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Rhizoctonia solani AG‐1 IA causes a necrotrophic rice disease and is a serious threat to rice production. To date, only a few effectors have been characterized in AG‐1 IA. We previously identified RsIA_CtaG/Cox11 and showed that infiltration of the recombinant protein into rice leaves caused disease‐like symptoms. In the present study, we further characterized the functionality of RsIA_CtaG/Cox11. RsIA_CtaG/Cox11 is an alternative transcript of cytochrome c oxidase copper chaperone Cox11 that starts from the second AUG codon, but contains a functional secretion signal peptide. RNA interference with RsIA_CtaG/Cox11 reduced the pathogenicity of AG‐1 IA towards rice and Nicotiana benthamiana without affecting its fitness or mycelial morphology. Transient expression of the RsIA_CtaG/Cox11‐GFP fusion protein demonstrated the localization of RsIA_CtaG/Cox11 to mitochondria. Agro‐infiltration of RsIA_CtaG/Cox11 into N. benthamiana leaves inhibited cell death by BAX and INF1. In contrast to rice, agro‐infiltration of RsIA_CtaG/Cox11 did not induce cell death in N. benthamiana. However, cell death was observed when it was coinfiltrated with Os_CoxVIIa, which encodes a subunit of cytochrome c oxidase. Os_CoxVIIa appeared to interact with RsIA_CtaG/Cox11. The cell death triggered by coexpression of RsIA_CtaG/Cox11 and Os_CoxVIIa is independent of the leucine‐rich repeat receptor kinases BAK1/SOBIR1 and enhanced the susceptibility of N. benthamiana to AG‐1 IA. Two of the three evolutionarily conserved cysteine residues at positions 25 and 126 of RsIA_CtaG/Cox11 were essential for its immunosuppressive activity, but not for cell death induction. This report suggests that RsIA_CtaG/Cox11 appears to have a dual role in immunosuppression and cell death induction during pathogenesis. [ABSTRACT FROM AUTHOR]

Ecological forests are an important part of terrestrial ecosystems, are an important carbon sink and play a pivotal role in the global carbon cycle. At present, the comprehensive utilization of optical and radar data has broad application prospects in forest parameter extraction and biomass estimation. In this study, tree and topographic data of 354 plots in key nature reserves of Liaoning Province were used for biomass analysis. Remote sensing parameters were extracted from Landsat 8 OLI and Sentinel-1A radar data. Based on the strong correlation factors obtained via Pearson correlation analysis, a linear model, BP neural network model and PSO neural network model were used to simulate the biomass of the study area. The advantages of the three models were compared and analyzed, and the optimal model was selected to invert the biomass of Liaoning province. The results showed that 44 factors were correlated with forest biomass (p < 0.05), and 21 factors were significantly correlated with forest biomass (p < 0.01). The comparison between the prediction results of the three models and the real results shows that the PSO-improved neural network simulation results are the best, and the coefficient of determination is 0.7657. Through analysis, it is found that there is a nonlinear relationship between actual biomass and remote sensing data. Particle swarm optimization (PSO) can effectively solve the problem of low accuracy in traditional BP neural network models while maintaining a good training speed. The improved particle swarm model has good accuracy and speed and has broad application prospects in forest biomass inversion. [ABSTRACT FROM AUTHOR]

Background: Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode. Methods: Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3‐V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed. Results: Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: R2 = 0.034, p = 0.01) and was higher in patients versus HCs. A total number of 24 taxa displayed significantly different abundance among OW, NW, and HCs. At the family level, the abundance of three taxa was remarkably increased in NW, one in OW, and one in HCs. At the genus level, five taxa were enriched in OW, eight in NW, and two in HCs. The relative abundance of the genera Megamonas was positively associated with BMI, while Eggerthella was negatively correlated with BMI. Functional prediction analysis revealed the metabolism of cofactors and vitamins and amino acid were highly enriched in OW compared to HCs. In addition, microbial functions involved in "lipid metabolism" were depleted while the "fructose and mannose metabolism" was enriched in OW compared to NW group. Conclusions: Specific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future. [ABSTRACT FROM AUTHOR]

Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium have yet to be verified. Hence, we conducted a randomized controlled pilot study to evaluate the efficacy of QTP monotherapy in patients with bipolar depression with mixed features defined by DSM-5 and compared the combination therapy of QTP plus valproate (QTP + V) versus QTP plus lithium (QTP + L) for those patients who responded insufficiently to QTP monotherapy. Data was analyzed according to the intent-to-treat population. Generalized linear mixed model was performed by using "nlme" package in R software. A total 56 patients were enrolled, among which, 35 patients responded to QTP alone, and 11 and 10 patients were randomly assigned to QTP + V and QTP + L group, respectively. Nearly 60% enrolled patients responded to QTP monotherapy at the first two weeks treatment. No statistically significant difference in efficacy between QTP + V and QTP + L was observed. In conclusion, QTP monotherapy appeared to be efficacious in patients with bipolar depression with mixed features, and for those who responded insufficiently to QTP, combining with either valproate or lithium appeared to have positive effects. [ABSTRACT FROM AUTHOR]

