Identifying cell type-specific transcription factor-mediated activity immune modules reveal implications for immunotherapy and molecular classification of pan-cancer.

Systematic investigation of tumor-infiltrating immune (TII) cells is important to the development of immunotherapies, and the clinical response prediction in cancers. There exists complex transcriptional regulation within TII cells, and different immune cell types display specific regulation patterns. To dissect transcriptional regulation in TII cells, we first integrated the gene expression profiles from single-cell datasets, and proposed a computational pipeline to identify TII cell type-specific transcription factor (TF) mediated activity immune modules (TF-AIMs). Our analysis revealed key TFs, such as BACH2 and NFKB1 play important roles in B and NK cells, respectively. We also found some of these TF-AIMs may contribute to tumor pathogenesis. Based on TII cell type-specific TF-AIMs, we identified eight CD8+ T cell subtypes. In particular, we found the PD1 + CD8+ T cell subset and its specific TF-AIMs associated with immunotherapy response. Furthermore, the TII cell type-specific TF-AIMs displayed the potential to be used as predictive markers for immunotherapy response of cancer patients. At the pan-cancer level, we also identified and characterized six molecular subtypes across 9680 samples based on the activation status of TII cell type-specific TF-AIMs. Finally, we constructed a user-friendly web interface CellTF-AIMs (http://bio-bigdata.hrbmu.edu.cn/CellTF-AIMs/) for exploring transcriptional regulatory pattern in various TII cell types. Our study provides valuable implications and a rich resource for understanding the mechanisms involved in cancer microenvironment and immunotherapy.

The uS10c-BPG2 module mediates ribosomal RNA processing in chloroplast nucleoids.

In plant chloroplasts, certain ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) are present in nucleoids, implying an association between nucleoids and ribosome biogenesis. In Arabidopsis, the YqeH-type GTPase Brassinazole-Insensitive Pale Green2 (BPG2) is a chloroplast nucleoid-associated RBF. Here, we investigated the relationship between nucleoids and BPG2-involved ribosome biogenesis steps by exploring how BPG2 targets ribosomes. Our findings demonstrate that BPG2 interacts with an essential plastid RP, uS10c, in chloroplast nucleoids in a ribosomal RNA (rRNA)-independent manner. We also discovered that uS10c is a haploinsufficient gene, as the heterozygous deletion of this gene leads to variegated shoots and chlorophyll aggregation. uS10c is integrated into 30S ribosomal particles when rRNA is relatively exposed and also exists in polysome fractions. In contrast, BPG2 exclusively associates with 30S ribosomal particles. Notably, the interaction between BPG2 and 30S particles is influenced by the absence of uS10c, resulting in BPG2 diffusing in chloroplasts instead of targeting nucleoids. Further, our results reveal that the loss of BPG2 function and the heterozygous deletion of uS10c impair the processing of 16S and 23S-4.5S rRNAs, reduce plastid protein accumulation, and trigger the plastid signaling response. Together, these findings indicate that the uS10c-BPG2 module mediates ribosome biogenesis in chloroplast nucleoids.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

ISL1-overexpressing BMSCs attenuate renal ischemia-reperfusion injury by suppressing apoptosis and oxidative stress through the paracrine action.

Ischemia-reperfusion injury (IRI) is a major event in renal transplantation, leading to adverse outcomes. Bone marrow mesenchymal stem cells (BMSCs) are novel promising therapeutics for repairing kidney injuries. The therapeutic efficacy of BMSCs with ISL1 overexpression in renal IRI and its underlying mechanism need to be investigated. The unilateral renal IRI rat model was established to mimic clinical acute kidney injury. Rats were injected with PBS, BMSCs-Scrambled or BMSCs-ISL1 via the tail vein at the timepoint of reperfusion, and then sacrificed after 24 h of reperfusion. The administration of BMSCs-ISL1 significantly improved renal function, inhibited tubular cells apoptosis, inflammation, oxidative stress in rats. In vitro, HKC cells subjected to H2O2 stimulation were pretreated with the conditioned medium (CM) of BMSCs-Scrambled or BMSCs-ISL1. The pretreatment of ISL1-CM attenuated apoptosis and oxidative stress induced by H2O2 in HKC cells. Our proteomic data suggested that haptoglobin (Hp) was one of the secretory proteins in ISL1-CM. Subsequent experiments confirmed that Hp was the important paracrine factor from BMSCs-ISL1 that exerted anti-apoptotic and antioxidant functions. Mechanistically, Hp played a cytoprotective role via the inhibition of ERK signaling pathway, which could be abrogated by Ro 67-7476, the ERK phosphorylation agonist. The results suggested that paracrine action may be the main mechanism for BMSCs-ISL1 to exert protective effects. As an important anti-apoptotic and antioxidant factor in ISL1-CM, Hp may serve as a new therapeutic agent for treating IRI, providing new insights for overcoming the long-term adverse effects of stem cell therapy.

