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Climate warming and drying has led to a sharp increase in nitrogen (N) emissions from the boreal peatland soils, but the underlying microbial-mediated mechanism is still unclear. We reviewed the responses of soil N transformation and emission in alpine peatland to temperature increases and water table changes, the interaction between soil anaerobic ammonia oxidation (Anammox) and NO3- dissimilatory reduction processes, and soil N2O production pathways and their contributions. There are several knowledge gaps. First, the amount of N loss in peatlands in alpine areas is seriously underestimated because most studies focused only on soil N2O emissions and ignored the release of N2. Second, the contribution of Anammox process to N2 emissions from peatlands is not quantified. Third, there is a lack of quantification of the relative contributions of Anammox, bacterial denitrification, and fungal co-denitrification processes to N2 loss. Finally, the decoupling mechanism of Anammox and NO3- reduction processes under a warming and drying climate scenario is not clear. Considering aforementioned shortages in previous studies, we proposed the directions and contents for future research. Through building an experimental platform with field warming and water level controlling, combining stable isotope, molecular biology, and metagenomics technology, the magnitude, composition ratio and main controlling factors of N emissions (N2O, NO, and N2) in boreal peatlands should be systematically investigated. The interaction among the main N loss processes in soils as well as the relative contributions of nitrification, anaerobic ammonia oxidation, and denitrification to N2O and N2 productions should be investigated and quantified. Furthermore, the sensitive microbial groups and the coupling between soil N transformations and microbial community succession should be clarified to reveal the microbiological mechanism underlying the responses of soil N turnover process to climate warming and drying.

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PURPOSE: This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. METHOD: The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. RESULTS: Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. CONCLUSION: The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.

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BACKGROUND: Shotgun metagenomic next-generation sequencing (mNGS) is widely used to detect pathogens in bronchoalveolar lavage fluid (BALF). However, mNGS is complex and expensive. This study explored the feasibility of targeted next-generation sequencing (tNGS) in distinguishing lower respiratory tract infections in clinical practice. METHODS: We used 229 retrospective BALF samples to establish thresholds and diagnostic values in a prospective cohort of 251 patients. After target pathogen selection, primer and probe design, optimization experiments, and bioinformatics analysis, multiplex PCR-based tNGS (mp-tNGS) and hybrid capture-based tNGS (hc-tNGS), targeting 198 and 3060 pathogens (DNA and RNA co-detection workflow) were established and performed. FINDINGS: mp-tNGS and hc-tNGS took 10.3 and 16 h, respectively, with low sequencing data sizes of 0.1 M and 1 M reads, and test costs reduced to a quarter and half of mNGS. The LoDs of mp-tNGS and hc-tNGS were 50-450 CFU/mL. mp-tNGS and hc-tNGS were highly accurate, with 86.5% and 87.3% (vs. 85.5% for mNGS) sensitivities and 90.0% and 88.0% (vs. 92.1% for mNGS) specificities. tNGS detection rates for casual pathogens were 84.3% and 89.5% (vs. 88.5% for mNGS), significantly higher than conventional microbiological tests (P < 0.001). In seven samples, tNGS detected Pneumocystis jirovecii, a fungus not detected by mNGS. Whereas mNGS detected six samples with filamentous fungi (Rhizopus oryzae, Aureobasidium pullulans, Aspergillus niger complex, etc.) which missed by tNGS. The anaerobic bacteria as pathogen in eight samples was failed to detect by mp-tNGS. INTERPRETATION: tNGS may offer a new, broad-spectrum, rapid, accurate and cost-effective approach to diagnosing respiratory infections. FUNDING: National Natural Science Foundation of China (81625014 and 82202535).

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At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832-1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.

