Absolute co-supplement and absolute co-coclosed modules

A module M is called an absolute co-coclosed (absolute co-supplement) module if whenever M ≅ T/X the submodule X of T is a coclosed (supplement) submodule of T. Rings for which all modules are absolute co-coclosed (absolute co-supplement) are precisely determined. We also investigate the rings whose (finitely generated) absolute co-supplement modules are projective. We show that a commutative domain R is a Dedekind domain if and only if every submodule of an absolute co-supplement R-module is absolute co-supplement. We also prove that the class Coclosed of all short exact sequences 0→A→B→C→0 such that A is a coclosed submodule of B is a proper class and every extension of an absolute co-coclosed module by an absolute co-coclosed module is absolute co-coclosed.Scientific and Technical Research Council of Turke

Comparing Effects of Redox Sensitivity of Organic Nanoparticles to Photodynamic Activity

Smart responsive nanomaterials, which are sensitive to biological signals, are promising therapeutic formulations. It has been well studied that redox potential is much different at both tissue and cellular level. In this work, three organic nanoparticles with variable redox sensitivity were fabricated, and their redox sensitivity was evaluated and compared in detail. First, diselenide, disulfide, and carbon–carbon bond containing porphyrin dimers TPP-SeSe/TPP-SS/TPP-CC were synthesized. Then, the corresponding self-assembled nanoparticles (TPP-SeSe/TPP-SS/TPP-CC NPs) were prepared via nanoprecipitation method. As-synthesized nanoparticles were utilized to systematically compare the stimuli responsiveness to reductive agents (e.g., glutathione) in different conditions, especially in the living cells, through the singlet oxygen generation ability and the cytotoxicity. A series of experimental results demonstrated that the diselenide bond shows better superiority in reduction sensitivity than that of the disulfide or carbon–carbon bond, which contributed to faster delivery of the photosensitizer and facilitated exertion of better PDT activity. These results highlight the potential of the diselenide bond to be developed as a novel and effective platform to fabricate more functional stimuli-responsive nanomaterials

Metal–Organic Framework@Porous Organic Polymer Nanocomposite for Photodynamic Therapy

The limitation for the biomedical application of porous organic polymers (POPs) is the big size and poor dispersibility in aqueous media. Herein, a nanoscale metal–organic framework (MOF)@POP composite, named <b>UNM</b>, has been synthesized by epitaxial growth of the photoactive porphyrin-POPs (H₂P-POP) on the outer surface of amine containing UiO-66 (UiO-AM). After the growth of POPs, the crystallization, pore structure, and size distribution of <b>UNM</b> are retained well. The formed <b>UNM</b> possesses a small size of less than 200 nm and could be internalized by cancer cells. Such light-activated <b>UNM</b> exhibits efficient ability to generate ¹O₂ under various experimental conditions, which can be further applied for PDT efficacy. The present work demonstrates the great potential of nanoscale porous polymers in biomedical fields and cancer treatment

Data_Sheet_1_Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways.DOCX

<p>Sepsis is reported to be an unusual systemic reaction to infection, accompanied by multiple-organ failure. Sepsis-induced cardiomyopathy (SIC), defined as damages and dysfunction of the heart, is essential in the pathogenesis of sepsis. Traditional Chinese formula, which has long been used to improve the situation of patients through multitarget regulation, is now gradually being used as complementary therapy. The present study aimed to investigate the effect of Qiang-Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its underlying mechanisms in mice. Survival test first showed that an oral administration of QX1 formula significantly increased the 7-days survival of septic mice from 22 to 40%. By estimating the secretion of serum cytokines, QX1 treatment dramatically inhibited the excessive production of interleukin-1β and tumor necrosis factor-α. Immunohistochemical staining illustrated that the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with that of the CLP surgery group. Western blotting confirmed that the activation of essential caspase family members, such as caspase-3, caspase-9, and caspase-12, was prohibited by treatment with QX1. Moreover, the abnormal expression of key regulators of endoplasmic reticulum (ER) and mitochondria-associated apoptosis in cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-X_L, and Bax, was effectively reversed by treatment with QX1 formula. This study provided a new insight into the role of QX1 formula in heart damage and potential complementary therapeutic effect of traditional Chinese medicine on sepsis.</p

