Cells in the tumor microenvironment (TME) communicate via membrane‐bound and secreted proteins, which are mostly glycosylated. Altered glycomes of malignant tumors influence behaviors of stromal ...cells. In this study, we showed that the loss of core‐1 β1,3‐galactosyltransferase (C1GALT1)‐mediated O‐glycosylation suppressed tumor growth in syngeneic head and neck cancer mouse models. O‐glycan truncation in tumor cells promoted the M1 polarization of macrophages, enhanced T‐cell‐mediated cytotoxicity, and reduced interleukin‐6 (IL‐6) levels in the secretome. Proteasomal degradation of IL‐6 was controlled by the O‐glycan at threonine 166. Both IL‐6/IL‐6R blockade and O‐glycan truncation in tumor cells induced similar pro‐inflammatory phenotypes in macrophages and cytotoxic T lymphocytes (CTLs). The combination of the O‐glycosylation inhibitor itraconazole and anti‐programmed cell death protein 1 (anti‐PD‐1) antibody effectively suppressed tumor growth in vivo. Collectively, our findings demonstrate that O‐glycosylation in tumor cells governs their crosstalk with macrophages and CTLs. Thus, targeting O‐glycosylation successfully reshapes the TME and consequently enhances the efficacy of anti‐PD‐1 therapy.
This study found that O‐glycan truncation induced proteasomal degradation of interleukin‐6 to suppress tumor growth by promoting M1 macrophage polarization and enhancing T cell‐mediated cytotoxicity in head and neck cancer in vitro and in vivo. Combining an O‐glycosylation inhibitor with anti‐programmed cell death protein 1 antibody effectively suppressed tumor growth, emphasizing the role of O‐glycosylation in modulating the tumor microenvironment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Teleworking has rapidly grown and become the prevailing work mode. Married teleworkers may experience increased work-family conflict, while single teleworkers may experience loneliness. This study ...aims to investigate how teleworkers' information reception quality (Time 1) influences their work-family conflict (Time 2), loneliness (Time 2), and well-being (Time 3) from the perspective of the job demands-resources model. The data were collected through a three-point survey involving 462 participants working from home in Taiwan. The results indicate a negative association between information accuracy and work-family conflict. Work-family conflict, in turn, mediates the relationship between information accuracy and well-being. Information timeliness, as the moderator, weakens the connection between information accuracy and work-family conflict. Additionally, information timeliness is negatively related to loneliness. Loneliness mediates the relationship between information timeliness and well-being. Information accuracy, as the moderator, strengthens the association between information timeliness and loneliness. No impact of information on family-work conflict was observed. Our findings suggest that organizations that convey precise and punctual messages to employees have distinct routes for reducing work-family interference and loneliness and ultimately improving employees’ well-being in remote work contexts. This study contributes to the wider telework literature through information experience.
•This study explores how teleworkers' information reception affects work-family conflict, loneliness, and well-being.•Accurate information reduces work-family conflict; timely information lessens loneliness.•Work-family conflict mediates accuracy's impact on well-being; loneliness mediates timeliness's impact on well-being.•Timeliness weakens accuracy's impact on work-family conflict; accuracy strengthens timeliness's effect on loneliness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Photocatalysts consisting of Z-scheme heterojunctions are commonly used in wastewater treatment due to their exceptional reactivity in photocatalysis and highly efficient visible-light ...utilization. In this work, Fe 2 O 3 -decorated MoO 3 rods were synthesized through a two-step method and their photodegradation of methylene blue (MB) was evaluated. The Fe 2 O 3 /MoO 3 rods were characterized by XRD, SEM, micro-Raman, XPS, UV–Vis DRS, and PL to investigate their structural, morphological, and optical properties. The results indicate that the photodegradation efficiency of Fe 2 O 3 /MoO 3 improved through a reduction in the gap energy and persistence of a 1D hexagonal prism structure. The degradation rate of MB was enhanced from 31.7 to 91.5% after irradiation for 180 min owing to electron–hole separation and Fenton-like process. Formation of the OH radical is a key factor in the photodegradation reaction and with the addition of H 2 O 2 the efficiency can further improve via a Fenton-like mechanism. Furthermore, the Z-scheme mechanism concurrently delineated. The Fe 2 O 3 /MoO 3 rod composites were also found to retain high photocatalytic efficiency after being reused five times, which may be useful for future applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
GalNAc‐type O‐glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with ...poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O‐glycans on AXL and determined AXL levels via the proteasome‐dependent pathway. In addition, the GALNT2‐promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.
TAM (TYRO3, AXL, and MERTK) receptors regulate a wide range of pathophysiological functions. Here, we show that TAM receptors are decorated with O‐glycans. GALNT2 can modify O‐glycans on AXL to increase AXL protein levels and in turn promote colon cancer cell invasiveness. This study highlights the role of GalNAc‐type O‐glycosylation in TAM receptor biology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study evaluates the effectiveness of an interactive E-book app training program in improving nurses' knowledge, attitudes, and confidence to prevent and care for pressure injury.
Randomized ...experimental study.
