[Intervention effect of narrative therapy on non-suicidal self-injury in adolescents with depressive disorder: a prospective randomized controlled study]. / å™äº‹æ²»ç–—å¯¹é’å°‘å¹´æŠ‘éƒç—‡æ‚£è€ éžè‡ªæ€æ€§è‡ªä¼¤çš„å¹²é¢„æ•ˆæžœï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the intervention effect of narrative therapy on non-suicidal self-injury (NSSI), as well as anxiety and depression symptoms in adolescents with depressive disorder. METHODS: Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping. The control group received conventional psychological support, while the intervention group received individual narrative therapy in addition to the conventional psychological support (twice a week, 60 minutes per session, for a total of 3 weeks). Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire, Children's Depression Inventory, and Children's Anxiety and Mood Scale before the intervention, at the end of the intervention, and one month after the intervention for both groups. RESULTS: A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study. At the end of the intervention and one month after the intervention, the intervention group showed a significant reduction in the NSSI frequency score, NSSI level, anxiety score, and depression score compared to before the intervention (P<0.017). Moreover, at the end of the intervention and one month after the intervention, the intervention group exhibited significantly lower NSSI frequency score, NSSI severity score, NSSI level, anxiety score and depression score compared to the control group (P<0.05). CONCLUSIONS: Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity, as well as anxiety and depression symptoms in adolescents with depressive disorder.

Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis.

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.

Analysis of the Performance of Recycled Insulation Concrete and Optimal Mix Ratio Design Based on Orthogonal Testing.

Construction and agricultural waste recycling have gained more and more attention recently as renewable resources. Straw and construction waste, both of which are widespread in northern Fujian, were investigated in this research. The orthogonal test was used to investigate the effects of recycled aggregate, straw, and glazed hollow beads on the mechanical and thermal properties of recycled insulation concrete. The influence of different factors on the macroscopic characteristics of recycled insulation concrete was examined using scanning electron microscopy (SEM). The optimal mix proportion for recycled insulation concrete that satisfies mechanical performance standards and provides superior insulation performance was then determined using the total efficacy coefficient method. According to the research findings, the heat conductivity of recycled insulation concrete decreases as its dried density decreases. A 100% recycled coarse aggregate replacement rate, 1% straw content, and 10% glazed hollow beads replacement rate are the optimal mix ratios for recycled insulation concrete. With a compressive strength of 20.98 MPa, a splitting tensile strength of 2.01 MPa, a thermal conductivity of 0.3776 W/(m·K), and a dry density of 1778.66 kg/m3, recycled insulation concrete has the optimal mix ratio. Recycled insulation concrete is a novel form of eco-friendly, energy-saving concrete that aims to achieve low-carbon energy savings and sustainable development by combining resource recycling with building energy savings to realize the recycling of solid waste resources, which has significant environmental, social, and economic benefits and broad market application potential.

Correction: Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Correction for 'Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway' by Zhou Lu Wei et al., Food Funct., 2023, https://doi.org/10.1039/d2fo02387c.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus.

OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Xiaoyaosan Exerts Antidepressant-Like Effect by Regulating Autophagy Involves the Expression of GLUT4 in the Mice Hypothalamic Neurons.

Many studies have proven that autophagy plays a pivotal role in the development of depression and it also affects the expression of GLUT4 in the hypothalamus. Xiaoyaosan has been shown to exert antidepressant effects in a variety of ways, but its underlying mechanism by which Xiaoyaosan regulates autophagy as well as GLUT4 in the hypothalamus remains unclear. Thus, in this study, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and set up autophagy blockade as a control to explore whether Xiaoyaosan exerts antidepressant effect by affecting autophagy. We examined the effects of Xiaoyaosan on behaviors exhibited during the open field test, tail suspension test and sucrose preference test, and the changes in autophagy in hypothalamic neurons as well as changes in GLUT4 and the related indicators of glucose metabolism in CUMS-induced depressive mouse model. We found that CUMS- and 3-MA-induced mice exhibited depressive-like behavioral changes, with decreased LC3 expression and increased p62 expression, suggesting decreased levels of autophagy in the mouse hypothalamus. The expression of GLUT4 was also decreased, and it was closely related to the level of autophagy through Rab8 and Rab10. Nevertheless, after the intervention of Xiaoyaosan, the above changes were effectively reversed. These results show that Xiaoyaosan can regulate the autophagy in hypothalamic neurons and the expression of GLUT4 in depressed mice.

Diagnostic value of bone marrow cell morphology in visceral leishmaniasis-associated hemophagocytic syndrome: Two case reports.

