Passion fruit HD-ZIP genes: Characterization, expression variance, and overexpression PeHB31 enhanced drought tolerance via lignin pathway.

The HD-ZIP (homeodomain-leucine zipper) genes hold significant importance in transcriptional regulation, especially in plant development and responses to abiotic stresses. However, a comprehensive study targeting HD-ZIP family members in passion fruit has been absent. In our current research, 34 HD-ZIP family members (PeHBs) were identified by bioinformatics analysis. Transcriptome analysis revealed that PeHBs exhibited distinct expression patterns when subjected to the four different abiotic stresses, and significant differential expression of PeHBs was also found among the three developmental stages of the fruit and between the purple and yellow genotype passion fruit leaves. An integrated metabolome and transcriptome analysis further revealed that the HD-ZIP III class gene PeHB31 (homologous to ATHB8), was co-upexpressed with lignans in yellow fruit P. edulis (commonly used as a resistance rootstock) when compared to purple fruit P. edulis. The transformation of Arabidopsis and yeast with the PeHB31 gene showed an enhancement in their capacity to withstand drought conditions. Notably, the transgenic Arabidopsis plants exhibited an increase in lignin content within the vascular tissues of their stems. This research lays the groundwork for future studies on the control mechanisms of lignin biosynthesis by HD-ZIP genes (especially HD-ZIP classes III and I) involved in drought tolerance.

A pharmacovigilance study of chronic kidney disease in diabetes mellitus patients with statin treatment by using the US Food and Drug Administration adverse event reporting system.

Background: Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients. Aim: To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients. Methods: This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases. Results: We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00-3.22; IC: 1.18, 95% CI: 1.07-1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10-21.13; IC: 3.70, 95% CI:3.44-3.93) compared with cases with one statin treatment history. Conclusion: The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.

A DNA double-strand break (DSB) jeopardizes genome integrity and endangers cell viability. Actively transcribed genes are particularly detrimental if broken and need to be repressed. However, it remains elusive how fast the repression is initiated and how far it influences the neighboring genes on the chromosome. We adopt a recently developed, very fast CRISPR to generate a DSB at a specific genomic locus with precise timing, visualize transcription in live cells, and measure the RNA polymerase II (RNAPII) occupancy near the broken site. We observe that a single DSB represses the transcription of the damaged gene in minutes, which coincides with the recruitment of a damage repair protein. Transcription repression propagates bi-directionally along the chromosome from the DSB for hundreds of kilobases, and proteasome is evoked to remove RNAPII in this process. Our method builds a foundation to measure the rapid kinetic events around a single DSB and elucidate the molecular mechanism.

Oligomerization-mediated autoinhibition and cofactor binding of a plant NLR.

Nucleotide-binding leucine-rich repeat (NLR) proteins have a pivotal role in plant immunity by recognizing pathogen effectors1,2. Maintaining a balanced immune response is crucial, as excessive NLR expression can lead to unintended autoimmunity3,4. Unlike most NLRs, plant NLR required for cell death 2 (NRC2) belongs to a small NLR group characterized by constitutively high expression without self-activation5. The mechanisms underlying NRC2 autoinhibition and activation are not yet understood. Here we show that Solanum lycopersicum (tomato) NRC2 (SlNRC2) forms dimers and tetramers, and higher-order oligomers at elevated concentrations. Cryo-electron microscopy (cryo-EM) reveals an inactive conformation of SlNRC2 within these oligomers. Dimerization and oligomerization not only stabilize the inactive state but also sequester SlNRC2 from assembling into an active form. Mutations at the dimeric or inter-dimeric interfaces enhance pathogen-induced cell death and immunity in Nicotiana (N.) benthamiana. The cryo-EM structures unexpectedly reveal inositol hexakisphosphate (IP6) or pentakisphosphate (IP5) bound to the inner surface of SlNRC2's C-terminal LRR domain as confirmed by mass spectrometry. Mutations at the IP-binding site impair inositol phosphate binding of SlNRC2 and pathogen-induced SlNRC2-mediated cell death in N. benthamiana. Together, our study unveils a novel negative regulatory mechanism of NLR activation and suggests inositol phosphates as cofactors of NRCs.

