Copper (Cu2+) and cyanide (CN-) ions pose substantial environmental and biological risks, necessitating the development of a sensitive and selective detection platform. Herein, we report 1,2-bis(2-benzo[d]thiazo-2-yl) disulfide (BT-DS), a fluorescent chemosensor, for sequentially detecting CN- and Cu2+. BT-DS exhibited a turn-on fluorescence response toward CN- and Cu2+ in DMF/H2O, which was not affected by interfering ions, and maintained a good detection ability over a broad pH range. The detection mechanism was investigated using fluorescence spectroscopy, high-resolution mass spectrometry, and 1H nuclear magnetic resonance spectroscopy. The limits of detection for CN- and Cu2+ were 0.82 and 0.40 μM, respectively, well below the permissible safe limit prescribed by the World Health Organization. Further, BT-DS was used for the fluorescence imaging of HeLa cells. It was also suitable for monitoring actual water samples, thereby supporting its practical applicability.

Coronavirus can cause diseases ranging from mild cough to severe COVID-19. Although vaccines and antiviral agents for coronaviruses are available, alternative strategies are still needed to address emerging variants in the future. Toxicodendron vernicifluum is known to be rich in flavonoids, which exhibit antioxidant, anti-inflammatory, anticancer, and antiviral activities. However, the antiviral activity of T. vernicifluum against coronaviruses has not been fully investigated. Here, we report that the T. vernicifluum ethanol extract (TVE) shows antiviral effects against human coronavirus. TVE treatment inhibited coronavirus replication as well as viral infectivity. To elucidate the active constituents responsible for this activity, comprehensive phytochemical profiling of TVE was performed using UPLC-Q-Orbitrap-MS, leading to the tentative identification of major phytochemicals. Based on this analytical profiling, individual compounds were isolated from TVE and evaluated for antiviral activity against coronavirus. We found that ethyl gallate, fisetin, butin, sulfuretin, and gallic acid exhibit antiviral activity against coronavirus.

Fungal extracts have been reported to exert diverse biological activities, including anti-inflammatory, antibacterial, and antiviral effects. However, the anti-coronaviral properties of fungal extracts remain largely unexplored. In this study, we demonstrated that the Penicillium compactum extract (PCE) inhibits the replication of human coronavirus. RD cells were infected with human coronavirus and subsequently treated with PCE. PCE treatment reduced the expression of viral proteins and ameliorated virus-induced cytopathic effects. In addition, PCE markedly decreased viral RNA levels in both the cells and the conditioned medium. Finally, we confirmed that PCE treatment reduced the production of infectious viral particles. Collectively, these findings indicate that PCE exhibits potent antiviral activity against human coronavirus.

Coronaviruses are responsible for both severe diseases, such as COVID-19, and mild illnesses, such as the common cold. Because coronaviruses are expected to remain continuously prevalent, alternative therapeutic strategies against coronavirus infections should be developed to respond to newly emerging variants. Since many antibiotics, including penicillin, have been isolated from fungi, we screened fungal extracts for antiviral activity against human coronavirus and found that the extract of Valsonectria inflata (VIE) exhibited antiviral effects against human coronavirus. Western blot analysis showed that VIE treatment decreased coronavirus protein expression. Quantitative RT-PCR (qRT-PCR) and plaque formation assays demonstrated that VIE treatment reduced coronavirus production, while scanning electron microscopy (SEM) analysis further confirmed a decrease in the production of infectious viral particles. Finally, VIE treatment ameliorated coronavirus-induced cytotoxicity. We also analyzed the components of VIE, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) revealed that VIE contains various secondary metabolites, including terpenoids. These results suggest that VIE may serve as a potential antiviral agent against coronavirus infections.

The tumor suppressor p53 plays a crucial role in preventing cancer development, and its dysfunction is frequently observed in various cancers. This study identifies a novel regulatory interaction between p53 and ITM2A. We found that p53 upregulates ITM2A expression, while ITM2A in turn inhibits p53 function, suggesting a negative feedback loop. ITM2A mRNA levels were reduced across multiple tumor types, particularly in those harboring mutant p53, and low ITM2A expression correlated with poor patient survival. Mechanistically, ITM2A physically interacts with p53, selectively modulates its phosphorylation (reducing Ser392 while enhancing Ser37), and promotes cytoplasmic accumulation of p53. These modifications collectively suppress p53-dependent transcription, an effect consistently observed across multiple cell lines under both basal conditions and upon physiological p53 activation by genotoxic stress. Conversely, ITM2A depletion enhances p53 nuclear accumulation and transcriptional activity. These findings reveal a novel autoregulatory circuit wherein p53 induces ITM2A expression, which then attenuates p53 activity, suggesting ITM2A as a potential prognostic marker and therapeutic target for cancers with dysregulated p53 signaling.