Necroptosis-related genes allow novel insights into predicting graft loss and diagnosing delayed graft function in renal transplantation.

Ischemia-reperfusion injury (IRI) is an inevitable pathophysiological phenomenon in kidney transplantation. Necroptosis is an undoubtedly important contributing mechanism in renal IRI. We first screened differentially expressed necroptosis-related genes (DENRGs) from public databases. Eight DENRGs were validated by independent datasets and verified by qRT-PCR in a rat IRI model. We used univariate and multivariate Cox regression analyses to establish a prognostic signature, and graft survival analysis was performed. Immune infiltrating landscape analysis and gene set enrichment analysis (GSEA) were performed to understand the underlying mechanisms of graft loss, which suggested that necroptosis may aggravate the immune response, resulting in graft loss. Subsequently, a delayed graft function (DGF) diagnostic signature was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) and exhibited robust efficacy in validation datasets. After comprehensively analyzing DENRGs during IRI, we successfully constructed a prognostic signature and DGF predictive signature, which may provide clinical insights for kidney transplant.

Cost-Effective Cathode Interlayer Material for Scalable Organic Photovoltaic Cells.

Organic photovoltaic (OPV) cells have demonstrated remarkable success on the laboratory scale. However, the lack of cathode interlayer materials for large-scale production still limits their practical application. Here, we rationally designed and synthesized a cathode interlayer, named NDI-Ph. Benefiting from their well-modulated work function and self-doping effect, NDI-Ph-based binary OPV cells achieve an excellent power conversion efficiency (PCE) of 19.1%. NDI-Ph can be easily synthesized on a 100 g scale with a low cost of 1.96 $ g-1 using low-cost raw materials and a simple postprocessing method. In addition, the insensitivity to the film thickness of NDI-Ph enables it to maintain a high PCE at various coating speeds and solution concentrations, demonstrating excellent adaptability for high-throughput OPV cell manufacturing. As a result, a module with 21.9 cm2 active area achieves a remarkable PCEactive of 15.8%, underscoring the prospects of NDI-Ph in the large-scale production of OPV cells.

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

Lactate promotes microglial scar formation and facilitates locomotor function recovery by enhancing histone H4 lysine 12 lactylation after spinal cord injury.

Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.

Biomimetic Multifunctional Graphene-Based Coating for Thermal Management, Solar De-Icing, and Fire Safety: Inspired from the Antireflection Nanostructure of Compound Eyes.

Due to the ubiquitous and inexhaustible solar source, photothermal materials have gained considerable attention for their potential in heating and de-icing. Nevertheless, traditional photothermal materials, exemplified by graphene, frequently encounter challenges emanating from their elevated reflectance. Inspired by ocular structures, this study uses the Fresnel equation to enhance the photo-thermal conversion efficiency of graphene by introducing a polydimethylsiloxane (PDMS)/silicon dioxide (SiO2) coating, which reduces the light reflectance (≈20%) through destructive interference. The designed coating achieves an equilibrium temperature of ≈77 °C at one sun and a quick de-icing in ≈65 s, all with a thickness of 5 µm. Simulations demonstrate that applying this coating to high-rise buildings results in energy savings of ≈31% in winter heating. Furthermore, the combination of PDMS/SiO2 and graphene confers a notable enhancement in thermal stability through a synergistic flame-retardant mechanism, effectively safeguarding polyurethane against high temperatures and conflagrations, leading to marked reduction of 58% and 28% in heat release rate and total heat release. This innovative design enhances the photo-thermal conversion, de-icing function, and flame retardancy of graphene, thereby advancing its applications in outdoor equipment, high-rise buildings, and aerospace vessels.

