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Chai Young Lee,1,&ast; Sun Hye Shin,1,&ast; Hye Sook Choi,2 Yunjoo Im,1 Bo-Guen Kim,1 Ju Yeun Song,1 Daegeun Lee,1 Hye Yun Park,1 Jun Hyeok Lim3 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hye Yun Park, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Tel +82-2-3410-3429, Fax +82-2-3410-3849, Email hyeyunpark@skku.edu Jun Hyeok Lim, Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea, Tel +82-32-890-1038, Fax +82-32-890-3099, Email jhl@Inha.ac.krPurpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD.Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score.Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (< 20 ng/mL), insufficiency (20– 29 ng/mL), and sufficiency (≥ 30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20– 4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08– 5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw.Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.Keywords: chronic obstructive pulmonary disease, vitamin D, respiratory symptoms, COPD assessment test, modified Medical Research Council

Ina Jeong,1,* Jae-Hyun Lim,2,* Dong Kyu Oh,3 Woo Jin Kim,4 Yeon-Mok Oh3 1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea; 2Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Purpose: As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues. Patients and methods: First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity

Joel Hua-Liang Lim,1 Hong Liang Tey,1,2 Wei-Sheng Chong,11Department of Dermatology, National Skin Centre, 2Lee Kong Chian School of Medicine, Nanyang Technologicial University, SingaporeAbstract: Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud was first typified in 1927. With the help of electron microscopy, it has been elucidated that CRP arises due to aberrant keratinization. However, till date, there is no clear consensus on the etiologic trigger for CRP. Prevailing postulates include a bacterial trigger by Dietzia papillomatosis (type strain N 1280T), an exaggerated cutaneous response to Malassezia furfur, an endocrine basis stemming from insulin resistance, ultraviolet light-induced epidermal change, amyloid deposition, and a loss-of-function mutation in keratin 16. CRP typically presents as asymptomatic hyperpigmented papules and plaques with peripheral reticulation over the nape, axillae, upper chest, and upper back, occasionally with extension superior to the forehead and inferior to the pubic region. Dermoscopy may be used in the evaluation of CRP, but its diagnosis is made on clinical grounds given its nonspecific histopathological findings. Although successful treatment with topical keratolytics, retinoids, or antifungals has been reported, antibiotics, such as minocycline, at anti-inflammatory doses have emerged as a preferred therapeutic option. In this article, we review the diagnostic considerations in CRP and its therapeutic options. Keywords: Gougerot, Carteaud, reticulate, papillomatous, diagnosis, treatment

Seung-Jun Seo,1,* Chung Wung Bark,2,* Jae-Hong Lim,1 Yong-Gun Kim3 1Industrial Technology Convergence Center, Pohang Accelerator Laboratory, POSTECH, Pohang, Gyeongbuk, 2Department of Electrical Engineering, Gachon University, Seongnam, 3Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea *These authors contributed equally to this work Objective: Maxillary sinus floor augmentation has been shown to be the most predictable surgical technique for enhancing the bone volume in the posterior area of the maxilla. The purpose of this study was to analyze the serial slice image segmentation of newly formed bone and bone substitutes after sinus floor elevation using synchrotron radiation X-ray micro-computed tomography (SR-µCT).Materials and methods: Bone biopsy specimens were collected after 6 months of sinus floor augmentation. From the six bone biopsy specimens, the cross-sectional images at every 8 µm along the apical direction from the inferior border using serial segmentation from three-dimensional reconstructed X-ray images were analyzed. The amount of new bone and bone substitutes were measured at each slicing image (300–430 images per specimen).Results: The bone dynamics between the new bone and bone substitutes along the inferior–superior direction in humans after maxillary sinus floor elevation (MSFE) were analyzed using the whole sample region. Although these observations suggest that the specimens are structurally inhomogeneous, sinus floor elevation was confirmed to be a reliable surgical procedure for increasing the amount of bone.Conclusion: SR-µCT is highly effective for obtaining high-resolution images. An analysis of biological specimens using SR-µCT is quite reliable and this technique will be an important tool in the wide field of tissue engineering. Keywords: maxillary sinus floor elevation, synchrotron radiation, micro-computed tomography, serial segmentation, new bone formation

