Foreign body-intestinal canal angle guides management of ingested foreign bodies in the lower gastrointestinal tract.

BACKGROUND: Determining whether prompt surgery is required for patient with ingested foreign bodies is clinically important. PURPOSE: To evaluate the potential value of computed tomography (CT) in guiding the selection of surgical treatment for patients with ingested foreign bodies in the lower gastrointestinal tract. METHODS: Between January 2014 and December 2023, we analyzed the data of 58 patients (median age: 65.4 years; range, 31-96 years) with ingested foreign bodies in the lower gastrointestinal tract who underwent CT examinations. Patients were treated either conservatively (35 cases) or surgically (23 cases). The angle between the long axis of the foreign body and the intestinal canal (FB-IC angle) was measured. CT findings and clinical variables were evaluated to identify potential indicators for surgical treatment through univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis revealed the FB-IC angle (P = 0.002), presence of free peritoneal gas (P = 0.002), white blood cell count (P = 0.018), and neutrophil count (P = 0.007) as significant factors associated with surgical treatment. Multivariate analysis demonstrated that the FB-IC angle (odds ratio, 1.033; P = 0.045) and the presence of free peritoneal gas (odds ratio, 41.335; P = 0.002) are independent indicators for surgical management. The FB-IC angle showed an area under the receiver operating characteristic curve of 0.755, with a cutoff value of 51.25 degrees. CONCLUSION: The FB-IC angle and presence of free peritoneal gas serve as potential predictive imaging markers for surgical intervention.

Arc-Discharge In Situ Synthesis of Dual-Carbonaceous-Layer-Coated SnS Nanoparticles with High Lithium-Ion Storage Capacity.

SnS-based carbon composites have garnered considerable concentration as prospective anode materials (AMs) for lithium-ion batteries (LIBs). Nevertheless, most SnS-based carbon composites underwent a two-phase or multistep preparation process and exhibited unsatisfactory LIB performance. In this investigation, we introduce a straightforward and efficient one-step arc-discharge technique for the production of dual-layer carbon-coated tin sulfide nanoparticles (SnS@C). The as-prepared composite is used as an AM for LIBs and delivers a high capacity of 1000.4 mAh g-1 at 1.0 A g-1 after 520 cycles. The SnS@C still maintains a capacity of 476 mAh g-1 after 390 cycles despite a higher current of 5.0 A g-1. The high specific capacity and long life are mainly attributed to a unique dual-carbon layers coating structure. The dual-carbon layers not only could effectively improve electrical conductivity and reduce charge-transfer resistance but also limit the alteration in bulk and self-aggregation of SnS nanoparticles. The SnS@C produced by the arc-discharge technique emerges as a promising applicant for AM in LIBs, and the arc-discharge technique provides an alternative way for synthesizing other transition metal sulfides supported on carbonaceous materials.

The PCNA-Pol δ complex couples lagging strand DNA synthesis to parental histone transfer for epigenetic inheritance.

Inheritance of epigenetic information is critical for maintaining cell identity. The transfer of parental histone H3-H4 tetramers, the primary carrier of epigenetic modifications on histone proteins, represents a crucial yet poorly understood step in the inheritance of epigenetic information. Here, we show the lagging strand DNA polymerase, Pol δ, interacts directly with H3-H4 and that the interaction between Pol δ and the sliding clamp PCNA regulates parental histone transfer to lagging strands, most likely independent of their roles in DNA synthesis. When combined, mutations at Pol δ and Mcm2 that compromise parental histone transfer result in a greater reduction in nucleosome occupancy at nascent chromatin than mutations in either alone. Last, PCNA contributes to nucleosome positioning on nascent chromatin. On the basis of these results, we suggest that the PCNA-Pol δ complex couples lagging strand DNA synthesis to parental H3-H4 transfer, facilitating epigenetic inheritance.

Multimodal and hemispheric graph-theoretical brain network predictors of learning efficacy for frontal alpha asymmetry neurofeedback.