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BACKGROUND: Accurately modeling respiratory motion in medical images is crucial for various applications, including radiation therapy planning. However, existing registration methods often struggle to extract local features effectively, limiting their performance. OBJECTIVE: In this paper, we aimed to propose a new framework called CvTMorph, which utilizes a Convolutional vision Transformer (CvT) and Convolutional Neural Networks (CNN) to improve local feature extraction. METHODS: CvTMorph integrates CvT and CNN to construct a hybrid model that combines the strengths of both approaches. Additionally, scaling and square layers are added to enhance the registration performance. We have evaluated the performance of CvTMorph on the 4D-Lung and DIR-Lab datasets and compared it with state-of-the-art methods to demonstrate its effectiveness. RESULTS: The experimental results have demonstrated CvTMorph to outperform the existing methods in terms of accuracy and robustness for respiratory motion modeling in 4D images. The incorporation of the convolutional vision transformer has significantly improved the registration performance and enhanced the representation of local structures. CONCLUSION: CvTMorph offers a promising solution for accurately modeling respiratory motion in 4D medical images. The hybrid model, leveraging convolutional vision transformer and convolutional neural networks, has proven effective in extracting local features and improving registration performance. The results have highlighted the potential of CvTMorph for various applications, such as radiation therapy planning, and provided a basis for further research in this field.

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Marine algal toxins have garnered significant attention in the research community for their unique biochemical properties and potential medical applications. These bioactive compounds, produced by microalgae, pose significant risks due to their high toxicity, yet offer promising therapeutic benefits. Despite extensive research identifying over 300 marine algal toxins, including azaspiracids, brevetoxins, cyclic imines, and yessotoxins, gaps remain in the understanding of their pharmacological potential. In this paper, we critically review the classification, bioactive components, toxicology, pharmacological activities, and mechanisms of these toxins, with a particular focus on their clinical applications. Our motivation stems from the increasing interest in marine algal toxins as candidates for drug development, driven by their high specificity and affinity for various biological receptors. We aim to bridge the gap between toxicological research and therapeutic application, offering insights into the advantages and limitations of these compounds in comparison to other bioactive substances. This review not only enhances the understanding of marine algal toxins' complexity and diversity, but also highlights their extensive application potential in medicine and bioscience, providing a foundation for future research and development in this field.

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OBJECTIVE: Reduced adiponectin (ADPN) levels have been implicated in the pathogenesis of prostate cancer (PCa). The role of glycolysis in cancer development and treatment has attracted increasing attention. The present study aimed to elucidate its impact on PCa and to explore the mechanistic involvement of glycolysis. METHODS: An RM-1 cell xenograft model of Adpn-knockout mice was used to corroborate the effects of glycolysis, AMP-activated protein kinase (AMPK) signaling, and autophagy on tumor xenograft progression. The effect of ADPN on PCa cells was evaluated using the Cell Counting Kit-8 (CCK-8), lactate levels, and flow cytometry. The expression of glycolysis-related genes was detected using real-time RT-PCR in LNCaP and PC-3 cells after incubation with ADPN. Autophagic flux after ADPN treatment was quantified by chloroquine intervention and confocal analysis of mRFP-GFP-LC3. Alterations in the levels of adiponectin receptor 1 (AdipoR1), AMPK, Unc-51-like kinase 1 (ULK1), autophagy-related protein 7 (ATG7), p62, and microtubule-associated protein 1 light chain 3 beta (LC3B) were assessed after incubation of LNCaP cells with ADPN. RESULTS: Proteomic analysis of xenograft tumors demonstrated significant upregulation of glycolysis in Adpn-/- mice. Lower levels of ADPN accelerated tumor xenograft growth, diminished p-AMPKα/AMPKα ratio and LC3B II/I ratio, and elevated levels of proliferating cell nuclear antigen (PCNA) within the tumor microenvironment. ADPN inhibited proliferation and glycolysis and potentiated apoptosis in both cell lines. Expression of glycolysis-related genes decreased after ADPN treatment. Autophagic flux was elevated, as evidenced by changes in autophagy-related proteins and confocal microscopy analysis of mRFP-GFP-LC3. It led to the suppression of p62 while inducing phosphorylation of AMPKα and upregulating AdipoR1, ULK1, ATG7, and LC3B II/I ratio. CONCLUSION: ADPN inhibited the proliferation and progression of PCa cell-derived tumor xenografts by inhibiting glycolysis. Specifically, ADPN effectively inhibits glycolysis and activates the downstream AMPK/ULK1 signaling pathway to suppress proliferation of PCa cells.

