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Abstract Background Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein–Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. Objectives We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. Methods We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). Results The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47–0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15–0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83–0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56–0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31–0.87) and 49.0% (95% CI: 0.31–0.68), respectively. Conclusions This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

BackgroundDachaihu decoction (Dachaihu tang) plays a crucial role in treating acute illnesses. Recently, a significant number of clinical studies on Dachaihu decoction for acute cholecystitis (AC) have been published. This study was conducted to assess the efficacy and safety of Dachaihu decoction in patients with this condition.MethodsTo identify relevant randomized controlled trials (RCTs), eight databases and three clinical trial registries were searched from inception to 30 June 2024. Two researchers independently screened and extracted data from eligible studies using EndNote X9 and Microsoft Office Excel 2019. RoB 2.0 was used to assess the risk of bias in the included studies. Stata 17.0 was used for data analysis. Publication bias and its impact on result stability were evaluated using a funnel plot and the “trim-and-fill” method. The quality of evidence was graded using the GRADE assessment system.ResultsThirty-three RCTs involving 2,851 participants were included. The treatment group demonstrated improved clinical efficacy (RR = 1.18; 95% CI = 1.13 to 1.24), significantly reduced length of hospital stay (MD = −1.78 days; 95% CI = –2.02 to −1.53), and the incidence of adverse events (RR = 0.31; 95% CI = 0.20 to 0.48). Additionally, there appeared to be reductions in the time for abdominal pain to resolve (MD = −1.92 days; 95% CI = –2.33 to −1.51), fever to disappear (MD = −1.52 days; 95% CI = –1.90 to −1.14), white blood cell count to return to normal (MD = −2.89 days; 95% CI = –3.32 to −2.46), alanine aminotransferase (ALT) levels (MD = −11.88 U/L; 95% CI = –15.29 to −8.47), aspartate aminotransferase (AST) levels (MD = −8.74 U/L; 95% CI = –9.76 to −7.72), neutrophil percentage (MD = −9.68; 95% CI = –11.33 to −8.03), TNF-α levels (SMD = −2.10 pg/L; 95% CI = –2.43 to −2.78), and certainty of evidence (moderate-to-low certainty).ConclusionDachaihu decoction may be an effective botanical formula for managing AC and a lower incidence of adverse events. However, due to the substantial risk of bias and heterogeneity across the included studies, these findings should be interpreted with caution and require further validation through well-designed, high-quality trials.Systematic Review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=573332.

Abstract Under Taiwan's National Health Insurance (NHI) system, it's crucial for all healthcare providers to accurately submit medical expense claims to the National Health Insurance Administration (NHIA) to avoid incorrect deductions. With changes in healthcare policies and adjustments in hospital management strategies, the complexity of claiming rules has resulted in hospitals expending significant manpower and time on the medical expense claims process. Therefore, this study utilizes the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) management approach to identify wasteful and non-value-added steps in the process. Simultaneously, it introduces Robotic Process Automation (RPA) tools to replace manual operations. After implementation, the study effectively reduces the process time by 380 min and enhances Process Cycle Efficiency (PCE) from 69.07 to 95.54%. This research validates a real-world case of Lean digital transformation in healthcare institutions. It enables human resources to be allocated to more valuable and creative tasks while assisting hospitals in providing more comprehensive and patient-centric services.

Introduction Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. Methods Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. Results Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02–2.02; I 2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74–1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14–1.87; I 2 =5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. Conclusions Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Abstract In this paper, we investigate the existence of mild solutions as well as optimal controls for non-autonomous impulsive evolution equations with nonlocal conditions. Using the Schauder’s fixed-point theorem as well as the theory of evolution family, we prove the existence of mild solutions for the concerned problem. Furthermore, without the Lipschitz continuity of the nonlinear term, the optimal control result is derived by setting up minimizing sequences twice. An example is given of the application of the results.

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs.Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs.Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available.Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = −2.73 h, 95% CI (−4.85, −0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = −1.24, 95% CI (−2.37, −0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = −19.31 h, 95% CI (−33.35, −5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)].Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials.Systematic review registration: PROSPERO, identifier CRD42021239936

Oocyte-dependent and cumulus cell-derived transforming growth factor-β promotes natriuretic peptide type C expression in mouse ampullary epithelial cells, which promotes sperm migration into the ampulla for fertilization.

