Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72 h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

Ethane/Ethylene Separations in Flexible Diamondoid Coordination Networks via an Ethane-Induced Gate-Opening Mechanism.

Separating ethane (C2H6) from ethylene (C2H4) is an essential and energy-intensive process in the chemical industry. Here, we report two flexible diamondoid coordination networks, X-dia-1-Ni and X-dia-1-Ni0.89Co0.11, that exhibit gate-opening between narrow-pore (NP) and large-pore (LP) phases for C2H6, but not for C2H4. X-dia-1-Ni0.89Co0.11 thereby exhibited a type F-IV isotherm at 273 K with no C2H6 uptake and a high uptake (111 cm3 g-1, 1 atm) for the NP and LP phases, respectively. Conversely, the LP phase exhibited a low uptake of C2H4 (12.2 cm3 g-1). This C2H6/C2H4 uptake ratio of 9.1 for X-dia-1-Ni0.89Co0.11 far surpassed those of previously reported physisorbents, many of which are C2H4-selective. In situ variable-pressure X-ray diffraction and modeling studies provided insight into the abrupt C2H6-induced structural NP to LP transformation. The promise of pure gas isotherms and, more generally, flexible coordination networks for gas separations was validated by dynamic breakthrough studies, which afforded high-purity (99.9%) C2H4 in one step.

A Versatile Platform to Generate Prodrugs with Rapid and Precise Albumin Hitchhiking and High Cargo Loading for Tumor-Targeted Chemotherapy.

Due to its tumor homing and long serum half-life, albumin is an ideal drug carrier for chemotherapy. For endogenous albumin hitchhiking with high cargo loading, a trimeric albumin-binding domain (ABD), i.e., ABD-Tri is designed by fusing an ABD with high specificity and affinity for albumin to a self-trimerizing domain (Tri) with an additional cysteine residue. ABD-Tri is highly (40 mg L-1) expressed as soluble and trimeric proteins in Escherichia coli (E. coli). Once mixed together, ABD-Tri rapidly and specifically forms a stable complex with albumin under physiological conditions without obviously changing its receptor- and cell-binding and tumor-homing properties. Maleimide-modified prodrugs are highly effectively conjugated to ABD-Tri to produce homogenous ABD-Tri-prodrugs with triple cargo loading under physiological conditions by thiol-maleimide click chemistry. Unlike the maleimide moiety, which can only mediate time- and concentration-dependent albumin binding, ABD-Tri mediated fast (within several minutes) albumin binding of drugs even at extremely low concentrations (µg mL-1). Compared to maleimide-modified prodrugs, ABD-Tri-prodrugs exhibit better tumor homing and greater in vivo antitumor effect, indicating that conjugation of chemical drug to ABD-Tri outperforms maleimide modification for endogenous albumin hitchhiking. The results demonstrate that ABD-Tri may serve as a novel platform to produce albumin-binding prodrugs with high cargo-loading capacity for tumor-targeted chemotherapy.

Amino-Functionalized Metal-Organic Frameworks Featuring Ultra-Strong Ethane Nano-Traps for Efficient C2H6/C2H4 Separation.

Developing high-performance porous materials to separate ethane from ethylene is an important but challenging task in the chemical industry, given their similar sizes and physicochemical properties. Herein, a new type of ultra-strong C2H6 nano-trap, CuIn(3-ain)4 is presented, which utilizes multiple guest-host interactions to efficiently capture C2H6 molecules and separate mixtures of C2H6 and C2H4. The ultra-strong C2H6 nano-trap exhibits the high C2H6 (2.38 mmol g-1) uptake at 6.25 kPa and 298 K and demonstrates a remarkable selectivity of 3.42 for C2H6/C2H4 (10:90). Additionally, equimolar C2H6/C2H4 exhibited a superior high separation potential ∆Q (2286 mmol L-1) at 298 K. Kinetic adsorption tests demonstrated that CuIn(3-ain)4 has a high adsorption rate for C2H6, establishing it as a new benchmark material for the capture of C2H6 and the separation of C2H6/C2H4. Notably, this exceptional performance is maintained even at a higher temperature of 333 K, a phenomenon not observed before. Theoretical simulations and single-crystal X-ray diffraction provide critical insights into how selective adsorption properties can be tuned by manipulating pore dimensions and geometry. The excellent separation performance of CuIn(3-ain)4 has been confirmed through breakthrough experiments for C2H6/C2H4 gas mixtures.

