Pathogenicity characteristics of different subgenotype pseudorabies virus in newborn piglets.

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.

A plug-and-play monofunctional platform for targeted degradation of extracellular proteins and vesicles.

Existing strategies use bifunctional chimaeras to mediate extracellular protein degradation. However, these strategies rely on specific lysosome-trafficking receptors to facilitate lysosomal delivery, which may raise resistance concerns due to intrinsic cell-to-cell variation in receptor expression and mutations or downregulation of the receptors. Another challenge is establishing a universal platform applicable in multiple scenarios. Here, we develop MONOTAB (MOdified NanOparticle with TArgeting Binders), a plug-and-play monofunctional degradation platform that can drag extracellular targets into lysosomes for degradation. MONOTAB harnesses the inherent lysosome-targeting ability of certain nanoparticles to obviate specific receptor dependency and the hook effect. To achieve high modularity and programmable target specificity, we utilize the streptavidin-biotin interaction to immobilize antibodies or other targeting molecules on nanoparticles, through an antibody mounting approach or by direct binding. Our study reveals that MONOTAB can induce efficient degradation of diverse therapeutic targets, including membrane proteins, secreted proteins, and even extracellular vesicles.

Enhancing response inhibition behavior through tDCS intervention in college students with smartphone addiction.

Smartphone addiction, emerging from excessive use of smartphones, poses a challenge to inhibitory control functions within society. This research employed transcranial direct current stimulation (tDCS) as an intervention alongside the stop signal task (SST) to explore behavioral distinctions between individuals with smartphone addiction and a non-addicted control group, focusing on the efficacy of tDCS intervention. The participant cohort comprised 80 individuals, divided into an addiction group (39 participants, with 19 receiving active tDCS and 20 receiving sham tDCS) and a control group (41 participants, with 20 receiving active tDCS and 21 receiving sham tDCS), with anodal stimulation applied over the right dorsolateral prefrontal cortex (dlPFC) and cathodal placement over the left arm. The findings indicate that university students struggling with smartphone addiction exhibit reduced inhibitory control compared to their non-addicted peers, while maintaining similar levels of general cognitive control. Remarkably, tDCS interventions were observed to enhance inhibitory control in both groups. Although the improvement in the addiction group appeared more pronounced numerically than in the control group, no significant interaction with group was noted. However, a higher percentage of participants in the smartphone addiction (SA) group exhibited enhanced response inhibition under active tDCS. This study demonstrates the inhibitory control deficits in individuals addicted to smartphones and underscores the potential of tDCS in enhancing response inhibition. It provides a valuable reference for future tDCS research targeting smartphone addiction and highlights the importance of developing healthier smartphone usage habits.

[Effectiveness analysis of biplanar vertical fixation and inverted triangle fixation with hollow screw for Pauwels type â ¢ femoral neck fracture in young and middle-aged patients].

Objective: To compare the effectiveness of biplanar vertical fixation and inverted triangle fixation with hollow screw for Pauwels type Ⅲ femoral neck fracture in young and middle-aged patients. Methods: The clinical data of 55 young and middle-aged patients with Pauwels type Ⅲ femoral neck fracture between June 2021 and December 2022 was retrospectively analyzed. All patients were treated with closed reduction and internal fixation with hollow screws, 25 cases were treated with biplanar vertical fixation (study group), 30 cases with inverted triangle fixation (control group). There was no significant difference in gender, age, affected side, cause of injury, underlying diseases, and time from injury to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy times, guide needle puncture times, starting time of weight bearing, time of full weight bearing, time of fracture healing, and complications were recorded and compared between the two groups. The hip joint function was evaluated by Harris score at 1 day, 6 months, 12 months after operation, and at last follow-up, and the pain relief was evaluated by visual analogue scale (VAS) score. The femoral neck shortening was measured on the X-ray film at last follow-up. Results: All patients were followed up 12-31 months (mean, 22.0 months), and there was no significant difference in follow-up time between the two groups ( P>0.05). The operation time, intraoperative blood loss, and fluoroscopy times in the study group were higher than those in the control group, but the difference was not significant ( P>0.05). The guide needle puncture times in the study group was more than that in the control group, and the time of starting weight bearing and the time of full weight bearing in the study group were shorter than those in the control group, the differences were significant ( P<0.05). Bony healing was achieved in both groups, and there was no significant difference in fracture healing time between the two groups ( P>0.05). No osteonecrosis of the femoral head and incision-related complication was found in the two groups during follow-up, and the femoral neck shortening length in the study group was significantly shorter than that in the control group at last follow-up ( P<0.05). There was no significant difference in Harris score between the two groups at 1 day after operation ( P>0.05), and the Harris score of the study group was significantly better than that of the control group at other time points ( P<0.05); there was no significant difference in VAS score between the two groups at each time point after operation ( P>0.05). Conclusion: Compared with the inverted triangle fixation, the treatment of Pauwels type Ⅲ femoral neck fracture with biplanar vertical fixation can effectively reduce femoral neck shortening without affecting fracture healing, and improve hip joint function in early stage.

