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Abstract Plant architecture is a main determinate of crop yield, and lateral branching significantly influences the number of inflorescences and seeds. The mechanism of axillary bud initiation remains unclear. This work aimed to examine how miRNAs regulate axillary bud initiation. By constructing a small RNA library and screening a mutant population, we revealed the initiation of axillary buds is specifically induced by miR394 and repressed by its target, LEAF CURLING RESPONSIVENESS (LCR). Using promoter-driven fluorescent tags and in situ hybridization, we showed that miR394 is localized in the center of the leaf axil where AMs are initiated. Through molecular and genetic research, we revealed that miR394/LCR may regulate REVOLUTA (REV) and SHOOT MERISTEMLESS (STM) to establish the axillary meristem. Immunoprecipitation-mass spectrometry studies revealed that LCR, as an F-box protein, may interact with TOPLESS (TPL) proteins and participate in ubiquitinated protein degradation. Our results reveal an important mechanism by which the miR394-regulated LCR accelerates the degradation of TPL to precisely modulate axillary bud initiation.

Abstract Background Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. Methods Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. Results 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p

Abstract Background The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. Methods Patients diagnosed with astrocytoma, IDH‐mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2–3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. Results A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki‐67 index (p

Abstract Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2–13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4–13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223–0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268–0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506–0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184–0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566–0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516–0.816), 0.654 (95% CI: 0.470–0.823), and 0.675 (95% CI: 0.491–0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Abstract Background The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH‐mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH‐mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes. Methods Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH‐mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. Results Altogether 33 patients with astrocytoma, IDH‐mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral‐necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas. Conclusions Our study scrutinized IDH‐mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.

Abstract Background Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system. Methods Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative. Discussion The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine. Trial registration ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.

BackgroundThe 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM).PurposeThis study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification.MethodsWe reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes.Results163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM.ConclusionOur study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

IntroductionGlioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors. This study aimed to characterize the clinical, radiological, molecular, and survival features of GBM under the current classification scheme and explore survival determinants.MethodsWe re-examined the genetic alterations of IDH-wildtype diffuse gliomas at our institute from 2011 to 2022, and enrolled GBMs for analysis after re-classification. Univariable and multivariable analyses were used to identify survival determinants.ResultsAmong 209 IDH-wildtype gliomas, 191 were GBMs, including 146 hist-GBMs (76%) and 45 mol-GBMs (24%). Patients with mol-GBMs were younger, less likely to develop preoperative motor dysfunction, and more likely to develop epilepsy than hist-GBMs. Mol-GBMs exhibited lower radiographic incidences of contrast enhancement and intratumoral necrosis. Common molecular features included copy-number changes in chromosomes 1, 7, 9, 10, and 19, as well as alterations in EGFR, TERT, CDKN2A/B, and PTEN, with distinct patterns observed between the two subtypes. The median overall survival (mOS) of GMB was 12.6 months. Mol-GBMs had a higher mOS than hist-GBMs, although not statistically significant (15.6 vs. 11.4 months, p=0.17). Older age, male sex, tumor involvement of deep brain structure or functional area, and genetic alterations in CDK4, CDK6, CIC, FGFR3, KMT5B, and MYB were predictors for a worse prognosis, while MGMT promoter methylation, maximal tumor resection, and treatment based on the Stupp protocol were predictive for better survival.ConclusionThe definition of GBM and its clinical, radiological, molecular, and prognostic characteristics have been altered under the current classification.

Urban agglomerations are becoming increasingly important in driving economic development in China. Accurate representation of the economic development status and spillover effects of cities within an urban agglomeration is the foundation of and an effective approach for promoting the coordinated development of that agglomeration. However, current studies of economic spillovers tend to focus on urban agglomerations as a whole, and there is a lack of scrutiny and validation of research data. Therefore, this study proposes a framework for detecting economic spillover effects within an urban agglomeration based on a prolonged night-time light dataset. Firstly, we explored the most suitable night-time light index to characterize the economic status. Then, we used this index to construct the economic network and hierarchical structure of the urban agglomeration. Finally, we explored the heterogeneity of spillover effects under the hierarchical structure. The results of a case study in the Pearl River Delta (PRD) urban agglomeration show that (1) the total night-time light in built-up areas (BNTL) has the highest Pearson correlation coefficient with GDP, which is 0.82; (2) there is an obvious hierarchical structure within the PRD; (3) there are significant and sustained economic spillover effects among the core cities, with Guangzhou–Foshan and Shenzhen–Dongguan having more obvious spillover effects; and (4) the economic spillover effects within the three metropolitan areas have different characteristics. The Guangzhou–Foshan–Zhaoqing metropolitan area is closely linked, to apparent differences in the pace of spillover effects. The Shenzhen–Dongguan–Huizhou metropolitan area has strong close linkages, with strong synchronization of spillover effects. The Zhuhai–Zhongshan–Jiangmen metropolitan area has not yet formed a stable synergistic development relationship. Overall, the framework can effectively reveal the hierarchical structure and different characteristics of economic spillovers within urban agglomerations, which can provide a scientific reference for policy making related to the coordinated development of such agglomerations.