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

Ji-Ho Lim1,*, Sung-Kyun You1,*, Jong-Suep Baek1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea, 2College of Pharmacy, Chonnam National University, Buggu, Gwangju, South Korea *These authors contributed equally to this workBackground: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects.Methods: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated.Results: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone.Conclusion: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.Keywords: gemcitabine, polymeric microparticulates, mucoadhesive, enteric coating, cellular uptake, oral absorption

Chang-Gu Keum1*, Young-Wook Noh1*, Jong-Suep Baek1, Ji-Ho Lim1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea; 2College of Pharmacy, Chonnam National University, Yongbongdong, Buggu, Gwangju, South Korea *These authors contributed equally to this work Background: Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Methods: Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2–5 minutes of sonication time, 70–130 W sonication power, and 5–25 mg drug loading. Results: A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Conclusion: Our research shows that the choice of surfactant is important for controlled release of docetaxel. Keywords: docetaxel, nanoparticles, poly (lactic-co-glycolic acid), formulation variables, sonication, encapsulation efficiency

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Objective: This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor-beta1 (TGF-beta1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia. Method: We estimated the levels of sEng and TGF-beta1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women. Results: sEng levels were higher in cases than in controls, whereas TGF-beta1 levels were lower (P < 0.001). sEng levels, but not TGF-beta1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery (P < 0.001) and were increased in cases destined to deliver a small gestational age neonate (P < 0.001). Moreover, sEng levels, but not TGF-beta1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure (r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria (r = 0.42, P < 0.001). Conclusion: Early midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates. [ABSTRACT FROM AUTHOR]

Patients undergoing treatment for cancer have reported a variety of work-related problems. The aim of this study was to investigate the impact of a cancer diagnosis on employment status, and to identify relevant associated factors. This prospective cohort study was conducted at the National Cancer Center in Korea. Male patients newly diagnosed with stomach, liver, or colorectal cancers were recruited. Patients were interviewed and asked to complete an employment questionnaire every 3 months for 24 months. Clinical, sociodemographic and work-related factors were assessed. There were 305 male patients who had a primary diagnosis of cancer and underwent appropriate treatment. Of the 305 male patients who were employed at the time of diagnosis, 53% lost their job, and of these 23% later reemployed. In a multivariate Cox regression analysis, job loss was significantly associated with years of education, job characteristics and disease stage. Reemployment was significantly associated with disease stage and cancer site. Change of employment was common among cancer patients in Korea. With an understanding of the factors involved, it should be possible to reduce unnecessary work cessation, and increase the rate of employment of cancer survivors. Copyright (c) 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the provision of acupuncture services in the general practice setting.

Background: Nontypeable Haemophilus influenzae (NTHi) is an important respiratory pathogen implicated as an infectious trigger in chronic obstructive pulmonary disease, but its molecular interaction with human lung epithelial cells remains unclear. Herein, we tested that the hypothesis that NTHi induces the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) via activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B in pulmonary alveolar epithelial cells.Methods: Human alveolar epithelial A549 cells were infected with different concentrations of NTHi. The phosphorylation of p38 MAPK was detected by Western blot analysis, the DNA binding activity of NF-kappa B was assessed by electrophoretic mobility shift assay (EMSA), and the expressions of COX-1 and 2 mRNA and PGE2 protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. The roles of Toll-like receptor (TLR) 2 and TLR4, well known NTHi recognizing receptor in lung epithelial cell and gram-negative bacteria receptor, respectively, on the NTHi-induced COX-2 expression were investigated in the HEK293 cells overexpressing TLR2 and TLR4 in vitro and in the mouse model of NTHi-induced pneumonia by using TLR2 and TLR4 knock-out mice in vivo. In addition, the role of p38 MAPK and NF-kappa B on the NTHi-induced COX-2 and PGE2 expression was investigated by using their specific chemical inhibitors.Results: NTHi induced COX-2 mRNA expression in a dose-dependent manner, but not COX-1 mRNA expression in A549 cells. The enhanced expression of PGE2 by NTHi infection was significantly decreased by pre-treatment of COX-2 specific inhibitor, but not by COX-1 inhibitor. NTHi induced COX-2 expression was mediated by TLR2 in the epithelial cell in vitro and in the lungs of mice in vivo. NTHi induced phosphorylation of p38 MAPK and up-regulated DNA binding activity of NF-kappa B. Moreover, the expressions of COX-2 and PGE2 were significantly inhibited by specific inhibitors of p38 MAPK and NF-kappa B. However, NTHi-induced DNA binding activity of NF-kappa B was not affected by the inhibition of p38 MAPK.Conclusion: NTHi induces COX-2 and PGE2 expression in a p38 MAPK and NF-kappa B-dependent manner through TLR2 in lung epithelial cells in vitro and lung tissues in vivo. The full understanding of the role of endogenous anti-inflammatory PGE2 and its regulation will bring new insight to the resolution of inflammation in pulmonary bacterial infections. [ABSTRACT FROM AUTHOR]