EEG neurofeedback using frontal alpha asymmetry (FAA) has been widely used for emotion regulation, but its effectiveness is controversial. Studies indicated that individual differences in neurofeedback training can be traced to neuroanatomical and neurofunctional features. However, they only focused on regional brain structure or function and overlooked possible neural correlates of the brain network. Besides, no neuroimaging predictors for FAA neurofeedback protocol have been reported so far. We designed a single-blind pseudo-controlled FAA neurofeedback experiment and collected multimodal neuroimaging data from healthy participants before training. We assessed the learning performance for evoked EEG modulations during training (L1) and at rest (L2), and investigated performance-related predictors based on a combined analysis of multimodal brain networks and graph-theoretical features. The main findings of this study are described below. First, both real and sham groups could increase their FAA during training, but only the real group showed a significant increase in FAA at rest. Second, the predictors during training blocks and at rests were different: L1 was correlated with the graph-theoretical metrics (clustering coefficient and local efficiency) of the right hemispheric gray matter and functional networks, while L2 was correlated with the graph-theoretical metrics (local and global efficiency) of the whole-brain and left the hemispheric functional network. Therefore, the individual differences in FAA neurofeedback learning could be explained by individual variations in structural/functional architecture, and the correlated graph-theoretical metrics of learning performance indices showed different laterality of hemispheric networks. These results provided insight into the neural correlates of inter-individual differences in neurofeedback learning. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09939-x.

The OsMOB1A-OsSTK38 kinase complex phosphorylates CYCLIN C, controlling grain size and weight in rice.

Grain size and weight are crucial yield-related traits in rice (Oryza sativa). Although certain key genes associated with rice grain size and weight have been successfully cloned, the molecular mechanisms underlying grain size and weight regulation remain elusive. Here, we identified a molecular pathway regulating grain size and weight in rice involving the MPS ONE BINDER KINASE ACTIVATOR-LIKE 1A-SERINE/THREONINE-PROTEIN KINASE 38-CYCLIN C (OsMOB1A-OsSTK38-OsCycC) module. OsSTK38 is a nuclear Dbf2-related kinase that positively regulates grain size and weight by coordinating cell proliferation and expansion in the spikelet hull. OsMOB1A interacts with and enhances the autophosphorylation of OsSTK38. Specifically, the critical role of the OsSTK38 S322 site in its kinase activity is highlighted. Furthermore, OsCycC, a component of the Mediator complex, was identified as a substrate of OsSTK38, with enhancement by OsMOB1A. Notably, OsSTK38 phosphorylates the T33 site of OsCycC. The phosphorylation of OsCycC by OsSTK38 influenced its interaction with the transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (OsKNAT7). Genetic analysis confirmed that OsMOB1A, OsSTK38 and OsCycC function in a common pathway to regulate grain size and weight. Taken together, our findings revealed a connection between the Hippo signalling pathway and the Cyclin-Dependent Kinase (CDK) module in eukaryotes. Moreover, they provide insights into the molecular mechanisms linked to yield-related traits and propose innovative breeding strategies for high-yielding varieties.

CHD2 Regulates Neuron-glioma Interactions in Pediatric Glioma.

High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons.

Melatonin application during cryopreservation improves the development and clinical outcomes of human vitrified-warmed oocytes.

In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10-9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.

BET bromodomain inhibition potentiates radiosensitivity in models of H3K27-altered diffuse midline glioma.

Diffuse midline glioma (DMG) H3K27-altered is one of the devastating childhood cancers. Radiation therapy remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance radiation anti-tumor activity using radiosensitizing agents, although none have been successful. Given this, there is a critical need for identifying effective therapeutics to enhance radiation sensitivity for the treatment of DMG. Using high-throughput radiosensitivity screening, we identified bromo- and extra-terminal domain (BET) protein inhibitors as potent radiosensitizers in DMG cells. Genetic and pharmacologic inhibition of BET bromodomain activity reduced DMG cell proliferation and enhanced radiation-induced DNA damage by inhibiting DNA repair pathways. RNA-seq and CUT & RUN showed that BET bromodomain inhibitors regulate the expression of DNA repair genes mediated by H3K27 acetylation at enhancers. BET bromodomain inhibitors enhanced DMG radiation-response in patient-derived xenografts as well as genetically engineered mouse models. Together, our results highlight BET bromodomain inhibitors as radiosensitizer and provide a rationale for developing combination therapy with radiation for the treatment of DMG.