BACKGROUND: Visceral leishmaniasis related-hemophagocytic lymphohistiocytosis (VL-HLH) is a hemophagocytic syndrome caused by Leishmania infection. VL-HLH is rare, especially in nonendemic areas where the disease is severe, and mortality rates are high. The key to diagnosing VL-HLH is to find the pathogen; therefore, the Leishmania must be accurately identified for timely clinical treatment. CASE SUMMARY: We retrospectively analyzed the clinical data, laboratory examination results, and bone marrow cell morphology of two children with VL-HLH diagnosed via bone marrow cell morphology at Kunming Children's Hospital of Yunnan, China. Both cases suspected of having malignant tumors at other hospitals and who were unresponsive to treatment were transferred to Kunming Children's Hospital. They are Han Chinese girls, one was 2 years old and the other one is 9 mo old. They had repeated fevers, pancytopenia, hepatosplenomegaly, hypertriglyceridemia, and hypofibrinogenemia over a long period and met the HLH-2004 criteria. Their HLH genetic test results were negative. Both children underwent chemotherapy as per the HLH-2004 chemotherapy regimen, but it was ineffective and accompanied by serious infections. We found Leishmania amastigotes in their bone marrow via morphological examination of their bone marrow cells, which showed hemophagocytic cells; thus, the children were diagnosed with VL-HLH. After being transferred to a specialty hospital for treatment, the condition was well-controlled. CONCLUSION: Morphological examination of bone marrow cells plays an important role in diagnosing VL-HLH. When clinically diagnosing secondary HLH, VL-HLH should be considered in addition to common pathogens, especially in patients for whom HLH-2004 chemotherapy regimens are ineffective. For infants and young children, bone marrow cytology examinations should be performed several times and as early as possible to find the pathogens to reduce potential misdiagnoses.

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress.

BACKGROUND: Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown. MATERIALS AND METHODS: A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD's antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed. RESULTS: CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats. CONCLUSIONS: SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.

Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder.

Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.

Quantification of fibrinogen-to-pre-albumin ratio provides an integrating parameter for differential diagnosis and risk stratification of early-stage colorectal cancer.

BACKGROUND: Circulating fibrinogen to pre-albumin ratio (FPR) and albumin to fibrinogen ratio (AFR) are effective factors for predicting the prognosis of colorectal cancer (CRC). However, the role of these two ratios in diagnosing early-stage CRC and identifying the stage II CRC subgroup with high relapse risk remains unknown. This study aimed to assess the potential of FPR and AFR in differential diagnosis and risk stratification of early-stage CRC. METHODS: A discovery (694 and 512 patients with benign colorectal polyps and stage I-II CRC, respectively) and validation (201 benign colorectal polyps cases and 202 stage I-II CRC individuals) cohorts were enrolled in this study. Receiver operating characteristic curve (ROC), Kaplan-Meier curve, and time-dependent ROC were used to evaluate the diagnostic efficacy of AFR and FPR in the two cohorts and overall population, and the discriminating role of FPR in identifying clinical high-relapse risk patients in comparison with common clinical characteristics in stage II CRC patients. RESULTS: The area under the curve (AUC) of the preoperative circulating FPR was higher than that of AFR in the diagnosis of stage I-II CRC from colorectal adenomas and benign colorectal polyps in the discovery and validation cohorts and overall population. Carcinoembryonic antigen (CEA) combined with FPR could effectively discriminate early-stage CRC from colorectal adenomas or benign polyps. Preoperative FPR could effectively distinguish stage II subgroups with high and low relapse risk. It was superior to common clinical characteristics in identifying high-risk surgical patients who could benefit from adjuvant chemotherapy (CT) [time-dependent AUC: 0.637 vs. 0.511, p < 0.001 for predicting recurrence-free survival (RFS); 0.719 vs. 0.501, p < 0.001 for predicting overall survival (OS)]. Furthermore, CT treated stage II patients with FPR > 20 had the highest recurrence (31.16%) and death rates (21.88%), with similar highest recurrence (30.70%) and death (26.82%) rates found in non-CT-treated patients with FPR > 20. Stage II CRC patients with 20 ≥ FPR > 15 could significantly benefit from postoperative CT, as the recurrence (33.30%) and death (35.71%) rates within non-CT treated patients were approximately five times higher than those of the CT-treated cases (6.77% and 7.41% for the recurrence and death rates, respectively). No significant difference in recurrence rate was observed between L-FPR (≤ 15) patients with (10.00%) or without CT (9.76%), indicating that these patients might not require to receive adjuvant CT after curative resection. CONCLUSIONS: Preoperative FPR combined with CEA is superior to common tumor biomarkers, FPR, or AFR in distinguishing early-stage CRC from benign colorectal polyps. Circulating FPR can be an effective biomarker for identifying high-risk patients and choosing suitable therapeutics for early-stage CRC.