Memristors have emerged as promising devices for enabling efficient multiply-accumulate (MAC) operations in crossbar arrays, crucial for analog in-memory computing (AiMC). However, variations in memristors and associated circuits can affect the accuracy of analog computing. Typically, this is mitigated by on-chip training, which is challenging for memristors with limited endurance. We present a hardware-software codesign using magnetic tunnel junction (MTJ)-based AiMC off-chip calibration that achieves software accuracy without costly on-chip training. Hardware-wise, MTJ devices exhibit ultralow cycle-to-cycle variations, as experimentally evaluated over 1 million mass-produced devices. Software-wise, leveraging this, we propose an off-chip training method to adjust deep neural network parameters, achieving accurate AiMC inference. We validate this approach with MAC operations, showing improved transfer curve linearity and reduced errors. By emulating large-scale neural network models, our codesigned MTJ-based AiMC closely matches software baseline accuracy and outperforms existing off-chip training methods, highlighting MTJ's potential in AI tasks.

Genetic modification of genes such as recombination activating gene 2 (RAG2) or interleukin-2 receptor-γ (IL2RG) results in pigs exhibiting severe combined immunodeficiency (SCID). Pigs presenting a SCID phenotype are important animal models that can be used to establish xenografts and to study immune system development and various immune-related pathologies. However, due to their immunocompromised nature, SCID pigs have shortened lifespans and are notoriously difficult to maintain. The failure-to-thrive phenotype makes the establishment of a breeding population of RAG2/IL2RG double-knockout pigs virtually impossible. Here, to overcome this limitation, we investigated whether reconstituting the immune system of SCID piglets with a fetal bone allograft would extend their lifespan. Following intramuscular transplantation, allografts gave rise to lymphocytes expressing T cell (CD3, CD4 and CD8), B cell (CD79α) and natural killer cell (CD335) lineage markers, which were detected in circulation as well in the spleen, liver, bone marrow and thymic tissues. The presence of lymphocytes indicates broad engraftment of donor cells in the recipient SCID pigs. Unlike unreconstituted SCID pigs, the engrafted animals thrived and reached puberty under standard housing conditions. This study demonstrates a novel method to extend the survival of SCID pigs, which may improve the availability and use of SCID pigs as a biomedical animal model., (© 2024. The Author(s).)

A 57-year-old female presented with chest discomfort and exertional dyspnea but no other respiratory symptoms or history of malignancy. Chest CT revealed multifocal centrilobular nodules with ground-glass opacity in both lungs. Thoracoscopic wedge resection was done, and histological examination confirmed interstitial meningothelial-like nodules, consistent with diffuse meningotheliomatosis. The patient was discharged without complications and showed no disease progression on follow-up CT at 3 months, maintaining stability during 6 months of outpatient observation. Diffuse pulmonary meningotheliomatosis is an exceedingly rare condition, but this may be one of the causative etiologies in patients with diffuse bilateral pulmonary nodules., Competing Interests: No conflict of interest exists., (© 2024 The Authors.)

