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Colitis is an inflammatory intestinal disease that lasts for a long time, has an unknown cause, and occurs repeatedly. It is usually accompanied by symptoms such as intestinal cell damage, intestinal immunity, and abnormal intestinal flora. Numerous studies have shown that dietary fiber, as a prebiotic, its metabolites can selectively improve the composition of the intestinal flora, which in turn improves the level of intestinal short-chain fatty acids, reduces the expression of inflammatory factors, and enhances the function of the intestinal immune barrier, thereby improving the inflammatory response of the organism. This anti-inflammatory effect of dietary fiber through its metabolites provides new research ideas to assist in the treatment of colitis. This paper outlines the pathogenesis of colitis, and the mechanism of interaction between dietary fiber and its metabolites with intestinal flora, inflammatory factors and immune cells, aiming to provide theoretical basis for the alleviation of colitis by dietary fiber and the development of functional foods.

Abstract The de novo construction of enantioenriched 3-hydroxyindolenines and 3-oxindoles from easily available starting materials has been highly desired. Herein, an enantioselectively intermolecular direct [3 + 2] annulation of aryl amine with 2,3-diketoesters to construct 3-hydroxyindolenines with a chiral tertiary alcohol has been disclosed. The results of control experiments and DFT calculation revealed that π − π interaction plays a pivotal role in the enantioselectivity-determining process of [3 + 2] annulation. The following unusual concerted [1,2]-ester migration provides a family of chiral 3-oxindoles in good to excellent yields with excellent enantioselectivity.

Abstract Campanumoea javanica Bl. (CJ) traditionally used in Southwestern China, is now widely consumed as a health food across the nation. Due to its similar efficacy to Codonopsis Radix (CR) and their shared botanical family, CJ is often used as a substitute for CR. According to the Chinese Pharmacopoeia, Codonopsis pilosula var. modesta (Nannf.) L.T. Shen (CPM), Codonopsis pilosula (Franch.) Nannf. (CP), and Codonopsis tangshen Oliv. (CT) are the primary sources of CR. However, details on the differences in composition, effectiveness, and compositional between CJ and CR are still limited. Besides, there is little evidence to support the application of CJ as a drug. In this study, we employed widely targeted metabolomics, network pharmacology analysis, and molecular docking to explore the disparities in metabolite profiles between CJ and CR and to predict the pharmacological mechanisms of the dominant differential metabolites of CJ and their potential medicinal applications. The widely targeted metabolomics results indicated that 1,076, 1,102, 1,102, and 1,093 compounds, most phenolic acids, lipids, amino acids, and flavonoids, were characterized in CJ, CPM, CP, and CT, respectively. There were an average of 1061 shared compounds in CJ and CRs, with 95.07% similarity in metabolic profiles. Most of the metabolites in CJ were previously unreported. Twelve of the seventeen dominant metabolites found in CJ were directly associated with treating cancer and lactation, similar to the traditional medicinal efficacy. The molecular docking results showed that the dominant metabolites of CJ had good docking activity with the core targets PIK3R1, PIK3CA, ESR1, HSP90AA1, EGFR, and AKT1. This study provides a scientific basis for understanding the similarities and differences between CJ and CR at the metabolome level, offering a theoretical foundation for developing innovative medications from CJ. Additionally, it significantly enhances the metabolite databases for both CJ and CR.

Abstract Cervical softening and dilation are critical for the successful term delivery of a fetus, with premature changes associated with preterm birth. Traditional clinical measures like transvaginal ultrasound and Bishop scores fall short in predicting preterm births and elucidating the cervix’s complex microstructural changes. Here, we introduce a magnetic resonance diffusion basis spectrum imaging (DBSI) technique for non-invasive, comprehensive imaging of cervical cellularity, collagen, and muscle fibers. This method is validated through ex vivo DBSI and histological analyses of specimens from total hysterectomies. Subsequently, retrospective in vivo DBSI analysis at 32 weeks of gestation in ten term deliveries and seven preterm deliveries with inflammation-related conditions shows distinct microstructural differences between the groups, alongside significant correlations with delivery timing. These results highlight DBSI’s potential to improve understanding of premature cervical remodeling and aid in the evaluation of therapeutic interventions for at-risk pregnancies. Future studies will further assess DBSI’s clinical applicability.