Pay attention to the application of indocyanine green fluorescence imaging technology in laparoscopic liver cancer resection.

Traditional laparoscopic liver cancer resection faces challenges, such as difficulties in tumor localization and accurate marking of liver segments, as well as the inability to provide real-time intraoperative navigation. This approach falls short of meeting the demands for precise and anatomical liver resection. The introduction of fluorescence imaging technology, particularly indocyanine green, has demonstrated significant advantages in visualizing bile ducts, tumor localization, segment staining, microscopic lesion display, margin examination, and lymph node visualization. This technology addresses the inherent limitations of traditional laparoscopy, which lacks direct tactile feedback, and is increasingly becoming the standard in laparoscopic procedures. Guided by fluorescence imaging technology, laparoscopic liver cancer resection is poised to become the predominant technique for liver tumor removal, enhancing the accuracy, safety and efficiency of the procedure.

Multiomics and machine learning-based analysis of pancancer pseudouridine modifications.

Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

Hypoxia Stimulates PYGB Enzymatic Activity to Promote Glycogen Metabolism and Cholangiocarcinoma Progression.

Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.

[Retracted] Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 1D and the flow cytometric data in Fig. 3K were strikingly similar to data appearing in different form in other papers by different authors at different research institutes that were under consideration for publication at around the same time.  Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 263, 2021; DOI: 10.3892/mmr.2021.11902].

Impact of Strontium, Magnesium, and Zinc Ions on the In Vitro Osteogenesis of Maxillary Sinus Membrane Stem Cells.

Human Maxillary Sinus Membrane Stem Cells (hMSMSCs) contribute significantly to bone formation following maxillary sinus floor augmentation (MSFA). The biological behavior of mesenchymal stem cells is notably influenced by varying concentrations of magnesium (Mg2+), strontium (Sr2+), and zinc (Zn2+) ions; however, their specific effects on hMSMSCs have not been comprehensively studied. We isolated hMSMSCs and identified their mesenchymal stem cell characteristics by flow cytometry and multilineage differentiation experiments. Subsequently, the hMSMSCs were cultured in media containing different concentrations of these metal ions. The proliferation and viability of hMSMSCs were assessed using CCK-8 and Calcein AM/PI staining. After osteogenic induction, cells were evaluated for alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red staining. Additionally, qRT-PCR was used to detect differences in osteogenic gene expression, and immunofluorescence staining was used to observe variations in OCN protein levels. The results indicated that 1 mM Mg2+, 0.01 mM Sr2+, and 0.001 mM Zn2+ significantly improved the proliferation and activity of hMSMSCs. These concentrations also notably enhanced ALP secretion, increased bone-related gene expression, and augmented osteocalcin expression and formation of extracellular calcium nodules, thereby improving osteogenic differentiation. However, higher concentrations of Mg2+, Sr2+, and Zn2+ decreased cell viability and osteogenic differentiation. Mg2+, Sr2+, and Zn2+ promote osteogenic differentiation and proliferation of hMSMSCs in a concentration-dependent manner, indicating that the type and concentration of ions in the extracellular environment can significantly alter hMSMSCs behavior, which is a crucial consideration for material design in maxillary sinus elevation applications.