As the regenerative mechanisms of biological organisms, self-healing provides useful functions for soft electronics or associated systems. However, there have been few examples of soft electronics where all components have self-healing properties while also ensuring compatibility between components to achieve multifunctional and resilient bio-integrated electronics. Here, we introduce a stretchable, biodegradable, self-healing conductor constructed by combination of two layers: (i) synthetic self-healing elastomer and (ii) self-healing conductive composite with additives. Abundant dynamic disulfide and hydrogen bonds of the elastomer and conductive composite enable rapid and complete recovery of electrical conductivity (~1000 siemens per centimeter) and stretchability (~500%) in response to repetitive damages, and chemical interactions of interpenetrated polymer chains of these components facilitate robust adhesion strength, even under extreme mechanical stress. System-level demonstration of soft, self-healing electronics with diagnostic/therapeutic functions for the urinary bladder validates the possibility for versatile, practical uses in biomedical research areas.

SeS 2 positive electrodes are promising components for the development of high-energy, non-aqueous lithium sulfur batteries. However, the (electro)chemical and structural evolution of this class of positive electrodes is not yet fully understood. Here, we use operando physicochemical measurements to elucidate the dissolution and deposition processes in the SeS 2 positive electrodes during lithium sulfur cell charge and discharge. Our analysis of real-time imaging reveals the pivotal role of Se in the SeS 2 nucleation process, while S enables selective depositions. During the initial discharge, SeS 2 converts into Se and S separately, with the dissolved Se acting as nucleation sites due to their lower nucleation potential. The Se effectively catalyzes the growth of S particles, resulting in improved lithium sulfur battery performance compared to cells using positive electrodes containing only Se or S as active materials. By adjusting the Se-to-S ratio, we demonstrate that a low concentration of Se enables uniform catalytic sites, promotes the homogeneous distribution of S and favours improved lithium sulfur battery performance., (© 2024. The Author(s).)

Evaluating dietary guidelines using diet quality (DQ) offers valuable insights into the healthfulness of a population's diet. We conducted a forensic analysis using DQ metrics to compare the Malaysian Dietary Guidelines (MDG-2020) with its former version (MDG-2010) in relation to cardiometabolic risk (CMR) for an adult Malaysian population. A DQ analysis of cross-sectional data from the Malaysia Lipid Study (MLS) cohort (n = 577, age: 20-65yrs) was performed using the healthy eating index-2015 (HEI-2015) framework in conformation with MDG-2020 (MHEI 2020 ) and MDG-2010 (MHEI 2010 ). Of 13 dietary components, recommended servings for whole grain, refined grain, beans and legumes, total protein, and dairy differed between MDGs. DQ score associations with CMR, dietary patterns and sociodemographic factors were examined. Out of 100, total DQ scores of MLS participants were 'poor' for both MHEI 2020 (37.1 ± 10.3) and MHEI 2010 (39.1 ± 10.4), especially among young adults, males, Malays, and those frequently 'eating out' as well as those with greatest adherence to Sugar-Sweetened Beverages pattern and lowest adherence to Food Plant pattern. Both metrics shared similar correlations with CMR markers, with MHEI 2020 exhibiting stronger correlations with WC, BF%, TG, insulin, HOMA2-IR, and small LDL than MHEI 2010 , primarily attributed to reduced refined grain serving. Notably, participants with the highest adherence to MHEI 2020 scores exhibited significantly reduced odds for elevated TG (AOR 0.44, 95% CI 0.21-0.93, p = 0.030), HOMA2-IR (AOR 0.44, 95% CI 0.21-0.88, p = 0.022), and hsCRP (AOR 0.54, 95% CI 0.31-0.96, p = 0.040, compared to those with the lowest adherence. Each 5-unit increase in MHEI 2020 scores reduced odds for elevated BMI (- 14%), WC (- 9%), LDL-C (- 32%), TG (- 15%), HOMA2-IR (- 9%) and hsCRP (- 12%). While MHEI 2020 scores demonstrated better calibration with CMR indicators, the overall sub-optimally 'poor' DQ scores of this population call for health promotion activities to target the public to achieve adequate intake of healthful fruits, non-starchy vegetables and whole grain, and moderate intake of refined grain, added sugar and saturated fat., (© 2024. The Author(s).)