As the filling material for the new nuclear fuel transport cask, the rigid polyurethane foam plays an important role in the safe transportation of the nuclear fuel assemblies, and therefore its reliability deserves special attention. Thermal analysis and long-term ageing test are commonly used to predict the service lifetime of rigid polyurethane foams, but they cannot fully consider the influences of mechanical loads like vibration, collision, and impact etc., which is not satisfactory for the transportation application. Herein, in addition to the conventional thermal analysis and long-term ageing methods, the random vibration testing was particularly conducted on the rigid polyurethane foam that has been used in the new nuclear fuel transport cask for the nuclear power plants in China, and its service lifetime was innovatively predicted by the intrinsic property of material, the resonance frequency. The result which can be easily obtained from the acceleration data through fast Fourier transform without additional test and treatment was in the same order of magnitude with that from the conventional methods, and is more rational and convenient, deserving recommended for the rigid polyurethane foams that are used in other applications involving mechanical loads.

Abstract Mammalian oogenesis features reliance on the mRNAs produced and stored during early growth phase. These are essential for producing an oocyte competent to undergo meiotic maturation and embryogenesis later when oocytes are transcriptionally silent. The fate of maternal mRNAs hence ensures the success of oogenesis and the quality of the resulting eggs. Nevertheless, how the fate of maternal mRNAs is determined remains largely elusive. RNA‐binding proteins (RBPs) are crucial regulators of oogenesis, yet the identity of the full complement of RBPs expressed in oocytes is unknown. Here, a global view of oocyte‐expressed RBPs is presented: mRNA‐interactome capture identifies 1396 RBPs in mouse oocytes. An analysis of one of these RBPs, LSM family member 14 (LSM14B), demonstrates that this RBP is specific to oocytes and associated with many networks essential for oogenesis. Deletion of Lsm14b results in female‐specific infertility and a phenotype characterized by oocytes incompetent to complete meiosis and early embryogenesis. LSM14B serves as an interaction hub for proteins and mRNAs throughout oocyte development and regulates translation of a subset of its bound mRNAs. Therefore, RNP complexes tethered by LSM14B are found exclusively in oocytes and are essential for the control of maternal mRNA fate and oocyte development.

Abstract Background The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. Methods We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P

A large number of complex biochemical reaction networks are included in the gene expression, cell development, and cell differentiation of in vivo cells, among other processes. Biochemical reaction-underlying processes are the ones transmitting information from cellular internal or external signaling. However, how this information is measured remains an open question. In this paper, we apply the method of information length, based on the combination of Fisher information and information geometry, to study linear and nonlinear biochemical reaction chains, respectively. Through a lot of random simulations, we find that the amount of information does not always increase with the length of the linear reaction chain; instead, the amount of information varies significantly when this length is not very large. When the length of the linear reaction chain reaches a certain value, the amount of information hardly changes. For nonlinear reaction chains, the amount of information changes not only with the length of this chain, but also with reaction coefficients and rates, and this amount also increases with the length of the nonlinear reaction chain. Our results will help to understand the role of the biochemical reaction networks in cells.

Steel arch bridges with inclined arch ribs under strong wind fields are prone to fatigue damage due to the stress concentration at the position of hanger connections. Therefore, it is essential to perform the wind-induced response analysis for specified shape hangers, such as inclined hangers, to determine the stress distribution and corresponding influencing factors. In this study, wind-induced response analysis for a fatigue-prone asymmetric steel arch bridge with inclined arch ribs is performed by the numerical simulation approach. The investigated bridge hangers’ models are established by using the COMSOL Multiphysics software. The wind-induced stress of the bridge hangers under different wind directions is obtained based on the finite element method. The influential factor of the stress distribution of the bridge hangers on both the windward side and the leeward side is discussed. In addition, the stress peaks of the long hanger and short hanger are achieved for further fatigue analysis. This paper provides a reference for determining the critical fatigue-prone position of an asymmetric steel arch bridge with inclined arch ribs.

Digital shearography is a technique that has recently been applied to material inspections that cannot be performed by the naked eyes, including the detection of air bubble defects in tires. Although digital shearography detects bubbles that are not visible to the naked eyes, the process of determining tire defects still relies on field operators, with inconsistent results depending on the experiences of the field operator personnel. New or different types of bubble defects that AI models have not previously recognized are often missed, resulting in an inadequate quality detection model. In this paper, we propose a bubble defect detection method based on an incremental YOLO architecture. The data for this research was provided by the largest tire manufacturer in Taiwan. In our research, we classify the defects into six distinct categories, pre-process the images to allow better detections of less-noticeable defects, increase the amount of training data used, and generate an initial training model with the YOLO framework. We also propose an incremental YOLO method using small-model training for previously unobserved defects to improve the model detection rate. We have observed detection accuracy and sensitivity of 98% and 90% in the experimental results, respectively. The methods proposed in this paper can assist tire manufacturers in achieving semi-automatic quality inspections and labor cost reductions.