Impact of Synthetic Variables on the Structural Diversity of TbIII-Carboxylate Frameworks: Gas Adsorption, Magnetism, and Organocatalysis Investigations.

In this work, three unique TbIII-carboxylate frameworks with the formula {[Tb2(OH)2(H2O)2(abtc)]·2H2O}n (1), {[Tb2(abtc)1.5(H2O)3(DMA)]·H2O}n (2) and {[Tb3(abtc)2.5(H2O)4]·H3O}n (3), each displaying structural variations, have been successfully synthesized by the solvothermal reactions of Tb(NO3)3·6H2O with the azo-containing ligand 3,3',5,5'-azobenzene tetracarboxylic acid (H4abtc) under varying conditions. Detailed single-crystal X-ray diffraction (SC-XRD) analysis manifested a remarkable diversity in these structures, demonstrating various coordination patterns of TbIII-metal nodes with the carboxylate groups of the organic linker, which contributed to the generation of intricate three-dimensional (3D) coordination networks with remarkable chemical resistance. Furthermore, frameworks 2 and 3, characterized by porous networks containing two and three independent TbIII-metal nodes, respectively, were both demonstrated to be efficient heterogeneous catalysts toward the cyanosilylation of imines under mild conditions with excellent reusability. In addition, direct current (Dc) magnetic susceptibility measurements conducted on frameworks 1, 2, and 3 indicated that there were obvious antiferromagnetic interactions among the TbIII-metal nodes, which suggests the involvement of intricate intra- and intertrimer exchange channels, adding another fascinating dimension to their physical properties.

Factors impacting outcomes of cochlear implantation in children at two University centres in China: Multi-year analysis from the Paediatric Implanted Recipient Observational Study (P-IROS).

OBJECTIVES: To identify factors affecting functional hearing performance and quality of life (QoL) outcomes in paediatric cochlear implantation (CI) recipients at two University centres in mainland China. METHODS: Two university centres in mainland China, part of the prospective longitudinal Paediatric Implanted Recipient Observational Study (P-IROS), contributed participant data. Participants were aged under 10 years at time of CI. Functional hearing performance and QoL measures were collected prior to device activation, and at 6-monthly intervals for 2 years post-implantation. Functional hearing endpoints including Categories of Auditory Performance-II (CAP-II) and QoL were evaluated and analysed using ordinal mixed-effects regression models. RESULTS: Data were from 288 children with a mean age at implant of 2.74 years. Overall follow-up at 1 year was 59% and 51% at 2 years. Younger age at implantation (p<0.001) and hearing aid use preimplantation (p=0.026) were associated with significant benefit. Bilateral device users (both CI and bimodal) achieved significantly better functional hearing performance on the CAP-II than unilateral CI users (p<0.001). Slower functional hearing improvements were observed in those with lower parental expectations compared to higher expectations (p<0.001). QoL improved over time but followed a different initial trajectory between centres. CONCLUSION: All participants demonstrated significant improvements in auditory performance and QoL over time. Younger age at CI, and bilateral/bimodal device fitting contributed to earlier improvements. Other potential factors that could help inform families, professionals, and health authorities about choice of hearing device and educational supports required included aetiology of hearing loss and level of maternal education.

Outcomes Using the Optimized Pitch and Language Strategy Versus the Advanced Combination Encoder Strategy in Mandarin-Speaking Cochlear Implant Recipients.