In this study, we explored the application of Short-Wave Infrared (SWIR) hyperspectral imaging combined with Competitive Adaptive Reweighted Sampling (CARS) and advanced regression models for the non-destructive assessment of protein content in dried laver. Utilizing a spectral range of 900-1700 nm, we aimed to refine the quality control process by selecting informative wavelengths through CARS and applying various preprocessing techniques (standard normal variate [SNV], Savitzky-Golay filtering [SG], Orthogonal Signal Correction [OSC], and StandardScaler [SS]) to enhance the model's accuracy. The SNV-OSC-StandardScaler- Support vector regression (SVR) model trained on CARS-selected wavelengths significantly outperformed the other configurations, achieving a prediction determination coefficient (Rp 2 ) of 0.9673, root mean square error of prediction of 0.4043, and residual predictive deviation of 5.533. These results highlight SWIR hyperspectral imaging's potential as a rapid and precise tool for assessing dried laver quality, aiding food industry quality control and dried laver market growth., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (© 2024 The Authors. Published by Elsevier Ltd.)

Obesity often leads to inadequate angiogenesis in expanding adipose tissue, resulting in inflammation and insulin resistance. We explored the role of placental growth factor (PlGF) in metabolic syndrome (MS) using mice models of type 2 diabetes, high-fat diet, or aging. Reduced serum PlGF levels were associated with decreased insulin sensitivity and development of MS features. PlGF was localized within endothelial cells and pericytes of adipose tissue. In vitro, low PlGF levels in hypoxic conditions worsened oxidative stress, apoptosis, and reduced autophagy. This was associated with a reduction in expression of vascular endothelial growth factor (VEGF)-A/VEGF-R1/-R2, which was influenced by a decrease and increase in PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa ++ /eNOS and PTEN/GSK3β axes, respectively. PlGF-knockout mice exhibited MS traits through alterations in the same signaling pathways, and these changes were mitigated by recombinant PlGF and metformin. These enhanced angiogenesis and lipid metabolism, underscoring PlGF's role in age-related MS and its potential as a therapeutic target., 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 © 2024. Published by Elsevier Inc.)

Introduction: Adolescents are especially susceptible to the harmful effects of secondhand smoke exposure. Mental health issues may be one of these negative consequences. This study aimed to explore the association between secondhand smoke exposure and anxiety among Korean adolescents., Methods: This study used the nationwide representative cross-sectional data obtained from the 4-year (2020-2023) Korea Youth Risk Behavior Survey. In total, 214514 individuals aged 12-18 years were included in this study (109910 males and 104604 females). Secondhand smoke exposure was assessed based on responses to questions concerning the days they were exposed (at home and in public places), while anxiety levels were measured using the Generalized Anxiety Disorder 7 scale. Multivariable logistic regression analysis divided by sex was performed to explore the association (p=0.0173 for interaction by secondhand smoke exposure and sex), and adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated., Results: Among the study population, 8.8% of the male and 15.6% of the female participants had anxiety. After adjusting for covariates, adolescents with secondhand smoke exposure had a higher likelihood of reporting anxiety than those without the exposure (male, OR=1.23; 95% CI: 1.16-1.29; female, OR=1.27; 95% CI: 1.21-1.33). In additional stratified analyses, this association was more prominent among those who were never smokers, were exposed for more days, and had severe levels of anxiety., Conclusions: This study found that secondhand smoke exposure was associated with anxiety in adolescents; hence, proper political interventions to reduce secondhand smoke exposure may be required., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Lim J.H. et al.)