The complete plastid genome of Kelloggia chinensis Franch. (Rubiaceae), an endemic species from East Asia.

Kelloggia chinensis Franch. is an herbal plant species endemic to East Asia. Its complete plastid genome sequence is 155, 665 bp in length, with a large single-copy (LSC) region of 85, 788 bp, a small single-copy (SSC) region of 16, 977 bp, and a pair of inverted repeat regions (IRs) of 26, 450 bp. The whole plastid genome contains 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of K. chinensis plastid genome is 37.1%. K. chinesis is evolutionarily close to tribe Rubieae according to the Maximum likelihood phylogenetic analysis based on 12 taxa.

Effects of Histone Modification in Major Depressive Disorder.

Major depressive disorder (MDD) is a disease associated with many factors; specifically, environmental, genetic, psychological, and biological factors play critical roles. Recent studies have demonstrated that histone modification may occur in the human brain in response to severely stressful events, resulting in transcriptional changes and the development of MDD. In this review, we discuss five different histone modifications, histone methylation, histone acetylation, histone phosphorylation, histone crotonylation and histone ß-hydroxybutyrylation, and their relationships with MDD. The utility of histone deacetylase (HDAC) inhibitors (HDACis) for MDD treatment is also discussed. As a large number of MDD patients in China have been treated with traditional Chineses medicine (TCM), we also discuss some TCM therapies, such as Xiaoyaosan (XYS), and their effects on histone modification. In summary, targeting histone modification may be a new strategy for elucidating the mechanism of MDD and a new direction for MDD treatment.

Spores morphology of the family Pteridaceae from Shandong Province, China.

In this article, we explored systematically the spore morphology of Pteridaceae by observation of the species distributed in Shandong Province using scanning electron microscopy (SEM). The results showed that the spore morphology of all the species in the family is tetrahedral and trilete. The characters of spore ornamentation are intraspecies stable, but significantly different among species and genera. Spore morphology is significant in exploring the phylogenetic relationships of Pteridaceae as well as in generic and specific delimitations.

Antidepressant Mechanism of Traditional Chinese Medicine Formula Xiaoyaosan in CUMS-Induced Depressed Mouse Model via RIPK1-RIPK3-MLKL Mediated Necroptosis Based on Network Pharmacology Analysis.

Background: Depression is a stress-related disorder that seriously threatens people's physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders. Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan. Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the "botanical drugs-active ingredients-target genes" network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1ß, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections. Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice. Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.

Potential therapeutic effect and methods of traditional Chinese medicine on COVID-19-induced depression: A review.

COVID-19 (coronavirus) has spread all over the world with a high infection rate. Currently, there are no targeted therapeutic drugs for COVID-19 as well as for stress induced by COVID-19. The unpredictable events of COVID-19 can trigger feelings of fear, worry, or unease in people, leading to stress-related disorders such as depression and anxiety. It has been reported that individuals, including COVID-19 patients, medical staff, and ordinary people, are under both physical and psychological pressure, and many of them have developed depression or anxiety during this pandemic. Traditional Chinese medicine (TCM) has been widely used in treating depression with relatively better safety and efficacy and may have an important role in treating stress-related disorders induced by COVID-19. In this review, we collected the common TCM treatment methods including Qigong, Acupuncture, Five Elements Musical Therapy, Five Elements Emotional Therapy, and Chinese herbal medicine from the databases of PubMed and the China National Knowledge Internet to illustrate the effect of TCM on depression. The better knowledge of TCM and implementation of TCM in COVID-19 clinics may help to effectively improve depression induced by COVID-19, may assist people to maintain a healthy physical and mental quality, and may alleviate the current shortage of medical resources.

Efficacy of Plant Growth-Promoting Bacteria Bacillus cereus YN917 for Biocontrol of Rice Blast.

Bacillus cereus YN917, obtained from a rice leaf with remarkable antifungal activity against Magnaporthe oryzae, was reported in our previous study. The present study deciphered the possible biocontrol properties. YN917 strain exhibits multiple plant growth-promoting and disease prevention traits, including production of indole-3-acetic acid (IAA), ACC deaminase, siderophores, protease, amylase, cellulase, and ß-1,3-glucanase, and harboring mineral phosphate decomposition activity. The effects of the strain YN917 on growth promotion and disease prevention were further evaluated under detached leaf and greenhouse conditions. The results revealed that B. cereus YN917 can promote seed germination and seedling plant growth. The growth status of rice plants was measured from the aspects of rice plumule, radicle lengths, plant height, stem width, root lengths, fresh weights, dry weights, and root activity when YN917 was used as inoculants. YN917 significantly reduced rice blast severity under detached leaf and greenhouse conditions. Genome analysis revealed the presence of gene clusters for biosynthesis of plant promotion and antifungal compounds, such as IAA, tryptophan, siderophores, and phenazine. In summary, YN917 can not only be used as biocontrol agents to minimize the use of chemical substances in rice blast control, but also can be developed as bio-fertilizers to promote the rice plant growth.

