Unveiling the therapeutic potential of IHMT-337 in glioma treatment: targeting the EZH2-SLC12A5 axis.

Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood-brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.

Quantification of Hepatic Steatosis on Dual-Energy CT in Comparison With MRI mDIXON-Quant Sequence in Breast Cancer.

OBJECTIVE: The study aimed to evaluate the correlation and diagnostic value of liver fat quantification in unenhanced dual-energy CT (DECT) using quantitative magnetic resonance imaging (MRI) mDIXON-Quant sequence as reference standard in patients with breast cancer. METHODS: Patients with breast cancer were prospectively recruited between June 2018 and April 2020. Each patient underwent liver DECT and MRI mDIXON-Quant examination. The DECT-fat volume fraction (FVF) and liver-spleen attenuation differences were compared with the MRI-proton density fat fraction using scatterplots, Bland-Altman plots, and concordance correlation coefficient. Receiver operating characteristic curves were established to determine the diagnostic accuracy of hepatic steatosis by DECT. RESULTS: A total of 216 patients with breast cancer (mean age, 50.08 ± 9.33 years) were evaluated. The DECT-FVF correlated well with MRI-proton density fat fraction ( r2 = 0.902; P < 0.001), which was higher than the difference in liver-spleen attenuation ( r2 = 0.728; P < 0.001). Bland-Altman analysis revealed slight positive bias; the mean difference was 3.986. The DECT-FVF yielded an average concordance correlation coefficient of 0.677, which was higher than the difference of liver-spleen attenuation (-0.544). The DECT-FVF and the difference in liver-spleen attenuation both lead to mild overestimation of hepatic steatosis. The areas under the curve of DECT-FVF (0.956) were higher than the difference in liver-spleen attenuation (0.807) in identifying hepatic steatosis ( P < 0.001). CONCLUSIONS: Dual-energy CT-FVF may serve as a reliable screening and quantitative tool for hepatic steatosis in patients with breast cancer.

Extracellular volume fraction determined by equilibrium contrast-enhanced CT for the prediction of the pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

OBJECTIVES: To determine the extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC). METHODS: The ECV fraction before NCRT (ECVpre) and/or ECV after NCRT (ECVpost) of rectal tumors was assessed, and ECVΔ was calculated as ECVpost - ECVpre. The histopathologic tumor regression grading (TRG) was assessed. pCR (TRG 0 grade) was defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Demographic and clinicopathological characteristics and ECV fraction were compared between the pCR and non-pCR groups. A mixed model was constructed by logistic regression. The performance for predicting pCR was assessed with the area under the receiver-operator curve (AUC). The AUCs of the different methods were compared by the method proposed by DeLong et al. RESULTS: Seventy-five patients were included; 17 achieved pCR, and 58 achieved non-pCR. The ECVpost (17.05 ± 2.36% vs. 29.94 ± 1.20%; p < 0.001) and ECVΔ (- 17.01 ± 3.01% vs. 0.44 ± 1.45%; p < 0.001) values in the pCR group were significantly lower than those in the non-pCR group. The mixed model that combined ECVpost with ECVΔ achieved an AUC of 0.92 (95% confidence interval (CI) = 0.81-0.98), which was higher than that of ECVpost (AUC, 0.91 (95% CI = 0.80-0.97); p = 0.60) or ECVΔ (AUC, 0.90 (95% CI = 0.79-0.97); p = 0.61). CONCLUSIONS: ECVpost and ECVΔ determined by using equilibrium contrast-enhanced CT were useful in distinguishing between pCR and non-pCR patients with LARC who received NCRT. KEY POINTS: • ECVpost and ECVΔ (ECVpost - ECVpre) differed significantly between the non-pCR and pCR groups. • ECVpre cannot be used to predict the efficacy of neoadjuvant chemoradiotherapy. • ECVpost combined with ECVΔ had the best performance with an AUC of 0.92 for predicting pCR after NCRT in LARC.

Quantitative parameters derived from dual-energy computed tomography for the preoperative prediction of early recurrence in patients with esophageal squamous cell carcinoma.

