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Background: Post-marketing surveillance is crucial for gathering data on vaccine reactogenicity, enhancing public trust in immunization, and promoting vaccine uptake. This study aims to characterize adverse events following immunization (AEFIs) and estimate the incidence rates of adverse reactions (ARs) associated with vaccines included in Taiwan’s Expanded Program on Immunization (EPI). This study utilizes data from Taiwan’s Vaccine Injury Compensation Program (VICP). Methods: Vaccine injury claims submitted to the VICP between 2014 and 2019 were analyzed. ARs were defined as AEFIs adjudicated as “related” or “indeterminate” by the VICP committee. Data on the annual number of vaccine doses administered were obtained from the Taiwan CDC, which helped calculate the AR incidence rates. Results: A total of 491 AEFI claims were reviewed, with 327 (66.6%) categorized as ARs. The AEFIs were mainly associated with the Bacillus Calmette–Guérin (BCG) vaccine (43.4%) and the seasonal influenza vaccine (22.0%). Most EPI vaccines demonstrated low AR incidence rates, ranging from 1.68 to 13.6 per million doses, with the exception of BCG, which exhibited 162.5 ARs per million doses. Shifting BCG immunization from below 5 months to at least 5 months reduced osteomyelitis incidence significantly, from 41.4 to 7.9 (p = 0.0014), but increased abscess and lymphadenitis cases. Conclusions: EPI vaccines in Taiwan are highly safe, with minimal AR incidences in the general population. The BCG vaccine remains an exception, occasionally causing severe ARs like osteomyelitis. Adjusting the immunization schedule to an older age may mitigate some of these adverse effects.

Rice bran, which is abundant in dietary fiber and phytochemicals, provides multiple health benefits. Nonetheless, its effects on neuroinflammation and gut microbiota in postmenopausal conditions are still not well understood. This study investigated the effects of rice bran and/or tea seed oil supplementation in d-galactose-injected ovariectomized (OVX) old mice fed a fructose drink. The combination of d-galactose injection, ovariectomy, and fructose drink administration creates a comprehensive model that simulates aging in females under multiple metabolic stressors, including oxidative stress, estrogen deficiency, and high-sugar diets, and allows the study of their combined impact on metabolic disorders and related diseases. Eight-week-old and 6–8-month-old female C57BL/6 mice were used. The mice were divided into six groups: a sham + young mice, a sham + old mice, an OVX + soybean oil, an OVX + soybean oil with rice bran, an OVX + tea seed oil (TO), and an OVX + TO with rice bran diet group. The OVX groups were subcutaneously injected with d-galactose (100 mg/kg/day) and received a 15% (v/v) fructose drink. The rice bran and tea seed oil supplementation formed 10% of the diet (w/w). The results showed that the rice bran with TO diet increased the number of short-chain fatty acid (SCFA)-producing Clostridia and reduced the number of endotoxin-producing Tannerellaceae, which mitigated imbalances in the gut–liver–brain axis. Rice bran supplementation reduced the relative weight of the liver, levels of hepatic triglycerides and total cholesterol; aspartate transaminase and alanine aminotransferase activity; brain levels of proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α; and plasma 8-hydroxy-2-deoxyguanosine. This study concludes that rice bran inhibits hepatic fat accumulation, which mitigates peripheral metaflammation and oxidative damage and reduces neuroinflammation in the brain.

To assess the effects of hydroxysafflor yellow A (HSYA) on ultraviolet A (UVA)-induced damage in HaCaT keratinocytes. HaCaT keratinocytes were UVA-irradiated, and the effects of HSYA on cell viability, reactive oxygen species (ROS) generation, lipid peroxidation, and messenger (m)RNA expression were measured. mRNA expressions of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and cyclooxygenase (COX)-2 were determined by a real-time polymerase chain reaction (RT-PCR). UVA exposure led to a decrease in cell viability and an increase in ROS generation in HaCaT keratinocytes. HSYA effectively increased the viability of HaCaT keratinocytes after UVA exposure and protected them from UVA-induced oxidative stress. Moreover, HSYA inhibited expressions of MMP-1, MMP-2, MMP-9, and COX-2 by HaCaT keratinocytes with UVA-induced photodamage. Our results suggest that HSYA can act as a free radical scavenger when keratinocytes are photodamaged. HSYA has the potential to be a skin-protective ingredient against UVA-induced photodamage.

During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our findings demonstrated that PKM2 differentially modulated head and neck tumorigenicity via metabolic reprogramming.

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021–June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24–48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24–48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24–48 h postpartum enhances early prediction and intervention.