Association Between Exposure to Multiple Toxic Metals in Follicular Fluid and the Risk of PCOS Among Infertile Women: The Mediating Effect of Metabolic Markers.

Polycystic ovary syndrome (PCOS) severely affects women's fertility and accompanies serious metabolic disturbances, affecting 5%-20% of women of reproductive age globally. We previously found that exposure to toxic metals in the blood raised the risk of PCOS, but the association between exposure to toxic metals and the risk of PCOS in the follicular fluid, the microenvironment for oocyte growth and development in females, and its effect on metabolism has not been reported. This study aimed to evaluate the associations between the concentrations of cadmium (Cd), mercury (Hg), barium (Ba) and arsenic (As) in FF and the risk of PCOS, and to explore the mediating effect of metabolic markers in FF on the above relationship. We conducted a case-control study, including 557 women with PCOS and 651 controls. Ba, Cd, Hg and As levels in FF were measured by ICP-MS, metabolites levels in FF was measured by LC-MS/MS among 168 participants randomly selected from all the participants. Logistic regression models were used to assess the association of a single metal level with the PCOS risk, and linear regression models were used to assess the relationships of a single metal level with clinical phenotype parameters and metabolites levels. Combined effect of metals mixture levels on the risk of PCOS were assessed via weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR). Medication analysis was performed to explore the role of metabolic markers on the relationship of toxic metals levels with the risk of PCOS. The exposure levels of Cd, Hg, Ba and As in FF were all positively and significantly associated with the PCOS risk (with respect to the highest vs. lowest tertile group: OR = 1.57, 95% CI = 1.17 ~ 2.12 for Cd, OR = 1.69, 95% CI = 1.22 ~ 2.34 for Hg, OR = 1.76, 95% CI = 1.32 ~ 2.34 for Ba, OR = 1.42, 95% CI = 1.05 ~ 1.91 for As). In addition, levels of metal mixture also significantly correlated with the risk of PCOS, Cd level contributed most to it. Moreover, we observed significant positive relationships between Cd level and LH (ß = 0.048, 95% CI = 0.002 ~ 0.094), T (ß = 0.077, 95% CI = 0.029 ~ 0.125) and HOMA-IR value (ß = 0.060, 95% CI = 0.012 ~ 0.107), as well as Hg level with LH, FSH/LH ratio and TC. Furthermore, we revealed that estrone sulfate, LysoPE 22:6 and N-Undecanoylglycine were significantly and positively mediating the association between Cd level and the risk of PCOS (with mediated proportion of 0.39, 0.24 and 0.35, respectively), and between Hg level and the risk of PCOS (with mediated proportion of 0.29, 0.20 and 0.46, respectively). These highly expressed metabolites significantly enriched in the fatty acid oxidation, steroid hormone biosynthesis and glycerophospholipids metabolism, which may explain the reason why the levels of Cd and Hg in FF associated with the phenotype of PCOS. Ba and As in FF was not found the above phenomenon. Our results suggested that exposure to multiple toxic metals (Cd, Hg, Ba and As) in FF associated with the increased risk of PCOS, Cd was a major contributor. Levels of Cd and Hg in FF significantly associated with the phenotype of PCOS. The above association may result from that Cd and Hg in FF related with the disturbance of fatty acid oxidation, steroid hormone biosynthesis and the glycerophospholipids metabolism.

The association between urinary incontinence and suicidal ideation: Findings from the National Health and Nutrition Examination Survey.

