Chronic pancreatitis-associated metabolic bone diseases: epidemiology, mechanisms, and clinical advances.

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.

A WNT mimetic with broad spectrum FZD-specificity decreases fibrosis and improves function in a pulmonary damage model.

BACKGROUND: Wnt/ß-catenin signaling is critical for lung development and AT2 stem cell maintenance in adults, but excessive pathway activation has been associated with pulmonary fibrosis, both in animal models and human diseases such as idiopathic pulmonary fibrosis (IPF). IPF is a detrimental interstitial lung disease, and although two approved drugs limit functional decline, transplantation is the only treatment that extends survival, highlighting the need for regenerative therapies. METHODS: Using our antibody-based platform of Wnt/ß-catenin modulators, we investigated the ability of a pathway antagonist and pathway activators to reduce pulmonary fibrosis in the acute bleomycin model, and we tested the ability of a WNT mimetic to affect alveolar organoid cultures. RESULTS: A WNT mimetic agonist with broad FZD-binding specificity (FZD1,2,5,7,8) potently expanded alveolar organoids. Upon therapeutic dosing, a broad FZD-binding specific Wnt mimetic decreased pulmonary inflammation and fibrosis and increased lung function in the bleomycin model, and it impacted multiple lung cell types in vivo. CONCLUSIONS: Our results highlight the unexpected capacity of a WNT mimetic to effect tissue repair after lung damage and support the continued development of Wnt/ß-catenin pathway modulation for the treatment of pulmonary fibrosis.

Engineering NH2-Cu-NH2 Triple-atom Sites in Defective MOFs for Selective Overall Photoreduction of CO2 into CH3COCH3.

Selective photoreduction of CO2 to multicarbon products, is an important but challenging task, due to high CO2 activation barriers and insufficient catalytic sites for C-C coupling. Herein, a defect engineering strategy for incorporating copper sites into the connected nodes of defective metal-organic framework UiO-66-NH2 for selective overall photo-reduction of CO2 into acetone. The Cu2+ site in well-modified CuN2O2 units served as a trapping site to capture electrons via efficient electron-hole separation, forming the active Cu+ site for CO2 reduction. Two NH2 groups in CuN2O2 unit adsorb CO2 and cooperated with copper ion to functionalize as a triple atom catalytic site, each interacting with one CO2 molecule to strengthen the binding of *CO intermediate to the catalytic site. The deoxygenated *CO attached to the Cu site interacted with *CH3 fixed at one amino group to form the key intermediate CO*-CH3, which interacted with the third reduction intermediate on another amino group to produce acetone. Our photocatalyst realizes efficient overall CO2 reduction to C3 product acetone CH3COCH3 with an evolution rate of 70.9 µmol gcat -1 h-1 and a selectivity up to 97 % without any adducts, offering a promising avenue for designing triple-atomic sites to producing C3 product from photosynthesis with water.

Superconductivity of cubic MB6 (M = Na, K, Rb, Cs).

Previous studies have shown that NaB6, KB6, and RbB6 adopting Pm3̄m are superconductors with a relatively high Tc under ambient conditions. In this paper, we conducted systematic structural and related properties research on CsB6 through a genetic evolution algorithm and total energy calculations based on density functional theory between 0 and 20 GPa. Our results reveal a cubic Pm3̄m CsB6, which is dynamically stable under the pressures we studied. We systematically calculated the formation enthalpies, electronic properties, and superconducting properties of Pm3̄m MB6 (M = Na, K, Rb, Cs). They all exhibit metallic features, and boron has high contributions to band structures, density of states, and electron-phonon coupling (EPC). The calculated results about the Helmholtz free energy difference of Pm3̄m CsB6 at 0, 10, and 20 GPa indicate that it is stable upon chemical decomposition (decomposition to simple substances Cs and B) from 0 to 400 K. The phonon density of states indicates that boron atoms occupy the high frequency area. The EPC results show that Pm3̄m CsB6 is a superconductor with Tc = 11.7 K at 0 GPa, close to NaB6 (13.1 K), KB6 (11.7 K), and RbB6 (11.3 K) at 0 GPa in our work, which indicates that boron atoms play an essential role in superconductivity: vibrations of B6 regular octagons lead to the high Tc of Pm3̄m MB6. Our work about Pm3̄m hexaborides provides a supplementary study on the borides of the group IA elements (without Fr and Li) and has an important guiding significance for the experimental synthesis of CsB6.

