to hypertrophic changes in normal chondrocytes by regulating RUNX2, suggesting that these two novel lncRNAs could be potential therapeutic targets for delaying or preventing OA development, especially for preventing chondrocyte hypertrophy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Sinapic acid (SA), a hydroxycinnamic acid, is known to confer protection against oxidative stress, inflammation, diabetes, and liver disease. However, the effectiveness of SA in improving obesity remains obscure. Therefore, this study evaluated anti-obesity efficacy of SA and to elucidate its mechanism of action. Male mice were maintained for 16 weeks on high-fat diet (HFD) alone or with SA (0.004%, w/w) and bodyweight, fat mass, adipocyte size, food intake, and biochemical and molecular markers were evaluated. SA-supplemented mice demonstrated markedly decreased fat mass and adipocyte size compared to unsupplemented group, without any changes in bodyweight and food intake between the two groups. Plasma adipocytokines levels including leptin, resistin, monocyte chemoattractant protein (MCP)-1 and interleukin-6 were also markedly reduced by SA supplementation. SA tended to lower plasma insulin level and improved homeostatic index of insulin resistance and intraperitoneal glucose tolerance test in HFD-induced obese mice. The anti-adiposity effect of SA was maybe owing to down-regulation of the mRNA expression of lipogenic genes, including acetyl coenzyme A ( CoA ) carboxylase , fatty acid synthesis , stearoyl - CoA desaturase 1 , and phosphatidate phosphatase , and peroxisome proliferator-activated receptor γ, a transcription factor responsible for governing lipid metabolism, in adipose tissues. SA significantly down-regulated pro-inflammatory nuclear factor kappa B , MCP-1 , tumor necrosis factor-α , and Toll-like receptor 4 mRNA expression in adipose tissue. Thus, SA could be beneficial for the development of functional foods or herbal medications to combat obesity., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2022 by The Korean Society of Food Science and Nutrition. All rights Reserved.)

Studies of changes in fatty acids in response to environmental temperature changes have been conducted in many species, particularly mammals. However, few studies have considered aquatic invertebrates, even though they are particularly vulnerable to changes in environmental temperature. In this review, we summarize the process by which animals synthesize common fatty acids and point out differences between the fatty acid profiles of vertebrates and those of aquatic invertebrates. Unlike vertebrates, some aquatic invertebrates can directly synthesize polyunsaturated fatty acids (PUFAs), which can be used to respond to temperature changes. Various studies have shown that aquatic invertebrates increase the degree of saturation in their fatty acids through an increase in saturated fatty acid production or a decrease in PUFAs as the temperature increases. In addition, we summarize recent studies that have examined the complex effects of temperature and combinational stressors to determine whether the degree of saturation in aquatic invertebrates is influenced by other factors. The combined effects of carbon dioxide partial pressure, food quality, starvation, salinity, and chemical exposures have been confirmed, and fatty acid profile changes in response to high temperature were greater than those from combinational stressors., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Cell reprogramming can satisfy the demands of obtaining specific cell types for applications such as tissue regeneration and disease modeling. Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized nodules. Bulk and single-cell RNA sequencing identified a distinct ciOG population. ciOG formed mineralized tissue in an ectopic site of immunodeficiency mice, unlike the original fibroblasts. Osteogenic reprogramming was modulated under engineered culture substrates. When generated on a nanofiber substrate ciOG accelerated bone matrix formation in a calvarial defect, indicating that the engineered biomaterial promotes the osteogenic capacity of ciOG in vivo. Furthermore, the ciOG platform recapitulated the genetic bone diseases Proteus syndrome and osteogenesis imperfecta, allowing candidate drug testing. The reprogramming of human fibroblasts into osteogenic cells with a chemical cocktail thus provides a source of specialized cells for use in bone tissue engineering and disease modeling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The freshwater water flea Daphnia magna is a planktonic animal belonging to the Cladocera. To evaluate differences between two D. magna strains (KIT and NIES) in terms of life parameters and fatty acid profiles, we examined several endpoints. In the D. magna KIT strain, the numbers of total and cumulative offspring were lower at 23 °C and higher at 14 °C than in the D. magna NIES strain. However, at 14 °C, the D. magna KIT strain showed an increased lifespan. Although the n-3/n-6 polyunsaturated fatty acids (PUFA) ratio was always decreased at a low temperature, the PUFA ratio in the KIT strain had a higher value on day 3 than the NIES strain, which gave it higher adaptability to low temperature. In addition, we identified the elongation of very long chain fatty acids (elovl) and fatty acid desaturase (fad) genes, which are involved in fatty acid biosynthesis pathways, in the genomes of both D. magna KIT and NIES. The Elovl and Fad genes in both D. magna strains were highly conserved, including tandem duplicated Elovl 1/7 genes. This study provides new information about the molecular basis for the difference in temperature sensitivity between two strains of D. magna., (Copyright © 2022. Published by Elsevier Inc.)