Ligand Defect-Induced Active Sites in Ni-MOF-74 for Efficient Photocatalytic CO2 Reduction to CO.

The conversion of CO2 into valuable carbon-based products using clean and renewable solar energy has been a significant challenge in photocatalysis. It is of paramount importance to develop efficient photocatalysts for the catalytic conversion of CO2 using visible light. In this study, the Ni-MOF-74 material is successfully modified to achieve a highly porous structure (Ni-74-Am) through temperature and solvent modulation. Compared to the original Ni-MOF-74, Ni-74-Am contains more unsaturated Ni active sites resulting from defects, thereby enhancing the performance of CO2 photocatalytic conversion. Remarkably, Ni-74-Am exhibits outstanding photocatalytic performance, with a CO generation rate of 1380 µmol g-1 h-1 and 94% CO selectivity under visible light, significantly surpassing the majority of MOF-based photocatalysts reported to date. Furthermore, experimental characterizations reveal that Ni-74-Am has significantly higher efficiency of photogenerated electron-hole separation and faster carrier migration rate for photocatalytic CO2 reduction. This work enriches the design and application of defective MOFs and provides new insights into the design of MOF-based photocatalysts for renewable energy and environmental sustainability. The findings of this study hold significant promise for developing efficient photocatalysts for CO2 reduction under visible-light conditions.

Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions.

Human induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating organoids rely on Matrigel, whose batch-to-batch variability and xenogeneic source pose challenges to mechanistic research and translation to human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived organoids developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific functions than organoids formed on Matrigel. We show that RWVs produce highly functional liver organoids in part by eliminating the need for Matrigel, which has adverse effects on hepatic lineage differentiation. RWV liver organoids sustain durable function over long-term culture and express a range of mature functional genes at levels comparable to adult human liver, while retaining some fetal features. Our results indicate that RWVs provide a simple and high-throughput way to generate Matrigel-free liver organoids suitable for research and clinical applications.

Platelet-derived growth factor receptor ß-targeted positron emission tomography imaging for the noninvasive monitoring of liver fibrosis.

PURPOSE: Noninvasive quantifying activated hepatic stellate cells (aHSCs) by molecular imaging is helpful for assessing disease progression and therapeutic responses of liver fibrosis. Our purpose is to develop platelet-derived growth factor receptor ß (PDGFRß)-targeted radioactive tracer for assessing liver fibrosis by positron emission tomography (PET) imaging of aHSCs. METHODS: Comparative transcriptomics, immunofluorescence staining and flow cytometry were used to evaluate PDGFRß as biomarker for human aHSCs and determine the correlation of PDGFRß with the severity of liver fibrosis. The high affinity affibody for PDGFRß (ZPDGFRß) was labeled with gallium-68 (68Ga) for PET imaging of mice with carbon tetrachloride (CCl4)-induced liver fibrosis. Binding of the [68Ga]Ga-labeled ZPDGFRß ([68Ga]Ga-DOTA-ZPDGFRß) for aHSCs in human liver tissues was measured by autoradiography. RESULTS: PDGFRß overexpressed in aHSCs was highly correlated with the severity of liver fibrosis in patients and CCl4-treated mice. The 68Ga-labeled ZPDGFRß affibody ([68Ga]Ga-DOTA-ZPDGFRß) showed PDGFRß-dependent binding to aHSCs. According to the PET imaging, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß increased with the accumulation of aHSCs and collagens in the fibrotic livers of mice. In contrast, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß decreased with spontaneous recovery or treatment of liver fibrosis, indicating that the progression and therapeutic responses of liver fibrosis in mice could be visualized by PDGFRß-targeted PET imaging. [68Ga]Ga-DOTA-ZPDGFRß also bound human aHSCs and visualized fibrosis in patient-derived liver tissues. CONCLUSIONS: PDGFRß is a reliable biomarker for both human and mouse aHSCs. PDGFRß-targeted PET imaging could be used for noninvasive monitoring of liver fibrosis in mice and has great potential for clinical translation.