Whole-genome sequence and annotation of Penstemon davidsonii.

Penstemon is the most speciose flowering plant genus endemic to North America. Penstemon species' diverse morphology and adaptation to various environments have made them a valuable model system for studying evolution. Here, we report the first full reference genome assembly and annotation for Penstemon davidsonii. Using PacBio long-read sequencing and Hi-C scaffolding technology, we constructed a de novo reference genome of 437,568,744 bases, with a contig N50 of 40 Mb and L50 of 5. The annotation includes 18,199 gene models, and both the genome and transcriptome assembly contain over 95% complete eudicot BUSCOs. This genome assembly will serve as a valuable reference for studying the evolutionary history and genetic diversity of the Penstemon genus.

Coactivator-associated arginine methyltransferase 1: A versatile player in cell differentiation and development.

Protein arginine methylation is a common post-translational modification involved in the regulation of various cellular functions. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that asymmetrically dimethylates histone H3 and non-histone proteins to regulate gene transcription. CARM1 has been found to play important roles in cell differentiation and development, cell cycle progression, autophagy, metabolism, pre-mRNA splicing and transportation, and DNA replication. In this review, we describe the molecular characteristics of CARM1 and summarize its roles in the regulation of cell differentiation and development in mammals.

Elucidating dynamic cell lineages and gene networks in time-course single cell differentiation.

Single cell RNA sequencing (scRNA-seq) technologies provide researchers with an unprecedented opportunity to exploit cell heterogeneity. For example, the sequenced cells belong to various cell lineages, which may have different cell fates in stem and progenitor cells. Those cells may differentiate into various mature cell types in a cell differentiation process. To trace the behavior of cell differentiation, researchers reconstruct cell lineages and predict cell fates by ordering cells chronologically into a trajectory with a pseudo-time. However, in scRNA-seq experiments, there are no cell-to-cell correspondences along with the time to reconstruct the cell lineages, which creates a significant challenge for cell lineage tracing and cell fate prediction. Therefore, methods that can accurately reconstruct the dynamic cell lineages and predict cell fates are highly desirable. In this article, we develop an innovative machine-learning framework called Cell Smoothing Transformation (CellST) to elucidate the dynamic cell fate paths and construct gene networks in cell differentiation processes. Unlike the existing methods that construct one single bulk cell trajectory, CellST builds cell trajectories and tracks behaviors for each individual cell. Additionally, CellST can predict cell fates even for less frequent cell types. Based on the individual cell fate trajectories, CellST can further construct dynamic gene networks to model gene-gene relationships along the cell differentiation process and discover critical genes that potentially regulate cells into various mature cell types.

LN-Net: Perfusion Pattern-Guided Deep Learning for Lymph Node Metastasis Diagnosis Based on Contrast-Enhanced Ultrasound Videos.

OBJECTIVE: The blood flow in lymph nodes reflects important pathological features. However, most intelligent diagnosis based on contrast-enhanced ultrasound (CEUS) video focuses only on CEUS images, ignoring the process of extracting blood flow information. In the work described here, a parametric imaging method for describing blood perfusion pattern was proposed and a multimodal network (LN-Net) to predict lymph node metastasis was designed. METHODS: First, the commercially available artificial intelligence object detection model YOLOv5 was improved to detect the lymph node region. Then the correlation and inflection point matching algorithms were combined to calculate the parameters of the perfusion pattern. Finally, the Inception-V3 architecture was used to extract the image features of each modality, with the blood perfusion pattern taken as the guiding factor in fusing the features with CEUS by sub-network weighting. DISCUSSION: The average precision of the improved YOLOv5s algorithm compared with baseline was improved by 5.8%. LN-Net predicted lymph node metastasis with 84.9% accuracy, 83.7% precision and 80.3% recall. Compared with the model without blood flow feature guidance, accuracy was improved by 2.6%. The intelligent diagnosis method has good clinical interpretability. CONCLUSION: A static parametric imaging map could describe a dynamic blood flow perfusion pattern, and as a guiding factor, it could improve the classification ability of the model with respect to lymph node metastasis.

Corrigendum: A national cross-sectional study on the influencing factors of low HPV vaccination coverage in mainland China.

[This corrects the article DOI: 10.3389/fpubh.2022.1064802.].