Abstract Nickel‐iron based hydr(oxy)oxides have been well recognized as one of the best oxygen‐evolving catalysts in alkaline water electrolysis. A crucial problem, however, is that iron leakage during prolonged operation would lead to the oxygen evolution reaction (OER) deactivation over time, especially under large current densities. Here, the NiFe‐based Prussian blue analogue (PBA) is designed as a structure‐flexible precursor for navigating an electrochemical self‐reconstruction (ECSR) with Fe cation compensation to fabricate a highly active hydr(oxy)oxide (NiFeOxHy) catalyst stabilized with NiFe synergic active sites. The generated NiFeOxHy catalyst exhibits the low overpotentials of 302 and 313 mV required to afford large current densities of 500 and 1000 mA cm−2, respectively. Moreover, its robust stability over 500 h at 500 mA cm−2 stands out among the NiFe‐based OER catalysts reported previously. Various in/ex situ studies indicate that the Fe fixation by dynamic reconstruction process can reinforce the Fe‐activated effect on the OER amenable to the industrial‐level large current conditions against the Fe leakage. This work opens up a feasible strategy to design highly active and durable catalysts via thermodynamically self‐adaptive reconstruction engineering.

IntroductionThe fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors released in 2021 formally defines pediatric-type diffuse gliomas. However, there is still little understanding of pediatric-type diffuse gliomas, and even less attention has been paid to adult patients. Therefore, this study describes the clinical radiological, survival, and molecular features of adult patients with pediatric-type glioma.MethodsAdult patients who underwent surgery from January 2011 to January 2022, classified as pediatric-type glioma, were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.ResultsAmong 596 adult patients, 20 patients with pediatric-type glioma were screened, including 6 with diffuse astrocytoma, MYB- or MYBL1-altered, 2 with diffuse midline glioma, H3 K27-altered, and 12 with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Pediatric high-grade glioma (pHGG) frequently showed tumor enhancement, peritumoral edema, and intratumoral necrosis. Adult patients with pHGG showed a longer life expectancy than adult patients with glioblastoma. Common molecular alterations included chromosome alterations and CDKN2A/B, PIK3CA, and PTEN, while altered KMT5B and MET were found to affect the overall survival.ConclusionOur study demonstrated adult patients with pediatric-type glioma. Notably, our research aims to expand the current understanding of adult patients with pediatric-type diffuse gliomas. Furthermore, personalized therapies consisting of targeted molecular inhibitors for MET and VEGFA may exhibit beneficial effects in the corresponding population.

BackgroundThe 5th edition of the World Health Organization (WHO) classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas. The major revision of the classification scheme effectuates significant changes in the diagnosis and management of glioma. This study aimed to depict the clinical, molecular, and prognostic characteristics of glioma and its subtypes according to the current WHO classification.MethodsPatients who underwent surgery for glioma at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing, polymerase chain reaction-based assay, and fluorescence in situ hybridization methods and enrolled in the analysis.ResultsThe enrolled 452 gliomas were reclassified into adult-type diffuse glioma (ntotal=373; astrocytoma, n=78; oligodendroglioma, n=104; glioblastoma, n=191), pediatric-type diffuse glioma (ntotal=23; low-grade, n=8; high-grade, n=15), circumscribed astrocytic glioma (n=20), and glioneuronal and neuronal tumor (n=36). The composition, definition, and incidence of adult- and pediatric-type gliomas changed significantly between the 4th and the 5th editions of the classification. The clinical, radiological, molecular, and survival characteristics of each subtype of glioma were identified. Alterations in CDK4/6, CIC, FGFR2/3/4, FUBP1, KIT, MET, NF1, PEG3, RB1, and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas.ConclusionsThe updated WHO classification based on histology and molecular alterations has updated our understanding of the clinical, radiological, molecular, survival, and prognostic characteristics of varied subtypes of gliomas and provided accurate guidance for diagnosis and potential prognosis for patients.