Structure and luminescence characteristics of self-activated vanadate garnet phosphors.

Vanadate phosphors include [VO4] tetrahedra with Td symmetry. Due to the charge transfer (CT) between V5+-O2-, the phosphor with [VO4] tetrahedra exhibits strong emission in the visible region and can effectively absorb ultraviolet (UV) light. Garnet structured vanadate phosphors have attracted much attention due to their easily controllable composition. In this paper, we successfully prepared phosphors with high quantum efficiency. The lattice structure and luminescent properties of the samples were studied in detail. Vanadate garnet phosphors have the same structure. The phosphors exhibit broadband emission peaks under 266 nm and 355 nm near-ultraviolet (UV) excitation, emitting bright greenish-white and yellowish-white light. The emission wavelength of the phosphor is red-shifted. The phosphors exhibit high internal quantum efficiency (IQE) for the NaSr2Mg2V3O12 and KCa2Mg2V3O12 samples. In this paper, the structure and luminescence characteristics of greenish-white-emitting and yellowish-white-emitting vanadate phosphors with high quantum efficiency are investigated.

Structural characterization of Li2(MgxZn1-x)2W2O9 for bluish-white luminescence in rare earth-free tungstate phosphors.

Self-activated phosphors have attracted considerable attention due to their low synthesis temperature, high excitation threshold, and broad emission spectrum. And self-activated tungstate phosphors are distinguished by their low cost and stable chemical properties. Generally, it is difficult to observe luminescence from tungstate phosphors at room temperature. Furthermore, blue-emitting tungstate phosphors with high quantum efficiency are rarely reported. In this study, we succeeded in discovering high quantum-efficiency bluish-white-emitting Li2(MgxZn1-x)2W2O9 phosphors and investigating their detailed crystal structures. Upon near-ultraviolet excitation at 266 nm, these phosphors exhibit a broadband emission peak. The red shift of emission is slight with increasing Zn content in Li2(MgxZn1-x)2W2O9. A highly compact octahedral [WO6] unit is observed in the Li2(MgxZn1-x)2W2O9 phosphors. The phosphors exhibit high internal quantum efficiencies (IQEs) of 68.70% (M = Mg), 43.90% (M = Mg0.5Zn0.5), and 22.90% (M = Zn), respectively. This study provides a bluish-white-emitting tungstate phosphor with high quantum efficiency.

The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.

High-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio predicts long-term adverse outcomes in patients who underwent percutaneous coronary intervention: A prospective cohort study.

High-sensitivity C-reactive protein (hsCRP) to high-density lipoprotein cholesterol (HDL-C) ratio (CHR) is associated with coronary artery disease (CAD), but its predictive value for long-term adverse outcomes in patients with CAD following percutaneous coronary intervention (PCI) remains unexplored and is the subject of this study. Patients with CAD who underwent PCI at the Korea University Guro Hospital-Percutaneous Coronary Intervention (KUGH-PCI) Registry since 2004 were included. Patients were categorized into tertiles according to their CHR. The end points were all-cause mortality (ACM), cardiac mortality (CM) and major adverse cardiac events (MACEs). Kaplan-Meier analysis, multivariate Cox regression, restricted cubic spline (RCS) and sensitivity analyses were performed. A total of 3260 patients were included and divided into Group 1 (CHR <0.830, N = 1089), Group 2 (CHR = 0.830-3.782, N = 1085) and Group 3 (CHR >3.782, N = 1086). Higher CHR tertiles were associated with progressively greater risks of ACM, CM and MACEs (log-rank, p < 0.001). Multivariate Cox regression showed that patients in the highest tertile had greater risks of ACM (HR: 2.127 [1.452-3.117]), CM (HR: 3.575 [1.938-6.593]) and MACEs (HR: 1.337 [1.089-1.641]) than those in the lowest tertile. RCS analyses did not reveal a significant non-linear relationship between CHR and ACM, CM or MACEs. The significant associations remained significant in the sensitivity analyses, RCS analyses with or without extreme values, subgroup analyses and multiple imputations for missing data. Elevated CHR is a novel, independent risk factor for long-term ACM, CM and MACEs in CAD patients following PCI.