The bacterial patterns suggesting the dynamic features of tick-associated microorganisms in hard ticks.

BACKGROUND: Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. RESULTS: Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. CONCLUSION: Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis.

Optimizing the efficiency of definitive endoderm (DE) differentiation is necessary for the generation of diverse organ-like structures. In this study, we used the small molecule inhibitor saracatinib (SAR) to enhance DE differentiation of human embryonic stem cells and induced pluripotent stem cells. SAR significantly improved DE differentiation efficiency at low concentrations. The interaction between SAR and Focal Adhesion Kinase (FAK) was explored through RNA-seq and molecular docking simulations, which further supported the inhibition of DE differentiation by p-FAK overexpression in SAR-treated cells. In addition, we found that SAR inhibited the nuclear translocation of Yes-associated protein (YAP), a downstream effector of FAK, which promoted DE differentiation. Moreover, the addition of SAR enabled a significant reduction in activin A (AA) from 50 to 10 ng/mL without compromising DE differentiation efficiency. For induction of the pancreatic lineage, 10 ng/ml AA combined with SAR at the DE differentiation stage yielded a comparative number of PDX1+/NKX6.1+ pancreatic progenitor cells to those obtained by 50 ng/ml AA treatment. Our study highlights SAR as a potential modulator that facilitates the cost-effective generation of DE cells and provides insight into the orchestration of cell fate determination.

Identification of candidate SNPs and genes associated with resistance to nervous necrosis virus in leopard coral grouper (Plectropomus leopardus) using GWAS.

The leopard coral grouper (Plectropomus leopardus), which has become increasingly popular in consumption due to its bright body color and great nutritional, holds a high economic and breeding potential. However, in recent years, the P.leopardus aquaculture industry has been impeded by the nervous necrosis virus (NNV) outbreak, leading to widespread mortality among fry and juvenile grouper. However, the genetic basis of resistance to NNV in P. leopardus remains to be investigated. In the present study, we conducted a genome-wide association analysis (GWAS) on 100 resistant and 100 susceptible samples to discover variants and potential genes linked with NNV resistance. For this study, 157,926 high-quality single nucleotide polymorphisms (SNPs) based on whole genome resequencing were discovered, and eighteen SNPs loci linked to disease resistance were discovered. We annotated six relevant candidate genes, including sik2, herc2, pip5k1c, npr1, mybpc3, and arhgap9, which showed important roles in lipid metabolism, oxidative stress, and neuronal survival. In the brain tissues of resistant and susceptible groups, candidate genes against NNV infection showed significant differential expression. The results indicate that regulating neuronal survival or pathways involved in lipid metabolism may result in increased resistance to NNV. Understanding the molecular mechanisms that lead to NNV resistance will be beneficial for the growth of the P. leopardus breeding sector. Additionally, the identified SNPs could be employed as biomarkers of disease resistance in P. leopardus, which will facilitate the selective breeding of grouper.

Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae.

Chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA), hydrogenated polyfluorooctane ether sulfonate (6:2 H-PFESA), and chlorinated polyfluorooctanesulfonate (Cl-PFOS) share structural similarities with the regulated perfluorooctanesulfonate (PFOS), but their toxic potential is rarely known. Here, the thyroid disrupting potential of these four compounds in zebrafish larvae has been comparably investigated. PFOS, Cl-PFOS, and 6:2 Cl-PFESA were accumulated in the larvae at similar levels, approximately 1.3-1.6 times higher than 6:2 H-PFESA. Additionally, PFOS, Cl-PFOS, and 6:2 Cl-PFESA exhibited stronger disruption than 6:2 H-PFESA on genetic regulation, particularly concerning thyroid hormone (TH) activation and action and on TH homeostasis in both free and total forms of thyroxine (T4) and 3,5,3'-triiodothyronine (T3). These results indicate that chlorination or oxygen insertion does not substantially alter the thyrotoxicity of PFOS, but hydrogenation mitigates it. Molecular docking analysis and the luciferase reporter gene assay provided mechanistic perspectives that the PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases.

