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Objectives: This study aimed to evaluate phenotypic associations between preoperative alkaline phosphatase (ALP) levels and clinical characteristics, and explore clinical factors associated for postoperative regrowth in craniofacial fibrous dysplasia. Methods: In this retrospective cohort (2003–2024), 71 surgically treated fibrous dysplasia patients were analyzed. Relationships between preoperative ALP (using age-stratified reference ranges) and key phenotypes (age at surgery, onset age, laterality, lesion type) were assessed via nonparametric tests. Associations with postoperative regrowth were assessed using Mann–Whitney U or Kruskal–Wallis tests for non-normally distributed continuous variables and χ2 or Fisher’s exact tests for categorical variables. Results: Preoperative ALP levels significantly correlated with younger surgical age (16–19 vs. ≥19 years: 244.0 vs. 107.0 U/L, p < 0.001), earlier onset (0–16 vs. >16 years: 114.0 vs. 83.0 U/L, p = 0.030), bilateral lesions (176.0 vs. 106.2 U/L, p = 0.006), and polyostotic subtype (polyostotic fibrous dysplasia vs. monostotic fibrous dysplasia: 162.0 vs. 87.5 U/L, p < 0.001). However, neither ALP levels (p = 0.061) nor abnormal ALP rates (p = 0.090) predicted regrowth. Crucially, bilateral lesions were significantly associated with regrowth (83.3% (5/6) vs. 21.5% (14/65); p = 0.005). The overall regrowth rate was 8.5% (6/71). Conclusions: Bilateral lesions demonstrate significant association with postoperative regrowth risk, potentially guiding surveillance intensity. ALP correlates with phenotypic burden but shows limited prognostic utility. These findings, interpreted considering retrospective constraints, warrant validation in larger cohorts.

The non-renewable primordial follicle (PF) pool underlies female reproductive longevity, yet PF numbers decline sharply before puberty for reasons that remain unclear. Here, we identify histone deacetylase 3 (HDAC3) in pregranulosa cells (pGCs) as a key suppressor of ferroptosis in PFs. Constitutively low HDAC3 expression in pGCs is essential for PF survival: conditional deletion of Hdac3 caused profound PF depletion and ultimately premature ovarian insufficiency. Loss of HDAC3 preferentially triggered ferroptosis, as supported by ferroptosis-associated transcriptional signatures and dysregulation of genes governing lipoxin biosynthesis and cellular iron homeostasis following Hdac3 depletion. Correspondingly, alterations in proteins central to ferroptotic pathways corroborated this mechanism. Together, these findings demonstrate that constitutive HDAC3 expression in pGCs safeguards the PF reserve by restraining ferroptosis and is therefore indispensable for female fertility.

Wrap-around artefacts in magnetic resonance imaging (MRI) are common, typically caused by anatomical structures outside the Field of View (FOV) overlapping into the imaging area. This paper reports a rare source of wrap-around artifact, a wet cotton ball, whose image was inadvertently included in cranial imaging, potentially leading to misdiagnosis as pathological conditions such as otomastoiditis, postoperative changes, or intracranial hemorrhage. Hence, there is a need to enhance MRI technologists' awareness of such artifacts. We analyzed four consecutive cases of cranial MRI scans with similar artifacts, all located on the right side of the brain but in different regions. On axial T2-weighted images (T2WI) and T2 fluid-attenuated inversion recovery (T2FLAIR) sequences, the artifacts appeared as oval-shaped, relatively well-defined heterogeneous high signals. On axial T1-weighted images (T1WI), signal intensity and border clarity varied, with artifact locations slightly more lateral compared to T2WI and T2FLAIR. The artifacts in the first three cases were not identified by the MRI technologists. However, in the fourth case, a patient with head trauma, the MRI technologist noticed inconsistencies in the artifact characteristics across different sequences, as well as similarities to a previous case of cranial trauma, which raised suspicion of an artifact. Systematic image analysis and equipment inspection subsequently revealed a wet cotton ball attached to the outer surface of the head-and-neck coil, inadvertently left there by a radiology nurse during preparation for a previous case. Upon removal of the cotton ball and rescanning the sequences with artifacts in cases 3 and 4, the artifacts disappeared, confirming the wet cotton ball as the source. Additionally, upon review, similar artifacts were found in the first two cases but overlooked due to various reasons. The aim of this study is to improve MRI technologists' recognition of artifacts caused by non-metallic foreign objects, avoiding misdiagnosis, and to prompt us to refine our examination protocols and enhance radiology nurses' awareness of MRI safety.

