miR156-PvSPL2 controls culm development by transcriptional repression of switchgrass CYTOKININ OXIDASE/DEHYDROGENASE4.

Culm development in grasses can be controlled by both miR156 and cytokinin. However, the crosstalk between the miR156-SPL module and the cytokinin metabolic pathway remains largely unknown. Here, we found CYTOKININ OXIDASE/DEHYDROGENASE4 (PvCKX4) plays a negative regulatory role in culm development of the bioenergy grass Panicum virgatum (switchgrass). Overexpression of PvCKX4 in switchgrass reduced the internode diameter and length without affecting tiller number. Interestingly, we also found that PvCKX4 was always upregulated in miR156 overexpressing (miR156OE) transgenic switchgrass lines. Additionally, upregulation of either miR156 or PvCKX4 in switchgrass reduced the content of isopentenyl adenine (iP) without affecting trans-zeatin (tZ) accumulation. It is consistent with the evidence that the recombinant PvCKX4 protein exhibited much higher catalytic activity against iP than tZ in vitro. Furthermore, our results showed that miR156-targeted SPL2 bound directly to the promoter of PvCKX4 to repress its expression. Thus, alleviating the SPL2-mediated transcriptional repression of PvCKX4 through miR156 overexpression resulted in a significant increase in cytokinin degradation and impaired culm development in switchgrass. On the contrary, suppressing PvCKX4 in miR156OE transgenic plants restored iP content, internode diameter, and length to wild-type levels. Most strikingly, the double transgenic lines retained the same increased tiller numbers as the miR156OE transgenic line, which yielded more biomass than the wild type. These findings indicate that the miR156-SPL module can control culm development through transcriptional repression of PvCKX4 in switchgrass, which provides a promising target for precise design of shoot architecture to yield more biomass from grasses.

RORα inhibits gastric cancer proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity.

BACKGROUND: Glycolysis is critical for harvesting abundant energy to maintain the tumor microenvironment in malignant tumors. Retinoic acid-related orphan receptor α (RORα) has been identified as a circadian gene. However, the association of glycolysis with RORα in regulating gastric cancer (GC) proliferation remains poorly understood. METHODS: Bioinformatic analysis and retrospective study were utilized to explore the role of RORα in cell cycle and glycolysis in GC. The mechanisms were performed in vitro and in vivo including colony formation, Cell Counting Kit-8 (CCK-8), Epithelial- mesenchymal transition (EMT) and subcutaneous tumors of mice model assays. The key drives between RORα and glycolysis were verified through western blot and chip assays. Moreover, we constructed models of high proliferation and high glucose environments to verify a negative feedback and chemoresistance through a series of functional experiments in vitro and in vivo. RESULTS: RORα was found to be involved in the cell cycle and glycolysis through a gene set enrichment analysis (GSEA) algorithm. GC patients with low RORα expression were not only associated with high circulating tumor cells (CTC) and high vascular endothelial growth factor (VEGF) levels. However, it also presented a positive correlation with the standard uptake value (SUV) level. Moreover, the SUVmax levels showed a positive linear relation with CTC and VEGF levels. In addition, RORα expression levels were associated with glucose 6 phosphate dehydrogenase (G6PD) and phosphofructokinase-2/fructose-2,6-bisphosphatase (PFKFB3) expression levels, and GC patients with low RORα and high G6PD or low RORα and high PFKFB3 expression patterns had poorest disease-free survival (DFS). Functionally, RORα deletion promoted GC proliferation and drove glycolysis in vitro and in vivo. These phenomena were reversed by the RORα activator SR1078. Moreover, RORα deletion promoted GC proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity in vitro and in vivo. Mechanistically, RORα was recruited to the G6PD and PFKFB3 promoters to modulate their transcription. Next, high proliferation and high glucose inhibited RORα expression, which indicated that negative feedback exists in GC. Moreover, RORα deletion improved fluorouracil chemoresistance through inhibition of glucose uptake. CONCLUSION: RORα might be a novel biomarker and therapeutic target for GC through attenuating glycolysis.

DNAJ protein gene expansion mechanism in Panicoideae and PgDNAJ functional identification in pearl millet.