Risk factors for residual lesions after total hysterectomy in patients with high-grade cervical intraepithelial neoplasia.

BACKGROUND: The purpose of this study was to predict the risk factors for residual lesions in patients with high-grade cervical intraepithelial neoplasia who underwent total hysterectomy. METHODS: This retrospective study included 212 patients with histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2-3) who underwent hysterectomy within 6 months after loop electrosurgical excision procedure (LEEP). Clinical data (e.g., age, menopausal status, HPV type, and Liquid-based cytology test(LCT) type), as well as pathological data affiliated with endocervical curettage (ECC), colposcopy, LEEP and hysterectomy, were retrieved from medical records. A logistic regression model was applied to estimate the relationship between the variables and risk of residual lesions after hysterectomy. RESULTS: Overall, 75 (35.4%) patients had residual lesions after hysterectomy. Univariate analyses revealed that positive margin (p = 0.003), glandular involvement (p = 0.017), positive ECC (p < 0.01), HPV16/18 infection (p = 0.032) and vaginal intraepithelial neoplasia (VaIN) I-III (p = 0.014) were factors related to the presence of residual lesions after hysterectomy. Conversely, postmenopausal status, age ≥ 50 years, ≤ 30 days from LEEP to hysterectomy, and LCT type were not risk factors for residual lesions. A positive margin (p = 0.025) and positive ECC (HSIL) (p < 0.001) were identified as independent risk factors for residual lesions in multivariate analysis. CONCLUSIONS: Our study revealed that positive incisal margins and ECC (≥ CIN2) were risk factors for residual lesions, while glandular involvement and VaIN were protective factors. In later clinical work, colposcopic pathology revealed that glandular involvement was associated with a reduced risk of residual uterine lesions. 60% of the patients with residual uterine lesions were menopausal patients, and all patients with carcinoma in situ in this study were menopausal patients. Therefore, total hysterectomy may be a better choice for treating CIN in menopausal patients with positive margins and positive ECC.

Sunitinib-induced endocapillary proliferative glomerulonephritis with IgA2 deposit in addition to thrombotic microangiopathy: a case report.

BACKGROUND: Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA). CASE PRESENTATION: This case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed. CONCLUSIONS: This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.

Spiritual care needs and their attributes among Chinese inpatients with advanced breast cancer based on the Kano model: a descriptive cross-sectional study.

BACKGROUND: Numerous previous research have established the need for spiritual care among patients with cancer globally. Nevertheless, there was limited research, primarily qualitative, on the spiritual care needs of Chinese inpatients with advanced breast cancer. Furthermore, the need for spiritual care was rarely explored using the Kano model. To better understand the spiritual care needs and attributes characteristics of inpatients with advanced breast cancer, this study examined the Kano model. METHODS: A descriptive cross-sectional design study was conducted in the oncology departments of three tertiary grade-A hospitals in China from October 2022 to May 2023. To guarantee high-quality reporting of the study, the Strengthening the Reporting of Observational Studies in Epidemiology Checklist was used. Data on the demographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale (NSTS), and the Kano model-based Nurse Spiritual Therapeutics Attributes Scale (K-NSTAs) were collected through convenience sampling. The Kano model, descriptive statistics, two independent samples t-tests, and one-way analysis of variance were used to analyze the data. RESULTS: The overall score for spiritual care needs was 31.16 ± 7.85. The two dimensions with the highest average scores, "create a good atmosphere" (3.16 ± 0.95), and the lowest average scores, "help religious practice" (1.72 ± 0.73). The 12 items were distributed as follows: three attractive attributes were located in Reserving Area IV; five one-dimensional attributes were distributed as follows: three one-dimensional attributes were located in Predominance Area I, and two were found in Improving Area II; two must-be attributes were located in Improving Area II; and two indifference attributes were located in Secondary Improving Area III. CONCLUSION: The Chinese inpatients with advanced breast cancer had a middle level of spiritual care needs, which need to be further improved. Spiritual care needs attributes were defined, sorted, categorized, and optimized accurately and perfectly by the Kano model. And "create a good atmosphere" and "share self-perception" were primarily one-dimensional and must-be attributes. In contrast, the items in the dimensions of "share self-perception" and "help thinking" were principally attractive attributes. Nursing administrators are advised to optimize attractive attributes and transform indifference attributes by consolidating must-be and one-dimensional attributes, which will enable them to take targeted spiritual care measures based on each patient's characteristics and unique personality traits.