Children with autism spectrum disorder (ASD) have difficulties in gestural communication during social interactions. However, the neural mechanisms involved in naturalistic gestural communication remain poorly understood. In this study, cortical activation patterns associated with gestural communication were examined in thirty-two children with and without ASD (mean age: 11.0 years, SE: 0.6 years). Functional near-infrared spectroscopy (fNIRS) was used to record cortical activation while children produced, observed, or imitated communicative gestures. Children with ASD demonstrated more spatial and temporal errors when performing and imitating communicative gestures. Although both typically developing (TD) children and children with ASD showed left-lateralized cortical activation during gesture production, children with ASD showed hyperactivation in the middle/inferior frontal gyrus (MIFG) during observation and imitation, and hypoactivation in the middle/superior temporal gyrus (MSTG) during gesture production compared to their TD peers. More importantly, children with ASD exhibited greater MSTG activation during imitation than during gesture production, suggesting that imitation could be an effective intervention strategy to engage cortical regions crucial for processing and producing gestures. Our study provides valuable insights into the neural mechanisms underlying gestural communication difficulties in ASD, while also identifying potential neurobiomarkers that could serve as objective measures for evaluating intervention effectiveness in children with ASD.

Sleeve gastrectomy achieves long-term weight control by reducing gastric volume. However, postoperative gastrointestinal symptoms and insufficient nutritional intake are likely to occur, which are not conducive to physical health. A retrospective study aimed to investigate changes in nutritional status and associated factors in patients after sleeve gastrectomy. Data were collected from the medical records of patients who underwent sleeve gastrectomy at a teaching hospital in Taiwan. Data from 120 patients who met the eligibility criteria were included in the analysis. The results show that sleeve gastrectomy has a strong weight loss effect. Within 12 months, the average body mass index of the patients decreased by 13.47 kg/m2. The number of morbidly obese patients decreased from 62 (51.7%) to 3 (2.5%). However, surgery is also associated with gastrointestinal symptoms and the threat of malnutrition. The number of patients with moderate to severe nutritional risk increased from 4 (3.3%) before surgery to 24 (20%) at 12-month follow-up. Likewise, the number of patients with anemia increased from 11 (9.2%) to 29 (24.17%). Gender, constipation, and diarrhea affected postoperative nutritional status. These findings suggest that patients after sleeve gastrectomy are at risk of malnutrition and require regular monitoring. Special attention should be given to women and patients with constipation or diarrhea, as they are at a particularly high risk of malnutrition.

Osteoarthritis (OA) is the most common age-related degenerative joint disease. Inflammaging, linking inflammation and aging, is found in senescent cells with the secretions of matrix-degrading proteins and proinflammatory cytokines. The senescence-associated secretory phenotype (SASP) plays a very important role in OA progression. However, there remains no effective way to suppress OA progression, especially by suppressing inflammaging and/or the chondrocyte SASP. Recent studies have shown that exosomes derived from hypoxia-cultured BMSCs can regenerate cartilage in OA animal models. Some reports have further indicated that exosomes secreted from MSCs contribute to the efficacy of MSC therapy in OA. However, whether hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos) can alleviate the chondrocyte SASP or OA progression remains unclear. Accordingly, we hypothesized that hypoxia-ADSC-Exos have a beneficial effect on the normal functions of human articular chondrocytes (HACs), can attenuate the SASP of OA-like HACs in vitro, and further suppress OA progression in rats. Hypoxia-ADSC-Exos were derived from ADSCs cultured in 1% O2 and 10% de-Exo-FBS for 48 h. The molecular and cell biological effects of hypoxia-ADSC-Exos were tested on IL1-β-induced HACs as OA-like HACs in vitro, and the efficacy of OA treatment was tested in ACLT-induced OA rats. The results showed that hypoxia-ADSC-Exos had the best effect on GAG formation in normal HACs rather than those cultured in normoxia or hypoxia plus 2% de-Exo-FBS. We further found that hypoxia-ADSC-Exos alleviated the harmful effect in OA-like HACs by decreasing markers of normal cartilage (GAG and type II collagen) and increasing markers of fibrous or degenerative cartilage (type I or X collagen), matrix degradation enzymes (MMP13 and ADAMT5), and inflammatory cytokines (TNFα and IL-6). More importantly, intra-articular treatment with hypoxia-ADSC-Exos suppressed OA progression, as evidenced by the weight-bearing function test and cartilage GAG quantification in ACLT rats. Moreover, through NGS and bioinformatic analysis, seven potential miRNAs were found in hypoxia-ADSC-Exos, which may contribute to regulating cellular oxidative stress and attenuating cell senescence. In summary, we demonstrated that hypoxia-ADSC-Exos, carrying potent miRNAs, not only improve normal HAC function but also alleviate HAC inflammaging and OA progression. The results suggest that hypoxia-ADSC-Exo treatment may offer another strategy for future OA therapy.

Rice bran, a byproduct of rice milling, is rich in fiber and phytochemicals and confers several health benefits. However, its effects on gut microbiota and obesity-related muscle atrophy in postmenopausal status remain unclear. In this study, we investigated the effects of rice bran on gut microbiota, muscle synthesis, and breakdown pathways in estrogen-deficient ovariectomized (OVX) mice receiving a high-fat diet (HFD). ICR female mice were divided into five groups: sham, OVX mice receiving control diet (OC); OVX mice receiving HFD (OH); OVX mice receiving control diet and rice bran (OR); and OVX mice receiving HFD and rice bran (OHR). After twelve weeks, relative muscle mass and grip strength were high in rice bran diet groups. IL-6, TNF-α, MuRf-1, and atrogin-1 expression levels were lower, and Myog and GLUT4 were higher in the OHR group. Rice bran upregulated the expression of occludin and ZO-1 (gut tight junction proteins). The abundance of Akkermansiaceae in the cecum was relatively high in the OHR group. Our finding revealed that rice bran supplementation ameliorated gut barrier dysfunction and gut dysbiosis and also maintained muscle mass by downregulating the expression of MuRf-1 and atrogin-1 (muscle atrophy-related factors) in HFD-fed OVX mice.