OBJECTIVES: The experimental Optimized Pitch and Language (OPAL) strategy enhances coding of fundamental frequency (F0) information in the temporal envelope of electrical signals delivered to channels of a cochlear implant (CI). Previous studies with OPAL have explored performance on speech and lexical tone perception in Mandarin- and English-speaking CI recipients. However, it was not clear which cues to lexical tone (primary and/or secondary) were used by the Mandarin CI listeners. The primary aim of the present study was to investigate whether OPAL provides improved recognition of Mandarin lexical tones in both quiet and noisy environments compared with the Advanced Combination Encoder (ACE) strategy. A secondary aim was to investigate whether, and to what extent, removal of secondary (duration and intensity envelope) cues to lexical tone affected Mandarin tone perception. DESIGN: Thirty-two CI recipients with an average age of 24 (range 7 to 57) years were enrolled in the study. All recipients had at least 1 year of experience using ACE. Each subject attended two testing sessions, the first to measure baseline performance, and the second to evaluate the effect of strategy after provision of some take-home experience using OPAL. A minimum take-home duration of approximately 4 weeks was prescribed in which subjects were requested to use OPAL as much as possible but were allowed to also use ACE when needed. The evaluation tests included recognition of Mandarin lexical tones in quiet and in noise (signal to noise ratio [SNR] +5 dB) using naturally produced tones and duration/intensity envelope normalized versions of the tones; Mandarin sentence in adaptive noise; Mandarin monosyllabic and disyllabic word in quiet; a subset of Speech, Spatial, and Qualities of hearing questionnaire (SSQ, speech hearing scale); and subjective preference for strategy in quiet and noise. RESULTS: For both the natural and normalized lexical tone tests, mean scores for OPAL were significantly higher than ACE in quiet by 2.7 and 2.9%-points, respectively, and in noise by 7.4 and 7.2%-points, respectively. Monosyllabic word recognition in quiet using OPAL was significantly higher than ACE by approximately 7.5% points. Average SSQ ratings for OPAL were significantly higher than ACE by approximately 0.5 points on a 10-point scale. In quiet conditions, 14 subjects preferred OPAL, 7 expressed a preference for ACE, and 9 reported no preference. Compared with quiet, in noisy situations, there was a stronger preference for OPAL (19 recipients), a similar preference for ACE (7 recipients), while fewer expressed no preference. Average daily take-home use of ACE and OPAL was 4.9 and 7.1 hr, respectively. CONCLUSIONS: For Mandarin-speaking CI recipients, OPAL provided significant improvements to lexical tone perception for natural and normalized tones in quiet and noise, monosyllabic word recognition in quiet, and subjective ratings of speech intelligibility. Subjects accessed both primary and secondary cues to lexical tone for perception in quiet and noise conditions. The benefits of lexical tone recognition were attributed to enhanced F0 rate cues encoded by OPAL, especially in a noisy environment. The OPAL strategy was well accepted by many of the Mandarin-speaking CI recipients.

Risk of incident type 2 diabetes in male NAFLD and NAFLD-free smokers: a 7-year post-cessation study.

BACKGROUND: We aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study. METHODS: The study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up: < 0 kg, 0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg. Cox proportional hazard models, adjusted for various variables, were used to estimate hazard ratios (HRs) for the association between post-cessation weight gain and incident T2DM in NAFLD and NAFLD-free individuals. RESULTS: At baseline, we included 1,409 NAFLD and 5150 NAFLD-free individuals. During a total of 39,259 person-years of follow-up, 222 (15.8%) NAFLD patients and 621 (12.1%) NAFLD-free participants quit smoking, with the corresponding means (standard deviations) of post-cessation weight gain being 2.24 (3.26) kg and 1.15 (3.51) kg, respectively. Among NAFLD individuals, compared to current smokers, the fully adjusted HRs (95% CI) for incident T2DM were 0.41 (0.06-3.01), 2.39 (1.21-4.70), 4.48 (2.63-7.63), and 6.42 (3.68-11.23) for quitters with weight gains < 0 kg, 0.0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg, respectively. For NAFLD-free individuals, we only observed a significant association between post-cessation weight gain ≥ 4.0 kg and the risk of incident T2DM (P < 0.001). Further analysis revealed that the impact of post-cessation weight gain on T2DM risk was not affected by alcohol consumption or obesity status at baseline. CONCLUSIONS: Mild post-cessation weight gain significantly increased the risk of T2DM in male NAFLD patients but not in male NAFLD-free individuals. Therefore, it is recommended that individuals with NAFLD manage their weight after quitting smoking.

Leveraging insights from cancer to improve tuberculosis therapy.