Characterization of Fe-Containing and Pb-Containing Nanoparticles Resulting from Corrosion of Plumbing Materials in Tap Water Using a Hyphenated ATM-DMA-spICP-MS System.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used to characterize metallic nanoparticles (NPs) assuming that all NPs are spherical and composed of pure element. However, environmental NPs generally do not meet these criteria, suggesting that spICP-MS may underestimate their true sizes. This study employed a system hyphenating the atomizer (ATM), differential mobility analyzer (DMA), and spICP-MS to characterize metallic NPs in tap water. Its performance was validated by using reference Au nanoparticles (AuNPs) and Ag-shelled AuNPs. The hyphenated system can determine the actual size and metal composition of both NPs with additional heating after ATM, while stand-alone spICP-MS misidentified the Ag-shelled AuNPs as smaller individual AgNPs and AuNPs. Dissolved metal ions could introduce artifact NPs after heating but could be eliminated by centrifugation. The hyphenated system was applied to characterize Fe-containing and Pb-containing NPs resulting from the corrosion of plumbing materials in tap water. The mode sizes of Fe-containing and Pb-containing NPs were determined to be 110 and 100 nm and the particle number concentrations were determined to be 4.99 × 107 and 1.40 × 106 #/mL, respectively. Cautions should be paid to potential changes in particle size induced by heating for metallic NPs with a low melting point or a high organic content.

Molecular transmission network analysis of newly diagnosed HIV-1 infections in Nanjing from 2019 to 2021.

OBJECTIVE: The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. METHODS: Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. RESULTS: A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P < 0.05). Furthermore, the analysis of larger clusters revealed that individuals aged ≥ 60, peasants, those without TDR, and individuals infected with the CRF119_0107 were more likely to be part of these clusters. CONCLUSIONS: This study revealed the high risk of local HIV transmission and high TDR prevalence in Nanjing, especially the rapid spread of CRF119_0107. It is crucial to implement targeted interventions for the molecular transmission clusters identified in this study to effectively control the HIV epidemic.

Unraveling nitrogen loss in paddy soils: A study of anaerobic nitrogen transformation in response to various irrigation practice.

Soil nitrogen (N) transformation processes, encompassing denitrification, anaerobic ammonium oxidation (anammox), and anaerobic ammonium oxidation coupled with iron reduction (Feammox), constitute the primary mechanisms of soil dinitrogen (N2) loss. Despite the significance of these processes, there is a notable gap in research regarding the assessment of managed fertilization and irrigation impacts on anaerobic N transformations in paddy soil, crucial for achieving sustainable soil fertility management. This study addressed the gap by investigating the contributions of soil denitrification, anammox, and Feammox to N2 loss in paddy soil across varying soil depths, employing different fertilization and irrigation practices by utilizing N stable isotope technique for comprehensive insights. The results showed that anaerobic N transformation processes decreased with increasing soil depth under alternate wetting and drying (AWD) irrigation, but increased with the increasing soil depth under conventional continuous flooding (CF) irrigation. The denitrification and anammox rates varied from 0.41 to 2.12 mg N kg-1 d-1 and 0.062-0.394 mg N kg-1 d-1, respectively, which accounted for 84.3-88.1% and 11.8-15.7% of the total soil N2 loss. Significant correlations were found among denitrification rate and anammox rate (r = 0.986, p < 0.01), Fe (Ⅲ) reduction rate and denitrification rate (r = 0.527, p < 0.05), and Fe(Ⅲ) reduction rate and anammox rate (r = 0.622, p < 0.05). Moreover, nitrogen loss was more pronounced in the surface layer of the paddy soil compared to the deep layer. The study revealed that denitrification predominantly contributed to N loss in the surface soil, while Feammox emerged as a significant N loss pathway at depths ranging from 20 to 40 cm, accounting for up to 26.1% of the N loss. It was concluded that fertilization, irrigation, and soil depth significantly influenced anaerobic N transformation processes. In addition, the CF irrigation practice is best option to reduce N loss under managed fertilization. Furthermore, the role of microbial communities and their response to varying soil depths, fertilization practices, and irrigation methods could enhance our understanding on nitrogen loss pathways should be explored in future study.