Abstract Forward‐looking radar imaging is a top priority due to a variety of applications. An airborne forward‐looking radar imaging approach via a modified propagator method (MPM) based on the planar phased array is proposed. It can obtain a better focusing effect without range migration correction. Through the MPM algorithm, the azimuth resolution can be enhanced greatly. Compared with the conventional synthetic aperture radar imaging algorithm, the left‐right ambiguity process can be avoided by generating two‐dimensional spatial spectra. Furthermore, the imaging results of different numbers of elements are given to provide an assessment of the imaging performance. Additionally, the authors proposed to apply the scanning planar phased array configuration to airborne forward‐looking two‐dimensional imaging for the first time. The validity of the method is proven by experiments. The image is more focused. Furthermore, the results of the experiments verify that the proposed method is fit for high‐speed situation and aircraft height variation condition.

Abstract The ever‐increasing ranges of starch applications have been restricted by some of its inherent adverse characteristics like retrogradability, gel opacity, low resistibility to variations of pH, and elevated shear/temperatures. Starch modification through various physical, chemical, and enzymatic methods has been proposed as the most mature platform to tackle such drawbacks. Along with their outstanding potential in enhancing the starch's technofunctional characteristics, physicochemical modifications could remarkably customize starch nutritional/digestibility attributes. For instance, physical modifications could remarkably change starch digestibility by manipulating the granular architecture while chemical approaches change it by altering the chemical structure of starch molecules, making them unrecognizable to digestive enzymes. Such alterations could even be more challenging upon applying a combination of starch modifications. The changes in starch digestibility through its modification via single, double, and multiple modifications have been overviewed in this review.

Abstract Apparently, understanding airway management status may help to reduce risk and improve clinical practice. Given these facts, our team conducted a second survey on the current status of airway management for mainland China following our 2016 national airway survey. The national survey was conducted from November 7 to November 28, 2022. An electronic survey was sent to the New Youth Anesthesia Forum, where Chinese anesthesiologists completed the questionnaire via WeChat. A total of 3783 respondents completed the survey, with a response rate of 72.14%. So far, in 2022, 34.84% of anesthesiologists canceled or delayed surgery at least once due to difficult airway. For the anticipated difficult airway management, 66.11% of physicians would choose awake intubation under sedation and topical anesthesia, while the percentage seeking help has decreased compared to the 2016 survey. When encountering an emergency, 74.20% of respondents prefer to use the needle cricothyrotomy, albeit less than a quarter have actually performed it. Anesthesiologists with difficult airway training experience reached 72.96%, with a significant difference in participation between participants in Tier 3 hospitals and those in other levels of hospitals (P

Abstract Analogous of pixels to two-dimensional pictures, voxels—in the form of either small cubes or spheres—are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.

Abstract Purpose Hepatocellular carcinoma (HCC) is the most prevalent malignancies worldwide. Recently, oxidative phosphorylation (OXPHOS) has received extensive concern as an emerging target in antitumor therapy. However, the OXPHOS-involved underlying genes and clinical utilization in HCC remain worth exploring. The present research aimed to create an OXPHOS-relevant signature in HCC. Patients and methods In this study, the prognostic signature genes linked with OXPHOS were identified, and prognostic models were built using least absolute shrinkage and selection operator (LASSO) cox regression analysis. Furthermore, the combination study of immune microenvironment and signature genes looked into the involvement of immune cells in signature-based genes in HCC. Following that, chemotherapeutic drug sensitivity and immunotherapy analysis was implemented to predict clinical efficacy in HCC patients. Finally, clinical samples were collected to measure the expression of OXPHOS-related signature genes. Results Following a series of screens, six prognostic signature genes related with OXPHOS were identified: MRPS23, MPV17, MAPK3, IGF2BP2, CDK5, and IDH2, on which a risk model was built. The findings revealed a significant drop in the survival rate of HCC patients as their risk score increased. Meanwhile, independent prognostic study demonstrated that the risk score could accurately identify HCC patients. Immuno-microenvironmental correlation research suggested that the prognostic characteristics could serve as a reference index for both immunotherapy and chemotherapy. Finally, RT-qPCR exhibited a trend in signature gene expression that was consistent with the results. Conclusion In this study, a total of six prognostic genes associated with OXPHOS were selected and a prognostic model was constructed, providing an essential reference for the study of OXPHOS in HCC.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

Nine Pezizomycotina strains were isolated from rotten dead branches and leaves collected from Guizhou Province. To obtain their accurate taxonomic placement, we provided the morphological characteristics of conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, SSU, LSU and tub2 gene sequences, confirmed our strains represented three novel species, Peglionia falcata, Neoascochyta pseudofusiformis and Neomicrosphaeropsis cylindrica. Peglionia falcata produced falcate conidia and Neoa. pseudofusiformis generated fusiform conidia, while Neom. cylindrica possessed cylindrical conidia. The phylogenetic results also supported them as novel taxa. All the new species in the present study were found as saprophytic on forest litter with high rainfall, which suggest they may have a certain effect on nutrient decomposition and redistribution in forest ecosystems. Thus, it opened a way for further research on related ecological roles and their application production.

