The role of RNA modifications in hepatocellular carcinoma: functional mechanism and potential applications.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.

Impact of human papillomavirus and coinfection with other sexually transmitted pathogens on male infertility.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Staphylococcus aureus. A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.

Effects of slurry ice treatment on the physicochemical changes and proteome of large yellow croaker (Larimichthys crocea).

Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker.

Similar usage of T-cell receptor ß-chain between tumor and adjacent normal tissue in hepatocellular carcinoma.

BACKGROUND: In this study, we comprehensively profiled the T-cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV-associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR. METHODS: High-throughput sequencing was used to determine the profile of complementarity-determining region 3 (CDR3) of the TCR-ß chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, RESULTS: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7-6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups. CONCLUSION: This study provided a large amount of information about the TCR lineage in HBV-associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

An unusual winter bloom of dinoflagellates with notable damage to kelp cultivation around Shandong peninsula, China.

In the coastal waters around Shandong peninsula, an unprecedented winter bloom of dinoflagellates Gonyaulax polygramma and Akashiwo sanguinea occurred in 2021 from late November to early December. The bloom affected a wide area of coastal waters extending from west to east along the northern Shandong peninsula and had a devastating blow to the kelp cultivation industry. Based on the remote-sensing data, the initiation of the bloom was traced back to the region adjacent to the mouth of the Yellow River in Laizhou Bay, where enhanced freshwater discharge from the Yellow River was recorded from September to November. It's proposed that the increased precipitation in the Yellow River basin associated with northward extension of the precipitation band in China could be an important reason for this winter bloom. This unusual winter bloom around Shandong peninsula highlights the potential risks of harmful algal blooms and their impacts on coastal ecosystems under the background of climate change.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum.

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2-9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 µM.

Site-selective S-gem-difluoroallylation of unprotected peptides with 3,3-difluoroallyl sulfonium salts.

Bench-stable 3,3-difluoroallyl sulfonium salts (DFASs), featuring tunable activity and their editable C-ß and gem-difluoroallyl group, proved to be versatile fluoroalkylating reagents for site-selective S-gem-difluoroallylation of cysteine residues in unprotected peptides. The reaction proceeds with high efficiency under mild conditions (ambient temperature and aqueous and weak basic conditions). Various protected/unprotected peptides, especially bioactive peptides, are site-selectively S-gem-difluoroallylated. The newly added gem-difluoroallyl group and other functional groups derived from C-ß of DFASs are poised for ligation with bio-functional groups through click and radical chemistry. This stepwise "doubly orthogonal" modification of peptides enables the construction of bioconjugates with enhanced complexity and functionality. This proof of principle is successfully applied to construct a peptide-saccharide-biotin chimeric bioconjugate, indicating its great potential application in medicinal chemistry and chemical biology.

Caspase-12 is Expressed in Purkinje Neurons and Prevents Psychiatric-Like Behavior in Mice.

Caspase-12 is a caspase family member for which functions in regulating cell death and inflammation have previously been suggested. In this study, we used caspase-12 lacZ reporter mice to elucidate the expression pattern of caspase-12 in order to obtain an idea about its possible in vivo function. Strikingly, these reporter mice showed that caspase-12 is expressed explicitly in Purkinje neurons of the cerebellum. As this observation suggested a function for caspase-12 in Purkinje neurons, we analyzed the brain and behavior of caspase-12 deficient mice in detail. Extensive histological analyses showed that caspase-12 was not crucial for establishing cerebellum structure or for maintaining Purkinje cell numbers. We then performed behavioral tests to investigate whether caspase-12 deficiency affects memory, motor, and psychiatric functions in mice. Interestingly, while the absence of caspase-12 did not affect memory and motor function, caspase-12 deficient mice showed depression and hyperactivity tendencies, together resembling manic behavior. Next, suggesting a possible molecular mechanistic explanation, we showed that caspase-12 deficient cerebella harbored diminished signaling through the brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic-AMP response binding protein axis, as well as strongly enhanced expression of the neuronal activity marker c-Fos. Thus, our study establishes caspase-12 expression in mouse Purkinje neurons and opens novel avenues of research to investigate the role of caspase-12 in regulating psychiatric behavior.

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases.

Myokines are a group of cytokines or polypeptides released from skeletal muscle during exercise. Growing evidence suggests that myokines are associated with the development of cardiovascular disease (CVD). Moreover, several myokines in peripheral blood exhibit dynamic changes in different CVD stages. This review summarizes the potential roles of myokines such as myostatin, irisin, brain-derived neurotrophic factor, mitsugumin 53, meteorin-like, and apelin in various CVD, including myocardial infarction, heart failure, atherosclerosis, hypertension, and diabetes. The association of these myokines with biomarkers currently being used in clinical practice is also discussed. Furthermore, the review considers the emerging role of myokines in CVD and addresses the challenges remaining in translating these discoveries into novel clinical biomarkers for CVD.

Longevity factor FOXO3a: A potential therapeutic target for age-related ocular diseases.