Effect of mineralized dentin matrix on the prognosis of bone defect and retained root after coronectomy.

OBJECTIVE: To investigate the impact of mineralized dentin matrix (MDM) on the prognosis on bone regeneration and migration of retained roots after coronectomy. MATERIALS AND METHODS: Patients were divided into three groups based on the type of bone graft after coronectomy: Group C (n = 20, collagen), Group T (n = 20, tricalcium phosphate (TCP) + collagen), and Group D (n = 20, MDM + collagen). CBCT scans, conducted immediately and 6 months after surgery, were analyzed using digital software. Primary outcomes, including changes in bone defect depth and retained root migration distance, were evaluated 6 months after surgery. RESULTS: After 6 months, both Groups D and T exhibited greater reduction of the bone defect and lesser retained root migration than Group C (p < 0.001). Group D had greater regenerated bone volume in the distal 2 mm (73 mm3 vs. 57 mm3, p = 0.011) and lesser root migration (2.18 mm vs. 2.96 mm, p < 0.001) than Group T. The proportion of completely bone embedded retained roots was also greater in Group D than in Group C (70.0% vs. 42.1%, p = 0.003). CONCLUSIONS: MDM is an appropriate graft material for improving bone defect healing and reducing retained root migration after coronectomy. CLINICAL RELEVANCE: MDM is an autogenous material prepared chairside, which can significantly improve bone healing and reduce the risk of retained root re-eruption. MDM holds promise as a routine bone substitute material after M3M coronectomy.

Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

Scavenging and release of REE and HFSE by Na-metasomatism in magmatic-hydrothermal systems.

Exploitable or potentially exploitable deposits of critical metals, such as rare-earth (REE) and high-field-strength elements (HFSE), are commonly associated with alkaline or peralkaline igneous rocks. However, the origin, transport and concentration of these metals in peralkaline systems remains poorly understood. This study presents the results of a mineralogical and geochemical investigation of the Na-metasomatism of alkali amphiboles and clinopyroxenes from a barren peralkaline granite pluton in NE China, to assess the remobilization and redistribution of REE and HFSE during magmatic-hydrothermal evolution. Alkali amphiboles and aegirine-augites from the peralkaline granites show evolutionary trends from sodic-calcic to sodic compositions, with increasing REE and HFSE concentrations as a function of increasing Na-index [Na#, defined as molar Na/(Na+Ca) ratios]. The Na-amphiboles (i.e., arfvedsonite) and aegirine-augites can be subsequently altered, or breakdown, to form hydrothermal aegirine during late- or post-magmatic alteration. Representative compositions analyzed by in-situ LA-ICPMS show that the primary aegirine-augites have high and variable REE (2194-3627 ppm) and HFSE (4194-16,862 ppm) contents, suggesting that these critical metals can be scavenged by alkali amphiboles and aegirine-augites. Compared to the primary aegirine-augites, the presentative early replacement aegirine (Aeg-I, Na# = 0.91-0.94) has notably lower REE (1484-1972) and HFSE (4351-5621) contents. In contrast, the late hydrothermal aegirine (Aeg-II, Na# = 0.92-0.96) has significantly lower REE (317-456 ppm) and HFSE (6.44-72.2 ppm) contents. Given that the increasing Na# from aegirine-augites to hydrothermal aegirines likely resulted from Na-metasomatism, a scavenging-release model can explain the remobilization of REE and HFSE in peralkaline granitic systems. The scavenging and release of REE and HFSE by Na-metasomatism provides key insights into the genesis of globally significant REE and HFSE deposits. The high Na-index of the hydrothermal aegirine might be useful as a geochemical indicator in the exploration for these critical-metals.

Mercapto-functionalized palygorskite modified the growth of Ligusticum Chuanxiong and restrained the Cd migration in the soil-plant system.