Objective: The present research set out to ascertain the roles of CC chemokine ligand 21 (CCL21) and cystathionine beta-synthase (CBS) in breast cancer (BC) cell biological behaviors and the relationship of CCL21 and CBS expression with the clinicopathological features of patients with BC. Methods: Immunohistochemistry of CCL21 or CBS was performed in 18 intraductal cancer tissues, 124 invasive BC tissues, 50 paraneoplastic tissues, 50 lobular hyperplasia tissues, and 30 normal breast tissues. For cell experiments, two human BC cell lines (MDA-MB-231 and MCF-7) and a human breast epithelial cell line (MCF-10A) were utilized to detect the expression of CCL21 and CBS. After loss- and gain-of-function assays for CCL21 or CBS, the expression of CBS and CCL21 was measured by quantitative real-time polymerase chain reaction and western blot. Additionally, BC cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2′-deoxyuridine staining, and BC cell migration was determined by scratch test and Transwell assay. Results: In the clinical data, the positive rate of CCL21 or CBS was significantly higher in invasive BC tissues than in intraductal BC tissues, lobular hyperplasia tissues, paraneoplastic tissues, and normal breast tissues (p < 0.05 or p < 0.01). CBS or CCL21 expression shared close association with the clinicopathological characteristics and the poor prognosis of BC patients. In cell experiments, overexpression of CCL21 or CBS enhanced the proliferative and migratory abilities of BC cells. Conclusion: CCL21 and CBS promoted BC cell migration and proliferation. CCL21 or CBS expression was strongly related to the poor prognosis of BC patients. [ABSTRACT FROM AUTHOR]

Biological invasion poses a huge threat to ecological security. Spartina alterniflora was introduced into China in 1979, and its arrival corresponded with negative effects on native ecosystems. To explore geographical variation of its expansion rate in coastal China, we selected 43 S. alterniflora sites from Tianjin Coastal New Area to Beihai. The area expansion rate, expansion rate paralleling and vertical to the shoreline were analysed based on Landsat images and field survey in 2015. Simple Ocean Data Assimilation (SODA) and climate data were collected to statistically analyse the influential factors of expansion rate. Results showed that significant difference of S. alterniflora area expansion rate among different latitude zones (P < 0.01), increasing from 6.08% at southern (21°N–23°N) to 19.87% in Bohai Bay (37°N–39°N) along latitude gradient. There was a significant difference in expansion rate vertical to shoreline in different latitude zones (P < 0.01) with the largest occurring in Bohai Bay (256 m/yr, 37°N–39°N), and showed an decreasing tendency gradually from north to south. No significant difference and latitudinal clines in expansion rate paralleling to shoreline were observed. Expansion rate had significant negative correlation with mean seawater temperature, the lowest seawater temperature, current zonal velocity and meridional velocity and presented a reducing trend as these biotic factors increased; however, they were not significantly correlated with the highest seawater temperature and mean seawater salinity. We identified significant correlations between expansion rate and annual mean temperature, the lowest temperature in January and annual precipitation, but there was little correlation with annual diurnal difference in temperature and the highest temperature in July. The rapid expansion rate in high-latitude China demonstrated a higher risk of potential invasion in the north; dynamic monitoring and control management should be established as soon as possible. [ABSTRACT FROM AUTHOR]

This study aims to investigate the mechanism of miR-23a-3p in regulating Treg dysfunction in Graves' disease (GD). The percentage of Treg cells and interleukin (IL)-17+ T cells were determined by flow cytometry. The expression of forkhead box P3 (FOXP3), sirtuin 1 (SIRT1), RAR-related orphan receptor gamma t (RORγt) and miR-23a-3p was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blot. CD4+ T cells were treated with SIRT1 specific inhibitor EX-527 or left untreated. MiR-23a-3p mimic or inhibitor were transfected into CD4+ T cells. Acetylation expression of FOXP3 was analyzed by immunoprecipitation. The suppressive function of Treg was analyzed by the carboxyfluorescein succinimidyl ester (CFSE) assay. The results showed that GD patients have significantly less Treg cells and more IL-17+ T cells. FOXP3 and miR-23a-3p were significantly down-regulated meanwhile SIRT1 and RORγt were up-regulated in GD patients. FOXP3 acetylation level of the GD group was lower than that of control groups. After EX-527 treatment, the percentage of Treg cells, expression and acetylation level of FOXP3 were significantly increased in the GD group. GD Tregs exhibited weaker suppressive activity, miR-23a-3p mimic suppressed SIRT1 expression and suppressive-activity of Tregs whereas it promoted the expression and acetylation level of FOXP3 in the GD group. Our findings suggest that the Treg function defect in GD patients is mediated by the abnormal acetylation of FOXP3, which is regulated by miR-23a-3p via targeting SIRT1. [ABSTRACT FROM AUTHOR]