This study investigated the efficacy of two natural compounds-celastrol, a heat shock protein (HSP) inducer, and Cblin peptide, a ubiquitination inhibitor-in counteracting muscle atrophy under real microgravity conditions. Both agents independently attenuated microgravity-induced reductions in myotube thickness, myosin heavy chain protein levels, and atrogene expression. Celastrol primarily enhanced HSP expression, whereas Cblin peptide inhibited insulin receptor substrate-1 degradation, thereby promoting insulin-like growth factor-1 signaling. Despite their distinct molecular actions, no synergistic or additive effects were observed when combined. These findings highlight the potential of celastrol and Cblin peptide as functional ingredients for mitigating muscle atrophy, particularly in the context of space travel. Notably, Cblin peptide is abundant in glycinin-rich soybean protein, and celastrol is derived from the root of Tripterygium wilfordii (Taiwan vine). Future applications may include incorporating these plant-derived compounds into space foods to improve the quality of life for astronauts in space.NEW & NOTEWORTHY This study evaluated the effects of celastrol and the Cblin peptide in mitigating muscle atrophy under microgravity conditions. Both compounds alleviated myotube atrophy through distinct mechanisms, though no synergistic effect was observed. Celastrol upregulated heat shock protein (HSP) expression, whereas Cblin prevented IRS-1 degradation, thereby enhancing IGF-1 signaling. Sourced from Tripterygium wilfordii and soybean protein, respectively, these agents may serve as functional space foods to help counteract muscle atrophy and support astronauts' health during spaceflight.

The spread of a coronavirus infection can result in a pandemic, similar to the coronavirus disease 2019 pandemic. Such an infection also accounts for a considerable portion of common cold cases. Although coronavirus medicines are already available, alternative treatments are still required as the coronavirus can produce many variants. Matairesinol, a lignan family compound, is the constituent of cereals, such as rye. We used the human coronavirus OC43 to evaluate the antiviral activity of matairesinol. Matairesinol treatment interferes with coronavirus replication. This treatment decreases the expression of coronavirus protein and RNA as well as the number of coronavirus-induced plaque formations. Our experimental results collectively indicate that matairesinol treatment can potentially reduce coronavirus replication.

AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis, and AMPK contributes to cell growth, apoptosis, and autophagy. Although most cell studies have been performed using two-dimensional (2D) cell culture, recent studies have demonstrated that the three-dimensional (3D) spheroid technique is helpful in various cell research fields, such as tumor biology, due to its resemblance to the 3D tissue structure. However, the role of AMPK in 3D spheroid formation has not been characterized clearly. This study used the AMPK knockout cell line to examine the role of AMPK in 3D spheroid formation and is the first report describing the generation of 3D spheroids using AMPK knockout cells. While control cells produced round spheroids with a similar length-to-width ratio, AMPK knockout produced an oval shape with a more significant length-to-width ratio. We demonstrate that AMPK knockout spheroids contain significantly more prominent lysosomes in each cell, indicating that autophagic flux is impaired in 3D spheroids. Finally, flow cytometry analysis showed that AMPK knockout spheroids contain more apoptotic cells than control cells. These results indicate that AMPK is required for efficient 3D spheroid formation.

Ultraviolet B (UVB) radiation can distort cellular homeostasis and predispose the skin to carcinogenesis. Amongst the deteriorating effects of the sun’s UVB radiation on cellular homeostasis is the formation of DNA photoproducts. These photoproducts can cause significant changes in the structure and conformation of DNA, inducing gene mutations which may accumulate to trigger the formation of skin cancer. Photoproducts are typically repaired by nucleotide excision repair. Notwithstanding, when the repair mechanism fails, apoptosis ensues to prevent the accumulation of mutations and to restore cellular homeostasis. This present study reports that T-cell protein tyrosine phosphatase (TC-PTP) can increase UVB-induced apoptosis by inhibiting autophagy-mediated cell survival of damaged keratinocytes. TC-PTP deficiency in 3PC mouse keratinocytes led to the formation of autophagic vacuoles and increased expression of LC3-II. We established human TC-PTP-deficient (TC-PTP/KO) HaCaT cells using the CRISPR/Cas9 system. TC-PTP/KO HaCaT cells exhibited increased cell survival upon UVB exposure, which was accompanied by increased expression of LC3-II and decreased expression of p62 compared to control cells. Pretreatment of TC-PTP/KO HaCaT cells with early-phase autophagy inhibitor, 3-methyladenine significantly decreased the expression of LC3-II and reduced cell survival in response to UVB irradiation in comparison with untreated TC-PTP/KO cells. Pretreatment of TC-PTP/KO HaCaT cells with late-phase inhibitor, chloroquine also significantly reduced cell viability with increased accumulation of LC3-II after UVB irradiation compared to untreated counterpart cells. While UVB significantly increased apoptosis in the engineered (Mock) cells, this was not observed in similarly treated TC-PTP/KO HaCaT cells. However, chloroquine treatment increased apoptosis in TC-PTP/KO HaCaT cells. Examination of human squamous cell carcinomas (SCCs) revealed that TC-PTP expression was inversely correlated with LC3 expression. Our findings suggest that TC-PTP negatively regulates autophagy-mediated survival of damaged cells following UVB exposure, which can contribute to remove damaged keratinocytes via apoptosis.