OBJECTIVES: This study aimed to assess the efficacy of quantitative parameters derived from dual-energy computed tomography (DECT) for the preoperative prediction of early recurrence (ER) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: In total, 78 patients with ESCC who underwent radical esophagectomy and DECT from June 2019 to August 2020 were enrolled in this study. Normalized iodine concentration (NIC) and electron density (Rho) in tumors were measured using arterial and venous phase images, whereas unenhanced images were used to determine the effective atomic number (Zeff). Univariate and multivariate Cox proportional hazards models were used to identify independent risk predictors of ER. Receiver operating characteristic curve analysis was performed using the independent risk predictors. ER-free survival curves were constructed using the Kaplan-Meier method. RESULTS: NIC in the arterial phase (A-NIC; hazards ratio [HR], 3.91; 95% confidence interval [CI], 1.79-8.56; p = 0.001) and pathological grade (PG; HR, 2.69; 95% CI, 1.32-5.49; p = 0.007) were identified as significant risk predictors of ER. The area under the curve of A-NIC for predicting ER in patients with ESCC was not significantly higher than that of PG (0.72 vs. 0.66, p = 0.441). In a stratified survival analysis, patients with high A-NIC or poorly differentiated ESCC had a higher rate of ER than those with low A-NIC or highly/moderately differentiated ESCC. CONCLUSIONS: A-NIC derived from DECT can be used to noninvasively predict preoperative ER in patients with ESCC, with an efficacy comparable to that of pathological grade. CLINICAL RELEVANCE STATEMENT: Preoperative quantitative measurement of dual-energy CT parameters can predict the early recurrence of esophageal squamous cell carcinoma and serve as an independent prognostic factor to guide clinical designation of personalized treatment. KEY POINTS: • Normalized iodine concentration in the arterial phase and pathological grade were independent risk predictors of early recurrence in patients with esophageal squamous cell carcinoma. • Normalized iodine concentration in the arterial phase may be a noninvasive imaging marker for preoperatively predicting early recurrence in patients with esophageal squamous cell carcinoma. • The efficacy of normalized iodine concentration in the arterial phase derived from dual-energy computed tomography for predicting early recurrence is comparable to that of pathological grade.

Comparison of selected photon shield and organ-based tube current modulation for radiation dose reduction in head computed tomography: A phantom study.

OBJECTIVE: The aim of this study is to investigate the radiation dose and image quality of head CT using SPS and OBTCM techniques. METHODS: Three anthropomorphic head phantoms (1-yr-old, 5-yr-old, and adult) were used. Images were acquired using four modes (Default protocol, OBTCM, SPS, and SPS+OBTCM). Absorbed dose to the lens, anterior brain (brain_A), and posterior brain (brain_P) was measured and compared. Image noise and CNR were assessed in the selected regions of interest (ROIs). RESULTS: Compared with that in the Default protocol, the absorbed dose to the lens reduced by up to 28.33%,71.38%, and 71.12% in OBTCM, SPS, and SPS+OBTCM, respectively. The noise level in OBTCM slightly (≤1.45HU) increased than that in Default protocol, and the SPS or SPS+OBTCM mode resulted in a quantitatively small increase (≤2.58HU) in three phantoms. There was no significant difference in CNR of different phantoms under varies scanning modes (p > 0.05). CONCLUSIONS: During head CT examinations, the SPS mode can reduce the radiation dose while maintaining image quality. SPS+OBTCM couldn't further effectively reduce the absorbed dose to the lens for 1-yr and 5-yr-old phantoms. Thus, SPS mode in pediatric and SPS+OBTCM mode in adult are better than other modes, and should be used in clinical practice.

Characteristics of in-hospital mortality of congenital heart disease (CHD) after surgical treatment in children from 2005 to 2017: a single-center experience.

BACKGROUND: To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children's CHD after thoracotomy. METHODS: This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. RESULTS: A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05). CONCLUSIONS: The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.

Resonance with subthreshold oscillatory drive organizes activity and optimizes learning in neural networks.