Pulmonary fibrosis (PF) is a chronic lung disorder characterized by the presence of scarred and thickened lung tissues. Although the Food and Drug Administration approved two antifibrotic drugs, pirfenidone, and nintedanib, that are currently utilized for treating idiopathic PF (IPF), the clinical therapeutic efficacy remains unsatisfactory. It is crucial to develop new drugs or treatment schemes that combine pirfenidone or nintedanib to achieve more effective outcomes for PF patients. Understanding the complex mechanisms underlying PF could potentially facilitate drug discovery. Previous studies have found that the activation of inflammasomes, including nucleotide-binding and oligomerization domain (NOD)-like receptor protein (NLRP)1, NLRP3, NOD-like receptor C4, and absent in melanoma (AIM)2, contributes to lung inflammation and fibrosis. This article aims to summarize the cellular and molecular regulatory cues that contribute to PF with a particular emphasis on the role of AIM2 inflammasome in mediating pathophysiologic events during PF development. The insights gained from this research may pave the way for the development of more effective strategies for the prevention and treatment of PF.

The retromolar canal is an anatomical variation that occurs in the mandibular bone. The retromolar canal typically originates in the mandibular canal on the distal side of the third molar and extends forward and upward to the retromolar foramen (RMF), which contains the neurovascular bundle. Accidentally damaging the neurovascular bundle in the retromolar canal during the extraction of the third molar, dental implant surgery, or maxillofacial orthognathic surgery may lead to subsequent complications such as incomplete local anesthesia, paresthesia, and bleeding during operation. The objective of this study was to investigate the prevalence of the RMF in the Taiwanese population in a medical center by using dental cone-beam computed tomography (CBCT) and to identify the position of the RMF in the mandibular bone. The dental CBCT images for the mandibular bone of 68 hemi-mandible were uploaded to the medical imaging software Mimics 15.1 to determine the prevalence of the RMF in the Taiwanese population and the three positional parameters of the RMF in the mandibular bone: (1) The diameter of the RMF, (2) the horizontal distance from the midpoint of the RMF to the distal cementoenamel junction of the second molar, and (3) the vertical distance from the midpoint of the RMF to the upper border of the mandibular canal. Seven RMFs were observed in the 68 hemi-mandibles. Thus, the RMF prevalence was 10.3%. In addition, the diameter of the RMF was 1.41 ± 0.30 mm (mean ± standard deviation), the horizontal distance from the midpoint of the RMF to the distal cementoenamel junction of the the second molar was 12.93 ± 2.87 mm, and the vertical distance from the midpoint of the RMF to the upper border of the mandibular canal below second molar was 13.62 ± 1.3487 mm. This study determined the prevalence of the RMF in the Taiwanese population in a medical center and its relative position in the mandibular bone. This information can provide clinicians with a reference for posterior mandible anesthesia and surgery to ensure medical safety.

Colorectal cancer (CRC) has the fourth-highest incidence of all cancer types, and its incidence has steadily increased in the last decade. The general transcription factor III (GTF3) family, comprising GTF3A, GTF3B, GTF3C1, and GTFC2, were stated to be linked with the expansion of different types of cancers; however, their messenger (m)RNA expressions and prognostic values in colorectal cancer need to be further investigated. To study the transcriptomic expression levels of GTF3 gene members in colorectal cancer in both cancerous tissues and cell lines, we first performed high-throughput screening using the Oncomine, GEPIA, and CCLE databases. We then applied the Prognoscan database to query correlations of their mRNA expressions with the disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) status of the colorectal cancer patient. Furthermore, proteomics expressions of GTF3 family members in clinical colorectal cancer specimens were also examined using the Human Protein Atlas. Finally, genomic alterations of GTF3 family gene expressions in colorectal cancer and their signal transduction pathways were studied using cBioPortal, ClueGO, CluePedia, and MetaCore platform. Our findings revealed that GTF3 family members’ expressions were significantly correlated with the cell cycle, oxidative stress, WNT/β-catenin signaling, Rho GTPases, and G-protein-coupled receptors (GPCRs). Clinically, high GTF3A and GTF3B expressions were significantly correlated with poor prognoses in colorectal cancer patients. Collectively, our study declares that GTF3A was overexpressed in cancer tissues and cell lines, particularly colorectal cancer, and it could possibly step in as a potential prognostic biomarker.