Background: Quality of life (QOL) is associated with mortality in dialysis patients. However, the impact of QOL index or score on elderly patients undergoing maintenance dialysis is unclear. We analyzed the relationship between QOL domains and survival in elderly end-stage renal disease (ESRD) patients on dialysis., Methods: We included 492 incident ESRD patients aged ≥65 years from a Korean nationwide prospective cohort study who were assessed for QOL with a follow-up duration of 67.3 ± 34.6 months after dialysis initiation. Their QOL was evaluated using the Kidney Disease Quality of Life (KDQOL) instrument, and the effect of each QOL domain on mortality was analyzed. Multivariable Cox regression analysis was performed to identify independent risk factors for death after adjusting for confounding factors., Results: Low physical component summary (PCS) and Short Form-36 score were significantly associated with low survival rate ( P  < .001 and P  = .017, respectively), whereas the mental component summary and ESRD-targeted item scores were not correlated with survival rate. Multivariable Cox regression analysis confirmed that only a high PCS score was associated with better survival (hazard ratio 0.71; 95% confidence interval 0.52-0.97; P  = .031). Linear regression analysis revealed that age, sex, modified Charlson comorbidity index, albumin and intact parathyroid hormone were associated with PCS. Among the PCS items, only the physical functioning score was significantly associated with mortality ( P  = .017)., Conclusion: PCS was an independent risk factor for death in elderly ESRD patients. A higher physical functioning score was associated with a better outcome, suggesting the importance of physical condition in elderly dialysis patients., Competing Interests: The authors declare no competing interests, (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p < 0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women., Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Formyl peptide receptor 2 (FPR2) is a receptor for formylated peptides and specific pro-resolving mediators, and is involved in various inflammatory processes. Here, we aimed to elucidate the role of FPR2 in dendritic cell (DC) function and autoimmunity-related central nervous system (CNS) inflammation by using the experimental autoimmune encephalomyelitis (EAE) model. EAE induction was accompanied by increased Fpr2 mRNA expression in the spinal cord. FPR2-deficient ( Fpr2 KO ) mice displayed delayed onset of EAE compared to wild-type (WT) mice, associated with reduced frequencies of Th17 cells in the inflamed spinal cord at the early stage of the disease. However, FPR2 deficiency did not affect EAE severity after the disease reached its peak. FPR2 deficiency in mature DCs resulted in decreased expression of Th17 polarizing cytokines IL6, IL23p19, IL1β, and thereby diminished the DC-mediated activation of Th17 cell differentiation. LPS-activated FPR2-deficient DCs showed upregulated Nos2 expression and nitric oxide (NO) production, as well as reduced oxygen consumption rate and impaired mitochondrial function, including decreased mitochondrial superoxide levels, lower mitochondrial membrane potential and diminished expression of genes related to the tricarboxylic acid cycle and genes related to the electron transport chain, as compared to WT DCs. Treatment with a NO inhibitor reversed the reduced Th17 cell differentiation in the presence of FPR2-deficient DCs. Together, by regulating DC metabolism, FPR2 enhances the production of DC-derived Th17-polarizing cytokines and hence Th17 cell differentiation in the context of neuroinflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lim, Neuwirth, Chung, Grossklaus, Soehnlein, Hajishengallis and Chavakis.)

Obstructive sleep apnea (OSA) is a common sleep disorder characterised by recurrent upper airway collapse during sleep. Alcohol consumption has been linked to an increased risk of OSA due to its effects on the upper airway and body mass index (BMI). We aimed to investigate the correlation between alcohol use disorders and OSA. We used 11,859 participants data from Korean National Health and Nutrition Examination Surveys. The variable of interest was alcohol use disorder, measured using the Alcohol Use Disorders Identification Test, and the dependent variable was the risk of OSA, measured using the Snoring, Tiredness, Observed apnea, high blood Pressure, BMI, age, neck circumference, and male gender questionnaires. Multiple logistic regression was used to assess the association between alcohol use disorder and OSA risk after adjusted analysis. A significant association was found between alcohol use disorder and OSA (adjusted odds ratio [aOR] 2.14, 95% confidence interval [CI] 1.93-2.37). In the unemployed group, those with alcohol use disorder had the highest odds of being at risk of OSA compared with those who did not have this disorder (aOR 2.45, 95% CI 2.04-2.95). The OSA risk increased as the snoring frequency, amount of alcohol consumed, and frequency of binge drinking increased. This study suggests an association between alcohol use disorders and the risk of OSA. The frequency of alcohol consumption, quantity of alcohol consumed, and snoring frequency were associated with the risk of OSA. Therefore, ceasing alcohol consumption is recommended as an effective approach to enhancing sleep quality., (© 2023 European Sleep Research Society.)