Network oscillations across and within brain areas are critical for learning and performance of memory tasks. While a large amount of work has focused on the generation of neural oscillations, their effect on neuronal populations' spiking activity and information encoding is less known. Here, we use computational modeling to demonstrate that a shift in resonance responses can interact with oscillating input to ensure that networks of neurons properly encode new information represented in external inputs to the weights of recurrent synaptic connections. Using a neuronal network model, we find that due to an input current-dependent shift in their resonance response, individual neurons in a network will arrange their phases of firing to represent varying strengths of their respective inputs. As networks encode information, neurons fire more synchronously, and this effect limits the extent to which further "learning" (in the form of changes in synaptic strength) can occur. We also demonstrate that sequential patterns of neuronal firing can be accurately stored in the network; these sequences are later reproduced without external input (in the context of subthreshold oscillations) in both the forward and reverse directions (as has been observed following learning in vivo). To test whether a similar mechanism could act in vivo, we show that periodic stimulation of hippocampal neurons coordinates network activity and functional connectivity in a frequency-dependent manner. We conclude that resonance with subthreshold oscillations provides a plausible network-level mechanism to accurately encode and retrieve information without overstrengthening connections between neurons.

Network and cellular mechanisms underlying heterogeneous excitatory/inhibitory balanced states.

Recent work has explored spatiotemporal relationships between excitatory (E) and inhibitory (I) signaling within neural networks, and the effect of these relationships on network activity patterns. Data from these studies have indicated that excitation and inhibition are maintained at a similar level across long time periods and that excitatory and inhibitory currents may be tightly synchronized. Disruption of this balance-leading to an aberrant E/I ratio-is implicated in various brain pathologies. However, a thorough characterization of the relationship between E and I currents in experimental settings is largely impossible, due to their tight regulation at multiple cellular and network levels. Here, we use biophysical neural network models to investigate the emergence and properties of balanced states by heterogeneous mechanisms. Our results show that a network can homeostatically regulate the E/I ratio through interactions among multiple cellular and network factors, including average firing rates, synaptic weights and average neural depolarization levels in excitatory/inhibitory populations. Complex and competing interactions between firing rates and depolarization levels allow these factors to alternately dominate network dynamics in different synaptic weight regimes. This leads to the emergence of distinct mechanisms responsible for determining a balanced state and its dynamical correlate. Our analysis provides a comprehensive picture of how E/I ratio changes when manipulating specific network properties, and identifies the mechanisms regulating E/I balance. These results provide a framework to explain the diverse, and in some cases, contradictory experimental observations on the E/I state in different brain states and conditions.

Complete nucleotide sequence of loquat virus A, a member of the family Betaflexiviridae with a novel genome organization.

Analysis of a loquat tree with leaf curl symptoms by deep sequencing revealed a novel virus with a single-stranded RNA genome, for which the name "loquat virus A" (LoVA) was proposed. The complete genome sequence comprised 7553 nucleotides (nt) and an additional poly(A) tail at the 3' terminus. Sequence comparisons of LoVA showed moderate similarity to cherry virus A (CVA), currant virus A (CuVA), and mume virus A (MuVA), which are members of the genus Capillovirus in the family Betaflexiviridae. Phylogenetic analysis of the full-genome nt sequence and replicase-like protein supported the placement of LoVA within the genus Capillovirus. However, it has a distinct genome organization, differing from recognized capilloviruses, as it contains three open reading frames (ORFs), with the coat protein (CP) expressed separately from the replication-associated protein (RP) rather than being encoded in the same ORF. This indicates that LoVA is a novel member of the genus Capillovirus in the family Betaflexiviridae with a distinct genomic organization.

Cortically coordinated NREM thalamocortical oscillations play an essential, instructive role in visual system plasticity.