Abstract Silica nanopores have electron channels and ion channels interpenetrating each other, which prompt the use of this structure for creating efficient electronic devices. In this study, silica nanopores membrane modified screen printed electrodes were applied in a smartphone-based electrochemiluminescence system for nitroaromatic explosives detection. Universal serial bus-on the go (USB-OTG) and camera on smartphone were used as the electrical stimulation and luminescence capture, respectively. ⎕Multimode methods including (red-green-blue) RGB, (hue-saturation-brightness) HSB, and Gray were proposed for luminescence analysis. Specific polypeptides were immobilized on the nanopores modified electrodes for nitroaromatic explosives sensing. With positive-charged tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy) 3 2+) as electrochemiluminescence label, the increase in luminescence was associated with the selective ion channels and the well-conductive electron channels in the negative-charged nanopores. Besides, on account of the large specific surface area, nanopores modified screen printed electrodes showed stable and uniform luminescence. Results showed that the nanopores-enhanced electrochemiluminescence on smartphone covered a linear dynamic range from 10−7 mg/mL to 10−3 mg/mL for nitroaromatic explosives detection with the detection limit of 2.3 × 10−9 mg/mL. Therefore, high-efficient photo-electricity conversion capabilities of nanopores made it a kind of promising platform for sensitive and stable electrochemiluminescence. Furthermore, smartphone-based electrochemiluminescence with disposable screen printed electrodes could facilitate the mobile monitoring of biochemical analytes in the fields of environment, security, and health. Highlights • Silica nanopores with electron and ion channels interpenetrating each other, showed uniform luminescence. • Integration of electrochemiluminescence on smartphone as the stimulation and luminescence capture, respectively. • Specific bifunctional polypeptides were immobilized on nanopores for nitroaromatic explosives sensing. • Multimode of (red-green-blue) RGB, (hue-saturation-brightness) HSB, and Gray proposed for luminescence analysis. • The smartphone-based system facilitated the mobile monitoring in the fields of environment, security, and health. [ABSTRACT FROM AUTHOR]

There is now growing interest in the use of Ultrasound-guided radiofrequency ablation (RFA) to treat hyperparathyroidism. But the efficacy and limitations of this treatment have not been described in sufficient detail. Assessing and contrasting the effectiveness and safety of RFA in treating primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). This retrospective study included 57 HPT patients (48 for PHPT and 9 for SHPT) who underwent RFA between January 2017 and April 2021. The serum intact parathyroid hormone (iPTH) and calcium, hyperplastic parathyroid volume, volume reduction rate (VRR) before and after RFA, clinical success rate, symptoms, and complications were analyzed and compared. In SHPT group, bone pain (7/9, 77.8%), skin pruritus (4/9, 44.4%), and multiple hyperplastic parathyroid glands (4/9, 44.4%) were more common compared to the PHPT group. After 12 months of follow-up, the serum iPTH, calcium, and the volume of PHPT and SHPT groups had decreased by more than 60%, 10%, and 90%, respectively (P < 0.05). In the VRR, 13 glands of SHPT (72.2%) and 42 glands of PHPT (87.5%) had achieved the clinical success. In addition, the preoperative and postoperative serum iPTH were higher in the SHPT group than in the PHPT group (P < 0.05). In terms of the serum iPTH and calcium, the PHPT group had substantially higher rates of clinical success, with 42 patients (87.5%) and 46 patients (95.8%) meeting the criteria, respectively compared to 3 patients (33.3%) and 6 patients (66.7%) of SHPT group (P < 0.05). After RFA, the clinical symptoms improved in both groups. The overall incidence of complications (hoarseness and postoperative hematoma) of RFA in the two groups was 10.5% (6/57), and hoarseness (3/9, 33.3%) of SHPT group was more common than PHPT group. All the complications were resolved spontaneously within 12 months after symptomatic treatments. In the treatment of PHPT and SHPT, ultrasound-guided RFA is both successful and safe. PHPT patients have better results in restoring normal iPTH by RFA, and have no considerable difference with the SHPT patients in terms of serum calcium, the volume of the ablation area, and the VRR. [ABSTRACT FROM AUTHOR]

To gain insight into liver and pancreas development, we investigated the target of 2F11, a monoclonal antibody of unknown antigen, widely used in zebrafish studies for labeling hepatopancreatic ducts. Utilizing mass spectrometry and in vivo assays, we determined the molecular target of 2F11 to be Annexin A4 (Anxa4), a calcium binding protein. We further found that in both zebrafish and mouse endoderm, Anxa4 is broadly expressed in the developing liver and pancreas, and later becomes more restricted to the hepatopancreatic ducts and pancreatic islets, including the insulin producing ß-cells. Although Anxa4 is a known target of several monogenic diabetes genes and its elevated expression is associated with chemoresistance in malignancy, its in vivo role is largely unexplored. Knockdown of Anxa4 in zebrafish leads to elevated expression of caspase 8 and Δ113p53 , and liver bud specific activation of Caspase 3 and apoptosis. Mosaic knockdown reveal that Anxa4 is required cell-autonomously in the liver bud for cell survival. This finding is further corroborated with mosaic anxa4 knockout studies using the CRISPR/Cas9 system. Collectively, we identify Anxa4 as a new, evolutionarily conserved hepatopancreatic factor that is required in zebrafish for liver progenitor viability, through inhibition of the extrinsic apoptotic pathway. A role for Anxa4 in cell survival may have implications for the mechanism of diabetic ß-cell apoptosis and cancer cell chemoresistance. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRs) are small non-coding RNAs that play important roles in cancer development where they can act as oncogenes or as tumor-suppressors. MiR-34a is a tumor suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in colorectal cancer (CRC). Aim: This study aims to show the dysregulation of miR-34a in CRC and to characterize the function and mechanism of miR-34a in CRC cell lines. Methods: The expression of miR-34a was detected using real-time PCR on CRC tissues and adjacent non-tumorous tissues. The ELISA was used to assess vascular endothelial growth factor (VEGF). The focal adhesion kinase (FAK) and phosphorylated FAK Y397 (pY397FAK) were measured by Western blot. The functions of miR-34a in vivo were measured by migration, invasion, CCK-8 assay and flow cytometry. Results: MiR-34a was significantly downregulated and pY397FAK was upregulated in CRC cancer tissues. It plays an important role in inhibiting migration and invasion and in increasing apoptosis of CRC cells. Bioinformatic analysis suggested that VEGF may be a target of miR-34a, and this hypothesis was proved by ELISA and RT-PCR. The level of pY397FAK that could be activated by VEGF was downregulated in miR-34a overexpression CRC cell lines. The phosphorylation of FAK at 397 sites in miR-34a-stable cell lines was completely rescued by extra VEGF treatment. Conclusion: MiR-34a is frequently downregulated in CRC and modulates the phosphorylation of FAK by negatively regulating VEGF. [ABSTRACT FROM AUTHOR]