Abstract The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory responses and scar proliferation, possibly leading to surgical failure. We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. Twelve New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (6 right eyes), trabeculectomy group (6 right eyes), and control group (12 left eyes). Results showed that all HA-Mg drainage plates were completely degraded ~4 months postoperatively. At the 5th month postoperatively, there was no statistical difference in the corneal endothelium density between the HA-Mg drainage plate group and the control group (p = 0.857). The intraocular pressure (IOP) level in the HA-Mg drainage plate implantation group was lower than in the other two groups. The trypan blue dye still drained from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation. HE staining revealed the scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded, with no obvious infiltration with the inflammatory cells. This study showed the safety and efficacy of HA-Mg glaucoma drainage plate in controlling IOP after implantation into the anterior chamber of rabbit eyes. Graphical abstract We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. This study evaluated the safety and efficacy of HA-Mg glaucoma drainage plate in controlling intraocular pressure after implantation into the anterior chamber of rabbit eyes.

Abstract Streptococcus gallolyticus (Sg) is a non-motile, gram-positive bacterium that causes infective endocarditis (inflammation of the heart lining). Because Sg has gained resistance to existing antibiotics and there is currently no drug available, developing effective anti-Sg drugs is critical. This study combined core proteomics with a subtractive proteomics technique to identify potential therapeutic targets for Sg. Several bioinformatics approaches were used to eliminate non-essential and human-specific homologous sequences from the bacterial proteome. Then, virulence, druggability, subcellular localization, and functional analyses were carried out to specify the participation of significant bacterial proteins in various cellular processes. The pathogen’s genome contained three druggable proteins, glucosamine-1phosphate N-acetyltransferase (GlmU), RNA polymerase sigma factor (RpoD), and pantetheine-phosphate adenylyltransferase (PPAT) which could serve as effective targets for developing novel drugs. 3D structures of target protein were modeled through Swiss Model. A natural product library containing 10,000 molecules from the LOTUS database was docked against therapeutic target proteins. Following an evaluation of the docking results using the glide gscore, the top 10 compounds docked against each protein receptor were chosen. LTS001632, LTS0243441, and LTS0236112 were the compounds that exhibited the highest binding affinities against GlmU, PPAT, and RpoD, respectively, among the compounds that were chosen. To augment the docking data, molecular dynamics simulations and MM-GBSA binding free energy were also utilized. More in-vitro research is necessary to transform these possible inhibitors into therapeutic drugs, though computer validations were employed in this study. This combination of computational techniques paves the way for targeted antibiotic development, which addresses the critical need for new therapeutic strategies against S. gallolyticus infections.

Abstract As urban development accelerates and natural disasters occur more frequently, the urgency of developing effective emergency shelter planning strategies intensifies. The shelter location selection method under the traditional multi-criteria decision-making framework suffers from issues such as strong subjectivity and insufficient data support. Artificial intelligence offers a robust data-driven approach for site selection; however, many methods neglect the spatial relationships of site selection targets within geographical space. This paper introduces an emergency shelter site selection model that combines a variational graph autoencoder (VGAE) with a random forest (RF), namely VGAE-RF. In the constructed urban spatial topological graph, based on network geographic information, this model captures both the latent features of geographic unit coupling and integrates explicit and latent features to forecast the likelihood of emergency shelters in the construction area. This study takes Beijing, China, as the experimental area and evaluates the reliability of different model methods using a confusion matrix, Receiver Operating Characteristic (ROC) curve, and Imbalance Index of spatial distribution as evaluation indicators. The experimental results indicate that the proposed VGAE-RF model method, which considers spatial semantic associations, displays the best reliability.