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Water splitting is an important approach to hydrogen production. But the efficiency of the process is always controlled by the oxygen evolution reaction process. In this study, a three-dimensional nickel-molybdenum binary nanoarray microstructure electrocatalyst is successfully synthesized. It is grown uniformly on Ni foam using a hydrothermal method. Attributed to their unique nanostructure and controllable nature, the Ni-Mo-based nanoarray samples show superior reactivity and durability in oxygen evolution reactions. The series of Ni-Mo-based electrocatalysts presents a competitive overpotential of 296 mV at 10 mA·cm-2 for an OER in 1.0 M KOH, corresponding with a low Tafel slope of 121 mV dec-1. The three-dimensional nanostructure has a large double-layer capacitance and plenty of channels for ion transfer, which demonstrates more active sites and improved charge transmission. This study provides a valuable reference for the development of non-precious catalysts for water splitting.

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The microbiome plays a crucial role in soil nitrogen (N) cycling and in regulating its bioavailability. However, the functional and genomic information of microorganisms encoding N cycling in response to copper (Cu) and cadmium (Cd) contamination is largely unknown. Here, metagenomics and genome binning were used to examine microbial N cycling in Cu and Cd co-contaminated red paddy soils collected from a polluted watershed in southern China. The results showed that soil Cu and Cd concentrations induced more drastic changes in microbial N functional and taxonomic traits than soil general properties. Soil Cu and Cd co-contamination stimulated microbial nitrification, denitrification, and dissimilatory nitrate reduction processes mainly by increasing the abundance of Nitrospira (phylum Nitrospirota), while inhibiting N fixation by decreasing the abundance of Desulfobacca. These contrasting changes in microbial N cycling processes suggested a potential risk of N loss in paddy soils. A high-quality genome was identified as belonging to Nitrospirota with the highest abundance in heavily contaminated soils. This novel Nitrospirota strain possessed metabolic capacities for N transformation and metal resistance. These findings elucidate the genetic mechanisms underlying soil N bioavailability under long-term Cu and Cd contamination, which is essential for maintaining agricultural productivity and controlling heavy metal pollution.

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Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming.

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Clinical metagenomics (CMg) Nanopore sequencing can facilitate infectious disease diagnosis. In China, sub-lineages ST11-KL64 and ST11-KL47 Carbapenem-resistant Klebsiella pneumoniae (CRKP) are widely prevalent. We propose PathoTracker, a specially compiled database and arranged method for strain feature identification in CMg samples and CRKP traceability. A database targeting high-prevalence horizontal gene transfer in CRKP strains and a ST11-only database for distinguishing two sub-lineages in China were created. To make the database user-friendly, facilitate immediate downstream strain feature identification from raw Nanopore metagenomic data, and avoid the need for phylogenetic analysis from scratch, we developed data analysis methods. The methods included pre-performed phylogenetic analysis, gene-isolate-cluster index and multilevel pan-genome database and reduced storage space by 10-fold and random-access memory by 52-fold compared with normal methods. PathoTracker can provide accurate and fast strain-level analysis for CMg data after 1 h Nanopore sequencing, allowing early warning of outbreaks. A user-friendly page ( http://PathoTracker.pku.edu.cn/ ) was developed to facilitate online analysis, including strain-level feature, species identifications and phylogenetic analyses. PathoTracker proposed in this study will aid in the downstream analysis of CMg.