3-Arylamino-quinoxaline-2-carboxamides inhibit the PI3K/Akt/mTOR signaling pathways to activate P53 and induce apoptosis.

Thirty-eight new 3-arylaminoquinoxaline-2-carboxamide derivatives were in silico designed, synthesized and their cytotoxicity against five human cancer cell lines and one normal cells WI-38 were evaluated. Molecular mechanism studies indicated that N-(3-Aminopropyl)-3-(4-chlorophenyl) amino-quinoxaline-2-carboxamide (6be), the compound with the most potent anti-proliferation can inhibit the PI3K-Akt-mTOR pathway via down regulating the levels of PI3K, Akt, p-Akt, p-mTOR and simultaneously inhibit the phosphorylation of Thr308 and Ser473 residues in Akt kinase to servers as a dual inhibitor. Further investigation revealed that 6be activate the P53 signal pathway, modulated the downstream target gene of Akt kinase such p21, p27, Bax and Bcl-2, caused the fluctuation of intracellular ROS, Ca2+ and mitochondrial membrane potential to induce cell cycle arrest and apoptosis in MGC-803 cells. 6be also display moderate anti-tumor activity in vivo while displaying no obvious adverse signs during the drug administration. The results suggest that 3-arylaminoquinoxaline-2-carboxamide derivatives might server as new scaffold for development of PI3K-Akt-mTOR inhibitor.

Identification of novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature review.

De novo germline variants of the casein kinase 2α subunit (CK2α) gene (CSNK2A1) have been reported in individuals with the congenital neuropsychiatric disorder Okur-Chung neurodevelopmental syndrome (OCNS). Here, we report on two unrelated children with OCNS and review the literature to explore the genotype-phenotype relationship in OCNS. Both children showed facial dysmorphism, growth retardation, and neuropsychiatric disorders. Using whole-exome sequencing, we identified two novel de novo CSNK2A1 variants: c.479A>G p.(H160R) and c.238C>T p.(R80C). A search of the literature identified 12 studies that provided information on 35 CSNK2A1 variants in various protein-coding regions of CK2α. By quantitatively analyzing data related to these CSNK2A1 variants and their corresponding phenotypes, we showed for the first time that mutations in protein-coding CK2α regions appear to influence the phenotypic spectrum of OCNS. Mutations altering the ATP/GTP-binding loop were more likely to cause the widest range of phenotypes. Therefore, any assessment of clinical spectra for this disorder should be extremely thorough. This study not only expands the mutational spectrum of OCNS, but also provides a comprehensive overview to improve our understanding of the genotype-phenotype relationship in OCNS.

Role of Chronic Inflammatory Ratios in Predicting Recurrence of Resected Patients with Stage I-III Mucinous Colorectal Adenocarcinoma.

BACKGROUND: Cancer-related inflammation is the main cause of the progression of mucinous colorectal adenocarcinoma (MCA). Circulating fibrinogen-to-pre-albumin ratio (FPR) is associated with the clinical outcome in colorectal cancer (CRC). However, the prognostic role of FPR and which is the best inflammatory prognostic biomarker within MCA remain unknown. METHODS: We enrolled 157 patients with stage I-III MCA in this study. Kaplan-Meier curve, Cox regression, and time-dependent receiver operation characteristic curve analysis were performed to assess the prognostic value and efficacy of the neutrophil-to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio (NPAR), albumin-to-alkaline phosphatase ratio (AAPR), albumin-to-globulin ratio (AGR), albumin-to-fibrinogen ratio (AFR), and FPR in these patients. RESULTS: We found that NAR, NPAR, and FPR were significantly associated with unsatisfactory recurrence-free survival (RFS) in patients with stage I-III MCA, and the predicted efficacy of FPR was superior to that of the other two inflammatory biomarkers. Moreover, patients with a high combined TNM-CA199-FPR score had worse outcomes, with a high predicted efficacy of up to 0.779 (0.703-0.856). Using FPR, the patient was monitored for the recurrence up to two months earlier than that achieved using the common imaging techniques (4 vs 6 median months) in stage I-III MCA patients undergoing radical resection. CONCLUSION: FPR is the preferred inflammatory biomarker and commonly used for predicting and monitoring recurrence in stage I-III MCA patients. The combined TNM-CA199-FPR score is an economical, simple, effective, and independent prognostic factor for localized disease.