The forkhead box protein O3 (FOXO3a) belongs to the subgroup O of the forkhead transcription factor family and plays an important role in regulating the aging process by participating in the regulation of various life processes, including cell cycle arrest, apoptosis, autophagy, oxidative stress, and DNA repair. The eye is an organ that is affected by aging earlier. However, the functional role and potential clinical applications of FOXO3a in age-related eye diseases have not received widespread attention and lacked comprehensive and clear clarification. In this review, we demonstrated the relationship between FOXO3a and visual system health, summarized the functional roles of FOXO3a in various eye diseases, and potential ocular-related therapies and drugs targeting FOXO3a in visual system diseases through a review and summary of relevant literature. This review indicates that FOXO3a is an important factor in maintaining the normal function of various tissues in the eye, and is closely related to the occurrence and development of ophthalmic-related diseases. Based on its vital role in the normal function of the visual system, FOXO3a has potential clinical application value in related ophthalmic diseases. At present, multiple molecules and drugs targeting FOXO3a have been reported to have the potential for the treatment of related ophthalmic diseases, but further clinical trials are needed. In conclusion, this review can facilitate us to grasp the role of FOXO3a in the visual system and provide new views and bases for the treatment strategy research of age-related eye diseases.

Hemolysis attributed to high dose vitamin C: Two case reports.

BACKGROUND: High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the safest alternative treatments. However, the severity of its adverse effects may have been underestimated. The most serious adverse effect is hemolysis, which may result in acute kidney injury or death. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered to be the main cause, the probability and pathological mechanism are not completely understood, leading to a lack of effective and standardized treatment methods. CASE SUMMARY: Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT. In contrast to previous cases, the lowest hemoglobin level in the two cases was < 50 g/L, which was lower than previously reported. This may be because Case 1 had chronic hepatitis B for many years, which caused abnormal liver reserve function, and Case 2 had grade II bone marrow suppression. Both patients improved and were discharged after blood replacement therapy. Our cases had the most severe degree of hemolysis but the best prognosis, suggesting that our treatment may be helpful for rescue of drug-induced hemolysis. This is the first review of the literature on hemolysis caused by HVCT, and we found that all patients with G6PD deficiency developed hemolysis after HVCT. CONCLUSION: G6PD deficiency should be considered as a contraindication to HVCT, and it is not recommended for patients with bone marrow suppression, moderate-to-severe anemia, hematopoietic abnormalities, or abnormal liver and kidney function. Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Dynamics and scale variations of blooms of Phaeocystis globosa "giant colony" ecotype and key environmental factors in the Beibu Gulf, China.

The Beibu Gulf has experienced blooms of Phaeocystis globosa "giant colony" ecotype (PGGCE), with noticeable variations in bloom scale across years. However, driving environmental factors and their roles remain poorly understood. In this study, we quantified dynamics of PGGCE cells in 2016-2017 and 2018-2019, and analyzed their correlations with environment factors. The results revealed that PGGCE blooms primarily occurred in Guangxi coast and western waters of Leizhou Peninsula during winter months, exhibiting distinct developmental processes. Bloom intensity, duration, and distribution differed significantly between two bloom events. In 2016-2017, peak PGGCE density exceeded 2.0 × 105 cells L-1 nearly double that of 2018-2019. Furthermore, bloom sustained five months during 2016-2017, compared to three months during 2018-2019. Prolonged period of low temperatures and elevated nitrate concentrations favored PGGCE growth and colony formation, resulting in a larger scale bloom during winter 2016 as opposed to winter 2018.

Porous Polypyrrolidines for Highly Efficient Recovery of Precious Metals through Reductive Adsorption Mechanism.

The recycling and utilization of precious metals have emerged as a critical research focus in advancing the development of the circular economy. Among numerous methods for recovering precious metals such as gold, adsorbents with both high adsorption selectivity and capacity have become key technologies. This article incorporated the N-phenylpyrrolidine into a flexible porous polynorbornene backbone to create a class of distinctive porous organic polymers, named BIT-POP-14-BIT-POP-17. Through a reductive capture mechanism, the reductive adsorption sites of N-phenylpyrrolidine coordinate selectively with precious metals, the reduced metal is captured by the hierarchically porous polymers with flexible backbone. This approach leads to remarkable gold recovery efficiency, achieving a record of 2321 mg g-1 at ambient conditions, and 3020 mg g-1 under UV light, surpassing the theoretical limit. The porous polymers are filled in a column for a continuous uptake of gold from waste printed circuit boards (PCBs), showing recovery efficiency toward gold as high as 95% after 84 h. Overall, this work offers a new perspective on designing novel adsorbents for precious metal recovery, providing inspiration for researchers to explore novel adsorption modes and contribute to the advancement of the circular economy.

MFPINC: prediction of plant ncRNAs based on multi-source feature fusion.