KEY MESSAGE: Analyze the evolutionary pattern of DNAJ protein genes in the Panicoideae, including pearl millet, to identify and characterize the biological function of PgDNAJ genes in pearl millet. Global warming has become a major factor threatening food security and human development. It is urgent to analyze the heat-tolerant mechanism of plants and cultivate crops that are adapted to high temperature conditions. The Panicoideae are the second largest subfamily of the Poaceae, widely distributed in warm temperate and tropical regions. Many of these species have been reported to have strong adaptability to high temperature stress, such as pearl millet, foxtail millet and sorghum. The evolutionary differences in DNAJ protein genes among 12 Panicoideae species and 10 other species were identified and analyzed. Among them, 79% of Panicoideae DNAJ protein genes were associated with retrotransposon insertion. Analysis of the DNAJ protein pan-gene family in six pearl millet accessions revealed that the non-core genes contained significantly more TEs than the core genes. By identifying and analyzing the distribution and types of TEs near the DNAJ protein genes, it was found that the insertion of Copia and Gypsy retrotransposons provided the source of expansion for the DNAJ protein genes in the Panicoideae. Based on the analysis of the evolutionary pattern of DNAJ protein genes in Panicoideae, the PgDNAJ was obtained from pearl millet through identification. PgDNAJ reduces the accumulation of reactive oxygen species caused by high temperature by activating ascorbate peroxidase (APX), thereby improving the heat resistance of plants. In summary, these data provide new ideas for mining potential heat-tolerant genes in Panicoideae, and help to improve the heat tolerance of other crops.

Differently Distributed Iron Deposition in Mild and Moderate Stroke with Small Artery Occlusion: A Pilot Voxel-Based Susceptibility Mapping Study.

BACKGROUND: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study's purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits. METHODS: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods. RESULTS: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier's analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions. CONCLUSIONS: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity.

Altered Neuromagnetic Activity in the Default Mode Network in Migraine and Its Subgroups (Episodic Migraine and Chronic Migraine).

BACKGROUND: The differences in the resting state spectral power and functional connectivity of the default mode network between people with migraine without aura (MwoA) and its subgroups differentiated by frequency (episodic migraine (EM) and chronic migraine (CM)) and healthy controls (HC) were investigated using magnetoencephalography. METHODS: In the resting state, the topological spatial structure of the brain in 33 MwoA patients and 22 HC was first studied using magnetoencephalography, followed by probing the neuroelectrical activity of 17 CM and 16 EM patients, to identify damage to their default mode network (DMN). The techniques used to investigate both spectral power and functional connectivity were minimum-paradigm estimation combined with Welch's technique and corrected amplitude envelope correlation. RESULTS: The differences between MwoA and its subgroups (CM and EM) and HC based on spectral power were mainly in the delta, theta, and alpha bands, while the differences in functional connectivity were primarily in the delta, alpha, and beta bands. In the delta and theta bands, the spectral power of MwoA and its subgroups (CM and EM) was higher than in the HC group. The spectral power of MwoA and its subgroups (CM and EM) was lower in the alpha band. In terms of functional connectivity, the corrected amplitude envelope correlation of MwoA and its subgroups (CM and EM) was lower than the HC group in the bands with spectral differences. People with EM and CM differed in the spectral power in the left medial prefrontal cortex and the right lateral temporal cortex in the alpha band, where correlation analysis and logistic regression analysis showed that the intensity of the spectral power of the left medial prefrontal cortex was negatively correlated with headache frequency. CONCLUSIONS: The spectral power of the left medial prefrontal cortex in the alpha band may serve as a biomarker that is associated with the number of monthly headache attacks and may be a potential neuromodulatory target for controlling migraine chronicity.

Combined Genome-Wide Association Study and Transcriptome Analysis Reveal Candidate Genes for Resistance to Rust (Puccinia graminis) in Dactylis glomerata.