Children with autism spectrum disorder (ASD) have difficulties with tool use and pantomime actions. The current study utilized functional near-infrared spectroscopy (fNIRS) to examine the neural mechanisms underlying these gestural difficulties. Thirty-one children with and without ASD (age (mean ± SE) = 11.0 ± 0.6) completed a naturalistic peg-hammering task using an actual hammer (hammer condition), pantomiming hammering actions (pantomime condition), and performing meaningless actions with similar joint motions (meaningless condition). Children with ASD exhibited poor praxis performance (praxis error: TD = 17.9 ± 1.7; ASD = 27.0 ± 2.6, p < 0.01), which was significantly correlated with their cortical activation (R = 0.257 to 0.543). Both groups showed left-lateralized activation, but children with ASD demonstrated more bilateral activation during all gestural conditions. Compared to typically developing children, children with ASD showed hyperactivation of the inferior parietal lobe and hypoactivation of the middle/inferior frontal and middle/superior temporal regions. Our findings indicate intact technical reasoning (typical left-IPL activation) but atypical visuospatial and proprioceptive processing (hyperactivation of the right IPL) during tool use in children with ASD. These results have important implications for clinicians and researchers, who should focus on facilitating/reducing the burden of visuospatial and proprioceptive processing in children with ASD. Additionally, fNIRS-related biomarkers could be used for early identification through early object play/tool use and to examine neural effects following gesture-based interventions.

This study investigated the impact of material properties of epoxy molding compounds on wafer warpage in fan-out wafer-level packaging. As there is currently a lack of comprehensive discussion on the various material property parameters of EMC materials, it is essential to identify the critical influencing factors and quantify the effects of each parameter on wafer warpage. The material properties include Young’s modulus of the epoxy molding compound before and after the glass transition temperature (Tg) range of 25–35 °C (EL) and 235–260 °C (EH), coefficient of thermal expansion (α1, α2), and the temperature change (∆T) between EL and EH. Results show that, within the range of extreme values of material properties, EL and α1 are the critical factors that affect wafer warpage during the decarrier process in fan-out packaging. α1 has a more significant impact on wafer warpage compared with EL. EH, α2, Tg, and ∆T have little influence on wafer warpage. Additionally, the study identified the optimized material property of the epoxy molding compound that can reduce the maximum wafer warpage in the X and Y directions from initial values of 7.34 mm and 7.189 mm to 0.545 mm and 0.45 mm, respectively, resulting in a reduction of wafer warpage of 92.58% (X direction) and 93.74% (Y direction). Thus, this study proposes an approach for evaluating the impact of material properties of epoxy molding compounds on wafer warpage in fan-out wafer-level packaging. The approach aims to address the issue of excessive wafer warpage due to material variation and to provide criteria for selecting appropriate epoxy molding compounds to enhance process yield in packaging production lines.

Drug hypersensitivity reactions are classified into immediate and delayed types, according to the onset time. In contrast to the immediate type, delayed drug hypersensitivity mainly involves T lymphocyte recognition of the drug antigens and cell activation. The clinical presentations of such hypersensitivity are various and range from mild reactions (e.g., maculopapular exanthema (MPE) and fixed drug eruption (FDE)), to drug-induced liver injury (DILI) and severe cutaneous adverse reactions (SCARs) (e.g., Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)). The common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, anti-viral drugs, etc. Delayed drug hypersensitivity is proposed to be initiated by different models of molecular recognition, composed of drug/metabolite antigen and endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction. Increasing the genetic variants of HLA loci and drug metabolic enzymes has been identified to be responsible for delayed drug hypersensitivity. Furthermore, preferential TCR clonotypes, and the activation of cytotoxic proteins/cytokines/chemokines, are also involved in the pathogenesis of delayed drug hypersensitivity. This review provides a summary of the current understanding of the molecular recognition, genetic susceptibility, and immune mediators of delayed drug hypersensitivity.

Inonotus obliquus (IO) is used as functional food to treat diabetes. This study investigated the effect of IO supplementation on body composition in relation to changes in energy expenditure and exercise performance. Male Institute of Cancer Research mice were divided into four groups (n = 8 per group) and orally administered IO once daily for 6 wk at 0 (vehicle), 824 (IO-1×), 1648 (IO-2×), and 2472 mg/kg (IO-3×). IO supplementation increased muscle volume, exhaustive treadmill time, and glycogen storage in mice. Serum free fatty acid levels after acute exercise improved in the IO supplementation group, which exhibited changes in energy expenditure through the peroxisome proliferator-activated receptor (PPAR) pathway. RNA sequencing revealed significantly increased PPAR signaling; phenylalanine, ascorbate, aldarate, and cholesterol metabolism; chemical carcinogenesis; and ergosterol biosynthesis in the IO group compared with the vehicle group. Thus, IO supplements as nutraceuticals have a positive effect on lipid transport and exercise performance. In addition, this study was only IO supplementation without training-related procedures.