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Aquaporins (AQPs) are a family of integral membrane proteins that selectively transport water and glycerol across the cell membrane. Because AQPs are involved in a wide range of physiological functions and pathophysiological conditions, AQP-based therapeutics may have the broad potential for clinical utility, including for disorders of water and energy balance. However, AQP modulators have not yet been developed as suitable candidates for clinical applications. In this study, to identify potential modulators of AQPs, we screened 31 natural products by measuring the water and glycerol permeability of mouse erythrocyte membranes using a stopped-flow light scattering method. None of the tested natural compounds substantially affected the osmotic water permeability. However, several compounds considerably affected the glycerol permeability. Stichoposide C increased the glycerol permeability of mouse erythrocyte membranes, whereas rhizochalin decreased it at nanomolar concentrations. Immunohistochemistry revealed that AQP7 was the main aquaglyceroporin in mouse erythrocyte membranes. We further verified the effects of stichoposide C and rhizochalin on aquaglyceroporins using human AQP3-expressing keratinocyte cells. Stichoposide C, but not stichoposide D, increased AQP3-mediated transepithelial glycerol transport, whereas the peracetyl aglycon of rhizochalin was the most potent inhibitor of glycerol transport among the tested rhizochalin derivatives. Collectively, stichoposide C and the peracetyl aglycon of rhizochalin might function as modulators of AQP3 and AQP7, and suggests the possibility of these natural products as potential drug candidates for aquaglyceroporin modulators.

Background: The calcar of the proximal humerus is a fundamental structure for medial humeral column support. This study aimed to assess the outcome of osteosynthesis across cases of unstable proximal humerus fractures (PHFs) with medial calcar comminution, following treatment with a PHILOS locking plate and medial support screw (MSS)., Methods: Between January 2010 and December 2018, we retrospectively analyzed the outcomes of 121 cases of osteosynthesis for PHFs with medial column disruption. For the medial support, at least one oblique screw was inserted within 5 mm of the subchondral bone in the inferomedial quadrant of the humeral head. All patients were categorized into two groups: 26 patients in the single MSS group, and 95 in the multiple MSS group. Follow-up after at least an year involved clinical and radiographic outcome evaluations, and correspondingly measuring the Constant-Murley score, University of California, Los Angeles (UCLA) shoulder scale, pain visual analogue scale (VAS), major complications, neck-shaft angle (NSA), humeral head height (HHH), and the eventual time to bone union. Risk factors for the major complications were assessed by multivariate logistic regression analyses., Results: The cohort's mean age was 64.4 ± 15.4 years, and the mean follow-up duration was 19.5 ± 7.6 months. At the final follow-up, between the single MSS and multiple MSS groups, no significant differences in the Constant-Murley score (p = 0.367), UCLA score (p = 0.558), VAS (p = 0.571), time to bone union (p = 0.621), NSA loss (p = 0.424), and HHH loss (p = 0.364) were observed. The incidence of complications (p = 0.446) based on the number of MSS were not significantly different. The initial insufficient reduction after surgery (of NSA < 125°) was found to be a significant risk factor for post-surgical complications., Conclusions: To treat unstable PHFs, the use of at least one MSS along with a locking plate system is sufficient to achieve satisfactory outcomes. Successful operative treatment using a locking plate for PHF treatment is inherent in anatomical fracture reduction, coupled with medial column support., (© 2024. The Author(s).)