Rust disease is a common plant disease that can cause wilting, slow growth of plant leaves, and even affect the growth and development of plants. Orchardgrass (Dactylis glomerata L.) is native to temperate regions of Europe, which has been introduced as a superior forage grass in temperate regions worldwide. Orchardgrass has rich genetic diversity and is widely distributed in the world, which may contain rust resistance genes not found in other crops. Therefore, we collected a total of 333 orchardgrass accessions from different regions around the world. Through a genome-wide association study (GWAS) analysis conducted in four different environments, 91 genes that overlap or are adjacent to significant single nucleotide polymorphisms (SNPs) were identified as potential rust disease resistance genes. Combining transcriptome data from susceptible (PI292589) and resistant (PI251814) accessions, the GWAS candidate gene DG5C04160.1 encoding glutathione S-transferase (GST) was found to be important for orchardgrass rust (Puccinia graminis) resistance. Interestingly, by comparing the number of GST gene family members in seven species, it was found that orchardgrass has the most GST gene family members, containing 119 GST genes. Among them, 23 GST genes showed significant differential expression after inoculation with the rust pathogen in resistant and susceptible accessions; 82% of the genes still showed significantly increased expression 14 days after inoculation in resistant accessions, while the expression level significantly decreased in susceptible accessions. These results indicate that GST genes play an important role in orchardgrass resistance to rust (P. graminis) stress by encoding GST to reduce its oxidative stress response.

The Role of EEG microstates in predicting oxcarbazepine treatment outcomes in patients with newly-diagnosed focal epilepsy.

PURPOSE: Microstates represent the global and topographical distribution of electrical brain activity from scalp-recorded EEG. This study aims to explore EEG microstates of patients with focal epilepsy prior to medication, and employ extracted microstate metrics for predicting treatment outcomes with Oxcarbazepine monotherapy. METHODS: This study involved 25 newly-diagnosed focal epilepsy patients (13 females), aged 12 to 68, with various etiologies. Patients were categorized into Non-Seizure-Free (NSF) and Seizure-Free (SF) groups according to their first follow-up outcomes. From pre-medication EEGs, four representative microstates were identified by using clustering. The temporal parameters and transition probabilities of microstates were extracted and analyzed to discern group differences. With generating sample method, Support Vector Machine (SVM), Logistic Regression (LR), and Naïve Bayes (NB) classifiers were employed for predicting treatment outcomes. RESULTS: In the NSF group, Microstate 1 (MS1) exhibited a significantly higher duration (mean±std. = 0.092±0.008 vs. 0.085±0.008, p = 0.047), occurrence (mean±std. = 2.587±0.334 vs. 2.260±0.278, p = 0.014), and coverage (mean±std. = 0.240±0.046 vs. 0.194±0.040, p = 0.014) compared to the SF group. Additionally, the transition probabilities from Microstate 2 (MS2) and Microstate 3 (MS3) to MS1 were increased. In MS2, the NSF group displayed a stronger correlation (mean±std. = 0.618±0.025 vs. 0.571±0.034, p < 0.001) and a higher global explained variance (mean±std. = 0.083±0.035 vs. 0.055±0.023, p = 0.027) than the SF group. Conversely, Microstate 4 (MS4) in the SF group demonstrated significantly greater coverage (mean±std. = 0.388±0.074 vs. 0.334±0.052, p = 0.046) and more frequent transitions from MS2 to MS4, indicating a distinct pattern. Temporal parameters contribute major predictive role in predicting treatment outcomes of Oxcarbazepine, with area under curves (AUCs) of 0.95, 0.70, and 0.86, achieved by LR, NB and SVM, respectively. CONCLUSION: This study underscores the potential of EEG microstates as predictive biomarkers for Oxcarbazepine treatment responses in newly-diagnosed focal epilepsy patients.

Interictal magnetic signals in new-onset Rolandic epilepsy may help with timing of treatment selection.

OBJECTIVE: With research progress on Rolandic epilepsy (RE), its "benign" nature has been phased out. Clinicians are exhibiting an increasing tendency toward a more assertive treatment approach for RE. Nonetheless, in clinical practice, delayed treatment remains common because of the "self-limiting" nature of RE. Therefore, this study aimed to identify an imaging marker to aid treatment decisions and select a more appropriate time for initiating therapy for RE. METHODS: We followed up with children newly diagnosed with RE, classified them into medicated and non-medicated groups according to the follow-up results, and compared them with matched healthy controls. Before beginning follow-up visits, interictal magnetic data were collected using magnetoencephalography in treatment-naïve recently diagnosed patients. The spectral power of the whole brain during initial diagnosis was determined using minimum normative estimation combined with the Welch technique. RESULTS: A difference was observed in the magnetic source intensity within the left caudal anterior cingulate and precentral and postcentral gyri in the delta band between the medicated and non-medicated groups. The results revealed good discriminatory ability within the receiver operator characteristic curve. In the medicated group, there was a specific change in the frontotemporal magnetic source intensity, which shifted from high to low frequencies, compared with the healthy control group. SIGNIFICANCE: The intensity of the precentral gyrus magnetic source within the delta band showed good specificity. Considering the rigor of initial treatment, the intensity of the precentral gyrus magnetic source can provide some help as an imaging marker for initial RE treatment, particularly for the timing of treatment initiation.