Background: Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of mitophagy in spatial memory mediated by neurogenesis during development. Methods: Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among mitophagy, neurogenesis, and behavioral performance during development. Results: The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of mitophagy in adult mice with UMI‐77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of mitophagy with Mdivi‐1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory. Conclusion: The observed decline in spatial memory in adult mice is associated with decreased mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing mitophagy to counteract age‐ or disease‐related cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Activating transcription factor-2 (ATF2) is a member of the basic leucine zipper family of DNA-binding proteins, which exhibits both oncogenic and tumor suppression activity in different tumors. However, the molecular mechanism of its dual function in cancer chemotherapy especially in gastric cancer has still not been elucidated. Methods: The protein expression and location of ATF2 in gastric cancer tissues was detected with immunohistochemistry assay, and the clinical significance was analyzed using TCGA and GEO database. The activation and impact of ATF2 in cisplatin treated cells were evaluated with western blot, incucyte live cell analysis, clone formation and tumor xenografts assays. Interaction between ATF2 and p53 was confirmed with immunoprecipitation and GST-pull down. Potential molecular mechanism of ATF2 in different p53 status cells was analyzed with RNA sequencing and real-time quantitative PCR. Results: ATF2 mainly located in the nucleus of cancer cells, higher ATF2 level was associated with poor five-year survival of gastric patients, especially in those undergone chemotherapy treatment. Cisplatin treatment significantly activated ATF2 in p53 mutant cells. ATF2 could interact with the trans-activation domain of p53 and enhance cisplatin sensitivity in p53 wild type cell lines, while promoted cell survival in mutant p53 cancer cells by affecting ERK1/2 pathway. Conclusions: This study confirmed the effect of ATF2 on cisplatin sensitivity was associated with the functional status of p53 in gastric cancer cells. Integrated analysis of ATF2 expression and P53 status could be used to evaluate the chemotherapy sensitivity and prognosis of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate whether peripheral T‐cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). Methods: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T‐cell subtype proportions, including CD3+, CD4+, CD8+ T‐cell, and natural killer (NK) cells, were enrolled. The Chi‐square test, t‐test, or one‐way analysis of variance were used to analyze group differences. Demographic profiles and T‐cell data were used to construct a random forest classifier‐based diagnostic model. Results: Totally, 98 cases of BD mania, 459 cases of BD depression (BD‐D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T‐cell, and NK cells among the three groups. Compared with MDD, the BD‐D group showed higher CD8+ but lower CD4+ T‐cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71–0.83) to distinguish BD‐D from MDD patients. Conclusion: These findings imply that BD and MDD patients may harbor different T‐cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis." The correction states that there was an error in Figure 6I of the original article. The WB blots of DDR2 in BT20 cells were mistakenly used twice in the Co-immunoprecipitation experiment, resulting in the incorrect representation of WB blots of IFITM1 in MDA-MB-231 cells. The correct figure has been provided in the updated version of the article. The publisher, Springer Nature, maintains a neutral stance on jurisdictional claims and institutional affiliations. [Extracted from the article]

Background: Most of the previous studies have demonstrated the potential antidepressive and anxiolytic role of prebiotic supplement in male subjects, yet few have females enrolled. Herein, we explored whether prebiotics administration during chronic stress prevented depression‐like and anxiety‐like behavior in a sex‐specific manner and the mechanism of behavioral differences caused by sex. Methods: Female and male C57 BL/J mice on normal diet were supplemented with or without a combination of fructo‐oligosaccharides (FOS) and galacto‐oligosaccharides (GOS) during 3‐ and 4‐week chronic restraint stress (CRS) treatment, respectively. C57 BL/J mice on normal diet without CRS were used as controls. Behavior consequences, gut microbiota, dysfunction of gut and brain–blood barriers, and inflammatory profiles were measured. Results: In the 3rd week, FOS + GOS administration attenuated stress‐induced anxiety‐like behavior in female, but not in male mice, and the anxiolytic effects in males were observed until the 4th week. However, protective effects of prebiotics on CRS‐induced depression were not observed. Changes in the gene expression of tight junction proteins in the distal colon and hippocampus, and decreased number of colon goblet cells following CRS were restored by prebiotics only in females. In both female and male mice, prebiotics alleviated stress‐induced BBB dysfunction and elevation in pro‐inflammatory cytokines levels, and modulated gut microbiota caused by stress. Furthermore, correlation analysis revealed that anxiety‐like behaviors were significantly correlated with levels of pro‐inflammatory cytokines and gene expression of tight junction proteins in the hippocampus of female mice, and the abundance of specific gut microbes was also correlated with anxiety‐like behaviors, pro‐inflammatory cytokines, and gene expression of tight junction proteins in the hippocampus of female mice. Conclusion: Female mice were more vulnerable to stress and prebiotics than males. The gut microbiota, gut and blood–brain barrier, and inflammatory response may mediate the protective effects of prebiotics on anxiety‐like behaviors in female mice. [ABSTRACT FROM AUTHOR]