BACKGROUND: Urinary incontinence (UI) might be linked to suicidal ideation, but we do not yet have all the relevant details. This study aimed to dig deeper into the connection between UI and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We examined 31,891 participants aged ≥ 20 years from NHANES 2005-2018 who provided complete information. We used standardized surveys to check for UI and signs of suicidal ideation. To better understand this relationship, we used statistical tools such as multivariable logistic regression, subgroup analysis, and sensitivity analyses. RESULTS: Among the 31,891 participants, 28.9% reported UI and 10.7% reported suicidal ideation. Those with UI exhibited a significantly greater incidence of suicidal ideation (15.5%) than did those without UI (8.8%, P < 0.001). After adjusting for various factors, including age, sex, marital status, socioeconomic status, educational level, lifestyle factors, and chronic comorbidities, UI remained significantly associated with suicidal ideation (OR:1.54, 95% CI = 1.39-1.7, P < 0.001). Among all types of UI, MUI participants were more likely to experience suicidal ideation. Compared with no UI, higher odds of suicidal ideation suffered from MUI (OR:2.11, 95%CI:1.83-2.44, P < 0.001), SUI (OR:1.4, 95%CI:1.19-1.65, P < 0.001), UUI(OR:1.37,95%CI:1.16-1.62, P < 0.001) after full adjustment. With the exception of individuals living with a partner, the remaining subgroups exhibited a positive correlation between urinary incontinence and suicidal ideation, considering that factors such as age, sex, and prevalent comorbidities such as hypertension, depression, and diabetes did not reveal any statistically significant interactions (all P > 0.05). Sensitivity analyses, incorporating imputed missing covariates, did not substantially alter the results (OR: 1.53, 95% CI: 1.4-1.68, P < 0.001). CONCLUSION: Urinary incontinence may correlate with increased suicidal ideation risk, priority screening for suicidal ideation and timely intervention are essential for individuals with urinary incontinence, but prospective studies are needed to verify the results.

Distribution Characteristics of Low-Molecular-Weight Organic Acids in Reclaimed Soil Filled with Fly Ash: A Study.

This study aims to assess the contents of different kinds of low-molecular-weight organic acids (LMWOAs) in reclaimed soil filled with fly ash in the Huainan mining area in China using high-performance liquid chromatography (HPLC). Using a mobile phase consisting of 0.1% phosphoric acid and acetonitrile in a volume ratio of 98:2, the detection was performed at a wavelength of 210 nm for 15 min. In addition, a cluster analysis was performed on the detected LMWOAs in the reclaimed soil. The correlations between the LMWOA and nutrient contents in the reclaimed soil were also analyzed. In total, eight and seven LMWOAs were detected in the reclaimed soil and filled fly ash, respectively. In contrast, no LMWOAs were detected in the fresh fly ash from a thermal power plant. The order of total LMWOA contents at different sampling points followed the order of farmland control soil > 1# (Triticum aestivum) > 4# (Phragmites australis) > 5# (Vigna radiata) > 2# (Sorghum bicolor) > 3# (Tamarix ramosissima) > fly ash-filled soil. The farmland control soil and fly ash-filled soil exhibited the highest and lowest LMWOA contents of 648.22 and 85.09 µg·g-1, respectively. The LMWOA contents in the reclaimed soil followed the order of oxalic acid > tartaric acid > malonic acid > lactic acid > acetic acid > citric acid > propionic acid > succinic acid. Indeed, oxalic acids exhibited the highest total amount of 1445.79 µg·g-1 and succinic acids exhibited the lowest total amount of 6.50 µg·g-1. The LMWOA contents in the reclaimed soil decreased with increasing soil depth, showing statistically significant differences between the 0-10 and 10-40 cm soil layers (p < 0.05). According to the obtained clustering results, the detected LMWOAs can be divided into two categories. The first category consisted of oxalic acid, while the second category included the remaining LMWOAs. The soil LMWOA contents of 4# (Phragmites australis) and 5# (Vigna radiata) were significantly different from those at the other sampling points. According to the Pearson correlation analysis results, the occurrence and characteristics of the soil LMWOAs can be controlled by regulating the pH values and available nutrient contents in the soil, thereby improving the eco-environmental conditions of the reclaimed rhizosphere.