A lateral flow assay (LFA) platform is a powerful tool for point-of-care testing (POCT), especially for self-testing. Although the LFA platform provides a simple and disposable tool for Coronavirus disease of 2019 (COVID-19) antigen (Ag) and antibody (Ab) screening tests, the lower sensitivity for low virus titers has been a bottleneck for practical applications. Herein, we report the combination of a microfluidic paper-based nanoelectrokinetic (NEK) preconcentrator and an LFA platform for enhancing the sensitivity and limit of detection (LOD). Biomarkers were electrokinetically preconcentrated onto a specific layer using the NEK preconcentrator, which was then coupled with LFA diagnostic devices for enhanced performance. Using this nanoelectrokinetic-assisted LFA (NEK-LFA) platform for self-testing, the severe acute respiratory syndrome coronavirus 2 Immunoglobulin G (SARS-CoV-2 IgG) sample was preconcentrated from serum samples. After preconcentration, the LOD of the LFA was enhanced by 32-fold, with an increase in analytical sensitivity (16.4%), which may offer a new opportunity for POCT and self-testing, especially in the COVID-19 pandemic and endemic global context., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The optimal indications for single-incision laparoscopic cholecystectomy (SILC) have not yet been established., Methods: This single-center retrospective study included consecutive patients who underwent SILC between April 2010 and June 2020. Difficult surgery (DS) (conversion to multiport or open cholecystectomy, adjacent organ injury, operation time of ≥90 minutes, or estimated blood loss of ≥100 mL) and poor postoperative outcome (PPO) (postoperative hospital stay ≥ 7 days or Clavien-Dindo grade ≥ II postoperative complications) were defined to comprehensively evaluate surgical difficulty and postoperative outcomes, respectively., Results: Of 1,405 patients (mean age, 51.2 years; 802 female [57.1%]), 427 (grade I, n = 358; grade II/III, n = 69) underwent SILC for acute cholecystitis (AC), 34 (2.4%) needed conversion to multiport (n = 33) or open cholecystectomy (n = 1), 7 (0.5%) had adjacent organ injury during surgery, and 49 (3.5%) developed postoperative complications. Of the patients, 89 and 52 had DS and PPO, respectively. In the multivariate analysis, grade I AC, grade II/III AC, and body mass index of ≥30 kg/m 2 were significant predictors of DS. Age of ≥70 years and DS were significant predictors of PPO. In a subgroup analysis of patients with AC, DS (9.5% vs. 27.5%, p < 0.001) and PPO (5.0% vs. 15.9%, p = 0.001) were more frequent in patients with grade II/III AC than in those with grade I AC., Conclusion: SILC is not recommended in patients with grade II/III AC and should be carefully performed by experienced and well-trained surgeons., (Copyright © 2022 The Journal of Minimally Invasive Surgery. All rights reserved.)