Piezo-Acoustic Resistive Switching Behaviors in High-Performance Organic-Inorganic Hybrid Perovskite Memristors.

Memristors are regarded as promising candidates for breaking the problems including high off-chip memory access delays and the hash rate cost of frequent data moving induced by algorithms for data-intensive applications of existing computational systems. Recently, organic-inorganic halide perovskites (OIHPs) have been recognized as exceptionally favorable materials for memristors due to ease of preparation, excellent electrical conductivity, and structural flexibility. However, research on OIHP-based memristors focuses on modulating resistive switching (RS) performance through electric fields, resulting in difficulties in moving away from complex external circuits and wire connections. Here, a multilayer memristor has been constructed with eutectic gallium and indium (EGaIn)/ MAPbI3 /poly(3,4-ethylenedioxythiophene): poly(4-styrenesulphonate) (PEDOT: PSS)/indium tin oxide (ITO) structure, which exhibits reproducible and reliable bipolar RS with low SET/RESET voltages, stable endurance, ultrahigh average ON/OFF ratio, and excellent retention. Importantly, based on ion migration activated by sound-driven piezoelectric effects, the device exhibits a stable acoustic response with an average ON/OFF ratio greater than 103 , thus realizing non-contact, multi-signal, and far-field control in RS modulation. This study provides a single-structure multifunctional memristor as an integrated architecture for sensing, data storage, and computing.

Metal chalcogenide nanorings for temperature-strain dual-mode sensing.

Most metal chalcogenides exhibit layered structures and anisotropic morphologies such as nanosheets, nanoplates, and nanotubes, as well as nanosheet-assembled nanoflowers. Unconventional morphologies such as nanorings may bring appealing properties to functional materials, but they have not been realized with metal chalcogenides. Herein, we report that Sn0.2Mo0.8S2 nanorings with a mixed 1T/2H phase were synthesized by etching SnS2 cores from Sn1-xMoxS2/SnS2 lateral heterostructures. Flexible electronic sensors based on these Sn0.2Mo0.8S2 nanorings exhibited excellent temperature and strain sensing performance, with a negative temperature coefficient of resistance of -0.013 °C-1 and a minimum detectable strain of 0.09%. In addition, the dual-functional flexible electronic sensors with easy fabrication and good wearability showed great promise for tracking human activities and monitoring inapparent health-related signals.

Narrative review of stereotactic body radiation therapy combined with tyrosine kinase inhibitors for oligometastatic EGFR-mutated non-small cell lung cancer: present and future developments.

Background and Objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC. Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC. Key Content and Findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness. Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.

A cost-effective approach to identify conservation priority for 30 × 30 biodiversity target on the premise of food security.

There is a growing consensus on expanding protected and conserved areas for biodiversity conservation. Nevertheless, it remains uncertain where to expand conserved areas as well as what appropriate management modalities to choose. Moreover, conserved areas expansion should be balanced with crop-related food security challenges. We developed a framework to identify cost-effective areas for expanding protected areas and other effective area-based conservation measures (OECMs), and applied it to China. By combining templates for biodiversity conservation priorities at global scale and the priority conservation areas based on 2413 vertebrates' extinction risk in China, we identified areas with high biodiversity conservation value. We then categorized the priority areas according to human impact, indicating the potential cost of management. As a result of combining the two aspects above, we identified the most cost-effective areas for expanding protected areas and OECMs while excluding both the current and predicted croplands that can be used for food security. The results show that China could expand its protected areas to 22.81 % of the country's land area and establish OECMs in areas accounting for 9.82 % and 17.37 % of the country's land area in a cost-effective approach in two scenarios. In the ambitious scenario, protected and conserved areas would account for a maximum of 40.18 % of terrestrial area, with an average 62.67 % coverage of the 2413 species' suitable habitat. To achieve the goals of protected and conserved areas in Kunming-Montreal Global Biodiversity Framework, countries could apply this framework to identify their protected areas and OECM expansion priorities.