A national cross-sectional study on the influencing factors of low HPV vaccination coverage in mainland China.

Background: HPV vaccine can block the infection of high-risk human papillomavirus and is an important measure to effectively reduce the incidence of cervical cancer and precancerous lesions. However, the HPV vaccination rate is still low in China. There are many factors. Therefore, it is important to study the influencing factors to provide basis for promoting the formulation of vaccination strategies. Methods: This study used a multi-stage sampling method to conduct a face-to-face questionnaire survey on women in different regions of China. The new general self-efficacy scale was used to measure the self-efficacy of the respondents. The short form of family health scale measured their family health. The t-test and binary Logistic regression analysis were used to screen the influencing factors of HPV vaccination. Restricted cubic spline model was used to analyze the influence trend of self-efficacy and family health on HPV vaccination rate. Results: (1) The HPV vaccination rate was low, especially in the ≤18 group. The place of residence, capita household income/month, individual self-efficacy and family health had a significant impact on HPV vaccination. (2) The restricted cubic spline model showed that self-efficacy positively promoted HPV vaccination, the correlation strength was statistically significant (χ2 =27.64, P<0.001) and non-linear (χ2 = 12.49, P = 0.0004); The poor family health hindered HPV vaccination, and the association strength was statistically significant (χ2 = 47.81, P < 0.001) and non-linear (χ2 = 9.96, P = 0.0016). Conclusion: It is necessary to strengthen the health education of HPV vaccination knowledge in the population to eliminate the hesitancy of vaccination. Free HPV vaccination strategies should be developed and encourage people of appropriate age to receive as early as possible. Self-efficacy and family health should be enhanced to increase HPV vaccination rate, so as to achieve the goal of reducing the incidence of cervical cancer and protecting women's health.

Ultrafine Co6W6C as an efficient anode catalyst for direct hydrazine fuel cells.

Ultrafine ternary carbide Co6W6C@C nanoparticles (NPs) were successfully synthesized and these NPs exhibited high catalytic activities for the hydrazine oxidation reaction (HzOR) under alkaline conditions. In a practical O2-hydrazine fuel cell test, its peak power density reached 203 mW cm-2, a value superior to that of the state-of-the-art commercial Pt/C catalyst.

Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.

Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.

Dicer-like proteins influence Arabidopsis root microbiota independent of RNA-directed DNA methylation.

BACKGROUND: Plants are naturally associated with root microbiota, which are microbial communities influential to host fitness. Thus, it is important to understand how plants control root microbiota. Epigenetic factors regulate the readouts of genetic information and consequently many essential biological processes. However, it has been elusive whether RNA-directed DNA methylation (RdDM) affects root microbiota assembly. RESULTS: By applying 16S rRNA gene sequencing, we investigated root microbiota of Arabidopsis mutants defective in the canonical RdDM pathway, including dcl234 that harbors triple mutation in the Dicer-like proteins DCL3, DCL2, and DCL4, which produce small RNAs for RdDM. Alpha diversity analysis showed reductions in microbe richness from the soil to roots, reflecting the selectivity of plants on root-associated bacteria. The dcl234 triple mutation significantly decreases the levels of Aeromonadaceae and Pseudomonadaceae, while it increases the abundance of many other bacteria families in the root microbiota. However, mutants of the other examined key players in the canonical RdDM pathway showed similar microbiota as Col-0, indicating that the DCL proteins affect root microbiota in an RdDM-independent manner. Subsequently gene analysis by shotgun sequencing of root microbiome indicated a selective pressure on microbial resistance to plant defense in the dcl234 mutant. Consistent with the altered plant-microbe interactions, dcl234 displayed altered characters, including the mRNA and sRNA transcriptomes that jointly highlighted altered cell wall organization and up-regulated defense, the decreased cellulose and callose deposition in root xylem, and the restructured profile of root exudates that supported the alterations in gene expression and cell wall modifications. CONCLUSION: Our findings demonstrate an important role of the DCL proteins in influencing root microbiota through integrated regulation of plant defense, cell wall compositions, and root exudates. Our results also demonstrate that the canonical RdDM is dispensable for Arabidopsis root microbiota. These findings not only establish a connection between root microbiota and plant epigenetic factors but also highlight the complexity of plant regulation of root microbiota. Video abstract.

LC-MS/MS coupled with chemometric analysis as an approach for the differentiation of bulbus Fritillaria unibracteata and Fritillaria ussuriensis.