Purpose: Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. Methods: Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. Results: Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10–0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). Conclusion: It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the roles of DDR2 and IFITM1 in breast cancer (BC). Methods: The expression of DDR2 and IFITM1 in BC tissues and cell lines was measured. DDR2 and/or IFITM1 were knocked down in BT20 and MDA-MB-231 cells, after which the viability, mobility and apoptosis of the cells were tested. Xenograft mouse models were established through subcutaneous tumor transplantation. Results: DDR2 and IFITM1 were highly expressed in invasive BC tissues and cell lines. Overexpression of DDR2 and/or IFITM1 was associated with poorer clinical outcomes and patient survival. Knockdown of DDR2 or IFITM1 suppressed the viability and invasiveness of BT20 and MDA-MB-231 cells and restrained the growth of xenograft tumors in nude mice. Simultaneous knockdown of IFITM1 and DDR2 surpassed knockdown of IFITM1 alone in suppressing BC development. Conclusions: DDR2 and IFITM1 are co-expressed to facilitate the malignant behaviors of BC cells and promote the development of tumors. [ABSTRACT FROM AUTHOR]

Percutaneous radiofrequency ablation (RFA) has been recommended as minimally invasive treatment for patients with symptomatic benign thyroid nodules (BTNs) because of the large number of clinical applications. This retrospective observational study sought to evaluate the clinical outcomes of RFA for BTNs. From 2014 to 2019, a sample size of 1289 patients treated by RFA were 262 ones with solid nodules and 1027 ones with cystic-solid nodule, respectively. The efficacy including the nodule maximal diameter reduction ratio (MDRR), the volume reduction ratio (VRR) and the cosmetic scores reduction ratio (CSRR). The results of the nodule MDRR and VRR in the cystic-solid nodule group were significantly better than those in the solid nodule group at the 3rd and 6th month, and the CSRR in the two groups showed statistically significant difference at the 3rd month. In a word, RFA is an effective method for symptomatic benign solid or cystic-solid nodules. The achieved MDRR and VRR in the cystic-solid nodule group were significantly better than those in the solid nodule group at the 3rd and 6th month. [ABSTRACT FROM AUTHOR]

Abstract: The microstructure and tensile property changes of a γTiAl-based alloy, Ti-47Al-2Cr-2Nb-0.15B, during isothermal and cyclic high temperature exposures have been investigated. Microstructure coarsening, including the fracture, dissolution and spheroidization of α2 lamellae, is considered to be the main cause of the evident tensile property decreases of the alloy after isothermal and cyclic high temperature exposures. Dislocation emission near the broken lamellae is also an important phenomenon in the microstructure degradation during cyclic high temperature exposure, which originated from the thermal mismatch between α2 and γ phases. [Copyright &y& Elsevier]

Phosphorus (P) is an essential nutrient, limiting plant growth and microbial activity in many ecosystems. However, a few studies have been conducted to investigate P dynamics and the factors driving P dynamics in peatland soils. Therefore, this study chose Zoige Plateau peatland (the largest peatland in China) to reveal P dynamics and the possible driving factors through fractionating soil P and investigating a series of abiotic and biotic factors. It is found that season, peatland type, and soil depth could strongly affect P dynamics. H 2 O–P and NaHCO 3 –P (labile P) had lower content, while NaOH–P, HCl–P, Mix-P, and Residual-P (non-labile P) were the dominant fractions. Besides, the sum of P fractions was higher than the traditional measurement of total P, suggesting P storage might be underestimated in peatland soils. Moreover, it is observed that biotic factors affected P fractions more than abiotic factors, and fungi affected refractory P more than bacteria. This study provides essential information for understanding P cycling in peatland soils and emphasizes specific microbes related to P cycling, which should be paid more attention to in the future. • Season, peatland type, and soil depths strongly affected P fractions in Zoige soil. • NaOH–P, HCl–P, Mix-P, and Residual-P were the dominant P fractions. • The sum of P fractions suggested P storage might be underestimated. • Biotic factors affected P dynamics more than abiotic factors in peatland soils. • Fungi played crucial roles in accumulating and solubilizing refractory P. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3) has been reported to repress the expression of various genes by eliminating acetyl group from histone. The objective of this study was to discuss the effect of HDAC3/microRNA-130a-3p (miR-130a-3p)/high-mobility group box 3 (HMGB3) on immune escape of breast cancer. HDAC3, miR-130a-3p and HMGB3 expression in breast cancer tissues and cells were tested, and the correlation between HDAC3, miR-130a-3p and HMGB3 was analyzed. CD8, CD69 and programmed cell death protein 1 (PD-1) expression was detected. MDA-MB-231 cells were treated with relative plasmid of HDAC3 or miR-130a-3p to test cell viability, migration, epithelial-mesenchymal transition (EMT) and apoptosis in MDA-MB-231 cells. The cytotoxicity of CD8+/CD69+/PD-1+T cells in MDA-MB-231 cells was tested, and CD8+/CD69+/PD-1+T cell proliferation and apoptosis before and after co-culture with MDA-MB-231 cells were detected. HDAC3 and HMGB3 expression were raised and miR-130a-3p expression was diminished in breast cancer tissues and cells. HDAC3 was negatively correlated with miR-130a-3p while miR-130a-3p was negatively correlated with HMGB3. Down-regulating HDAC3 or up-regulating miR-130a-3p restrained cell viability, migration, EMT and anti-CD8+/CD69+/PD-1+T cytotoxicity and facilitated apoptosis of breast cancer cells. HDAC3 regulated HMGB3 by mediating miR-130a-3p expression. Down-regulating miR-130a-3p reversed the role of HDAC3 reduction on breast cancer cells. HDAC3 regulated CD8+/CD69+/PD-1+T cell proliferation and apoptosis by mediating miR-130a-3p. This study provides evidence that HDAC3 increases HMGB3 expression to promote the immune escape of breast cancer cells via down-regulating miR-130a-3p. [ABSTRACT FROM AUTHOR]