Two long-standing questions in neuroscience are how sleep promotes brain plasticity and why some forms of plasticity occur preferentially during sleep vs. wake. Establishing causal relationships between specific features of sleep (e.g., network oscillations) and sleep-dependent plasticity has been difficult. Here we demonstrate that presentation of a novel visual stimulus (a single oriented grating) causes immediate, instructive changes in the firing of mouse lateral geniculate nucleus (LGN) neurons, leading to increased firing-rate responses to the presented stimulus orientation (relative to other orientations). However, stimulus presentation alone does not affect primary visual cortex (V1) neurons, which show response changes only after a period of subsequent sleep. During poststimulus nonrapid eye movement (NREM) sleep, LGN neuron overall spike-field coherence (SFC) with V1 delta (0.5-4 Hz) and spindle (7-15 Hz) oscillations increased, with neurons most responsive to the presented stimulus showing greater SFC. To test whether coherent communication between LGN and V1 was essential for cortical plasticity, we first tested the role of layer 6 corticothalamic (CT) V1 neurons in coherent firing within the LGN-V1 network. We found that rhythmic optogenetic activation of CT V1 neurons dramatically induced coherent firing in LGN neurons and, to a lesser extent, in V1 neurons in the other cortical layers. Optogenetic interference with CT feedback to LGN during poststimulus NREM sleep (but not REM or wake) disrupts coherence between LGN and V1 and also blocks sleep-dependent response changes in V1. We conclude that NREM oscillations relay information regarding prior sensory experience between the thalamus and cortex to promote cortical plasticity.

Discovery and Survey of a New Mandarivirus Associated with Leaf Yellow Mottle Disease of Citrus in Pakistan.

During biological indexing for viruses in citrus trees, in a collection of Symons sweet orange (SSO) (Citrus sinensis L. Osbeck) graft inoculated with bark tissues of citrus trees from the Punjab Province in Pakistan, several SSO trees exhibited leaf symptoms of vein yellowing and mottle. High-throughput sequencing by Illumina of RNA preparation depleted of ribosomal RNAs from one symptomatic tree, followed by BLAST analyses, allowed identification of a novel virus, tentatively named citrus yellow mottle-associated virus (CiYMaV). Genome features of CiYMaV are typical of members of the genus Mandarivirus (family Alphaflexiviridae). Virus particles with elongated flexuous shape and size resembling those of mandariviruses were observed by transmission electron microscopy. The proteins encoded by CiYMaV share high sequence identity, conserved motifs, and phylogenetic relationships with the corresponding proteins encoded by Indian citrus ringspot virus (ICRSV) and citrus yellow vein clearing virus (CYVCV), the two current members of the genus Mandarivirus. Although CYVCV is the virus most closely related to CiYMaV, the two viruses can be serologically and biologically discriminated from each other. A reverse-transcription PCR method designed to specifically detect CiYMaV revealed high prevalence (62%) of this virus in 120 citrus trees from the Punjab Province, Pakistan, where the novel virus was found mainly in mixed infection with CYVCV and citrus tristeza virus. However, a preliminary survey on samples from 200 citrus trees from the Yunnan Province, China failed to detect CiYMaV in this region, suggesting that the molecular, serological, and biological data provided here are timely and can help to prevent the spread of this virus in citrus-producing countries.

Molecular characterization of a new badnavirus infecting green Sichuan pepper (Zanthoxylum schinifolium).

A new virus with a circular double-stranded DNA genome was discovered in green Sichuan pepper with vein clearing symptoms. Its complete genome of 8,014 bp contains three open reading frames (ORF) on the plus strand, which is typical of members of the genus Badnavirus in the family Caulimoviridae. Sequence comparisons revealed that the new virus has the highest nucleotide sequence identity with grapevine vein-clearing virus (GVCV). In particular, the identity of the two viruses in the ORF3 RT-RNase H region is 71.9%, which is below the species demarcation cutoff of 80% for badnaviruses. Phylogenetic analysis also placed the new virus with GVCV in a cluster. The virus was tentatively named "green Sichuan pepper vein clearing-associated virus" (GSPVCaV). The geographical distribution and genetic diversity of GSPVCaV were studied. Another isolate was found to be highly divergent.

Improved charge separation of NiS nanoparticles modified defect-engineered black TiO2 hollow nanotubes for boosting solar-driven photocatalytic H2 evolution.