INTRODUCTION: Bulbus Fritillaria unibracteata Hsiao et K.C. Hsia is an important traditional Chinese medicine, widely used for the treatment of coughs, phlegm and asthma for thousands of years. Due to an increasing demand in clinic practices, a variety of substitutes have appeared in the market, resulting in a big challenge in the differentiation of bulbus F. unibracteata and its substitutes. AIM: To differentiate bulbus F. unibracteata and its substitutes (bulbus Fritillaria ussuriensis Maxim.) based on their main isosteroidal alkaloid contents, and to test the potentiality of chemometrics as a tool for discrimination. MATERIALS AND METHODS: The nine isosteroidal alkaloids in 61 batches of Fritillariae bulbus were simultaneously quantitated by liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to classify the two kinds of Fritillariae bulbus. RESULTS: Quantitative analysis showed that there were differences in the content of the nine alkaloids between two kinds of Fritillariae bulbus. According to the content of nine isosteroidal alkaloids, bulbus of F. unibracteata and F. ussuriensis were successfully distinguished by PCA model. Among these isosteroidal alkaloids, verticine and verticinone may be used as potential chemical markers for the identification and differentiation between the two kinds of Fritillaria bulbus. CONCLUSION: The LC-MS/MS method coupled with PCA would be a powerful strategy to differentiate bulbus F. unibracteata and substitute specimens for quality evaluation and control.

Synthesis and Mechanism Studies of a High-Nuclear Mn72W48 Cluster.

A high-nuclear Mn72W48 cluster has been successfully synthesized by employing acetate coordinated Mn12 and Na2WO4 as starting materials. To investigate the synthesis mechanism, a series of synthesis experiments and high-resolution ESI-MS tests were designed and conducted. These experimental results demonstrate that inorganic tungstates exhibit better coordination capacity and variability than organic acetates in Mn12. Furthermore, a series of low nuclearity Mn clusters and Mn-W species were successfully detected and a possible synthesis mechanism of Mn72W48 was proposed. These results show that inorganic tungstate ligands have a great potential to construct high-nuclear transition-metal-oxo clusters by forming various intermediates.

Normalization of large-scale behavioural data collected from zebrafish.

Many contemporary neuroscience experiments utilize high-throughput approaches to simultaneously collect behavioural data from many animals. The resulting data are often complex in structure and are subjected to systematic biases, which require new approaches for analysis and normalization. This study addressed the normalization need by establishing an approach based on linear-regression modeling. The model was established using a dataset of visual motor response (VMR) obtained from several strains of wild-type (WT) zebrafish collected at multiple stages of development. The VMR is a locomotor response triggered by drastic light change, and is commonly measured repeatedly from multiple larvae arrayed in 96-well plates. This assay is subjected to several systematic variations. For example, the light emitted by the machine varies slightly from well to well. In addition to the light-intensity variation, biological replication also created batch-batch variation. These systematic variations may result in differences in the VMR and must be normalized. Our normalization approach explicitly modeled the effect of these systematic variations on VMR. It also normalized the activity profiles of different conditions to a common baseline. Our approach is versatile, as it can incorporate different normalization needs as separate factors. The versatility was demonstrated by an integrated normalization of three factors: light-intensity variation, batch-batch variation and baseline. After normalization, new biological insights were revealed from the data. For example, we found larvae of TL strain at 6 days post-fertilization (dpf) responded to light onset much stronger than the 9-dpf larvae, whereas previous analysis without normalization shows that their responses were relatively comparable. By removing systematic variations, our model-based normalization can facilitate downstream statistical comparisons and aid detecting true biological differences in high-throughput studies of neurobehaviour.

A high-nuclearity isopolyoxotungstate based manganese cluster: one-pot synthesis and step-by-step assembly.

A manganese(iii,iv)-tungsten(vi) supercluster based on 72 manganese ions (48 MnIV and 24 MnIII) and 48 tungsten(vi) centers [{MnIV24MnIII12O28(H2O)23}2(W24O120)2]40- has been prepared from the carboxylic Mn12 cluster. Its structure comprises two unprecedented cage-like Mn36W24 cores linked via two Mn-O-W bonds, leading to a Mn72W48 assembly. The inorganic synthetic mechanism was investigated through different synthesis methods and comprehensive ESI-MS tests.