Purpose: PR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed.Methods: In this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression.Results: ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER+/PR+/HER2- and ER+/PR-/HER2- groups.Conclusions: In conclusion, this study indicated in ER+/HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation. [ABSTRACT FROM AUTHOR]

Rice is one of the most important cereal crops, providing the daily dietary intake for approximately 50% of the global human population. Here, we re-sequenced 259 rice accessions, generating 1371.65 Gb of raw data. Furthermore, we performed genome-wide association studies (GWAS) on 13 agronomic traits using 2.8 million single nucleotide polymorphisms (SNPs) characterized in 259 rice accessions. Phenotypic data and best linear unbiased prediction (BLUP) values of each of the 13 traits over two years of each trait were used for the GWAS. The results showed that 816 SNP signals were significantly associated with the 13 agronomic traits. Then we detected candidate genes related to target traits within 200 kb upstream and downstream of the associated SNP loci, based on linkage disequilibrium (LD) blocks in the whole rice genome. These candidate genes were further identified through haplotype block constructions. This comprehensive study provides a timely and important genomic resource for breeding high yielding rice cultivars. • We re-sequenced 259 rice accessions, generating 1371.65 Gb of raw data. • We performed genome-wide association studies (GWAS) on 13 agronomic traits using 2.8 million single nucleotide polymorphisms (SNPs) characterized in 259 rice accessions. • The candidate genes related to target traits were identified through haplotype block constructions. [ABSTRACT FROM AUTHOR]

Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome‐gut‐brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome‐targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health‐related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation. [ABSTRACT FROM AUTHOR]

The mitotic serine/threonine kinase aurora kinase-A (AURKA) has been identified as carcinogenic in hepatocellular carcinoma (HCC). AURKAPS1, a long non-coding RNA (lncRNA), is the pseudo-gene of AURKA, which play important roles in the cancer. Its underlying functions and mechanisms in liver cancer progression remain largely unknown. The mRNA expression of AURKAPS1 in HCC tumor tissues was significantly higher, which is associated with tumor size and TNM stage. The high expression of AURKAPS1 promotes cell movement, migration and invasion. AURKAPS1 can increases the protein expression of RAC1, promotes the activation of ERK, and enhance the formation of membrane ruffles by binding with miR-182, miR-155 and miR-142 competively. Thus, AURKAPS1 could be a useful marker, and the combination of AURKAPS1/miRNAs (miR-142, miR-155 and miR-182) may be a new theoretical basis for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell immunotherapy has achieved promising therapeutic effects in the treatment of hematological malignancies. However, there are still many obstacles, including on-target off-tumor antigen expression, that prevent successful application to solid tumors. We designed a tumor microenvironment (TME) regulated system chimeric antigen receptor T (MRS.CAR-T) which can only be auto-activated in the solid TME. B7-H3 was selected as the target antigen for esophageal carcinoma. An element comprising a human serum albumin (HSA) binding peptide and a matrix metalloproteases (MMPs) cleavage site was inserted between the 5' terminal signal peptide and single chain fragment variable (scFv) of the CAR skeleton. Upon administration, HSA bound the binding peptide in MRS.B7-H3.CAR-T effectively and promoted proliferation and differentiation into memory cells. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3 as the antigen recognition site in the scFv was cloaked by HSA. The anti-tumor function of MRS.B7-H3.CAR-T was recovered once the cleavage site was cleaved by MMPs in the TME. The anti-tumor efficacy associated with MRS.B7-H3.CAR-T cells was improved compared to classic B7-H3.CAR-T cells in vitro and less IFN-γ was released, suggesting a treatment that may induce less extent of cytokine release syndrome-mediated toxicity. In vivo, MRS.B7-H3.CAR-T cells had strong anti-tumor activity and were safe. MRS.CAR-T represents a novel strategy to improve the efficacy and safety of CAR-T therapy in solid tumors. • MRS.CAR-T is an auto-regulated CAR-T which only has anti-tumor function in solid tumor microenvironment. • MRS.CAR-T can bind with human serum albumin, grow faster and produce more memory T cells than classic CAR-T. • MRS.CAR-T is more effective and safer than conventional CAR-T. [ABSTRACT FROM AUTHOR]