Abstract Background Abdominal CT scans are vital for diagnosing abdominal diseases but have limitations in tissue analysis and soft tissue detection. Dual-energy CT (DECT) can improve these issues by offering low keV virtual monoenergetic images (VMI), enhancing lesion detection and tissue characterization. However, its cost limits widespread use. Purpose To develop a model that converts conventional images (CI) into generative virtual monoenergetic images at 40 keV (Gen-VMI40keV) of the upper abdomen CT scan. Methods Totally 444 patients who underwent upper abdominal spectral contrast-enhanced CT were enrolled and assigned to the training and validation datasets (7:3). Then, 40-keV portal-vein virtual monoenergetic (VMI40keV) and CI, generated from spectral CT scans, served as target and source images. These images were employed to build and train a CI-VMI40keV model. Indexes such as Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), and Structural Similarity (SSIM) were utilized to determine the best generator mode. An additional 198 cases were divided into three test groups, including Group 1 (58 cases with visible abnormalities), Group 2 (40 cases with hepatocellular carcinoma [HCC]) and Group 3 (100 cases from a publicly available HCC dataset). Both subjective and objective evaluations were performed. Comparisons, correlation analyses and Bland-Altman plot analyses were performed. Results The 192nd iteration produced the best generator mode (lower MAE and highest PSNR and SSIM). In the Test groups (1 and 2), both VMI40keV and Gen-VMI40keV significantly improved CT values, as well as SNR and CNR, for all organs compared to CI. Significant positive correlations for objective indexes were found between Gen-VMI40keV and VMI40keV in various organs and lesions. Bland-Altman analysis showed that the differences between both imaging types mostly fell within the 95% confidence interval. Pearson’s and Spearman’s correlation coefficients for objective scores between Gen-VMI40keV and VMI40keV in Groups 1 and 2 ranged from 0.645 to 0.980. In Group 3, Gen-VMI40keV yielded significantly higher CT values for HCC (220.5HU vs. 109.1HU) and liver (220.0HU vs. 112.8HU) compared to CI (p

An optimization method of fracturing fluid volume strength was introduced taking well X-1 in Biyang Sag of Nanxiang Basin as an example. The characteristic curves of capillary pressure and relative permeability were obtained from history matching between forced imbibition experimental data and core-scale reservoir simulation results and taken into a large scale reservoir model to mimic the forced imbibition behavior during the well shut-in period after fracturing. The optimization of the stimulated reservoir volume (SRV) fracturing fluid volume strength should meet the requirements of estimated ultimate recovery (EUR), increased oil recovery by forced imbibition and enhancement of formation pressure and the fluid volume strength of fracturing fluid should be controlled around a critical value to avoid either insufficiency of imbibition displacement caused by insufficient fluid amount or increase of costs and potential formation damage caused by excessive fluid amount. Reservoir simulation results showed that SRV fracturing fluid volume strength positively correlated with single-well EUR and an optimal fluid volume strength existed, above which the single-well EUR increase rate kept decreasing. An optimized increase of SRV fracturing fluid volume and shut-in time would effectively increase the formation pressure and enhance well production. Field test results of well X-1 proved the practicality of established optimization method of SRV fracturing fluid volume strength on significant enhancement of shale oil well production.

Abstract Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants’ trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people’s trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.

Abstract Background Achieving a net zero greenhouse gas United States (US) economy is likely to require both deep sectoral mitigation and additional carbon dioxide removals to offset hard-to-abate emissions. Enhancing the terrestrial carbon sink, through practices such as the adoption of no-till and cover cropping agricultural management, could provide a portion of these required offsets. Changing domestic agricultural practices to optimize carbon content, however, might reduce or shift US agricultural commodity outputs and exports, with potential implications on respective global markets and land use patterns. Here, we use an integrated energy-economy-land-climate model to comprehensively assess the global land, trade, and emissions impacts of an adoption of domestic no-till farming and cover cropping practices based on carbon pricing. Results We find that the adoption of these practices varies depending on which aspects of terrestrial carbon are valued. Valuation of all terrestrial carbon resulted in afforestation at the expense of domestic agricultural production. In contrast, a policy valuing soil carbon in agricultural systems specifically indicates strong adoption of no-till and cover cropping for key crops. Conclusions We conclude that under targeted terrestrial carbon incentives, adoption of no-till and cover cropping practices in the US could increase the terrestrial carbon sink with limited effects on crop availability for food and fodder markets. Future work should consider integrated assessment modeling of non-CO2 greenhouse gas impacts, above ground carbon storage changes, and capital and operating cost considerations.

Abstract Digital modeling is an essential means for preserving and passing down historical culture within cultural heritage. Point cloud registration technology, by aligning point cloud data captured from multiple perspectives, enhances the accuracy of reconstructing the complex structures of artifacts and buildings and provides a reliable digital foundation for their protection, exhibition, and research. Due to the challenges posed by complex morphology, noise, and missing data when processing cultural heritage data, this paper proposes a point cloud registration method based on the Diffusion Transformer (PointDT). Compared to traditional methods, the Diffusion Transformer can better capture both the global features and local structures of point cloud data, more accurately capturing the geometric and semantic information of the target point cloud, thereby achieving precise digital reconstruction. In this study, we trained our method using indoor datasets such as 3DMatch and large-scale outdoor datasets like KITTI, and validated it on various cultural heritage datasets, including those of the Terracotta Warriors and heritage buildings. The results demonstrate that this method not only significantly improves accuracy but also shows advantages in computational efficiency.

Abstract Background China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. Methods From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). Results Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P

Abstract Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.

Abstract Background Horsfieldia hainanensis Merr., an indicator species of China’s humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. Results and discussion The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30–35℃.

AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Abstract Federated learning is a distributed machine learning paradigm where the goal is to collaboratively train a high quality global model while private training data remains local over distributed clients. However, heterogenous data distribution over clients is severely challenging for federated learning system, which severely damage the quality of model. In order to address this challenge, we propose global prototype distillation (FedGPD) for heterogenous federated learning to improve performance of global model. The intuition is to use global class prototypes as knowledge to instruct local training on client side. Eventually, local objectives will be consistent with the global optima so that FedGPD learns an improved global model. Experiments show that FedGPD outperforms previous state-of-art methods by 0.22% ~1.28% in terms of average accuracy on representative benchmark datasets.

Abstract Individual may response to drug treatment differently due to their genetic variants located in enhancers. These variants can alter transcription factor’s (TF) binding strength, affect enhancer’s chromatin activity or interaction, and eventually change expression level of downstream gene. Here, we propose a computational framework, PERD, to Predict the Enhancers Responsive to Drug. A machine learning model was trained to predict the genome-wide chromatin accessibility from transcriptome data using the paired expression and chromatin accessibility data collected from ENCODE and ROADMAP. Then the model was applied to the perturbed gene expression data from Connectivity Map (CMAP) and Cancer Drug-induced gene expression Signature DataBase (CDS-DB) and identify drug responsive enhancers with significantly altered chromatin accessibility. Furthermore, the drug responsive enhancers were related to the pharmacogenomics genome-wide association studies (PGx GWAS). Stepping on the traditional drug-associated gene signatures, PERD holds the promise to enhance the causality of drug perturbation by providing candidate regulatory element of those drug associated genes.

Abstract Background Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery. Results We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice. Conclusion Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke. Graphical Abstract

Abstract Background We aimed to establish a novel method for automatically constructing three-dimensional (3D) median sagittal plane (MSP) for mandibular deviation patients, which can increase the efficiency of aesthetic evaluating treatment progress. We developed a Euclidean weighted Procrustes analysis (EWPA) algorithm for extracting 3D facial MSP based on the Euclidean distance matrix analysis, automatically assigning weight to facial anatomical landmarks. Methods Forty patients with mandibular deviation were recruited, and the Procrustes analysis (PA) algorithm based on the original mirror alignment and EWPA algorithm developed in this study were used to construct the MSP of each facial model of the patient as experimental groups 1 and 2, respectively. The expert-defined regional iterative closest point algorithm was used to construct the MSP as the reference group. The angle errors of the two experimental groups were compared to those of the reference group to evaluate their clinical suitability. Results The angle errors of the MSP constructed by the two EWPA and PA algorithms for the 40 patients were 1.39 ± 0.85°, 1.39 ± 0.78°, and 1.91 ± 0.80°, respectively. The two EWPA algorithms performed best in patients with moderate facial asymmetry, and in patients with severe facial asymmetry, the angle error was below 2°, which was a significant improvement over the PA algorithm. Conclusions The clinical application of the EWPA algorithm based on 3D facial morphological analysis for constructing a 3D facial MSP for patients with mandibular deviated facial asymmetry deformity showed a significant improvement over the conventional PA algorithm and achieved the effect of a dental clinical expert-level diagnostic strategy.

Ag-based solid solutions have gained significant attention in the electronic packaging field due to their remarkable plasticity. In this work, the generalized planar fault energy (GPFE), critical strength and stresses, and electronic properties after adding solutes with different types and size misfits were studied for Ag-based solid solutions. Furthermore, we explored the underlying mechanism behind the impact of solutes on the plasticity of Ag and confirmed it through transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analyses. Importantly, we introduced the novel concepts of size and chemical misfit factors, electronic factors, and twinning factor into the plasticity enhancement mechanism of Ag-based solution systems. The predictions based on these factors were in agreement with experimental observations using TEM and HRTEM. Remarkably, the (Ag)–Bi system exhibited the lowest critical resolved shear stress for slip and twinning, as well as the most superior plasticity, positioning it as a crucial candidate for future development. This study presents a scientific framework for designing and developing Ag-based solid solutions with excellent plasticity, encompassing size/chemical factors, electronic factors, and twinning factor.