Data_Sheet_2_Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways.DOCX

<p>Sepsis is reported to be an unusual systemic reaction to infection, accompanied by multiple-organ failure. Sepsis-induced cardiomyopathy (SIC), defined as damages and dysfunction of the heart, is essential in the pathogenesis of sepsis. Traditional Chinese formula, which has long been used to improve the situation of patients through multitarget regulation, is now gradually being used as complementary therapy. The present study aimed to investigate the effect of Qiang-Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its underlying mechanisms in mice. Survival test first showed that an oral administration of QX1 formula significantly increased the 7-days survival of septic mice from 22 to 40%. By estimating the secretion of serum cytokines, QX1 treatment dramatically inhibited the excessive production of interleukin-1β and tumor necrosis factor-α. Immunohistochemical staining illustrated that the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with that of the CLP surgery group. Western blotting confirmed that the activation of essential caspase family members, such as caspase-3, caspase-9, and caspase-12, was prohibited by treatment with QX1. Moreover, the abnormal expression of key regulators of endoplasmic reticulum (ER) and mitochondria-associated apoptosis in cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-X_L, and Bax, was effectively reversed by treatment with QX1 formula. This study provided a new insight into the role of QX1 formula in heart damage and potential complementary therapeutic effect of traditional Chinese medicine on sepsis.</p

Enhancing Therapeutic Efficacy of Cisplatin by Blocking DNA Damage Repair

Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, we combined a PP2A inhibitor LB (4-(3-carboxy-7-oxa-bicyclo[2.2.1]­heptane-2-carbonyl) piperazine-1-carboxylic acid <i>tert</i>-butyl ester) and the DNA damage chemotherapeutic drug cisplatin through a simple physical superposition. The two drugs administrated at a ratio of 1:1 exhibited an optional synergistic antitumor efficacy <i>in vitro</i> and <i>in vivo</i>. LB was demonstrated to specifically activate the protein kinase B (Akt) and mitogen-activated protein kinases (MAPK) signaling pathways by PP2A inhibition to overcome cell cycle arrest caused by cisplatin-induced DNA damage

DataSheet_1_Development of a prognostic Neutrophil Extracellular Traps related lncRNA signature for soft tissue sarcoma using machine learning.pdf

BackgroundSoft tissue sarcoma (STS) is a highly heterogeneous musculoskeletal tumor with a significant impact on human health due to its high incidence and malignancy. Long non-coding RNA (lncRNA) and Neutrophil Extracellular Traps (NETs) have crucial roles in tumors. Herein, we aimed to develop a novel NETsLnc-related signature using machine learning algorithms for clinical decision-making in STS.MethodsWe applied 96 combined frameworks based on 10 different machine learning algorithms to develop a consensus signature for prognosis and therapy response prediction. Clinical characteristics, univariate and multivariate analysis, and receiver operating characteristic curve (ROC) analysis were used to evaluate the predictive performance of our models. Additionally, we explored the biological behavior, genomic patterns, and immune landscape of distinct NETsLnc groups. For patients with different NETsLnc scores, we provided information on immunotherapy responses, chemotherapy, and potential therapeutic agents to enhance the precision medicine of STS. Finally, the gene expression was validated through real-time quantitative PCR (RT-qPCR).ResultsUsing the weighted gene co-expression network analysis (WGCNA) algorithm, we identified NETsLncs. Subsequently, we constructed a prognostic NETsLnc signature with the highest mean c-index by combining machine learning algorithms. The NETsLnc-related features showed excellent and stable performance for survival prediction in STS. Patients in the low NETsLnc group, associated with improved prognosis, exhibited enhanced immune activity, immune infiltration, and tended toward an immunothermal phenotype with a potential immunotherapy response. Conversely, patients with a high NETsLnc score showed more frequent genomic alterations and demonstrated a better response to vincristine treatment. Furthermore, RT-qPCR confirmed abnormal expression of several signature lncRNAs in STS.ConclusionIn conclusion, the NETsLnc signature shows promise as a powerful approach for predicting the prognosis of STS. which not only deepens our understanding of STS but also opens avenues for more targeted and effective treatment strategies.</p