Participants were recruited from a teaching hospital in Taiwan. The study was carried out between 20 March 2014 to 1 April 2016. In total, 164 participants were randomly assigned to a pressure injury E-book app training program (n = 86) or a conventional education program (n = 78) with a one-month follow-up. Outcome variables were levels of pressure injury knowledge, attitudes, and confidence of pressure injury care.
Participants answered 51.96% of the pressure injury knowledge questions correctly before the intervention and 75.5% after the intervention. The pressure injury attitude score was slightly positive, with moderate confidence in pressure injury care. The knowledge, attitudes, and confidence of pressure injury care of the two groups in the pretest and posttest groups increased significantly. Analysis of covariance indicated that nurses in the pressure injury E-book app group had significantly greater improvement in knowledge, attitudes, and pressure injury care confidence as compared with the control group.
The pressure injury E-book app interactive training program was effective in improving nurses' knowledge and attitudes toward pressure injury care and in enhancing their confidence in pressure injury care; therefore, this program has potential for nurses' in-service education in both Taiwan and worldwide.
E-book apps allow individuals to control the time and place of learning. Direct observation of procedural skills can provide feedback to trainees on techniques to ensure learning effectiveness and pressure injury care quality.
Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic ...neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.
Photolyase uses blue light to restore the major ultraviolet (UV)-induced DNA damage, the cyclobutane pyrimidine dimer (CPD), to two normal bases by splitting the cyclobutane ring. Our earlier studies ...showed that the overall repair is completed in 700 ps through a cyclic electron-transfer radical mechanism. However, the two fundamental processes, electron-tunneling pathways and cyclobutane ring splitting, were not resolved. Here, we use ultrafast UV absorption spectroscopy to show that the CPD splits in two sequential steps within 90 ps and the electron tunnels between the cofactor and substrate through a remarkable route with an intervening adenine. Site-directed mutagenesis reveals that the active-site residues are critical to achieving high repair efficiency, a unique electrostatic environment to optimize the redox potentials and local flexibility, and thus balance all catalytic reactions to maximize enzyme activity. These key findings reveal the complete spatio-temporal molecular picture of CPD repair by photolyase and elucidate the underlying molecular mechanism of the enzyme’s high repair efficiency.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and ...exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A‐modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non‐cancer cells. PP2A‐modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A‐modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A‐modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A‐modulating functions in cancer and disease treatments.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Discovering drug candidates for the modulation of metastasis is of great importance in inhibiting oral cancer malignancy. Although most pomegranate extract applications aim at the antiproliferation ...of cancer cells, its antimetastatic effects remain unclear, especially for oral cancer cells. The aim of this study is to evaluate the change of two main metastasis characters, migration and invasion of oral cancer cells. Further, we want to explore the molecular mechanisms of action of pomegranate extract (POMx) at low cytotoxic concentration. We found that POMx ranged from 0 to 50 μg/mL showing low cytotoxicity to oral cancer cells. In the case of oral cancer HSC‐3 and Ca9‐22 cells, POMx inhibits wound healing migration, transwell migration, and matrix gel invasion. Mechanistically, POMx downregulates matrix metalloproteinase (MMP)‐2 and MMP‐9 activities and expressions as well as epithelial‐mesenchymal transition (EMT) signaling. POMx upregulates extracellular signal‐regulated kinases 1/2 (ERK1/2), but not c‐Jun N‐terminal kinase (JNK) and p38 expression. Addition of ERK1/2 inhibitor (PD98059) significantly recovered the POMx‐suppressed transwell migration and MMP‐2/−9 activities in HSC‐3 cells. Taken together, these findings suggest to further test low cytotoxic concentrations of POMx as a potential antimetastatic therapy against oral cancer cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neuroblastoma (NB) is characterized by several malignant phenotypes that are difficult to treat effectively without combination therapy. The therapeutic implication of mitochondrial ClpXP protease ...ClpP and ClpX has been verified in several malignancies, but is unknown in NB. Firstly, we observed a significant increase in ClpP and ClpX expression in immature and mature ganglion cells as compared to more malignant neuroblasts and less malignant Schwannian-stroma-dominant cell types in human neuroblastoma tissues. We used ONC201 targeting ClpXP to treat NB cells, and found a significant suppression of mitochondrial protease, i.e., ClpP and ClpX, expression and downregulation of mitochondrial respiratory chain subunits SDHB and NDUFS1. The latter was associated with a state of energy depletion, increased reactive oxygen species, and decreased mitochondrial membrane potential, consequently promoting apoptosis and suppressing cell growth of NB. Treatment of NB cells with ONC201 as well as the genetic attenuation of ClpP and ClpX through specific short interfering RNA (siRNA) resulted in the significant upregulation of the tumor suppressor alpha thalassemia/mental retardation X-linked (ATRX) and promotion of neurite outgrowth, implicating mitochondrial ClpXP proteases in
-amplified NB cell differentiation. Furthermore, ONC201 treatment significantly decreased MYCN protein expression and suppressed tumor formation with the reactivation of ATRX expression in
-amplified NB-cell-derived xenograft tumors. Taken together, ONC201 could be the potential agent to provide diversified therapeutic application in NB, particularly in NB with
amplification.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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