Primary liver cancer is the fifth leading death of cancers in men, and hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancer cases. Sorafenib is a first-line drug for advanced-stage HCC patients. Sorafenib is a multi-target kinase inhibitor that blocks tumor cell proliferation and angiogenesis. Despite sorafenib treatment extending survival, some patients experience side effects, and sorafenib resistance does occur. 3-Hydroxymethyl glutaryl-CoA synthase 2 (HMGCS2) is the rate-limiting enzyme for ketogenesis, which synthesizes the ketone bodies, β-hydroxybutyrate (β-HB) and acetoacetate (AcAc). β-HB is the most abundant ketone body which is present in a 4:1 ratio compared to AcAc. Recently, ketone body treatment was found to have therapeutic effects against many cancers by causing metabolic alternations and cancer cell apoptosis. Our previous publication showed that HMGCS2 downregulation-mediated ketone body reduction promoted HCC clinicopathological progression through regulating c-Myc/cyclin D1 and caspase-dependent signaling. However, whether HMGCS2-regulated ketone body production alters the sensitivity of human HCC to sorafenib treatment remains unclear. In this study, we showed that HMGCS2 downregulation enhanced the proliferative ability and attenuated the cytotoxic effects of sorafenib by activating expressions of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-P38, and p-AKT. In contrast, HMGCS2 overexpression decreased cell proliferation and enhanced the cytotoxic effects of sorafenib in HCC cells by inhibiting ERK activation. Furthermore, we showed that knockdown HMGCS2 exhibited the potential migratory ability, as well as decreasing zonula occludens protein (ZO)-1 and increasing c-Myc expression in both sorafenib-treated Huh7 and HepG2 cells. Although HMGCS2 overexpression did not alter the migratory effect, expressions of ZO-1, c-Myc, and N-cadherin decreased in sorafenib-treated HMGCS2-overexpressing HCC cells. Finally, we investigated whether ketone treatment influences sorafenib sensitivity. We showed that β-HB pretreatment decreased cell proliferation and enhanced antiproliferative effect of sorafenib in both Huh7 and HepG2 cells. In conclusion, this study defined the impacts of HMGCS2 expression and ketone body treatment on influencing the sorafenib sensitivity of liver cancer cells.

Background and aims: Digital food viewing is a vital skill for connecting dieticians to e-health. The aim of this study was to integrate a novel pedagogical framework that combines interactive three- (3-D) and two-dimensional (2-D) food models into a formal dietetic training course. The level of agreement between the digital food models (first semester) and the effectiveness of educational integration of digital food models during the school closure due to coronavirus disease 2019 (COVID-19) (second semester) were evaluated. Method: In total, 65 second-year undergraduate dietetic students were enrolled in a nutritional practicum course at the School of Nutrition and Health Sciences, Taipei Medical University (Taipei, Taiwan). A 3-D food model was created using Agisoft Metashape. Students’ digital food viewing skills and receptiveness towards integrating digital food models were evaluated. Results: In the first semester, no statistical differences were observed between 2-D and 3-D food viewing skills in food identification (2-D: 89% vs. 3-D: 85%) and quantification (within ±10% difference in total calories) (2-D: 19.4% vs. 3-D: 19.3%). A Spearman correlation analysis showed moderate to strong correlations of estimated total calories (0.69~0.93; all p values < 0.05) between the 3-D and 2-D models. Further analysis showed that students who struggled to master both 2-D and 3-D food viewing skills had lower estimation accuracies than those who did not (equal performers: 28% vs. unequal performers:16%, p = 0.041), and interactive 3-D models may help them perform better than 2-D models. In the second semester, the digital food viewing skills significantly improved (food identification: 91.5% and quantification: 42.9%) even for those students who struggled to perform digital food viewing skills equally in the first semester (equal performers: 44% vs. unequal performers: 40%). Conclusion: Although repeated training greatly enhanced students’ digital food viewing skills, a tailored training program may be needed to master 2-D and 3-D digital food viewing skills. Future study is needed to evaluate the effectiveness of digital food models for future “eHealth” care.

The purpose of this study was to investigate the protective effects of the water extract of fermented rice bran (FRB) on liver damage and intestinal injury in old rats fed a high-fat (HF) diet. Rice bran (RB) was fermented with Aspergillus kawachii, and FRB was produced based on a previous study. Male Sprague Dawley rats at 36 weeks of age were allowed free access to a standard rodent diet and water for 8 weeks of acclimation then randomly divided into four groups (six rats/group), including a normal control (NC) group (normal diet), HF group (HF diet; 60% of total calories from fat), HF + 1% FRB group (HF diet + 1% FRB w/w), and HF + 5% FRB group (HF diet + 5% FRB w/w). It was found that the antioxidant ability of FRB was significantly increased when compared to RB. After 8 weeks of feeding, the HF group exhibited liver damage including an increased non-alcoholic fatty liver disease score (hepatic steatosis and inflammation) and higher interleukin (IL)-1β levels, while these were attenuated in the FRB-treated groups. Elevated plasma leptin levels were also found in the HF group, but the level was down-regulated by FRB treatment. An altered gut microbiotic composition was observed in the HF group, while beneficial bacteria including of the Lactobacillaceae and Lachnospiraceae had increased after FRB supplementation. In conclusion, it was found that FRB had higher anti-oxidative ability and showed the potential for preventing liver damage induced by a HF diet, which might be achieved through regulating imbalanced adipokines and maintaining a healthier microbiotic composition.