Purpose: This study was performed to investigate the role of the perioperative neutrophil-to-lymphocyte ratio (NLR) as an early predictor of major postoperative complications after total gastrectomy for gastric cancer., Methods: This single-center, retrospective study reviewed consecutive patients with gastric cancer who underwent total gastrectomy at a single institution from March 2009 to March 2021. The postoperative complications were graded according to the Clavien-Dindo classification. We analyzed the patient demographics and surgical outcomes according to the grade of postoperative complications in the major complications group (≥grade III) and the no major complications group (

Regenerating defective bone in patients with diabetes mellitus remains a significant challenge due to high blood glucose level and oxidative stress. Here we aim to tackle this issue by means of a drug- and cell-free scaffolding approach. We found the nanoceria decorated on various types of scaffolds (fibrous or 3D-printed one; named nCe-scaffold) could render a therapeutic surface that can recapitulate the microenvironment: modulating oxidative stress while offering a nanotopological cue to regenerating cells. Mesenchymal stem cells (MSCs) recognized the nanoscale (tens of nm) topology of nCe-scaffolds, presenting highly upregulated curvature-sensing membrane protein, integrin set, and adhesion-related molecules. Osteogenic differentiation and mineralization were further significantly enhanced by the nCe-scaffolds. Of note, the stimulated osteogenic potential was identified to be through integrin-mediated TGF-β co-signaling activation. Such MSC-regulatory effects were proven in vivo by the accelerated bone formation in rat calvarium defect model. The nCe-scaffolds further exhibited profound enzymatic and catalytic potential, leading to effectively scavenging reactive oxygen species in vivo. When implanted in diabetic calvarium defect, nCe-scaffolds significantly enhanced early bone regeneration. We consider the currently-exploited nCe-scaffolds can be a promising drug- and cell-free therapeutic means to treat defective tissues like bone in diabetic conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Backgrounds/aims: Postoperative pain management is a key to enhanced recovery after surgery. The aim of this study was to evaluate clinical effect of preoperative intravenous (IV) non-steroidal anti-inflammatory drugs (NSAIDs) on relief of postoperative pain in patients after laparoscopic cholecystectomy., Methods: This single center, retrospective study was conducted between September 2019 and May 2020. A total of 163 patients were divided into two groups: Ibuprofen group (preoperative IV ibuprofen, n = 77) and Ketorolac group (preoperative IV ketorolac, n = 86). The primary outcome was postoperative pain score measured immediately in the recovery room., Results: There was no difference in demographic characteristics between the two groups of patients. Postoperative pain score measured immediately in the recovery room was significantly higher in the Ibuprofen group than in the Ketorolac group (mean value: 5.09 vs. 4.61; p = 0.027). The number of patients who needed analgesics immediately in the recovery room was also higher in the Ibuprofen group than in the Ketorolac group (28 [36.4%] vs. 18 [20.9%]; p = 0.036)., Conclusions: In this study, preoperative IV injection with ketorolac reduced postoperative pain and analgesic requirement in the recovery room more effectively than that with ibuprofen. However, both showed similar effects on peak pain and pain at discharge. Numbers of patients requiring additional analgesics were also similar between the two groups.

Backgrounds/aims: Early recovery after surgery has become a popular trend. The aim of this study was to evaluate effect of nutritional intervention using Encover, an oral nutritional supplement, in patients undergoing hepato-biliary-pancreatic surgery., Methods: This single center, prospective case-control study was conducted in Gangnam Severance Hospital from September 2018 to April 2019. Through randomization, patients were divided into an experimental group (30 patients) and a control group (30 patients). At postoperative seven days, the experimental group was instructed to take two packs of Encover (JW Pharmaceutical, Seoul, Korea) daily for seven days. Body cell mass index was measured at seven days after surgery and 14 days after discharge and Patient-Generated Subjective Global Assessment (PG-SGA) was performed at 14 days after discharge., Results: Body cell mass index during outpatient follow-up was significantly decreased compared to that at discharge in both groups. However, the amount of body cell mass index showed no significant difference between postoperative seven days and outpatient follow- up in either group. During outpatient follow-up, the experimental group had a higher mean value of PG-SGA score than the control group (11.32 ± 3.46 vs. 9.48 ± 3.97; p = 0.037)., Conclusions: Short-term Encover doses after surgery may not produce significant results in weight gain or other body cell mass index. Encover did not significantly affect other dietary conditions based on PG-SGA.