Ligusticum Chuanxiong is an essential medicinal and edible plant, but it is highly susceptible to the enrichment of soil Cadmium (Cd), which seriously affects its medical safety. However, the control of Cd uptake by Ligusticum Chuanxiong is little reported. In this study, we reported that a green Mercapto-functionalized palygorskite (MPAL) effectively promoted Ligusticum Chuanxiong growth, and restrained the Cd uptake by Ligusticum Chuanxiong both in the mildly contaminated soil (M-Soil) and severely contaminated soil (S-Soil). The experimental results demonstrated that the application of MPAL significantly increased the biomass and antioxidant enzyme activity of Ligusticum Chuanxiong. In the M-Soil, the Cd content in the roots, stems, and leaves of Ligusticum Chuanxiong decreased markedly by 82.46-86.66%, 64.17-71.73%, and 64.94-76.66%, respectively, after the MPAL treatment. In the S-Soil, MPAL application decreased the Cd content in roots, stems, and leaves by 89.43-98.92%, 24.19-86.22%, and 67.14-77.90%, respectively. Based on Diethylenetriamine Pentaacetic Acid (DTPA) extraction, the immobilization efficiency of MPAL for Cd in soils ranged from 22.01% to 77.04%. Additionally, the HOAc extractable Cd was transformed into reducible and oxidizable fractions. Furthermore, MPAL enhanced the activities of soil alkaline phosphatase, and urease, but decreased sucrase activity. Environmental toxicological analysis indicated that MPAL reduced the potential ecological risk of Cd in the soil. These findings revealed that MPAL can effectively reduce Cd accumulation in Ligusticum Chuanxiong and promote plant growth, suggesting its potential as a viable amendment for remediating Cd-contaminated soils.

Research on an SICM Scanning Image Resolution Enhancement Algorithm.

Scanning ion conductance microscopy (SICM) enables the non-invasive three-dimensional imaging of live cells and other structures in physiological environments. However, when imaging complex samples, SICM faces challenges such as having a low temporal resolution during slow scanning and a reduced signal-to-noise ratio during fast scanning, making it difficult to simultaneously improve both temporal and spatial resolution. To address these issues, this paper proposes an algorithm for enhancing image resolution under high-speed scanning. Firstly, scanning images are preprocessed using a median filtering algorithm to remove the salt-and-pepper noise generated during high-speed scanning. Next, the Canny edge detection algorithm is employed to extract the edges of the image targets. To avoid blurring the edges, the new edge-directed interpolation (NEDI) algorithm is then used to fill the edges, while non-edge areas are filled using bilinear interpolation, thereby enhancing the image resolution. Finally, the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) are used to analyze the imaging of articular chondrocytes. The results show that under a scanning speed of 480 nm/ms, the proposed algorithm improves the temporal resolution of imaging by 60% compared to traditional 2× resolution imaging, increases the peak signal-to-noise ratio of the scanning images by 7 dB, and achieves a structural similarity of 0.97. Therefore, the proposed algorithm effectively removes noise during high-speed scanning and improves the SICM scanning imaging resolution, thereby avoiding the reduction in temporal resolution when scanning larger resolution samples and effectively enhancing the performance of SICM scanning imaging.

Enhancing surgical decision-making in NEC with ResNet18: a deep learning approach to predict the need for surgery through x-ray image analysis.

Background: Necrotizing enterocolitis (NEC) is a severe neonatal intestinal disease, often occurring in preterm infants following the administration of hyperosmolar formula. It is one of the leading causes of neonatal mortality in the NICU, and currently, there are no clear standards for surgical intervention, which typically depends on the joint discretion of surgeons and neonatologists. In recent years, deep learning has been extensively applied in areas such as image segmentation, fracture and pneumonia classification, drug development, and pathological diagnosis. Objective: Investigating deep learning applications using bedside x-rays to help optimizing surgical decision-making in neonatal NEC. Methods: Through a retrospective analysis of anteroposterior bedside chest and abdominal x-rays from 263 infants diagnosed with NEC between January 2015 and April 2023, including a surgery group (94 cases) and a non-surgery group (169 cases), the infants were divided into a training set and a validation set in a 7:3 ratio. Models were built based on Resnet18, Densenet121, and SimpleViT to predict whether NEC patients required surgical intervention. Finally, the model's performance was tested using an additional 40 cases, including both surgical and non-surgical NEC cases, as a test group. To enhance the interpretability of the models, the study employed 2D-Grad-CAM technology to describe the models' focus on significant areas within the x-ray images. Results: Resnet18 demonstrated outstanding performance in binary diagnostic capability, achieving an accuracy of 0.919 with its precise lesion imaging and interpretability particularly highlighted. Its precision, specificity, sensitivity, and F1 score were significantly high, proving its advantages in optimizing surgical decision-making for neonatal NEC. Conclusion: The Resnet18 deep learning model, constructed using bedside chest and abdominal imaging, effectively assists clinical physicians in determining whether infants with NEC require surgical intervention.