Background High-risk neuroblastoma is associated with a poor prognosis, making it crucial to identify patients within this group who face an even higher risk of adverse outcomes. Objective To determine if integrating clinical indicators and venous-phase enhanced computed tomography radiomics features could improve the prediction of overall survival in high-risk neuroblastoma. Materials and methods We retrospectively included high-risk neuroblastoma patients treated at a primary institution, randomly stratifying them into a training set (70%) and a test set (30%). Univariate and multivariate Cox regression analyses were used to identify independent clinical risk factors. We then extracted radiomics features from venous-phase enhanced computed tomography images. Clinical risk factors, radiomics score, and combined model were evaluated in the training, test, and external validation sets. Results The training, test, and validation sets included 70, 30, and 40 patients, respectively. Neuron-specific enolase was identified as the independent clinical risk factor, with concordance indices of 0.616, 0.627, and 0.595 in the training, test, and validation sets, respectively. The radiomics score achieved concordance indices of 0.699, 0.690, and 0.684 in the training, test, and validation sets, respectively. The combined model showed concordance indices of 0.730, 0.707, and 0.690 in the training, test, and validation sets, respectively. The combined model predicted 5-year overall survival with an area under the receiver operating characteristic curve of 0.780 in the training set, 0.742 in the test set, and 0.710 in the validation set. Conclusion Combining neuron-specific enolase and venous-phase enhanced computed tomography radiomics improves survival prediction in high-risk neuroblastoma. Graphical Abstract

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

Premature ovarian insufficiency (POI) is an accelerated reduction in ovarian function inducing infertility. Folliculogenesis defects have been reported to trigger POI as a consequence of ovulation failure. However, the underlying mechanisms remain unclear due to the genetic complexity and heterogeneity of POI. We used whole genome sequencing (WGS), conditional knockout mouse models combined with laser capture microdissection (LCM), and RNA/ChIP sequencing to analyze the crucial roles of polycomb repressive complex 1 (PRC1) in clinical POI and mammalian folliculogenesis. A deletion mutation of , the key component of PRC1, was identified in a 17-year-old patient. However, deleting in granulosa cells (GCs) did not induce infertility until its homolog, , was deleted simultaneously. Double deficiency of BMI1/MEL18 eliminated PRC1 catalytic activity, upregulating cyclin-dependent kinase inhibitors (CDKIs) and thus blocking GC proliferation during primary-to-secondary follicle transition. This defect led to damaged intercellular crosstalk, eventually resulting in gonadotropin response failure and infertility. Our findings highlighted the pivotal role of PRC1 as an epigenetic regulator of gene transcription networks in GC proliferation during early folliculogenesis. In the future, a better understanding of molecular details of PRC1 structural and functional abnormalities may contribute to POI diagnosis and therapeutic options.

With increasingly stringent emission regulations and demand for fuel economy by the public, the combustion and emission problems of automotive diesel engines during transient operation have become vital and urgent issues. In this study, combustion deterioration has been experimentally analyzed using a heavy-duty turbocharged diesel engine running under transient conditions (constant speed and increasing torque). Optimization of the transient combustion process was performed by adjusting the fuel injection parameters. The results indicated that the notable combustion deterioration relative to steady state operation while transient was a function of the delay in the air-supply to the turbocharged engine, and took the form of combustion phasing delay, resulting in rapidly increasing smoke emission and fuel consumption. However, the delay in combustion phasing can be controlled by advancing the fuel injection timing, effectively increasing thermal efficiency. Unfortunately, smoke and NOx emissions increased at the same time. The deterioration in combustion phasing can also be improved by increasing injection pressure, resulting in decreased smoke emission while NOx emission increased. It is worth noting that the effective thermal efficiency first increased and then decreased as fuel injection pressure increased during transient operation.

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonialyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.

The phytohormone cytokinin (CK) positively regulates the activity and function of the shoot apical meristem (SAM), which is a major parameter determining seed production. The rice (Oryza sativa L.) Gn1a / OsCKX2 (Grain number 1a / Cytokinin oxidase 2) gene, which encodes a cytokinin oxidase, has been identified as a major quantitative trait locus contributing to grain number improvement in rice breeding practice. However, the molecular mechanism of how the expression of OsCKX2 is regulated in planta remains elusive. Here, we report that the zinc finger transcription factor DROUGHT AND SALT TOLERANCE (DST) directly regulates OsCKX2 expression in the reproductive meristem. DST-directed expression of OsCKX2 regulates CK accumulation in the SAM and, therefore, controls the number of the reproductive organs. We identify that DST ʳᵉᵍ¹, a semidominant allele of the DST gene, perturbs DST-directed regulation of OsCKX2 expression and elevates CK levels in the reproductive SAM, leading to increased meristem activity, enhanced panicle branching, and a consequent increase of grain number. Importantly, the DST ʳᵉᵍ¹ allele provides an approach to pyramid the Gn1a -dependent and Gn1a -independent effects on grain production. Our study reveals that, as a unique regulator of reproductive meristem activity, DST may be explored to facilitate the genetic enhancement of grain production in rice and other small grain cereals.

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.A broadly neutralizing antibody (bnAb) response is required to combat SARS-CoV-2 variants of concern (VOCs). The authors isolated and characterized a large panel of sarbecovirus bnAbs from vaccinated individuals who had recovered from COVID-19, finding that many of these antibodies were able to neutralize all VOCs, including Omicron, and demonstrate prophylaxis in mice infected with diverse sarbecoviruses.