Introduction: Melanoma is a malignant tumor that seriously affects patients. The pathogenesis of malignant melanoma is complex, and the cell cycle is closely related to tumor progression. Based on the catalog of cancer somatic mutations, we found that overexpression of the E2F3gene ranked first in percentage increase in not only melanoma but also in all human cancer tissues. However, there are few studies on the high expression of E2F3 and its carcinogenic mechanism in melanoma. Methods and results: We found that E2F3 showed extensive copy number amplification that was positively correlated with the expression level. Patients with high copy number had a significantly poorer prognosis. We also found that E2F3 levels were significantly negatively correlated with promoter methylation. However, we showed that the E2F3 promoter region is hypomethylated, and in normal cells or tumor cells, the methylation level did not correlate with expression. Finally, we knocked down the E2F3 gene in melanoma cells by shRNA. Colony formation, anchorage-dependent growth, and EdU cell proliferation experiments showed a significant decrease in proliferation. Flow cytometry showed a significant increase in the G0/G1 ratio. Conclusion: It can be speculated that copy number amplification and other mechanisms result in the high expression of E2F3 in melanoma, which promotes tumor progression by involving the cell cycle. E2F3 is a good target for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Patchouli alcohol (patchoulol), a sesquiterpenoid specifically synthesized by herbal plant Pogostemon cablin , has a variety of pharmacological and biological activities and is widely utilized in the medical and cosmetic industries. However, there are few studies on the transcriptional modulation of patchoulol biosynthesis. Some studies have reported that basic leucine zipper (bZIP) transcription factors (TFs) participate in the biosynthesis of plant terpenoids, but there is no report that bZIP TFs are involved in the modulation of patchoulol biosynthesis. This study was conducted to explain the regulation of patchoulol biosynthesis by PcbZIP44, a bZIP TF identified in patchouli for the first time. PcbZIP44 was highly expressed in roots and stems, and its encoded protein was nuclear localized revealed by protoplast subcellular localization experiment. According to the results of the transient dual-luciferase assay and yeast one-hybrid (Y1H) assays, PcbZIP44 can bind to the PcPTS (patchoulol synthase) gene promoter to repress its activity. Overexpression of the PcbZIP44 gene significantly reduced the content of patchoulol and resulted in a significant down-regulation of the PcPTS gene at the transcriptional level. Correspondingly, virus-induced PcbZIP44 gene silencing (VIGS) significantly increased the content of patchoulol and resulted in a significant up-regulation of the PcPTS gene at the transcriptional level. Therefore, these results suggested that PcbZIP44 negatively regulates patchoulol biosynthesis by inhibiting the PcPTS gene in P. cablin. • PcbZIP44 binds to the PcPTS promoter and represses its expression. • Potential PcbZIP44-binding motifs were identified in PcPTS promoter. • Overexpression of PcbZIP44 markedly reduced patchoulol production in patchouli. • VIGS of PcbZIP44 significantly increased patchoulol production in patchouli. • PcbZIP44-mediated regulation of patchoulol biosynthesis is hypothesized. [ABSTRACT FROM AUTHOR]

The fabrication of Fe 3 O 4 @Au composites as a novel resonance light scattering (RLS) probe for the sensitive detection of Alzheimer׳s amyloid-β peptide (Aβ) was demonstrated. Amino groups coated magnetic Fe 3 O 4 nanoparticles were covered with gold shell by the classical Frens method. The resultant colloids were characterized with X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS) and UV–visible spectra. The results indicated that the composite particles with core/shell structure and an average diameter of ~320 nm were stable and biocompatible. The RLS intensity of Fe 3 O 4 @Au composites was significantly enhanced by interacting with Aβ. Under optimal conditions, good linear relationship between the ratio of RLS intensity I / I 0 at 463.0 nm and the logarithmic value of Aβ concentration in the range of 5.0×10 –15 –5.56×10 −9 M was found. The limit of detection (LOD) was 1.2×10 −15 M. The proposed method is simple, sensitive and cost-effective and complementary to other existing methods for protein analysis. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-200a expression levels were decreased while mitochondrial transcription factor A (TFAM) mRNA expression levels were increased in breast cancer (BC) tissues and cell lines, and identified TFAM as a novel direct target of miR-200a. Overexpression of miR-200a suppressed TFAM protein expression, mtDNA copy number, and attenuated cell proliferation. Forced expression of TFAM can partly rescue the inhibitory effect of miR-200a in the cells. Taken together, these findings will shed light on the role and mechanism of miR-200a in regulating BC cells growth and mtDNA copy number via miR-200a/TFAM axis, and miR-200a may serve as a potential therapeutic target in BC in the future. [ABSTRACT FROM AUTHOR]