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Taxus, a rare and protected genus predominantly distributed across the Northern Hemisphere's temperate regions, has garnered global attention due to its significant potential in medical research and pharmaceutical development, bolstered by advancements in cultivation techniques and medical technology. This review primarily focuses on the chemical constituents and pharmacological activities of Taxus, underscoring the progress and potential of these components in clinical applications. Recent studies have revealed that Taxus contains not only taxane active components but also flavonoids and polysaccharides with distinct activities. These compounds from Taxus exhibit potent antitumor, anti-inflammatory, immunomodulatory, antibacterial, and antidiabetic properties with evident mechanisms of action. Notably, the representative compound, paclitaxel, has demonstrated significant efficacy in treating various cancers, such as ovarian, breast, and lung cancer. This paper also reviews the basic situation of Taxus drug formulations, with extracts primarily administered orally and monomeric taxanes typically via injection, reflecting a mature development stage with ongoing research into oral formulations. Finally, this review summarizes the pharmacokinetic characteristics of crucial compounds in Taxus, including their absorption, distribution, metabolism, and excretion patterns in the human body. These pharmacokinetic profiles provide crucial guidance for evaluating the overall dosing regimen of Taxus and its components. The paper concludes with a forward-looking analysis of the potential applications of these compounds in disease treatment, envisioning their role in the future of medical and pharmaceutical advancements.

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Q fever is a worldwide distribution disease caused by Coxiella burnetii（C. burnetii）, an obligate intracellular, Gram-negative acidophilic bacterium belonging to γ-proteobacterium. Most patients present with acute Q-fever accompanied by atypical flu-like symptoms, with only 1%-5% of cases may develop into persistent and focally infected foci, mainly manifest as endocarditis, osteomyelitis and prosthetic arthritis. In this case, the patient experienced an unexplained and uninterrupted fever up to 39.2 °C for a week, accompanied by chills and headaches, as well as abnormal liver function. The laboratory reported negative results for blood culture and respiratory-associated pathogens, however, the metagenomic next-generation sequencing (mNGS) reported that detection of 20 sequence reads of C. burnetii in the patient's peripheral blood. In addition, the patient had traveled to Sri Lanka, Iraq and Saudi Arabia before illness. In clinical, the treatment regimen was adjusted from empirically intravenous moxifloxacin 400 mg a day for 1 week to continuously oral minocyline 100 mg twice daily for 2 weeks. The patient was in good health without any adverse sequelae during outpatient visitation and the phone calls follow-up. In conclusion, the mNGS does provide an early and timely diagnostic basis for rare and difficult to culture pathogens, which contributes to the success of clinical anti-infection.

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BACKGROUND: Haematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features. RESULTS: A total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections. CONCLUSIONS: Analysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life. Video Abstract.

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INTRODUCTION: Ruptured abdominal aortic aneurysms (RAAAs) are among the most dangerous emergencies in vascular surgery, with a high death rate and numerous risk factors influencing perioperative death. Therefore, identifying the critical risk factors for RAAAs is crucial to increasing their survival rate. Our aim was to identify those risk factors from a wide range of parameters. METHODS: Retrospective analysis of hospitalized RAAA patients treated at this center between May 2004 and January 2023. After comparing the preoperative data of patients who survived and those who died, high-risk characteristics influencing the perioperative care of RAAA patients were identified, and logistic regression analysis was carried out. The mean follow-up time was 45.34 months. RESULTS: During the study period, a total of 155 patients (average age 67.4 ± 71.93 years, 123 (78.85%) males, 32 (20.51%) females) were enrolled. The patients participating in the group were divided into survival group (n = 123) and death group (n = 27). The main differences included hemodynamic instability (51.9% vs 28.5%; P = 0.019), sudden cardiac arrest (14.8% vs 1.6%; P = 0.010), deterioration of consciousness (40.7% vs 17.1%; P = 0.007), renal impairment (22.2% vs 2.4%; P = 0.001), and chronic kidney disease (18.5% vs3.2%; P = 0.010). There is also a history of cancer (Ca) (18.5% vs 4.1%; P = 0.021). Risk factors for endovascular aneurysm repair (EVAR) include diastolic blood pressure ≤50 mm Hg (36.4% vs 8.0%; P = 0.025), renal function impairment (18.2% vs 0; P = 0.015), and chronic kidney disease (27.3% vs 4.0%; P = 0.028). Risk factors for open surgical repair (OSR) include diastolic blood pressure ≤50 mm Hg (40.0% vs 6.3%; P = 0.014). Finally, the previously mentioned statistically significant factors were analyzed by logistic regression analysis, and it was found that diastolic blood pressure ≤50 mm Hg, cardiac arrest, renal function damage, and Ca history were independent risk factors. We followed 123 individuals and 14 were lost to follow-up, with an overall survival rate of 43.8%. CONCLUSIONS: Hemodynamics, which includes shock, blood pressure, cardiac arrest, deterioration of consciousness, and other conditions, are the primary risk factors for the perioperative death of a ruptured abdominal aortic aneurysm. Simultaneously, diastolic blood pressure ≤50 mm Hg was found to be associated with risk factors for OSR, whereas renal function impairment, chronic renal illness, and diastolic blood pressure ≤50 mm Hg were associated with the risk for EVAR.