A Systematic Review of Quality of Life in Patients with Short Bowel Syndrome and Their Caregivers.

Purpose: Understanding the quality of life and the factors that influence it for patients with short bowel syndrome (SBS) and their caregivers is of utmost importance in order to enhance their well-being. Therefore, This study aimed to provide a comprehensive understanding of the impact of SBS on patients and their caregivers, as well as its associated factors, by synthesizing the available evidence. Methods: A systematic review of the literature was done using PubMed, Embase databases, CNKI, and ISPOR conference papers. Included articles were manually searched to identify any other relevant studies. Quality was assessed using appropriate Joanna Briggs Institute critical appraisal tools. Results: This review included 16 studies, comprising 15 observational studies and 1 randomized controlled trial. The findings revealed that the QoL of patients with SBS was lower than that of the general population regarding physical functioning and psychological domain. Meanwhile, caregivers experienced challenges in maintaining their QoL. The QoL of SBS patients was found to be influenced by various factors such as treatment, age, sex, stoma, and small intestine length. Among them, the treatment is the most noteworthy factor that can be effectively improved through external interventions. Conclusion: While numerous studies have provided insights into the compromised QoL experienced by individuals with SBS and their caregivers, there remains a scarcity of large-sample quantitative investigations examining the determinants of QoL. The existing body of literature on caregivers is also notably deficient.

Several Feature Extraction Methods Combined with Near-Infrared Spectroscopy for Identifying the Geographical Origins of Milk.

Milk is a kind of dairy product with high nutritive value. Tracing the origin of milk can uphold the interests of consumers as well as the stability of the dairy market. In this study, a fuzzy direct linear discriminant analysis (FDLDA) is proposed to extract the near-infrared spectral information of milk by combining fuzzy set theory with direct linear discriminant analysis (DLDA). First, spectral data of the milk samples were collected by a portable NIR spectrometer. Then, the data were preprocessed by Savitzky-Golay (SG) and standard normal variables (SNV) to reduce noise, and the dimensionality of the spectral data was decreased by principal component analysis (PCA). Furthermore, linear discriminant analysis (LDA), DLDA, and FDLDA were employed to transform the spectral data into feature space. Finally, the k-nearest neighbor (KNN) classifier, extreme learning machine (ELM) and naïve Bayes classifier were used for classification. The results of the study showed that the classification accuracy of FDLDA was higher than DLDA when the KNN classifier was used. The highest recognition accuracy of FDLDA, DLDA, and LDA could reach 97.33%, 94.67%, and 94.67%. The classification accuracy of FDLDA was also higher than DLDA when using ELM and naïve Bayes classifiers, but the highest recognition accuracy was 88.24% and 92.00%, respectively. Therefore, the KNN classifier outperformed the ELM and naïve Bayes classifiers. This study demonstrated that combining FDLDA, DLDA, and LDA with NIR spectroscopy as an effective method for determining the origin of milk.

The speed of neutral evolution on graphs.

The speed of evolution on structured populations is crucial for biological and social systems. The likelihood of invasion is key for evolutionary stability. But it makes little sense if it takes long. It is far from known what population structure slows down evolution. We investigate the absorption time of a single neutral mutant for all the 112 non-isomorphic undirected graphs of size 6. We find that about three-quarters of the graphs have an absorption time close to that of the complete graph, less than one-third are accelerators, and more than two-thirds are decelerators. Surprisingly, determining whether a graph has a long absorption time is too complicated to be captured by the joint degree distribution. Via the largest sojourn time, we find that echo-chamber-like graphs, which consist of two homogeneous graphs connected by few sparse links, are likely to slow down absorption. These results are robust for large graphs, mutation patterns as well as evolutionary processes. This work serves as a benchmark for timing evolution with complex interactions, and fosters the understanding of polarization in opinion formation.