High-Entropy Alloy Electrocatalysts Bidirectionally Promote Lithium Polysulfide Conversions for Long-Cycle-Life Lithium-Sulfur Batteries.

High-entropy alloys (HEAs) have attracted considerable attention, owing to their exceptional characteristics and high configurational entropy. Recent findings demonstrated that incorporating HEAs into sulfur cathodes can alleviate the shuttling effect of lithium polysulfides (LiPSs) and accelerate their redox reactions. Herein, we synthesized nano Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs on hollow carbons (HCs; denoted as HEA/HC) by a facile pyrolysis strategy. The HEA/HC nanostructures were further integrated into hypha carbon nanobelts (HCNBs). The solid-solution phase formed by the uniform mixture of the five metal elements, i.e., Pt0.25Cu0.25Fe0.15Co0.15Ni0.2 HEAs, gave rise to a strong interaction between neighboring atoms in different metals, resulting in their adsorption energy transformation across a wide, multipeak, and nearly continuous spectrum. Meanwhile, the HEAs exhibited numerous active sites on their surface, which is beneficial to catalyzing the cascade conversion of LiPSs. Combining density functional theory (DFT) calculations with detailed experimental investigations, the prepared HEAs bidirectionally catalyze the cascade reactions of LiPSs and boost their conversion reaction rates. S/HEA@HC/HCNB cathodes achieved a low 0.034% decay rate for 2000 cycles at 1.0 C. Notably, the S/HEA@HC/HCNB cathode delivered a high initial areal capacity of 10.2 mAh cm-2 with a sulfur loading of 9 mg cm-2 at 0.1 C. The assembled pouch cell exhibited a capacity of 1077.9 mAh g-1 at the first discharge at 0.1 C. The capacity declined to 71.3% after 43 cycles at 0.1 C. In this work, we propose to utilize HEAs as catalysts not only to improve the cycling stability of lithium-sulfur batteries, but also to promote HEAs in energy storage applications.

State-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection.

The intricate relationship between prestimulus alpha oscillations and visual contrast detection variability has been the focus of numerous studies. However, the causal impact of prestimulus alpha traveling waves on visual contrast detection remains largely unexplored. In our research, we sought to discern the causal link between prestimulus alpha traveling waves and visual contrast detection across different levels of mental fatigue. Using electroencephalography (EEG) alongside a visual detection task with 30 healthy adults (13 females; 17 males), we identified a robust negative correlation between prestimulus alpha forward traveling waves (FTW) and visual contrast threshold (VCT). Inspired by this correlation, we utilized 45°/-45° phase-shifted transcranial alternating current stimulation (tACS) in a sham-controlled, double-blind, within-subject experiment with 33 healthy adults (23 females; 10 males) to directly modulate these alpha traveling waves. After the application of 45° phase-shifted tACS, we observed a substantial decrease in FTW and an increase in backward traveling waves (BTW), along with a concurrent increase in VCT, compared with the sham condition. These changes were particularly pronounced under low fatigue state. The findings of state-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection. Moreover, our study highlights the potential of 45°/-45° phase-shifted tACS in cognitive modulation and therapeutic applications.Significance Statement Visual contrast detection, despite consistent stimuli, frequently exhibits variability. This variability has been linked to prestimulus alpha neural oscillations in prior studies. Recently, there has been increased interest in exploring large-scale alpha traveling waves and their connection with visual processing. Yet, the role of these traveling waves in visual contrast detection remains unclarified. Through a combination of visual detection tasks, EEG data analysis, and 45°/-45° phase-shifted tACS, our study elucidates how prestimulus alpha traveling waves exert a potential causal influence on visual contrast detection.