Background/Objectives: Recently, concerns about age-related conditions, such as sarcopenia and chronic inflammation, have increased owing to the global acceleration of population aging. Notably, these conditions are interrelated and further exacerbate functional decline in older adults. Therefore, this study aimed to evaluate the efficacy of a novel bioactive compound, DuoX (a mixture of the postbiotic beLP1 and Cichorium intybus L.), in alleviating muscle wasting and chronic inflammation. Specifically, the mixture consisted of inulin-rich C. intybus L. root extract, known for its anti-inflammatory effects, and beLP1, a postbiotic previously shown to exert anti-sarcopenic effects. Methods: To assess the multifunctional effects of the DuoX, dexamethasone-induced sarcopenia models (C2C12 myotubes and an in vivo rat model) and a lipopolysaccharide-stimulated RAW 264.7 macrophage inflammation model were established. Results: Pretreatment with DuoX prevented the dexamethasone-induced reduction in myotube diameter and effectively inhibited muscle degradation by downregulating the expression of atrogin-1 caused by dexamethasone treatment. In rats with DEX-induced sarcopenia, DuoX prevented muscle weight loss, grip strength reduction, and the upregulation of atrogin-1 expression in vivo. In lipopolysaccharide-stimulated RAW 264.7 macrophages, DuoX significantly reduced nitric oxide production and cyclooxygenase-2 protein expression and suppressed p38 and ERK phosphorylation in the MAPK signaling pathway, thereby alleviating inflammatory responses. Conclusions: DuoX holds promise as a dual-functional candidate with both anti-sarcopenic and anti-inflammatory properties. Further preclinical and clinical studies are required to validate its therapeutic efficacy and safety in humans, which may contribute to the development of preventive strategies for healthy aging.

Coronavirus can induce various diseases, from mild common cold to severe COVID-19. Coronavirus can be continuously prevalent, similar to the influenza virus, due to its frequent mutation of the RNA genome. Therefore, diverse methods are required to treat coronavirus-related diseases. Chrysanthemum zawadskii, found in Asian countries including Korea, has been traditionally used to treat various diseases, including cough, pneumonia, and common cold. However, the antiviral effects of Chrysanthemum zawadskii have not been reported yet. Here, we demonstrated that Chrysanthemum zawadskii ethanol extract (CZE) treatment interferes with the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43). CZE treatment ameliorates beta-coronavirus-induced cytotoxicity and reduces plaque formation. CZE treatment inhibits the coronavirus protein and RNA expression, indicating CZE inhibits coronavirus replication. HPLC analysis showed that CZE contains many antiviral compounds, such as luteolin and isochlorogenic acid. These results indicate that CZE is a potent medicinal herb for treating coronavirus-related diseases.

Coronaviruses are RNA viruses with a high mutation rate that cause many human diseases, from severe COVID-19 to mild common cold. Therefore, discovering various medicines is required to reduce the symptoms of coronavirus infection. This report showed that the ethanol extract of the aerial parts of Elsholtzia ciliata (ECE) and its constituents can inhibit HCoV-OC43 (Human Coronavirus OC43) replication. HCoV-OC43, a human betacoronavirus genetically related to SARS-CoV-2, was used as a surrogate virus under BSL-2 conditions. To evaluate the antiviral properties of ECE, viral RNA levels were quantified using qRT-PCR, and viral protein expression was analyzed through Western blotting. ECE reduced coronavirus-induced plaque formation and viral RNA and protein expression in coronavirus-infected cells and conditioned media. Additionally, this was confirmed to have an inhibitory activity on virus production and improved cytopathic effects. ECE showed no cytotoxicity up to 40 µg/mL in vitro. As Elsholtzia ciliata has traditionally been consumed as a tea, oral administration could be a suitable route for further in vivo investigation. The main components of ECE were revealed by HPLC analysis and were isolated into four single compounds 1-4. Among them, luteolin-7-O-glucoside was effective in inhibiting the replication of coronavirus. Luteolin-7-O-glucoside demonstrated greater antiviral activity than ECE, with an estimated IC50 of 2 µM (around 1 µg/mL) compared to 5 µg/mL for ECE. This finding suggests that luteolin-7-O-glucoside could be a key contributor to the antiviral activity of the ECE. Finally, these results collectively suggest that Elsholtzia ciliata can be used as a potential antiviral treatment.