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BACKGROUND: Clinical impact of plasma metagenomic next-generation sequencing (mNGS) on infection diagnosis and antimicrobial therapy in immunocompromised patients with suspected infection remains unclear. METHODS: Between March and December 2022, 424 cases with fever, infection history, mechanical ventilation, or imaging abnormalities underwent plasma mNGS testing at a single center. Eleven patients have received solid organ transplantation, and the remaining patients were categorised into febrile neutropenia (FN), non-neutropenia (NN), and non-haematologic disease (NTHD) groups based on immunosuppression severity. The diagnostic rate of infection and the utilisation of antimicrobial agents based on mNGS were assessed. RESULTS: The use of mNGS significantly improved the diagnostic rates for fungi in the FN (56.1%, P = 0.003) and NN (58.8%, P = 0.008) groups versus the NHD group (33.3%). Positive impacts associated with therapy were significantly greater than negative impacts across all three groups (all P < 0.001), and the utilisation of escalation therapy was significantly more frequent in the FN group than in the NN groups (P = 0.006). Over 70% of cases with negative mNGS results across the three groups underwent de-escalation therapy, with >1/3 being discontinued, preventing antimicrobial overuse. CONCLUSIONS: Plasma mNGS has a clinically confirmed positive impact in immunocompromised patients with neutropenia, improving the diagnosis of fungal infections and antimicrobial therapy.

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Reactive oxygen species (ROS) play a complex role in interactions between plant viruses and their host plants. They can both help the plant defend against viral infection and support viral infection and spread. This review explores the various roles of ROS in plant-virus interactions, focusing on their involvement in symptom development and the activation of plant defense mechanisms. The article discusses how ROS can directly inhibit viral infection, as well as how they can regulate antiviral mechanisms through various pathways involving miRNAs, virus-derived small interfering RNAs, viral proteins, and host proteins. Additionally, it examines how ROS can enhance plant resistance by interacting with hormonal pathways and external substances. The review also considers how ROS might promote viral infection and transmission, emphasizing their intricate role in plant-virus dynamics. These insights offer valuable guidance for future research, such as exploring the manipulation of ROS-related gene expression through genetic engineering, developing biopesticides, and adjusting environmental conditions to improve plant resistance to viruses. This framework can advance research in plant disease resistance, agricultural practices, and disease control.

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With the intensive research on the pathogenesis of Alzheimer's disease (AD), inhibition of HDAC6 appears to be a potential therapeutic approach for AD. In this paper, a series of tetrahydro-ß-carboline derivatives with hydroxamic acid group were fast synthesized. Among all, the most potent 15 selectively inhibited HDAC6 with IC50 of 15.2 nM and markedly increased acetylated alpha-tubulin levels. In cellular assay, 15 showed excellent neurotrophic effect by increasing the expression of GAP43 and Beta-3 tubulin markers. Besides, 15 showed neuroprotective effects in PC12 or SH-SY5Y cells against H2O2 and 6-OHDA injury through activation of Nrf2, catalase and Prx II, and significantly reduced H2O2-induced reactive oxygen species (ROS) production. In vivo, 15 significantly attenuated zebrafish anxiety-like behaviour and memory deficits in a SCOP-induced zebrafish model of AD. To sum up, multifunctional 15 might be a good lead to develop novel tetrahydrocarboline-based agents for the treatment of AD.

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