4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution leaving other phosphorylation sites intact. S82A mice were fertile and exhibited no gross developmental or behavioral abnormalities, but the homozygotes developed diffuse and severe polycystic liver and kidney disease with aging, and lymphoid malignancies after irradiation. Sublethal irradiation caused immature T-cell lymphoma only in S82A mice while S82A homozygous mice have normal T-cell hematopoiesis before irradiation. Whole genome sequencing identified PTEN mutations in S82A lymphoma and impaired PTEN expression was verified in S82A lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to polycystic proliferative disease and lymphoma under certain stressful circumstances, such as aging and irradiation.

Tropical cyclones (TCs) are often accompanied by heavy precipitation, which may lead to natural disasters and a serious threat to life and property. However, they also provide indispensable water resources. Studying the temporal and spatial characteristics of TC precipitation is of great importance for TC precipitation forecasting, TC disaster mitigation, and water resource utilization. Guangdong is one of the most frequently and severely TC-affected provinces in China. Due to the different methods used to identify TC precipitation, the conclusions offered by the existing studies are often inconsistent. Moreover, their analyses of the spatiotemporal characteristics of TC precipitation in Guangdong are not sufficiently thorough. In this study, we first selected the historical TCs that affected Guangdong from 1961 to 2020, using an objective separation method for TC wind and rain, based on the observation data from 86 national meteorological stations in Guangdong Province. From these observations covering the past 60 years, the temporal and spatial variations in TC precipitation in Guangdong for four different periods, namely the first rainy season (FRS), the second rainy season (SRS), the non-rainy season (NRS), and over the whole year (WY), were then explored using statistical analysis and multiple cluster methods. The results show that TC frequencies in the four periods all showed a decreasing trend. TC precipitation also showed a decreasing trend in the SRS and NRS, as well as for the WY, but showed a slightly increasing trend in the FRS. Both TC frequency and TC precipitation showed an apparent inter-annual fluctuation and a quasi-periodic pattern. The spatial distribution of TC precipitation in the four periods all showed a decreasing trend from the coastal to the inland stations, but the western coastal areas had higher TC precipitation values than the eastern coastal areas for the SRS, NRS, and WY periods. The spatial variations of TC precipitation in Guangdong in the four periods of the last six decades were quite similar, exhibiting three primary spatial modes and six patterns. Among them, the spatial distribution of TC precipitation being less than normal across the whole province is the most common pattern. The 86 stations can be classified into six groups when using the spatial clustering method and into four groups when using the time-series clustering method. Stations with higher TC precipitation and large inter-annual fluctuations are often distributed in the coastal areas, while stations with less precipitation and small inter-annual fluctuations are distributed in inland areas. However, the primary areas that are affected by TCs may vary in the different periods.

Deep learning (DL) is widely applied in the field of hyperspectral image (HSI) classification and has proved to be an extremely promising research technique. However, the deployment of DL-based HSI classification algorithms in mobile and embedded vision applications tends to be limited by massive parameters, high memory costs, and the complex networks of DL models. In this article, we propose a novel, extremely lightweight, non-deep parallel network (HyperLiteNet) to address these issues. Based on the development trends of hardware devices, the proposed HyperLiteNet replaces the deep network by the parallel structure in terms of fewer sequential computations and lower latency. The parallel structure can extract and optimize the diverse and divergent spatial and spectral features independently. Meanwhile, an elaborately designed feature-interaction module is constructed to acquire and fuse generalized abstract spectral and spatial features in different parallel layers. The lightweight dynamic convolution further compresses the memory of the network to realize flexible spatial feature extraction. Experiments on several real HSI datasets confirm that the proposed HyperLiteNet can efficiently decrease the number of parameters and the execution time as well as achieve better classification performance compared to several recent state-of-the-art algorithms.

Even though there are different types of after-school settings, numerous studies have focused on formal after-school settings (i.e., after-school programs or ASPs) and their association with children’s academic, physical, and social-emotional behaviors. The few findings from informal settings are also outdated. To bridge this gap, our study aimed to locate the interrelations between after-school settings and the behavioral outcomes of children with a particular emphasis on children’s delinquency and emotional-behavioral problems. We used the U.S. national dataset, fifth wave of Fragile Families and Child Wellbeing (nine-year follow-up), with the binary logistic and ordinary least square regression analyses. With a sample size of 3320, we found that children in parental care were reported to commit less delinquency than children in ASPs. Also, children in non-adult care were reported to have more emotional-behavioral problems than children in ASPs. Educators, school social workers, and policymakers should consider the impact of ASPs on children whose parents are not able to spend significant amounts of time with them. In particular, public assistance should be utilized in such a way that helps parents to achieve their children’s positive behavioral outcomes. At the same time, government and community assistance should be provided to enhance the quality of ASPs for the positive results of emotional-behavioral problems of elementary school students.