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme catalyzing de novo biosynthesis of guanine nucleotides, aggregates under certain circumstances into a type of non-membranous filamentous macrostructure termed “cytoophidium” or “rod and ring” in several types of cells. However, the biological significance and underlying mechanism of IMPDH assembling into cytoophidium remain elusive. In mouse ovaries, IMPDH is reported to be crucial for the maintenance of oocyte–follicle developmental synchrony by providing GTP substrate for granulosa cell natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system to produce cGMP for sustaining oocyte meiotic arrest. Oocytes and the associated somatic cells in the ovary hence render an exciting model system for exploring the functional significance of formation of IMPDH cytoophidium within the cell. We report here that IMPDH2 cytoophidium forms in vivo in the growing oocytes naturally and in vitro in the cumulus-enclosed oocytes treated with IMPDH inhibitor mycophenolic acid (MPA). Inhibition of IMPDH activity in oocytes and preimplantation embryos compromises oocyte meiotic and developmental competences and the development of embryos beyond the 4-cell stage, respectively. IMPDH cytoopidium also forms in vivo in the granulosa cells of the preovulatory follicles after the surge of luteinizing hormone (LH), which coincides with the resumption of oocyte meiosis and the reduction of IMPDH2 protein expression. In cultured COCs, MPA-treatment causes the simultaneous formation of IMPDH cytoopidium in cumulus cells and the resumption of meiosis in oocytes, which is mediated by the MTOR pathway and is prevented by guanosine supplementation. Therefore, our results indicate that cytoophidia do form in the oocytes and granulosa cells at particular stages of development, which may contribute to the oocyte acquisition of meiotic and developmental competences and the induction of meiosis re-initiation by the LH surge, respectively.

Completion of the first meiosis is an essential prerequisite for producing a functionally normal egg for fertilization and embryogenesis, but the precise mechanisms governing oocyte meiotic progression remains largely unclear. Here, we report that echinoderm microtubule associated protein (EMAP) like 1 (EML1), a member of the conserved EMAP family proteins, plays a crucial role in the control of oocyte meiotic progression in the mouse. Female mice carrying an ENU-induced nonsense mutation (c.1956T > A; p.Tyr652∗) of Eml1 are infertile, and the majority of their ovulated oocytes contain abnormal spindles and misaligned chromosomes. In accordance with the mutant oocyte phenotype, we find that EML1 is colocalized with spindle microtubules during the process of normal oocyte meiotic maturation, and knockdown (KD) of EML1 by specific morpholinos in the fully grown oocytes (FGOs) disrupts the integrity of spindles, and delays meiotic progression. Moreover, EML1-KD oocytes fail to progress to metaphase II (MII) stage after extrusion of the first polar body, but enter into interphase and form a pronucleus containing decondensed chromatins. Further analysis shows that EML1-KD impairs the recruitment of γ-tubulin and pericentrin to the spindle poles, as well as the attachment of kinetochores to microtubules and the proper inactivation of spindle assembly checkpoint at metaphase I (MI). The loss of EML1 also compromises the activation of maturation promoting factor around the time of oocyte resumption and completion of the first meiosis, which, when corrected by WEE1/2 inhibitor PD166285, efficiently rescues the phenotype of oocyte delay of meiotic resumption and inability of reaching MII. Through IP- mass spectrometry analysis, we identified that EML1 interacts with nuclear distribution gene C (NUDC), a critical mitotic regulator in somatic cells, and EML1-KD disrupts the specific localization of NUDC at oocyte spindles. Taken together, these data suggest that EML1 regulates acentrosomal spindle formation and the progression of meiosis to MII in mammalian oocytes, which is likely mediated by distinct mechanisms.

Abstract Post‐translational modification of proteins by N‐linked glycosylation is crucial for many life processes. However, the exact contribution of N‐glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N‐glycosylation, is identified to be indispensable for oocyte development in mice. Dpagt1 missense mutation (c. 497A>G; p. Asp166Gly) causes female subfertility without grossly affecting other functions. Mutant females ovulate fewer eggs owing to defective development of growing follicles. Mutant oocytes have a thin and fragile zona pellucida (ZP) due to the reduction in glycosylation of ZP proteins, and display poor developmental competence after fertilization in vitro. Moreover, completion of the first meiosis is accelerated in mutant oocytes, which is coincident with the elevation of aneuploidy. Mechanistically, transcriptomic analysis reveals the downregulation of a number of transcripts essential for oocyte meiotic progression and preimplantation development (e.g., Pttgt1, Esco2, Orc6, and Npm2) in mutant oocytes, which could account for the defects observed. Furthermore, conditional knockout of Dpagt1 in oocytes recapitulates the phenotypes observed in Dpagt1 mutant females, and causes complete infertility. Taken together, these data indicate that protein N‐glycosylation in oocytes is essential for female fertility in mammals by specific control of oocyte development.