Desalination Performance of MoS2 Membranes with Different Single-Pore Sizes: A Molecular Dynamics Simulation Study.

Utilizing molecular dynamics simulations, we examined how varying pore sizes affect the desalination capabilities of MoS2 membranes while keeping the total pore area constant. The total pore area within a MoS2 nanosheet was maintained at 200 Å2, and the single-pore areas were varied, approximately 20, 30, 40, 50, and 60 Å2. By comparing the water flux and ion rejection rates, we identified the optimal single-pore area for MoS2 membrane desalination. Our simulation results revealed that as the single-pore area expanded, the water flux increased, the velocity of water molecules passing the pores accelerated, the energy barrier decreased, and the number of water molecules within the pores rose, particularly between 30 and 40 Å2. Balancing water flux and rejection rates, we found that a MoS2 membrane with a single-pore area of 40 Å2 offered the most effective water treatment performance. Furthermore, the ion rejection rate of MoS2 membranes was lower for ions with lower valences. This was attributed to the fact that higher-valence ions possess greater masses and radii, leading to slower transmembrane rates and higher transmembrane energy barriers. These insights may serve as theoretical guidance for future applications of MoS2 membranes in water treatment.

Liver injury associated with endothelin receptor antagonists: a pharmacovigilance study based on FDA adverse event reporting system data.

BACKGROUND: Endothelin receptor antagonists are commonly used in clinical practice, with concerns about their hepatotoxicity. AIM: This study aimed to conduct a comprehensive pharmacovigilance study based on FDA adverse event reporting system data to evaluate the possible association between endothelin receptor antagonists and drug-induced liver injury. METHOD: Adverse event reports from FDA adverse event reporting system between January 2004 and December 2022 were analyzed. Disproportionality algorithms, including reporting odds ratio and information component, were used to evaluate the association between endothelin receptor antagonists and liver injury. Sex- and age-stratified analyses of drug-induced liver injury events were also conducted in relation to endothelin receptor antagonists. RESULTS: Significant associations between bosentan, macitentan, and liver injury were identified. Bosentan showed a strong link with liver injury, with reporting odds ratios for cholestatic injury at 7.59 (95% confidence interval: 6.90-8.35), hepatocellular injury at 5.63 (5.29-6.00), and serious drug-related hepatic disorders events at 1.33 (1.24-1.43). Drug-induced liver injury signals associated with bosentan were detected in all age groups. Macitentan was associated with liver injury, with reporting odds ratios for hepatic failure at 1.64 (1.39-1.94), cholestatic injury at 1.62 (1.43-1.83), and serious drug-related hepatic disorders events at 1.40 (1.29-1.51). No drug-induced liver injury signal was detected for ambrisentan, and no significant sex differences were observed in drug-induced liver injury events. CONCLUSION: Both bosentan and macitentan are associated with liver injury. Routine monitoring of serum aminotransferase levels is recommended, especially in patients at higher risk of liver injury. Further research into drug-drug interactions involving endothelin receptor antagonists is warranted.

CD177 on neutrophils engages stress-related behavioral changes in male mice.

Persistent psychological stress can affect immune homeostasis and is a key factor in the development of depression. Many efforts are focused on the identifcation of pathways that link the immune system and mood disorders. Here, we found that psychological stress caused an increase in the frequency of brain-associated neutrophils and the level of neutrophil-specific antigen CD177 on peripheral neutrophils in male mice. Upregulated levels of blood CD177 are associated with depression in humans. Neutrophil depletion or Cd177 deficiency protected mice from stress-induced behavioral deficits. Importantly, adoptive transfer of CD177+ neutrophils from stressed mice increased the frequency of brain-associated leukocytes, including neutrophils, and caused behavioral defects in naive mice. These effects may be related to the endothelial adhesion advantage of CD177+ neutrophils and the interference of serine protease on endothelial junction. Our findings suggest a critical link between circulating CD177+ neutrophils and psychological stress-driven behavioral disorder.