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Rainfall-derived inflow/infiltration (RDII) modelling during heavy rainfall events is essential for sewer flow management. In this study, two machine learning algorithms, random forest (RF) and long short-term memory (LSTM), were developed for sewer flow prediction and RDII estimation based on field monitoring data. The study implemented feature engineering for extracting physically significant features in sewer flow modelling and investigated the importance of the relevant features. The results from two case studies indicated the superior capability of machine learning models in RDII estimation in the combined and separated sewer systems, and LSTM model outperformed the two models. Compared to traditional methods, machine learning models were capable of simulating the temporal variation in RDII processes and improved prediction accuracy for peak flows and RDII volumes in storm events. HIGHLIGHTS Machine learning models, particularly the LSTM model, outperformed traditional methods in estimating RDII in sewer systems.; Feature engineering techniques allowed for the extraction of physically significant features in sewer flow modelling.; Machine learning models successfully simulated the temporal variation in RDII processes, resulting in improved accuracy for predicting peak flows and RDII volumes during storm events.;

Abstract Background CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. Methods The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. Results OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. Conclusions We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

Highlights Si/C Composite and Nanostructure Engineering: Advanced Si/C composites and multidimensional nanostructures address key challenges in silicon anodes, like volume expansion and unstable SEI, enhancing LIBs performance. Artificial SEI, Prelithiation, and Binders: Focus on stable artificial SEI layers, efficient prelithiation, and cutting-edge binders to improve Coulombic efficiency and reduce capacity loss, enhancing Si anode durability and efficiency. Real-World Application and Scalability: Analysis of these strategies highlights scalability and commercial viability, transitioning Si-anode technologies to practical, high-performance LIBs applications.

Abstract Xanthomonas oryzae pv. oryzae (Xoo) injects major transcription activator-like effectors (TALEs) into plant cells to activate susceptibility (S) genes for promoting bacterial leaf blight in rice. Numerous resistance (R) genes have been used to construct differential cultivars of rice to identify races of Xoo, but the S genes were rarely considered. Different edited lines of rice cv. Kitaake were constructed using CRISPR/Cas9 gene-editing, including single, double and triple edits in the effector-binding elements (EBEs) located in the promoters of rice S genes OsSWEET11a, OsSWEET13 and OsSWEET14. The near-isogenic lines (NILs) were used as tracers to detect major TALEs (PthXo1, PthXo2, PthXo3 and their variants) in 50 Xoo strains. The pathotypes produced on the tracers determined six major TALE types in the 50 Xoo strains. The presence of the major TALEs in Xoo strains was consistent with the expression of S genes in the tracers, and it was also by known genome sequences. The EBE editing had little effect on agronomic traits, which was conducive to balancing yield and resistance. The rice-tracers generated here provide a valuable tool to track major TALEs of Xoo in Asia which then shows what rice cultivars are needed to combat Xoo in the field.

Abstract Background Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4’-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma. Methods In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination. Results The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs. Conclusion Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.

Abstract Due to theintricate and interdependent nature of the smart grid, it has encountered an increasing number of security threats in recent years. Currently, conventional security measures such as firewalls, intrusion detection, and malicious detection technologies offer specific protection based on their unique perspectives. However, as the types and concealment of attacksincrease, these measures struggle to detect them promptly and respond accordingly. In order to meet the social demand for the accuracy and computation speed of the power network security risk evaluation model, the study develops a fusion power network security risk evaluation algorithm by fusing the flash search algorithm with the support vector machine. This algorithm is then used as the foundation for building an improved power network security risk evaluation model based on the fusion algorithm.The study's improved algorithm's accuracy is 96.2%, which is higher than the accuracy of the other comparative algorithms; its error rate is 3.8%, which is lower than the error rate of the other comparative algorithms; and its loss function curve convergence is quicker than that of the other algorithms.The risk evaluation model's accuracy is 97.8%, which is higher than the accuracy of other comparative models; the error rate is 1.9%, which is lower than the error rate of other comparative models; the computing time of the improved power network security risk evaluation model is 4.4 s, which is lower than the computing time of other comparative models; and its expert score is high. These findings are supported by empirical analysis of the improved power network security risk evaluation model proposed in the study. According to the study's findings, the fusion algorithm and the upgraded power network security risk evaluation model outperform other approaches in terms of accuracy and processing speed. This allows the study's maintenance staff to better meet the needs of the community by assisting them in identifying potential security hazards early on and taking the necessary preventative and remedial action to ensure the power system's continued safe operation.