In this article, we discuss the existence of positive solution to a nonlinear p-Laplacian fractional differential equation whose nonlinearity contains a higher-order derivative $$\displaylines{ D_{0^+}^{\beta}\phi_p\big(D_{0^+}^{\alpha}u(t)\big) +f\big(t,u(t),u'(t),\dots,u^{(n-2)}(t)\big)=0,\quad t\in ( 0,1 ),\cr u(0)=u'(0)=\dots=u^{(n-2)}(0)=0,\cr u^{(n-2)}(1)=au^{(n-2)}(\xi)=0,\quad D_{0^+}^{\alpha}u(0)=D_{0^+}^{\alpha}u(1)=0, }$$ where ${n-1}1$, $\phi_{p}^{-1}=\phi_q$, $\frac{1}{p}+\frac{1}{q}=1$. $D_{0^+}^{\alpha}$, $D_{0^+}^{\beta}$ are the standard Riemann-Liouville fractional derivatives, and $f\in C((0,1)\times[0,+\infty)^{n-1},[0,+\infty))$. The Green's function of the fractional differential equation mentioned above and its relevant properties are presented, and some novel results on the existence of positive solution are established by using the mixed monotone fixed point theorem and the upper and lower solution method. The interesting of this paper is that the nonlinearity involves the higher-order derivative, and also, two examples are given in this paper to illustrate our main results from the perspective of application.

A comparative study of two types of third-generation Chinese soft-shelled turtles (Trionyx sinensis) from the Yangtze River (i.e., Type A with black spots on the carapace and Type B without spots) was conducted to evaluate the effect of selective breeding on their nutritional composition. Our nutrient analysis results indicated that both types were high-quality aquatic products with high protein and low fat contents. The amino acid contents in the muscle of type A were significantly higher than those of type B (P < 0.05), but no significant differences were observed in the calipash. Additionally, the amino acid score (AAS) in the muscle of type A was >1, which was significantly higher than that of type B (P<0.05). The contents of all fatty acids and EPA+DHA were significantly higher in Type A than in type B (P<0.05), whereas there were no significant differences in the fatty acid composition of the calipash of the two types (P > 0.05). The muscle atherogenicity index (AI) and thrombogenicity index (TI) of the two types were 0.42-0.45 and 0.33-0.34, respectively, which were significantly lower than that of the calipash (P<0.05). The hypocholesterolemic/hypercholesterolemic fatty acid ratio (HH) was 3.91-3.89, which was significantly higher than that of the calipash (P<0.05). Additionally, the collagen content of type A calipash was significantly higher than that of type B (P<0.05). Collectively, our findings indicated that selective breeding could improve the nutritional value of T. sinensis from the Yangtze River. [ABSTRACT FROM AUTHOR]

In this article, we study the existence of mild solutions and approximate controllability for non-autonomous impulsive evolution equations with nonlocal conditions in Banach space. The existence of mild solutions and some conditions for approximate controllability of these non-autonomous impulsive evolution equations are given by using the Krasnoselskii's fixed point theorem, the theory of evolution family and the resolvent operator. In particular, the impulsive functions are supposed to be continuous and the nonlocal item is divided into Lipschitz continuous and completely bounded. An example is given as an application of the results. [ABSTRACT FROM AUTHOR]

Abstract Cortical neurogenesis is a fundamental process of brain development that is spatiotemporally regulated by both intrinsic and extrinsic cues. Although recent evidence has highlighted the significance of transcription factors in cortical neurogenesis, little is known regarding the role of RNA-binding proteins (RBPs) in the post-transcriptional regulation of cortical neurogenesis. Here, we report that meiosis arrest female 1 (MARF1) is an RBP that is expressed during neuronal differentiation. Cortical neurons expressed the somatic form of MARF1 (sMARF1) but not the oocyte form (oMARF1). sMARF1 was enriched in embryonic brains, and its expression level decreased as brain development progressed. Overexpression of sMARF1 in E12.5 neuronal progenitor cells promoted neuronal differentiation, whereas sMARF1 knockdown decreased neuronal progenitor differentiation in vitro. We also examined the function of sMARF1 in vivo using an in utero electroporation technique. Overexpression of sMARF1 increased neuronal differentiation, whereas knockdown of sMARF1 inhibited differentiation in vivo. Moreover, using an RNase domain deletion mutant of sMARF1, we showed that the RNase domain is required for the effects of sMARF1 on cortical neurogenesis in vitro. Our results further elucidate the mechanisms of post-transcriptional regulation of cortical neurogenesis by RBPs.

Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control. [ABSTRACT FROM AUTHOR]