High-Flow Nasal Oxygen versus Conventional Nasal Cannula in Preventing Hypoxemia in Elderly Patients Undergoing Gastroscopy with Sedation: A Randomized Controlled Trial.

Background: We aimed to compare the prevention of hypoxemia using High-flow nasal oxygen (HFNO) or regular nasal tubing (CNC) in elderly patients undergoing gastroscopy with sedation. Methods: This study was a prospective, randomized, controlled trial conducted at a single center. We included elective patients aged 65 and above who were undergoing gastroscopy with sedation. In the intervention group (HFNO), we set the oxygen flow rate to 60 liters per minute with an oxygen fraction (FiO2) of 0.6, while in the control group (CNC), it was 6 liters per minute. The primary outcome was the occurrence of hypoxemia (defined as Spo2 < 90%). Results: A total of 125 participants were enrolled (HFNO group: n = 63; CNC group: n = 62). The occurrence of hypoxemia was found to be significantly lower in the HFNO group compared to the CNC group (3.2% vs. 22.6%, p = 0.001). Additionally, a significantly shorter duration of low oxygen levels was observed in the HFNO group [0.0 seconds (0.0-13.0)] compared to the CNC group [0.0 seconds (0.0-124.0), p<0.001]. Moreover, a higher minimum Spo2 value was achieved in the HFNO group [99.0% (98.0-100.0) vs. 96.5% (91.0-99.0), p < 0.001], and a shorter recovery time was recorded [0.5 minutes (0.0-0.5) vs. 0.5 minutes (0.0-1.0), p = 0.016] in comparison to the CNC group. There were no differences in terms of comfort level [0 (0-4) vs. 0 (0-5), p = 0.268] between the two groups. Conclusions: The HFNO system was determined to be a safe and highly effective method for oxygen delivery, leading to a reduction in the occurrence of hypoxemia in elderly patients undergoing gastroscopy with sedation. It is recommended that HFNO be considered as the standard approach for management in this population.

Chikusetsu Saponin IVa liposomes modified with a retro-enantio peptide penetrating the blood-brain barrier to suppress pyroptosis in acute ischemic stroke rats.

BACKGROUND: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application. RESULT: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats. CONCLUSION: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.

The efficacy of bandage contact lens in relieving the aggravation of dry eye disease after complicated cataract or/and IOL surgery.

PURPOSE: In the present study, we aimed to evaluate the efficacy of the bandage contact lens (BCLs) in the treatment of dry eye disease (DED) after complicated cataract or/and intraocular lens (IOL) surgery. METHODS: In this retrospective, single-centered, observational study, we collected data from 69 patients who underwent complicated cataract or/and IOL surgery. Of these, 35 cases wore their own BCLs immediately after the operation, while the other 34 cases did not have their own BCLs and were instead covered with gauze. The Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp microscope examination, keratograph analysis, and Schirmer I test were measured at baseline, 1 week and 1 month postoperatively. RESULTS: In the BCL group, the score of the OSDI questionnaire was significantly decreased at 1 week and 1 month postoperatively compared with baseline levels (P = 0.000, collectively). Moreover, the fluorescein staining score of the BCL group was remarkably decreased 1-week and 1-month postoperatively compared with the non-BCL group (P = 0.000 and P = 0.000, respectively). Furthermore, the redness score of the BCL group was also better compared with the non-BCL group at 1 week and 1 month postoperatively (P = 0.014 and P = 0.004, respectively). CONCLUSIONS: Complicated cataract or/and IOL surgery would intensify the DED. Early application of BCLs postoperatively improved patients' comfort and alleviated dry eye-related symptoms and signs. Furthermore, this mechanism might involve the acceleration of corneal epithelial healing, the alleviation of ocular stress response and the stabilization of the tear film. TRIAL REGISTRATION: Trial registration ClinicalTrials, NCT04120389. Registered 10 October 2019-retrospectively registered.