Abstract Background Potato (Solanum tuberosum L.) production is seriously threatened by the oomycete Phytophthora infestans (P. infestans). However, it remains unclear how the two potato cultivars, Q9 (moderately resistant) and Atl (susceptible), initiate distinct defense responses after inoculation with P. infestans. To uncover the underlying process, we investigated the dynamic gene expression profiles and the functions of the differentially expressed genes (DEGs). Results The results showed that the numbers of up-regulated DEGs were 1345, 1063 and 1694 in Q9 and 272, 603 and 2554 in Atl at 1 day post inoculation (dpi), 3 dpi and 5 dpi, respectively. Meanwhile, the down-regulated DEGs were 1557, 1417 and 389 in Q9 and 114, 364 and 2528 in Atl simultaneously. KEGG enrichment analysis revealed that plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were significantly enriched in Q9 at the later stage. Furthermore, DEGs associated with plant-pathogen interaction and phenylpropanoid biosynthesis showed higher expression levels in Q9 compared to Atl, especially at the later stage. The expressions of eight DEGs were validated by quantitative real-time PCR (qRT-PCR), which further verified the accuracy of the transcriptomics analysis. In addition, DEGs that were exclusively up-regulated and down-regulated in Q9 were analyzed, which may contribute to the resistance of Q9. Transient expression analysis revealed that four DEGs, including StHP1, StMYB2, StHSP3 and StNAC5, exhibited increased tolerance to P. infestans, indicating a positive role in enhancing the resistance of Q9. Conclusion Therefore, the DEGs associated with plant-pathogen interaction, phenylpropanoid biosynthesis and MAPK signaling pathway were involved in regulating late blight, and the expression level of the related genes significantly increased in Q9. In addition, StHP1, StHSP3 and the transcription factors, including StMYB2 and StNAC5, played positive roles in improving the resistance of potato Q9 to P. infestans. These findings provide useful information for further understanding the molecular mechanism of potato resistance to late blight. Furthermore, our study identified novel resistance genes that can be used in resistance breeding and functional research. Graphical abstract

Abstract Background GAox is a key enzyme involved in GA biosynthesis pathway and plays an important role in regulating various processes in plant life cycle. However, it has not been systematic, studies have been conducted in potato, which is the world's fourth largest food crop. Methods In this work, we systematically identified GAox gene family (StGAox) in potato by analyzing the potato genome sequence using a set of bioinformatics approaches, and analyze their physical, chemical properties, distribution on chromosomes, gene structure, conserved motifs, gene duplication events and expression patterns were analyzed. Results The results showed that a total of 33 GAox proteins were identified and unevenly distributed on 10 chromosomes. Based on their protein structure and phylogenetic characteristics, these 33 StGAoxes were divided into 5 distinct subclasses. Collinearity analysis revealed that there were 5 pairs of duplicated genes in the StGAox gene family, and all of which evolved under purifying selection. Analysis of RNA-seq data of double haploid (DM) potatoes under different tissues, abiotic stresses and hormone treatments showed that PG0002068, PG0024249 and PG0027963 were higher expressed in leaves, PG009427, PG0026762, PG0009021 and PG0021095 were higher expressed in tubers, PG2003479, PG0024249, PG0005698, and PG0009021were higher expressed in shoots than those of other tissues. In addition, the expression of PG0002068, PG2003479, PG0032156, PG0024249, and PG0021292 were up-regulated under mannitol and drought stress. Conclusions Comparative genome-wide analysis of StGAox genes and their expression analyses revealed that members of this family may be involved in tissue-specific developmental and abiotic stress responses. Graphical Abstract

Abstract Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.

Abstract During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1β, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.

Abstract Background Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. Results The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. Conclusion This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Abstract In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2–200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2–200 kb targets using a short-read sequencer.

Abstract Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light–dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light–dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA β-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA β oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.

High-quality lacustrine shale beds within the Paleogene Hetaoyuan Formation in the Biyang Sag, Nanxiang Basin, exhibit significant potential for shale oil resources. Previous studies on the oil-bearing potential and hydrocarbon occurrence of shales in the Biyang Sag were relatively limited, potentially hindering advancements for shale oil exploration. This study focuses on the shales found in the third sub-member of the third member within the Hetaoyuan Formation in well Y1, which locates in the southern area of the Biyang Sag. Through various geochemical analyses such as Rock-Eval pyrolysis, multi-temperature pyrolysis and X-ray diffraction, this research systematically investigates the shale oil contents, hydrocarbon occurrence characteristics, and influencing factors. These results indicate that the lithofacies assemblages of the shale primarily consist of felsic shale facies, dolomitic shale facies and mixed shale facies, with a well-developed laminar structure. The source rock quality is classified as good to excellent, and the thermal maturity stage of oil window. The predominant organic maceral is sapropelic, with organic matter types ranging from Ⅰ to Ⅱ1. Oil content increases with burial depth, ranged from adsorbed hydrocarbons in the upper section to free hydrocarbons in the lower section. Detrital mineral content and total organic carbon (TOC) content are identified as the main factors influencing free and adsorbed hydrocarbon content, respectively. Overall, the oil saturation index (OSI) of the shale in the lower section of the Hetaoyuan Formation exceeds 100 mg/g, with an average free hydrocarbon content over 3 mg/g, indicating promising prospects for shale oil exploration and development.