Non-coding RNAs (ncRNAs) are recognized as pivotal players in the regulation of essential physiological processes such as nutrient homeostasis, development, and stress responses in plants. Common methods for predicting ncRNAs are susceptible to significant effects of experimental conditions and computational methods, resulting in the need for significant investment of time and resources. Therefore, we constructed an ncRNA predictor(MFPINC), to predict potential ncRNA in plants which is based on the PINC tool proposed by our previous studies. Specifically, sequence features were carefully refined using variance thresholding and F-test methods, while deep features were extracted and feature fusion were performed by applying the GRU model. The comprehensive evaluation of multiple standard datasets shows that MFPINC not only achieves more comprehensive and accurate identification of gene sequences, but also significantly improves the expressive and generalization performance of the model, and MFPINC significantly outperforms the existing competing methods in ncRNA identification. In addition, it is worth mentioning that our tool can also be found on Github ( https://github.com/Zhenj-Nie/MFPINC ) the data and source code can also be downloaded for free.

BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Ubiquitin-specific protease-7 promotes expression of airway mucin MUC5AC via the NF-κB signaling pathway.

Chronic obstructive pulmonary disease (COPD) and other respiratory diseases frequently present with airway mucus hypersecretion, which not only affects the patient's quality of life but also poses a constant threat to their life expectancy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, affects cell differentiation, tissue growth, and disease development. However, its role in airway mucus hypersecretion induced by COPD remains elusive. In this study, USP7 expression was significantly upregulated in airway epithelial samples from patients with COPD, and USP7 was also overexpressed in mouse lung and human airway epithelial cells in models of airway mucus hypersecretion. Inhibition of USP7 reduced the expression of nuclear factor kappa B (NF-κB), phosphorylated-NF-κB (p-NF-κB), and phosphonated inhibitor of nuclear factor kappa B (p-IκBα), and alleviated the airway mucus hypersecretion in vivo and in vitro. Further research revealed that USP7 stimulated airway mucus hypersecretion through the activation of NF-κB nuclear translocation. In addition, the expression of mucin 5AC (MUC5AC) was suppressed by the NF-κB inhibitor erdosteine. These findings suggest that USP7 stimulates the NF-κB signaling pathway, which promotes airway mucus hypersecretion. This study identifies one of the mechanisms regulating airway mucus secretion and provides a new potential target for its prevention and treatment.

ATP6AP2, a regulator of LRP6/ß-catenin protein trafficking, promotes Wnt/ß-catenin signaling and bone formation in a cell type dependent manner.

Wnt/ß-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how Wnt/ß-catenin signaling is regulated in OBs remain elusive. ATP6AP2, an accessory subunit of V-ATPase, plays important roles in multiple cell types/organs and multiple signaling pathways. However, little is known whether and how ATP6AP2 in OBs regulates Wnt/ß-catenin signaling and bone formation. Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions. Conditionally knocking out (CKO) ATP6AP2 in the OB-lineage cells (Atp6ap2Ocn-Cre) reduced trabecular, but not cortical, bone formation and bone mass. Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs, but not osteocytes. Additional in vitro and in vivo studies revealed impaired ß-catenin signaling in ATP6AP2-KO BMSCs and OBs, but not osteocytes, under both basal and Wnt stimulated conditions, although LRP5 was decreased in ATP6AP2-KO osteocytes, but not BMSCs. Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression of ß-catenin phosphorylation, but necessary for LRP6/ß-catenin and N-cadherin/ß-catenin protein complex distribution at the cell membrane, thus preventing their degradation. Expression of active ß-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs. Taken together, these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability, and thus regulating ß-catenin levels, demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/ß-catenin signaling and trabecular bone formation.

Construed Organizational Ethical Climate and Whistleblowing Behavior: The Moderated Mediation Effect of Person-Organization Value Congruence and Ethical Leader Behavior.

An organizational ethical climate enhances the degree of collaboration and cohesion among employees and facilitates the development and interests of organizations. Such roles lead to organizational sustainable development and survival. Therefore, the importance of ethical climate in organizations is becoming increasingly apparent. In this background, this study aims to explore whether an organizational ethical climate can improve whistleblowing behavior and the mediating role of organizational identification in promoting whistleblowing behavior. Most previous studies have only focused on the mediating or moderating role of the model. This study expands the research field, adds the dual moderation of person-organization value congruence and leader ethical behavior, and verifies two moderated mediation models. Overall, the purpose of this study is to determine the behavior of employees under the influence of an organizational ethical climate and, on this basis, propose suggestions for strengthening organizational ethical climate, expanding the scope of research on organizational climate and providing a theoretical basis for related research. In order to achieve the research goals, the data were collected from 344 Chinese SMEs for empirical analysis. The results showed that an organizational ethical climate has no direct impact on whistleblowing behavior but could have a positive effect on whistleblowing formation through the mediating variable of organizational identification. In addition, person-organization value congruence and leader ethical behavior significantly moderated the mediating role of organizational identification between organizational ethical climate and whistleblowing behavior. Finally, the directions that can contribute to future research were suggested.