This study successfully established a strip warpage simulation model of the flip-chip process and investigated the effects of structural design and process (molding, post-mold curing, pretreatment, and ball mounting) on strip warpage. The errors between simulated and experimental values were found to be less than 8%. Taguchi analysis was employed to identify the key factors affecting strip warpage, which were discovered to be die thickness and substrate thickness, followed by mold compound thickness and molding temperature. Although a greater die thickness and mold compound thickness reduce the strip warpage, they also substantially increase the overall strip thickness. To overcome this problem, design criteria are proposed, with the neutral axis of the strip structure located on the bump. The results obtained using the criteria revealed that the strip warpage and overall strip thickness are effectively reduced. In summary, the proposed model can be used to evaluate the effect of structural design and process parameters on strip warpage and can provide strip design guidelines for reducing the amount of strip warpage and meeting the requirements for light, thin, and short chips on the production line. In addition, the proposed guidelines can accelerate the product development cycle and improve product quality with reduced development costs.

The purpose of this study was to investigate the beneficial effects of synbiotics on liver damage, intestinal health, and muscle loss, and their relevance in rats with chronic ethanol feeding. Thirty Wistar rats fed with a control liquid diet were divided into control and synbiotics groups, which were respectively provided with water or synbiotics solution (1.5 g/kg body weight/day) for 2 weeks. From the 3rd to 8th week, the control group was divided into a C group (control liquid diet + water) and an E group (ethanol liquid diet + water). The synbiotics group was separated in to three groups, SC, ASE, and PSE. The SC group was given a control liquid diet with synbiotics solution; the ASE group was given ethanol liquid diet with synbiotics solution, and the PSE group was given ethanol liquid diet and water. As the results, the E group exhibited liver damage, including increased AST and ALT activities, hepatic fatty changes, and higher CYP2E1 expression. Intestinal mRNA expressions of occludin and claudin-1 were significantly decreased and the plasma endotoxin level was significantly higher in the E group. In muscles, beclin-1 was significantly increased in the E group. Compared to the E group, the PSE and ASE groups had lower plasma ALT activities, hepatic fatty changes, and CYP2E1 expression. The PSE and ASE groups had significantly higher intestinal occludin and claudin-1 mRNA expressions and lower muscular beclin-1 expression when compared to the E group. In conclusion, synbiotics supplementation might reduce protein expression of muscle protein degradation biomarkers such as beclin-1 in rats with chronic ethanol feeding, which is speculated to be linked to the improvement of intestinal tight junction and the reduction of liver damage.

According to statistics 2020, female breast cancer (BRCA) became the most commonly diagnosed malignancy worldwide. Prognosis of BRCA patients is still poor, especially in population with advanced or metastatic. Particular functions of each members of the solute carrier 35A (SLC35A) gene family in human BRCA are still unknown regardless of awareness that they play critical roles in tumorigenesis and progression. Using integrated bioinformatics analyses to identify therapeutic targets for specific cancers based on transcriptomics, proteomics, and high-throughput sequencing, we obtained new information and a better understanding of potential underlying molecular mechanisms. Leveraging BRCA dataset that belongs to The Cancer Genome Atlas (TCGA), which were employed to clarify SLC35A gene expression levels. Then we used a bioinformatics approach to investigate biological processes connected to SLC35A family genes in BRCA development. Beside that, the Kaplan–Meier estimator was leveraged to explore predictive values of SLC35A family genes in BCRA patients. Among individuals of this family gene, expression levels of SLC35A2 were substantially related to poor prognostic values, result from a hazard ratio of 1.3 (with 95 percent confidence interval (95% CI: 1.18–1.44), the p for trend (ptrend) is 3.1 × 10−7). Furthermore, a functional enrichment analysis showed that SLC35A2 was correlated with hypoxia-inducible factor 1A (HIF1A), heat shock protein (HSP), E2 transcription factor (E2F), DNA damage, and cell cycle-related signaling. Infiltration levels observed in specific types of immune cell, especially the cluster of differentiation found on macrophages and neutrophils, were positively linked with SLC35A2 expression in multiple BRCA subclasses (luminal A, luminal B, basal, and human epidermal growth factor receptor 2). Collectively, SLC35A2 expression was associated with a lower recurrence-free survival rate, suggesting that it could be used as a biomarker in treating BRCA.

The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.

The most common ventricular premature contractions (VPCs) originate from the right ventricular outflow tract (RVOT), but the molecular mechanisms of altered cytoskeletons of VPC-induced cardiomyopathy remain unexplored. We created a RVOT bigeminy VPC pig model (n = 6 in each group). Echocardiography was performed. The histopathological alternations in the LV myocardium were analyzed, and next generation sequencing (NGS) and functional enrichment analyses were employed to identify the differentially expressed genes (DEGs) responsible for the histopathological alternations. Finally, a cell silencing model was used to confirm the key regulatory gene and pathway. VPC pigs had increased LV diameters in the 6-month follow-up period. A histological study showed more actin cytoskeleton disorganization and actin accumulation over intercalated disc, Z-line arrangement disarray, increased β-catenin expression, and cardiomyocyte enlargement in the LV myocardium of the VPC pigs compared to the control pigs. The NGS study showed actin cytoskeleton signaling, RhoGDI signaling, and signaling by Rho Family GTPases and ILK Signaling presented z-scores with same activation states. The expressions of Rac family small GTPase 2 (Rac2), the p-cofilin/cofilin ratio, and the F-actin/G-actin ratio were downregulated in the VPC group compared to the control group. Moreover, the intensity and number of actin filaments per cardiomyocyte were significantly decreased by Rac2 siRNA in the cell silencing model. Therefore, the Rac2/cofilin pathway was found to play a crucial role in the sarcomere morphology and Z-line arrangement disarray induced by RVOT bigeminy VPCs.