Summary: Here, we generated a genome-scale shRNA library targeting long intergenic noncoding RNAs (lincRNAs) in the mouse. We performed an unbiased loss-of-function study in mouse embryonic stem cells (mESCs) and identified 20 lincRNAs involved in the maintenance of pluripotency. Among these, TUNA (Tcl1 Upstream Neuron-Associated lincRNA, or megamind) was required for pluripotency and formed a complex with three RNA-binding proteins (RBPs). The TUNA-RBP complex was detected at the promoters of Nanog, Sox2, and Fgf4, and knockdown of TUNA or the individual RBPs inhibited neural differentiation of mESCs. TUNA showed striking evolutionary conservation of both sequence- and CNS-restricted expression in vertebrates. Accordingly, knockdown of tuna in zebrafish caused impaired locomotor function, and TUNA expression in the brains of Huntington’s disease patients was significantly associated with disease grade. Our results suggest that the lincRNA TUNA plays a vital role in pluripotency and neural differentiation of ESCs and is associated with neurological function of adult vertebrates. [ABSTRACT FROM AUTHOR]

Although the liver and ventral pancreas are thought to arise from a common multipotent progenitor pool, it is unclear whether these progenitors of the hepatopancreas system are specified by a common genetic mechanism. Efforts to determine the role of Hnf1b and Wnt signaling in this crucial process have been confounded by a combination of factors, including a narrow time frame for hepatopancreas specification, functional redundancy among Wnt ligands, and pleiotropic defects caused by either severe loss of Wnt signaling or Hnf1b function. Using a novel hypomorphic hnf1ba zebrafish mutant that exhibits pancreas hypoplasia, as observed in HNF1B monogenic diabetes, we show that hnf1ba plays essential roles in regulating β-cell number and pancreas specification, distinct from its function in regulating pancreas size and liver specification, respectively. By combining Hnf1ba partial loss of function with conditional loss of Wnt signaling, we uncover a crucial developmental window when these pathways synergize to specify the entire ventrally derived hepatopancreas progenitor population. Furthermore, our in vivo genetic studies demonstrate that hnf1ba generates a permissive domain for Wnt signaling activity in the foregut endoderm. Collectively, our findings provide a new model for HNF1B function, yield insight into pancreas and β-cell development, and suggest a new mechanism for hepatopancreatic specification. [ABSTRACT FROM AUTHOR]

Background and Aims: Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures. Methods: Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes' correlations with the symptoms and their durations, respectively, have been analyzed. Results: Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively. Conclusions: The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients. [ABSTRACT FROM AUTHOR]

PTK7 is an essential component of the Wnt/planar cell polarity (PCP) pathway. We provide evidence that the Wnt/PCP pathway converges with pericellular proteolysis in both normal development and cancer. Here, we demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP), a key proinvasive proteinase, functions as a principal sheddase of PTK7. MT1-MMP directly cleaves the exposed PKP621?LI sequence of the seventh Ig-like domain of the full-length membrane PTK7 and generates, as a result, an N-terminal, soluble PTK7 fragment (sPTK7). The enforced expression of membrane PTK7 in cancer cells leads to the actin cytoskeleton reorganization and the inhibition of cell invasion. MT1-MMP silencing and the analysis of the uncleavable L622D PTK7 mutant confirm the significance of MT1-MMP proteolysis of PTK7 in cell functions. Our data also demonstrate that a fine balance between the metalloproteinase activity and PTK7 levels is required for normal development of zebrafish (Danio rerio). Aberration of this balance by the proteinase inhibition or PTK7 silencing results in the PCP-dependent convergent extension defects in the zebrafish. Overall, our data suggest that the MT1-MMP-PTK7 axis plays an important role in both cancer cell invasion and normal embryogenesis in vertebrates. Further insight into these novel mechanisms may promote understanding of directional cell motility and lead to the identification of therapeutics to treat PCP-related developmental disorders and malignancy. [ABSTRACT FROM AUTHOR]

Background: The E2A gene, which encodes two basic helix–loop–helix transcription factors, E12 and E47, regulates colorectal cancer progression and epithelial-mesenchymal transition. However, whether E2A regulates the tumor-initiating capacity of colorectal cancer is unclear. Thus, we have studied E2A expression in the initiation of colorectal cancer in vivo and in vitro. Methods: Immunohistochemistry and immunoblot were performed to determine protein levels of E2A in colorectal cancer specimens and cells. RNAi was employed to downregulate E2A expression, and the subsequent change in protein level was evaluated by immunoblot. Sphere-forming assay and enumeration of liver metastasis in mouse models were used to identify the tumor formation ability of colorectal cancer cells. Results: E2A expression in colorectal cancer clinical specimens was inversely associated with patients' progression-free survival. Functional studies demonstrated that E2A significantly decreased tumor formation in vitro and in vivo. Furthermore, nuclear translocation of beta-catenin and activation of the Wnt/beta-catenin pathway occurred after suppression of E2A in colorectal cancer cells. FoxM1 was identified as a down-stream target by mRNA microarray, implying that FoxM1 plays a main role in determining how E2A regulates the tumor-initiating capacity of colorectal cancer. Conclusion: E2A suppresses tumor-initiating capacity by targeting the FoxM1-Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]