Melanoma is visible unlike other types of cancer, but it is still challenging to diagnose correctly because of the difficulty in distinguishing between benign nevus and melanoma. We conducted a robust investigation of melanoma, identifying considerable differences in local elastic properties between nevus and melanoma tissues by using atomic force microscopy (AFM) indentation of histological specimens. Specifically, the histograms of the elastic modulus of melanoma displayed multimodal Gaussian distributions, exhibiting heterogeneous mechanical properties, in contrast with the unimodal distributions of elastic modulus in the benign nevus. We identified this notable signature was consistent regardless of blotch incidence by sex, age, anatomical site (e.g., thigh, calf, arm, eyelid, and cheek), or cancer stage (I, IV, and V). In addition, we found that the non-linearity of the force-distance curves for melanoma is increased compared to benign nevus. We believe that AFM indentation of histological specimens may technically complement conventional histopathological analysis for earlier and more precise melanoma detection.

Background: To date, a surgical method for single-incision laparoscopic cholecystectomy (SILC) has not been standardized. Therefore, this study aimed to introduce a standardized surgical method for SILC, in addition to reporting our experience over 10 years., Methods: Patients who underwent SILC at a single institution between April 2010 and December 2019 were included in this study. We analyzed the patient demographics and surgical outcomes according to the surgical method used: phase 1 (Konyang standard method, KSM) comprising initial 3-channel SILC, phase 2 (modified KSM, mKSM) comprising 4-channel SILC with a snake retractor, and phase 3 (commercial mKSM, C-mKSM) using a commercial 4-channel port., Results: Of 1372 patients (mean age, 51.3 years; 781 [56.9%] women), 418 (30.5%) surgeries were performed for acute cholecystitis (AC), 33 (2.4%) were converted to multiport or open cholecystectomy, and 49 (3.6%) developed postoperative complications. The mean operation time (OT) and length of postoperative hospital stay (LOS) were 51.9 min and 2.6 days, respectively. Overall, 325 patients underwent SILC with the KSM, 660 with the mKSM, and 387 with the C-mKSM. In the C-mKSM group, the number of patients with AC was the lowest (26.8% vs. 38.2% vs. 20.4%, p < 0.001) and the OT (51.7 min vs. 55.4 min vs. 46.1 min, p < 0.001), estimated blood loss (24.5 mL vs. 15.5 mL vs. 6.1 mL, p < 0.001), and LOS (2.8 days vs. 2.5 days vs. 2.3 days, p = 0.001) were significantly improved. The surgical outcomes were better in the non-AC group than in the AC group., Conclusion: Based on our 10 year experience, C-mKSM is a safe and feasible method of SILC in selected patients, although there were lower percentage of patients with AC compared to other groups., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dysfunction of mRNA or RNA-binding proteins (RBPs) causes cellular aging and age-related degenerative diseases; however, information regarding the mechanism through which RBP-mediated posttranscriptional regulation affects cellular aging and related disease processes is limited. In this study, PUM1 was found to be associated with the self-renewal capacity and aging process of human mesenchymal stem cells (MSC). PUM1 interacted with the 3'-untranslated region of Toll-like receptor 4 (TLR4) to suppress TLR4 mRNA translation and regulate the activity of nuclear factor-κB (NF-κB), a master regulator of the aging process in MSCs. PUM1 overexpression protected MSCs against H 2 O 2 -induced cellular senescence by suppressing TLR4-mediated NF-κB activity. TLR4-mediated NF-κB activation is a key regulator in osteoarthritis (OA) pathogenesis. PUM1 overexpression enhanced the chondrogenic potential of MSCs even under the influence of inflammation-inducing factors, such as lipopolysaccharide (LPS) or interleukin-1β (IL-1β), whereas the chondrogenic potential was reduced following the PUM1 knockdown-mediated TLR4 activation. PUM1 levels decreased under inflammatory conditions in vitro and during OA progression in human and mouse disease models. PUM1 knockdown in human chondrocytes promoted chondrogenic phenotype loss, whereas PUM1 overexpression protected the cells from inflammation-mediated disruption of the chondrogenic phenotype. Gene therapy using a lentiviral vector encoding mouse PUM1 showed promise in preserving articular cartilage integrity in OA mouse models. In conclusion, PUM1 is a novel suppressor of MSC aging, and the PUM1-TLR4 regulatory axis represents a potential therapeutic target for OA., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)