NiS nanoparticles modified black TiO2 hollow nanotubes (NBTNs) are successfully synthesized via surface hydrogenation and the facile solvothermal method. The unique structure with intensified surface and interface characteristics endow NBTNs with more catalytic sites, and increase charge carrier separation efficiency with an extended charge lifetime, overwhelmingly promoting its photocatalytic performance. The resultant NBTNs possess a relatively high surface area and pore size of ∼89 m2 g-1 and ∼9.8 nm, respectively. The resultant NBTNs exhibit an excellent solar-driven photocatalytic hydrogen rate (3.17 mmol h-1 g-1), which is almost as high as that of Pt as cocatalyst, in which the apparent quantum yield of 5.4% (420 nm) is recorded for the NBTNs sample. Moreover, the turnover number can be up to 116 000 within 48 h and the turnover frequency is 2400 for NiS. This novel strategy could provide a better understanding of cocatalyst photocatalytic mechanisms, and a scheme simultaneously regulating the morphology and structure of photocatalysts for promoting H2 generation.

The role of an Sb-oxidizing bacterium in modulating antimony speciation and iron plaque formation to reduce the accumulation and toxicity of Sb in rice (Oryza sativa L.).

Microbial antimony (Sb) oxidation in the root rhizosphere and the formation of iron plaque (IP) on the root surface are considered as two separate strategies to mitigate Sb(III) phytotoxicity. Here, the effect of an Sb-oxidizing bacterium Bacillus sp. S3 on IP characteristics of rice exposed to Sb(III) and its alleviating effects on plant growth were investigated. The results revealed that Fe(II) supply promoted IP formation under Sb(III) stress. However, the formed IP facilitated rather than hindered the uptake of Sb by rice roots. In contrast, the combined application of Fe(II) and Bacillus sp. S3 effectively alleviated Sb(III) toxicity in rice, resulting in improved rice growth and photosynthesis, reduced oxidative stress levels, enhanced antioxidant systems, and restricted Sb uptake and translocation. Despite the ability of Bacillus sp. S3 to oxidize Fe(II), bacterial inoculation inhibited the formation of IP, resulting in a reduction in Sb absorption on IP and uptake into the roots. Additionally, the bacterial inoculum enhanced the transformation of Sb(III) to less toxic Sb(V) in the culture solution, further influencing the adsorption of Sb onto IP. These findings highlight the potential of combining microbial Sb oxidation and IP as an effective strategy for minimizing Sb toxicity in sustainable rice production systems.

Efficient removal of Sb(III) from wastewater using selenium nanoparticles synthesized by Psidium guajava plant extract.

Antimony (Sb) pollution in aquatic ecosystems has emerged as a critical environmental issue on a global scale, emphasizing the urgent need for cost-effective and user-friendly technologies to remove Sb compounds from water sources. In this study, a novel adsorbent, selenium nanoparticles (SeNPs), was synthesized using the aqueous extract of Psidium guajava L. leaves (AEP) for the purpose of eliminating Sb(III) from aqueous solutions. The biosynthesized SeNPs was characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray fluorescence spectrometer (XRF), Fourier Transform-Infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) analysis techniques. Additionally, the removal efficiency of the SeNPs for Sb(III) was systematic investigated under the effects of SeNPs dose, temperature, pH and re-usability. The results of this study showed that the adsorption data fitted well into pseudo-second order model, while the Sips modeling demonstrated a high adsorption capacity (62.7 mg/g) of SeNPs for Sb(III) ions at 303.15 K from aqueous solution. The exothermic enthalpy change of - 22.59 kJ/mol and negative Gibbs free energy change assured the viability of the adsorption process under the considered temperature conditions. Surface functional groups on SeNPs like carboxyl, amide, hydroxyl, carbonyl, and methylene significantly facilitate the adsorption processes. Furthermore, the removal efficiencies of Sb in the two actual Sb mine wastewater samples were remarkably high, achieving nearly to 100% with 1.5 g/L SeNPs within 48 h. This outcome underscores the potential of SeNPs as a highly promising solution for efficiently remediating Sb from aquatic environments, owing to their cost-effectiveness, ease of regeneration, and rapid uptake capabilities.

Biosynthetic selenium nanoparticles (Bio-SeNPs) mitigate the toxicity of antimony (Sb) in rice (Oryza sativa L.) by limiting Sb uptake, improving antioxidant defense system and regulating stress-related gene expression.