Table_2_Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways.DOCX

<p>Sepsis is reported to be an unusual systemic reaction to infection, accompanied by multiple-organ failure. Sepsis-induced cardiomyopathy (SIC), defined as damages and dysfunction of the heart, is essential in the pathogenesis of sepsis. Traditional Chinese formula, which has long been used to improve the situation of patients through multitarget regulation, is now gradually being used as complementary therapy. The present study aimed to investigate the effect of Qiang-Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its underlying mechanisms in mice. Survival test first showed that an oral administration of QX1 formula significantly increased the 7-days survival of septic mice from 22 to 40%. By estimating the secretion of serum cytokines, QX1 treatment dramatically inhibited the excessive production of interleukin-1β and tumor necrosis factor-α. Immunohistochemical staining illustrated that the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with that of the CLP surgery group. Western blotting confirmed that the activation of essential caspase family members, such as caspase-3, caspase-9, and caspase-12, was prohibited by treatment with QX1. Moreover, the abnormal expression of key regulators of endoplasmic reticulum (ER) and mitochondria-associated apoptosis in cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-X_L, and Bax, was effectively reversed by treatment with QX1 formula. This study provided a new insight into the role of QX1 formula in heart damage and potential complementary therapeutic effect of traditional Chinese medicine on sepsis.</p

Table_1_Development of a prognostic Neutrophil Extracellular Traps related lncRNA signature for soft tissue sarcoma using machine learning.docx

BackgroundSoft tissue sarcoma (STS) is a highly heterogeneous musculoskeletal tumor with a significant impact on human health due to its high incidence and malignancy. Long non-coding RNA (lncRNA) and Neutrophil Extracellular Traps (NETs) have crucial roles in tumors. Herein, we aimed to develop a novel NETsLnc-related signature using machine learning algorithms for clinical decision-making in STS.MethodsWe applied 96 combined frameworks based on 10 different machine learning algorithms to develop a consensus signature for prognosis and therapy response prediction. Clinical characteristics, univariate and multivariate analysis, and receiver operating characteristic curve (ROC) analysis were used to evaluate the predictive performance of our models. Additionally, we explored the biological behavior, genomic patterns, and immune landscape of distinct NETsLnc groups. For patients with different NETsLnc scores, we provided information on immunotherapy responses, chemotherapy, and potential therapeutic agents to enhance the precision medicine of STS. Finally, the gene expression was validated through real-time quantitative PCR (RT-qPCR).ResultsUsing the weighted gene co-expression network analysis (WGCNA) algorithm, we identified NETsLncs. Subsequently, we constructed a prognostic NETsLnc signature with the highest mean c-index by combining machine learning algorithms. The NETsLnc-related features showed excellent and stable performance for survival prediction in STS. Patients in the low NETsLnc group, associated with improved prognosis, exhibited enhanced immune activity, immune infiltration, and tended toward an immunothermal phenotype with a potential immunotherapy response. Conversely, patients with a high NETsLnc score showed more frequent genomic alterations and demonstrated a better response to vincristine treatment. Furthermore, RT-qPCR confirmed abnormal expression of several signature lncRNAs in STS.ConclusionIn conclusion, the NETsLnc signature shows promise as a powerful approach for predicting the prognosis of STS. which not only deepens our understanding of STS but also opens avenues for more targeted and effective treatment strategies.</p

Effects of heat stress on TER and on FD4 permeability in IEC-6 cell monolayers.

<p>IEC-6 cells on Transwell membranes were exposed at 42°C for 0, 3, 6 or 12 h. (A) TER values were monitored across cell monolayers at the indicated times. (B) Permeability of FD4 across the cell monolayer was measured. Data are presented as means ± SEM from three independent experiments and differences among mean values were assessed by one-way ANOVA. p<0.05 and *** p<0.001 compared with the control group.</p