Exploring and exploiting the microenvironmental similarities between pulmonary tuberculosis (TB) granulomas and malignant tumors has revealed new strategies for more efficacious host-directed therapies (HDTs). This opinion article discusses a paradigm shift in TB therapeutic development, drawing on critical insights from oncology. We summarize recent efforts to characterize and overcome key shared features between tumors and granulomas, including excessive fibrosis, abnormal angiogenesis, hypoxia and necrosis, and immunosuppression. We provide specific examples of cancer therapy application to TB to overcome these microenvironmental abnormalities, including matrix-targeting therapies, antiangiogenic agents, and immune-stimulatory drugs. Finally, we propose a new framework for combining HDTs with anti-TB agents to maximize therapeutic delivery and efficacy while reducing treatment dosages, duration, and harmful side effects to benefit TB patients.

Robust two-color physically unclonable patterns from controlled aggregation of a single organic luminophore.

This research presents a new approach to create two-color luminescent physically unclonable functions (PUFs) using an organic luminophore with tunable emission colors. These PUFs offer high security and stable performance, significantly enhancing anti-counterfeiting capabilities by exponentially increasing encoding capacity through dual-color integration and complex pattern formation.

Epididymal cysts in children: frequency, clinical characteristics, and management strategies.

Background: Epididymal cysts (ECs) are uncommon in the pediatric population. The objective of this study was to evaluate the frequency, clinical characteristics, and management strategies of ECs in children. Methods: We performed a retrospective review of pediatric scrotal ultrasounds between January 2014 and August 2022 to identify children with ECs. Results: One hundred and forty-three children boys were found to have ECs, with 95 being pre-pubertal and 48 post-pubertal. The age of the patients ranged from 1 day to 18 years, with a mean age of 10.64 ± 4.55 years. The size of the cysts varied from 2 mm to 35 mm. The most common comorbidities observed were hydrocele, testicular microlithiasis and varicocele. The majority of ECs were detected through routine physical examination. Conservative management was employed for all patients, except for one who required surgical excision. Resolution of ECs occurred in 12 patients, while a reduction in cyst size was observed in 6 cases. Conversely, 2 patients experienced an increase in cyst size, and 6 patients exhibited an increase in cyst number during the follow-up period. Conclusion: Conservative management is the preferred approach for the majority of cases, with surgical intervention reserved for specific instances.

Macroinvertebrate community dynamics following wetland restoration: Insights from taxonomic structure and functional feeding groups in response to water quality.

Continuous wetland restoration initiatives in China are increasing, due to the global degradation of wetland ecosystems. However, monitoring of the restoration situation remains incomplete. In this study, we investigated the effects of wetland restoration on the macroinvertebrate taxonomic structure and feeding functional groups (FFGs) in the Naolihe National Nature Reserve (NNNR). Macroinvertebrate taxonomic diversity can be used to monitor wetlands, and we hypothesized that FFGs serve the same function. We calculated the diversity index, performed a non-metric multidimensional analysis based on macroinvertebrate taxonomics and FFGs, and subsequently, performed a t-test on the results. The results showed that macroinvertebrate diversity and FFGs analyses were in general agreement with taxonomic diversity, indicating that the macroinvertebrate community in the wetland with five years of fallow land was resembled that of the natural wetland. In contrast, the macroinvertebrate community in the wetland with two years of fallow differed significantly from that in the natural wetland. Additionally, the results of the ecosystem attributes based on biomass and FFGs showed that restored wetlands exhibited lower habitat stability than natural wetlands. Nutrients (NH4 +-N, NO3 --N, and total phosphorus) explained the changes in macroinvertebrate FFGs in the restored wetlands to a greater extent than in the natural wetlands. The results of this study highlight the importance of macroinvertebrate FFGs in wetland monitoring, which supports the use of macroinvertebrate FFGs in the NNNR to monitor wetland restoration.

miR-1915-3p regulates megakaryocytic and erythroid differentiation by targeting SOCS4.

BACKGROUND: Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. METHODS: We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. RESULTS: In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. CONCLUSIONS: miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.