This study aimed to investigate distress levels, using the distress thermometer (DT), and the factors associated with distress in postoperative patients with pancreatobiliary cancer. This study retrospectively investigated 155 patients who underwent surgery for pancreatobiliary cancer between December 1, 2019 and September 30, 2021. The DT and problem list were used to measure distress. Descriptive statistics, t-test, and multivariate logistic regression analysis were used to analyze the data. Of the 155 patients, 16.8% (n = 26) and 83.2% (n = 129) were in the mild-distress and moderate-to-severe distress groups, respectively. The average DT score was 6.21; that for the mild-distress and moderate-to-severe distress groups was 2.46 and 6.97, respectively. More patients in the moderate-to-severe distress group reported having problems of "sadness" (χ 2  = 4.538, P < 0.05), "indigestion" (χ 2  = 10.128, P < 0.001), "eating" (χ 2  = 6.147, P < 0.013), and "getting around" (χ 2  = 4.275, P < 0.039) than in the mild-distress group. In addition, occupation status (odds ratio [OR] = 0.342, 95% confidence interval [CI] = 0.133-0.879, P = 0.026) and indigestion (OR = 5.897, 95% CI = 1.647-21.111, P = 0.006) were independent risk factors for the presence of severe distress. Patients with pancreatobiliary cancer demonstrated elevated levels of psychological distress. Healthcare providers should therefore be vigilant when evaluating patients for distress and providing appropriate referrals, particularly those who are unemployed or have indigestion., (© 2024. The Author(s).)

Background: The association between atopic dermatitis and childhood overweight and obesity has been studied extensively, but the results are inconclusive; most studies have focused on body mass index as a measure of obesity, with few investigating the relationship with underweight. Therefore, this study aimed to investigate the association between body mass index levels and atopic dermatitis in Korean adolescents., Methods: 3-year (2019-2021) of Korea Youth Risk Behavior Web-based Survey were used. Body mass index was used to measure obesity and a recent diagnosis within the past year was used as the criterion for atopic dermatitis. Multiple logistic regression analyses were performed to explore the associations. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated., Results: A total of 144,183 adolescents aged 12-18 years were included in this study (74,704 males and 69,479 females). Over the past year, 5.4% of males and 7.3% of females were diagnosed with atopic dermatitis in the study population. Adolescents with normal weight (males [OR: 1.19, CI: 1.02-1.38]; females [OR: 1.26, CI: 1.10-1.43]) and overweight (males [OR: 1.37, CI: 1.16-1.61]; females [OR: 1.37, CI: 1.19-1.58]) were more likely to develop atopic dermatitis than underweight., Conclusion: Increased degree of obesity may contribute to the development of atopic dermatitis. The normal-weight and obese adolescents had higher likelihood of developing atopic dermatitis compared with the underweight adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O 2 -• ) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.

A comprehensive molecular understanding of carbohydrate aggregation is key to optimize carbohydrate utilization and to engineer bioinspired analogues with tailored shape1s and properties. However, the lack of well-defined synthetic standards has substantially hampered advances in this field. Herein, we employ a phosphorylation-assisted strategy to synthesize previously inaccessible long oligomers of cellulose, chitin, and xylan. These oligomers were subjected to enzyme-triggered assembly (ETA) for the on-demand formation of well-defined carbohydrate nanomaterials, including elongated platelets, helical bundles, and hexagonal particles. Cryo-electron microscopy and electron diffraction analysis provided molecular insights into the aggregation behavior of these oligosaccharides, establishing a direct connection between the resulting morphologies and the oligosaccharide primary sequence. Our findings demonstrate that ETA is a powerful approach to elucidate the intrinsic aggregation behavior of carbohydrates in nature. Moreover, the ability to access a diverse array of morphologies, expanded with a non-natural sequence, underscores the potential of ETA, coupled with sequence design, as a robust tool for accessing programmable glycan architectures., (© 2024 Wiley‐VCH GmbH.)

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.)

Ageratum conyzoides , an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a R878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss., Competing Interests: Declaration of interests P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. M.G.N. is an advisory board member of Cell and scientific founder of Lemba, TTxD, and Biotrip., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)