Self-Supervised Joint Learning for pCLE Image Denoising.

Probe-based confocal laser endoscopy (pCLE) has emerged as a powerful tool for disease diagnosis, yet it faces challenges such as the formation of hexagonal patterns in images due to the inherent characteristics of fiber bundles. Recent advancements in deep learning offer promise in image denoising, but the acquisition of clean-noisy image pairs for training networks across all potential scenarios can be prohibitively costly. Few studies have explored training denoising networks on such pairs. Here, we propose an innovative self-supervised denoising method. Our approach integrates noise prediction networks, image quality assessment networks, and denoising networks in a collaborative, jointly trained manner. Compared to prior self-supervised denoising methods, our approach yields superior results on pCLE images and fluorescence microscopy images. In summary, our novel self-supervised denoising technique enhances image quality in pCLE diagnosis by leveraging the synergy of noise prediction, image quality assessment, and denoising networks, surpassing previous methods on both pCLE and fluorescence microscopy images.

OsAAP8 mutation leads to significant improvement in the nutritional quality and appearance of rice grains.

Members of the permease gene family are responsible for important biological functions in the growth and development of rice. Here, we show that OsAAP8 is a constitutive expression gene, and its translated protein is localized on the cell membrane. Mutation of the OsAAP8 can promote the expression of genes related to protein and amylopectin synthesis, and also promote the enlargement of protein bodies in its endosperm, leading to an increase in the protein, amylopectin, and total amino acid content of grains in OsAAP8 mutants. Seeds produced by the OsAAP8 mutant were larger, and the chalkiness traits of the OsAAP8 mutants were significantly reduced, thereby improving the nutritional quality and appearance of rice grains. The OsAAP8 protein is involved in the transport of various amino acids; OsAAP8 mutation significantly enhanced the root absorption of a range of amino acids and might affect the distribution of various amino acids. Therefore, OsAAP8 is an important quality trait gene with multiple biological functions, which provides important clues for the molecular design of breeding strategies for developing new high-quality varieties of rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01473-w.

Unveiling convergent and divergent intrinsic brain network alternations in depressed adolescents engaged in non-suicidal self-injurious behaviors with and without suicide attempts.

AIMS: Limited understanding exists regarding the neurobiological mechanisms underlying non-suicidal self-injury (NSSI) and suicide attempts (SA) in depressed adolescents. The maturation of brain network is crucial during adolescence, yet the abnormal alternations in depressed adolescents with NSSI or NSSI+SA remain poorly understood. METHODS: Resting-state functional magnetic resonance imaging data were collected from 114 depressed adolescents, classified into three groups: clinical control (non-self-harm), NSSI only, and NSSI+SA based on self-harm history. The alternations of resting-state functional connectivity (RSFC) were identified through support vector machine-based classification. RESULTS: Convergent alterations in NSSI and NSSI+SA predominantly centered on the inter-network RSFC between the Limbic network and the three core neurocognitive networks (SalVAttn, Control, and Default networks). Divergent alterations in the NSSI+SA group primarily focused on the Visual, Limbic, and Subcortical networks. Additionally, the severity of depressive symptoms only showed a significant correlation with altered RSFCs between Limbic and DorsAttn or Visual networks, strengthening the fact that increased depression severity alone does not fully explain observed FC alternations in the NSSI+SA group. CONCLUSION: Convergent alterations suggest a shared neurobiological mechanism along the self-destructiveness continuum. Divergent alterations may indicate biomarkers differentiating risk for SA, informing neurobiologically guided interventions.

Metagenomic Insights into Potential Impacts of Antibacterial Biosynthesis and Anthropogenic Activity on Nationwide Soil Resistome.