Abstract Unraveling the effect of spatially separated bifunctional sites on catalytic reactions is significant yet challenging. In this report, we investigate the role of spatial separation on the oxidation of methane in a series of Cu-exchanged aluminosilicate zeolites. Regulation of the bifunctional sites is done either through studying a physical mixture of Cu-exchanged zeolites and acidic zeolites or by systematically varying the Cu and acid density within a family of zeolite materials. We show that separated Cu and acid sites are beneficial for the formation of hydrocarbons while high-density Cu sites, which are closer together, facilitate the production of CO2. By contrast, a balance of the spatial separation of Cu and acid sites shows more favorable formation of methanol. This work will further guide approaches to methane oxidation to methanol and open an avenue for promoting hydrocarbon synthesis using methanol as an intermediate.

Abstract Copper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.

Abstract The application of fertilizer to ensure the steady improvement of crop yield has become the main means of agricultural production. However, it remains to be determined whether fertilization practices with different combinations of nitrogen (N), phosphorus (P), potassium (K), and organic (O) fertilizers play a positive role in the sustainability of maize yield and the soil in which it is grown. Therefore,this meta-analysis extracted 2663 data points from 76 studies to systematically analyze and explore the effects of different fertilization measures on maize yield, soil nutrients, water content and water use efficiency (WUE) in northern China. Articles addressing this topic showed that fertilization effectively increased the soil nutrient content and maize yield. The soil organic matter (SOM) increased by 2.36 (N)–55.38% (NPO), total nitrogen content increased by 6.10 (N)–56.39% (NPO), available phosphorus content increased by 17.12 (N)–474.74% (NPO), and available potassium content changed by − 2.90 (NP)–64.40% (NPO). Soil moisture increased by 3.59% under a single organic fertilizer application and decreased by 4.27–13.40% under the other treatments. Compared with no fertilization, the yield increase of fertilized maize reached 11.65–220.42%. NP, NPK and NPKO contributed the most to increased yield in lithological, black and fluvo-aquic soils, respectively. The effects of different fertilization practices on maize yield varied in response to the same meteorological factors. The WUE increased from 9.51 to 160.72%. In conclusion, rational fertilization can improve the soil nutrient content and increase maize yield. The combined application of chemical and organic fertilizer showed the greatest increase in yield and WUE. Organic fertilizer application alone increased soil moisture. Our results provide a theoretical basis for fertilizer application and for improving the soil structure for maize cultivation in northern China.

Abstract Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by dynamin-like GTPase atlastin (ATL). This fundamental process relies on GTP-dependent domain rearrangements in the N-terminal region of ATL (ATLcyto), including the GTPase domain and three-helix bundle (3HB). However, its conformational dynamics during the GTPase cycle remain elusive. Here, we combine single-molecule FRET imaging and molecular dynamics simulations to address this conundrum. Different from the prevailing model, ATLcyto can form a loose crossover dimer upon GTP binding, which is tightened by GTP hydrolysis for membrane fusion. Furthermore, the α-helical motif between the 3HB and transmembrane domain, which is embedded in the surface of the lipid bilayer and self-associates in the crossover dimer, is required for ATL function. To recycle the proteins, Pi release, which disassembles the dimer, activates frequent relative movements between the GTPase domain and 3HB, and subsequent GDP dissociation alters the conformational preference of the ATLcyto monomer for entering the next reaction cycle. Finally, we found that two disease-causing mutations affect human ATL1 activity by destabilizing GTP binding-induced loose crossover dimer formation and the membrane-embedded helix, respectively. These results provide insights into ATL-mediated homotypic membrane fusion and the pathological mechanisms of related disease.

Abstract Background The lack of effective understanding of the pain mechanism of McCune–Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma. Objective This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD). Methods We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: “McCune–Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase”, as well as other keywords were systematically searched. Papers published between January 2018 and May 2023 were selected for finding. Initial screening was performed by reading the titles and abstracts, and available literature was screened against the inclusion and exclusion criteria. Results In this review, we systematically analyzed the cutting-edge advances in this disease, synthesized the findings, and discussed the differences. With regard to the complete mechanistic understanding of the pain condition in FD/MAS, in particular, we collated new findings on new pathways, neurotrophic factor receptors, purinergic receptors, interferon-stimulating factors, potassium channels, protein kinases, and corresponding hormonal modulation and their respective strengths and weaknesses. Conclusion This paper focuses on basic research to explore FD/MAS pain mechanisms. New nonneuronal and molecular mechanisms, mechanically loaded responsive neurons, and new targets for potential clinical interventions are future research directions, and a large number of animal experiments, tissue engineering techniques, and clinical trials are still needed to verify the effectiveness of the targets in the future.