5H-Benzimidazo[1,2-c]quinazoline-6-thione (BI-QT), was synthesized as a benzimidazole-based probe to detect H2S. BI-QT exhibits a fluorescent "turn-on" response in DMSO/H2O (9:1, HEPES 10 mM, pH 7.4) upon the addition of H2S. The BI-QT probe can determine micromolar (0-600 µM) H2S concentrations in aqueous systems, with a detection limit of 1.12 µM. Interestingly, BI-QT exhibited an ultrafast response to H2S, with maximum intensity achieved almost instantly when exposed to H2S. BI-QT is largely unaffected by pH and responds reliably over the wide 4-11 pH range, which highlights its applicability to various physiological scenarios. UV-vis, fluorescence, and 1H NMR spectroscopic analyses investigated the sensing mechanism. The practicality of the probe was demonstrated using water samples and living cells.

Feline Coronavirus (FCoV) is a viral pathogen of cats and a highly contagious virus. Cats in a cattery can be infected by up to 100%, and even household cats are infected by 20–60%. Some strains of FCoV are known to induce a fatal disease in cats named Feline Infectious Peritonitis (FIP). However, no effective treatments are available. We demonstrated that compound C (dorsomorphin) can potentially inhibit feline coronavirus replication. Compound C treatment decreased the FCoV-induced plaque formation and cytopathic effect in FCoV-infected cells. Compound C treatment also significantly reduced the amount of viral RNA and viral protein in the cells in a dose-dependent manner. Our findings suggest that compound C is potentially useful for feline coronavirus-related diseases.

A benzimidazole-based probe, BIPMA (2-(1H-benzo[d]imidazol-2-yl)-N-(pyridin-2-ylmethyl)aniline), was designed and synthesized to detect Cu2+ ions. BIPMA exhibited a fluorescent "turn-on" mechanism when bound to Cu2+ ions in an acetonitrile/water mixture (5:5, v/v, HEPES 10 mM, pH 7.4) owing to the synergistic effect of the chelation-enhanced fluorescence and internal charge-transfer mechanisms. Moreover, the BIPMA probe effectively detected nanomolar-range concentrations (0-400 nM) of Cu2+ ions in an aqueous system with a detection limit of 4.80 nM; this value is significantly lower than that set by the U.S. Environmental Protection Agency (approximate to 20 mu M). Additionally, BIPMA showed an ultrafast response to Cu2+ ions, with a maximum intensity achieved 25 s after adding Cu2+. Furthermore, BIPMA detected Cu2+ ions in solutions with a pH range of 5-11, without being influenced by pH, underscoring its applicability under various physiological conditions. Density functional theory studies revealed that internal charge transfer was responsible for emission. Finally, BIPMA effectively detected Cu2+ ions in real water samples and living cells.

The SARS-CoV-2 pandemic caused millions of deaths due to its prominent infectivity and mortality. Although the vaccines and medicines for SARS-CoV-2 are on the market, new coronavirus variants like influenza are expected to reemerge continuously. Therefore, effective and inexpensive medicines will be required to respond to SARS-CoV-2 variants. Here, we used herbal plant extracts to search for effective compounds that can interfere with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and found that Selaginella tamariscina extract (STE) can reduce SARS-CoV-2 RdRp activity. The HCoV-OC43 beta coronavirus model was used to examine whether STE treatment could inhibit coronavirus replication and reduce coronavirus-induced cytotoxicity. Next, we searched the active compound of STE and found that amentoflavone is the main active compound of STE. Finally, we demonstrated that amentoflavone inhibits SARS-CoV-2 RdRp and coronavirus replication. Our results collectively indicate that amentoflavone from STE is possibly beneficial in responding to coronavirus-related diseases, including SARS-CoV-2.

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.

Coronavirus can cause various diseases, from mild symptoms to the recent severe COVID-19. The coronavirus RNA genome is frequently mutated due to its RNA nature, resulting in many pathogenic and drug-resistant variants. Therefore, many medicines should be prepared to respond to the various coronavirus variants. In this report, we demonstrated that Forsythia viridissima fruit ethanol extract (FVFE) effectively reduces coronavirus replication. We attempted to identify the active compounds and found that actigenin from FVFE effectively reduces human coronavirus replication. Arctigenin treatment can reduce coronavirus protein expression and coronavirus-induced cytotoxicity. These results collectively suggest that arctigenin is a potent natural compound that prevents coronavirus replication.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits SARS-CoV-2 3CL-protease, and computational modeling demonstrated that it interacts with key residues of 3CL-protease. Further, the treatment decreased the number of plaques formed by human coronavirus OC43 (HCoV-OC43) infection and decreased viral protein and RNA levels in the media. These results indicate that eupatin inhibits coronavirus replication.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N, and RDRP). Therefore, compounds 1-3 are inhibitors of 3CLpro and HCoV-OC43 proliferation.