The presence of antibiotic resistance genes (ARGs) in soils has received extensive attention regarding its impacts on environmental, animal, and human systems under One Health. However, the health risks of soil ARGs and microbial determinants of soil resistomes remain poorly understood. Here, a nationwide metagenomic investigation of ARGs in cropland and forest soils in China was conducted. The findings indicated that the abundance and richness of high-risk (i.e., mobilizable, pathogen-carriable and clinically relevant) ARGs in cropland soils were 25.7 times and 8.4 times higher, respectively, compared to those identified in forest soils, suggesting the contribution of agricultural practices to the elevated risk level of soil resistomes. The biosynthetic potential of antibacterials best explained the total ARG abundance (Mantel's r = 0.52, p < 0.001) when compared with environmental variables and anthropogenic disturbance. Both microbial producers' self-resistance and antagonistic interactions contributed to the ARG abundance, of which self-resistance ARGs account for 14.1 %- 35.1 % in abundance. With the increased biosynthetic potential of antibacterials, the antagonistic interactions within the microbial community were greatly enhanced, leading to a significant increase in ARG abundance. Overall, these findings advance our understanding of the emergence and dissemination of soil ARGs and provide critical implications for the risk control of soil resistomes.

Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

Direct de/carboxylation of cannabidiolic acid (CBDA) and cannabidiol (CBD) from hemp plant material under supercritical CO2.

Many organic reactions rely on CO2 sources to generate important structural units and valuable chemicals. In this study, we compared the effects of cannabidiol (CBD) and cannabidiolic acid (CBDA) on the supercritical CO2 (scCO2)-induced de/carboxylation reaction. The results showed that CBD was directly carboxylated in the ortho-position to form CBDA with up to 62% conversion. Meanwhile, CBDA decarboxylation occurred on hemp plant material via varying composition. Mechanistic studies revealed that CBD carboxylation was influenced not only by the physical properties of scCO2, but also by the vegetable matrix.

MED1 IDR acetylation reorganizes the transcription preinitiation complex, rewires 3D chromatin interactions and reprograms gene expression.

With our current appreciation of the complexity of eukaryotic transcription, whose dysregulation drives diseases including cancer, it is becoming apparent that identification of key events coordinating multiple aspects of transcriptional regulation is of special importance. To elucidate how assembly of RNA polymerase II (Pol II) with Mediator complex preinitiation complexes (PICs) and formation of transcription-permissive 3D chromatin organization are coordinated, we studied MED1, a representative subunit of the Mediator complex that acts to establish functional preinitiation complexes (PICs) that forms biomolecular condensates through an intrinsically disordered region (IDR) to facilitate transcription, and is implicated in the function of estrogen receptor α (hereafter ER) in ER-positive breast cancer (ER+ BC) cells. We found that MED1 is acetylated at 6 lysines in its IDR and, further, that MCF7 ER+ BC cells in which endogenous MED1 is replaced by an ectopic 6KR (non-acetylatable) mutant (6KR cells) exhibit enhanced cell growth and elevated expression of MED1-dependent genes. These results indicate an enhanced function of 6KR MED1 that may be attributed to two mechanisms: (1) reorganized PIC assembly, as indicated by increased MED1 and Pol II, decreased MED17, and equivalent ERα occupancies on chromatin, particularly at active enhancers and promoters; (2) sub-TAD chromatin unfolding, as revealed by HiCAR (Hi-C on accessible regulatory DNA) analyses. Furthermore, in vitro assays demonstrate distinct physio-chemical properties of liquid-liquid phase separation (LLPS) for 6KR versus 6KQ MED1 IDRs, and for non-acetylated versus CBP-acetylated WT MED1 IDR fragments. Related, Pol II CTD heptads are sequestered in 6KR and control WT MED1 IDR condensates, but not 6KQ and CBP-acetylated WT MED1 IDR condensates. These findings, in conjunction with recent reports of PIC structures, indicate that MED1 coordinates reorganization of the PIC machinery and the rewiring of regional chromatin organization through acetylation of its IDR. This study leads to an understanding of how the transition in phase behavior of a transcription cofactor acts as a mechanistic hub integrating linear and spatial chromatin functions to support gene expression, and have potential therapeutic implications for diseases involving MED1/Mediator-mediated transcription control.