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the world. Sorafenib is the first-line drug for patients with advanced HCC. However, long-term treatment with sorafenib often results in reduced sensitivity of tumor cells to the drug, leading to acquired resistance. Identifying biomarkers which can predict the response to sorafenib treatment may represent a clinical challenge in the personalized treatment era. Niemann-Pick type C2 (NPC2), a secretory glycoprotein, plays an important role in regulating intracellular free cholesterol homeostasis. In HCC patients, downregulation of hepatic NPC2 is correlated with poor clinical pathological features through regulating mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation. This study aimed to investigate the roles of secretory NPC2-mediated free cholesterol levels as biomarkers when undergoing sorafenib treatment and evaluate its impact on acquired sorafenib resistance in HCC cells. Herein, we showed that NPC2 downregulation and free cholesterol accumulation weakened sorafenib’s efficacy through enhancing MAPK/AKT signaling in HCC cells. Meanwhile, NPC2 overexpression slightly enhanced the sorafenib-induced cytotoxic effect. Compared to normal diet feeding, mice fed a high-cholesterol diet had much higher tumor growth rates, whereas treatment with the free cholesterol-lowering agent, hydroxypropyl-β-cyclodextrin, enhanced sorafenib’s tumor-inhibiting ability. In addition, sorafenib treatment induced higher NPC2 secretion, which was mediated by inhibition of the Ras/Raf/MAPK kinase (MEK)/ERK signaling pathway in HCC cells. In both acquired sorafenib-resistant cell and xenograft models, NPC2 and free cholesterol secretion were increased in culture supernatant and serum samples. In conclusion, NPC2-mediated free cholesterol secretion may represent a candidate biomarker for the likelihood of HCC cells developing resistance to sorafenib.

Biomaterials are widely used for effectively controlling bleeding in oral/dental surgical procedures. Here, gelatin methacryloyl (GelMA) was synthesized by grafting methacrylic anhydride on gelatin backbone, and phenyl isothiocyanate-modified gelatin (Gel-Phe) was synthesized by conjugating different gelatin/phenyl isothiocyanate molar ratios (G/P ratios) (i.e., 1:1, 1:5, 1:10, 1:15, 1:25, 1:50, 1:100, and 1:150) with gelatin polymer chains. Afterward, we combined GelMA and Gel-Phe as an injectable and photo-crosslinkable bioadhesive. This hybrid material system combines photo-crosslinking chemistry and supramolecular interactions for the design of bioadhesives exhibiting a highly porous structure, injectability, and regulable mechanical properties. By simply regulating the G/P ratio (1:1–1:15) and UV exposure times (15–60 s), it was possible to modulate the injectability and mechanical properties of the GelMA/Gel-Phe bioadhesive. Moreover, we demonstrated that the GelMA/Gel-Phe bioadhesive showed low cytotoxicity, a highly porous network, and the phenyl-isothiourea and amine residues on Gel-Phe and GelMA polymers with synergized hemostatic properties towards fast blood absorption and rapid clotting effect. An in vitro porcine skin bleeding and an in vitro dental bleeding model confirmed that the bioadhesive could be directly extruded into the bleeding site, rapidly photo-crosslinked, and reduced blood clotting time by 45%. Moreover, the in situ crosslinked bioadhesive could be easily removed from the bleeding site after clotting, avoiding secondary wound injury. Overall, this injectable GelMA/Gel-Phe bioadhesive stands as a promising hemostatic material in oral/dental surgical procedures.

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form “functional” CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.

Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions.

Neonatal pancreatic cell clusters (NPCCs) are potential tissues for the treatment of diabetes. Different from adult cells, they continuously proliferate and differentiate after transplantation. In this study, we utilized magnetic resonance imaging (MRI) to detect and monitor implanted NPCCs. NPCCs were isolated from one-day-old neonatal pigs, cultured for three days, and then incubated overnight with the contrast agent chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles. In vitro, Prussian blue staining and MR scans of CSPIO-labeled NPCCs were performed. In vivo, we transplanted 2000 CSPIO-labeled NPCCs under the kidney capsule of nondiabetic nude mice. Recipients were scanned with 7.0T MRI. Grafts were removed for histology with insulin and Prussian blue staining. After being incubated overnight with CSPIO, NPCCs showed positive iron staining and appeared as dark spots on MR scans. After transplantation of CSPIO-labeled NPCCs, persistent hypointense areas were observed at recipients’ implant sites for up to 54 days. Moreover, histology showed colocalization of the insulin and iron staining in 15-, 51- and 55-day NPCC grafts. Our results indicate that transplanted NPCCs survived and differentiated to β cells after transplantation, and that MRI is a useful tool for the detection and monitoring of CSPIO-labeled NPCC grafts.

Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members’ gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.

The use of image-based dietary assessments (IBDAs) has rapidly increased; however, there is no formalized training program to enhance the digital viewing skills of dieticians. An IBDA was integrated into a nutritional practicum course in the School of Nutrition and Health Sciences, Taipei Medical University Taiwan. An online IBDA platform was created as an off-campus remedial teaching tool to reinforce the conceptualization of food portion sizes. Dietetic students’ receptiveness and response to the IBDA, and their performance in food identification and quantification, were compared between the IBDA and real food visual estimations (RFVEs). No differences were found between the IBDA and RFVE in terms of food identification (67% vs. 71%) or quantification (±10% of estimated calories: 23% vs. 24%). A Spearman correlation analysis showed a moderate to high correlation for calorie estimates between the IBDA and RFVE (r ≥ 0.33~0.75, all p < 0.0001). Repeated IBDA training significantly improved students’ image-viewing skills [food identification: first semester: 67%; pretest: 77%; second semester: 84%) and quantification [±10%: first semester: 23%; pretest: 28%; second semester: 32%; and ±20%: first semester: 38%; pretest: 48%; second semester: 59%] and reduced absolute estimated errors from 27% (first semester) to 16% (second semester). Training also greatly improved the identification of omitted foods (e.g., condiments, sugar, cooking oil, and batter coatings) and the accuracy of food portion size estimates. The integration of an IBDA into dietetic courses has the potential to help students develop knowledge and skills related to “e-dietetics”.

There is increasing evidence showing the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass synthesis and function. However, the role of omega-3 fatty acids remains unclear. Therefore, we conducted a meta-analysis to evaluate the potential effects of omega-3 fatty acids on sarcopenia-related performances among the elderly. Eligible literature and reports of randomized controlled trials were comprehensively searched from the PubMed, Cochrane Library, ClinicalTrials.gov, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases until July 2018. A total of 10 articles were available for the meta-analysis. There were minor benefits for muscle mass gain (0.33 kg; 95% CI: 0.05, 0.62) and timed up and go performance (−0.30 s; 95% CI: −0.43, −0.17). Subgroup analyses regarding muscle mass and walk speed indicated that omega-3 fatty acid supplements at more than 2 g/day may contribute to muscle mass gain (0.67 kg; 95% CI: 0.16, 1.18) and improve walking speed, especially for those receiving more than 6 months of intervention (1.78 m/sec; 95% CI: 1.38, 2.17). Our findings provide some insight into the effects of omega-3 fatty acids on muscle mass, especially for those taking supplements at more than 2 g/day. We also observed that a long period of omega-3 fatty acids supplementation may improve walking speed.

Background: The accurate determination of cell confluence is a critical step for generating reasonable results of designed experiments in cell biological studies. However, the cell confluence of the same culture may be diversely predicted by individual researchers. Herein, we designed a systematic quantification scheme implemented on the Matlab platform, the so-called “Confluence-Viewer” program, to assist cell biologists to better determine the cell confluence. Methods: Human normal oral fibroblasts (hOFs) seeded in 10 cm culture dishes were visualized under an inverted microscope for the acquisition of cell images. The images were subjected to the cell segmentation algorithm with top-hat transformation and the Otsu thresholding technique. A regression model was built using a quadratic model and shape-preserving piecewise cubic model. Results: The cell segmentation algorithm generated a regression curve that was highly correlated with the cell confluence determined by experienced researchers. However, the correlation was low when compared to the cell confluence determined by novice students. Interestingly, the cell confluence determined by experienced researchers became more diverse when they checked the same images without a time limitation (up to 1 min). Conclusion: This tool could prevent unnecessary human-made mistakes and meaningless repeats for novice researchers working on cell-based studies in health care or cancer research.

Calycosin, an isoflavonoid phytoestrogen, isolated from Radix Astragali, was reported to possess anti-tumor, anti-inflammation, and osteogenic properties, but its impact on osteoclast differentiation remains unclear. In this study, we examined the effects of calycosin on osteoclastogenesis induced by RANKL. The results showed that calycosin significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). Calycosin also dose-dependently suppressed the formation of bone resorption pits by mature osteoclasts. In addition, the expression of osteoclatogenesis-related genes, including cathepsin K (CtsK), tartrate-resistant acid phosphatase (TRAP), and MMP-9, was significantly inhibited by calycosin. Furthermore, the results indicated that calycosin down-regulated the expression levels of NFATc1 and c-Fos through suppressing the activation of NF-κB and MAPKs. Our results indicate that calycosin has an inhibitory role in the bone loss by preventing osteoclast formation, as well as its bone resorptive activity. Therefore, calycosin may be useful as a therapeutic reagent for bone loss-associated diseases.