Nanotechnology offers a promising and innovative approach to mitigate biotic and abiotic stress in crop production. In this study, the beneficial role and potential detoxification mechanism of biogenic selenium nanoparticles (Bio-SeNPs) prepared from Psidium guajava extracts in alleviating antimony (Sb) toxicity in rice seedlings (Oryza sativa L.) were investigated. The results revealed that exogenous addition of Bio-SeNPs (0.05 g/L) into the hydroponic-cultured system led to a substantial enhancement in rice shoot height (73.3%), shoot fresh weight (38.7%) and dry weight (28.8%) under 50 µM Sb(III) stress conditions. Compared to Sb exposure alone, hydroponic application of Bio-SeNPs also greatly promoted rice photosynthesis, improved cell viability and membrane integrity, reduced reactive oxygen species (ROS) levels, and increased antioxidant activities. Meanwhile, exogenous Bio-SeNPs application significantly lowered the Sb accumulation in rice roots (77.1%) and shoots (35.1%), and reduced its root to shoot translocation (55.3%). Additionally, Bio-SeNPs addition were found to modulate the subcellular distribution of Sb and the expression of genes associated with Sb detoxification in rice, such as OsCuZnSOD2, OsCATA, OsGSH1, OsABCC1, and OsWAK11. Overall, our findings highlight the great potential of Bio-SeNPs as a promising alternative for reducing Sb accumulation in crop plants and boosting crop production under Sb stress conditions.

Selenium bio-nanocomposite based on extracellular polymeric substances (EPS): Synthesis, characterization and application in alleviating cadmium toxicity in rice (Oryza sativa L.).

Selenium nanoparticles (SeNPs) have gained significant attention owing to their favorable bioavailability and low toxicity, making them widely applications in the fields of medicine, food and agriculture. In this study, bacterial extracellular polymeric substances (EPS) were used as a novel stabilizer and capping agent to prepare dispersed SeNPs. Results show that EPS-SeNPs presented negative potential (-38 mV), spherical morphologies with average particle size about 100-200 nm and kept stable at room temperature for a long time. X-ray diffraction (XRD) analysis demonstrated that the synthesized nanoparticles were pure amorphous nanoparticles, and X-ray photoelectron spectroscopy (XPS) spectrum showed a spike at 55.6 eV, indicating the presence of zero-valent nano­selenium. Fourier-transform infrared spectroscopy (FTIR) and three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy analysis confirmed proteins and polysaccharides in EPS played a crucial role in the synthesis of EPS-SeNPs. Compared to EPS or sodium selenite (Na2SeO3), EPS-SeNPs showed a relatively moderate result in terms of scavenging free radicals in vitro. In contrast, EPS-SeNPs demonstrated lower toxicity to rice seeds than Na2SeO3. Notably, the exogenous application of EPS-SeNPs effectively alleviated the growth inhibition and oxidative damaged caused by cadmium (Cd), and significantly reduced Cd accumulation in rice plants.

The Role of CCTA-derived Cardiac Structure and Function Analysis in the Prediction of Readmission in Nonischemic Heart Failure.

Cardiac function and structure significantly impact nonischemic heart failure (HF) patient outcomes. This study investigated 236 patients (107 nonischemic heart failure, 129 healthy) to assess the relationship between coronary computed tomography angiography (CCTA)-derived parameters and clinical outcomes. Among the nonischemic heart failure patients, 37.3% experienced readmissions. In this group, specific CCTA measurements were identified as significant predictors of readmission: epicardial adipose tissue (CTEAT) at 54.49 cm3 (HR: 1.05; 95% CI: 1.03-1.07; P < 0.001), cardiac muscle mass to lumen volume (CTV/M) at 20% (HR: 0.59; 95% CI: 0.48-0.72; P < 0.001), peri-coronary adipose (CTPCAT) at -64.68 HU (HR: 1.1; 95% CI: 1.03-1.16; P = 0.002) for the right coronary artery, -81.07 HU (HR: 1.3; 95% CI: 1.1-1.53; P = 0.002) for the left anterior descending artery, and -73.42 HU (HR: 1.33; 95% CI: 1.18-1.51; P < 0.001) for the circumflex branch of the left coronary artery. In patients with nonischemic heart failure, increased CTEAT, CTPCAT, and CTV/M independently predicted rehospitalization.

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.