Genome-Wide Association Study in Acute Tubulointerstitial Nephritis.

SIGNIFICANCE STATEMENT: Polymorphisms of HLA genes may confer susceptibility to acute tubulointerstitial nephritis (ATIN), but small sample sizes and candidate gene design have hindered their investigation. The first genome-wide association study of ATIN identified two significant loci, risk haplotype DRB1*14-DQA1*0101-DQB1*0503 (DR14 serotype) and protective haplotype DRB1*1501-DQA1*0102-DQB1*0602 (DR15 serotype), with amino acid position 60 in the peptide-binding groove P10 of HLA-DR ß 1 key. Risk alleles were shared among different causes of ATIN and HLA genotypes associated with kidney injury and immune therapy response. HLA alleles showed the strongest association. The findings suggest that a genetically conferred risk of immune dysregulation is part of the pathogenesis of ATIN. BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare immune-related disease, accounting for approximately 10% of patients with unexplained AKI. Previous elucidation of the relationship between genetic factors that contribute to its pathogenesis was hampered because of small sample sizes and candidate gene design. METHODS: We undertook the first two-stage genome-wide association study and meta-analysis involving 544 kidney biopsy-defined patients with ATIN and 2346 controls of Chinese ancestry. We conducted statistical fine-mapping analysis, provided functional annotations of significant variants, estimated single nucleotide polymorphism (SNP)-based heritability, and checked genotype and subphenotype correlations. RESULTS: Two genome-wide significant loci, rs35087390 of HLA-DQA1 ( P =3.01×10 -39 ) on 6p21.32 and rs2417771 of PLEKHA5 on 12p12.3 ( P =2.14×10 -8 ), emerged from the analysis. HLA imputation using two reference panels suggested that HLA-DRB1*14 mainly drives the HLA risk association . HLA-DRB1 residue 60 belonging to pocket P10 was the key amino acid position. The SNP-based heritability estimates with and without the HLA locus were 20.43% and 10.35%, respectively. Different clinical subphenotypes (drug-related or tubulointerstitial nephritis and uveitis syndrome) seemed to share the same risk alleles. However, the HLA risk genotype was associated with disease severity and response rate to immunosuppressive therapy. CONCLUSIONS: We identified two candidate genome regions associated with susceptibility to ATIN. The findings suggest that a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.

Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Kinesophobia and its related factors in patients after percutaneous coronary intervention: A cross-sectional study.

OBJECTIVES: To explore the postoperative kinesophobia of patients after percutaneous coronary intervention (PCI) and its related factors. BACKGROUND: Percutaneous coronary intervention is an effective method to treat coronary heart disease (CHD), and cardiac rehabilitation is an important auxiliary method after PCI. However, the compliance of patients with cardiac rehabilitation after PCI is not good, among which kinesophobia is an important influencing factor. DESIGN: A descriptive cross-sectional design was implemented, and the high-quality reporting of the study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology Statement. METHODS: In total, 351 inpatients who underwent PCI in three tertiary grade-A hospitals in China were selected by convenient sampling method. We use one-way ANOVA and multiple linear regression analysis to determine the relevant related factors. RESULTS: The kinesophobia of patients after PCI was negatively correlated with chronic illness resource utilization and sense of personal mastery, and positively correlated with illness perception. Education level, clinical classification of CHD, exercise habits, chronic illness resource utilization, illness perception and sense of personal mastery entered the regression equation, which could explain 78.1% of the total variation. CONCLUSION: The level of kinesiophobia of patients after PCI is high. Education level, clinical classification of CHD, exercise habits, chronic illness resource utilization, illness perception and sense of personal mastery are the related factors of kinesiophobia of patients after PCI. RELEVANCE TO CLINICAL PRACTICE: By reducing the level of exercise fear of patients after PCI, patients are more likely to accept and adhere to the cardiac rehabilitation plan, thus improving their prognosis and improving their quality of life. PATIENT OR PUBLIC CONTRIBUTION: The patient underwent PCI in the research hospital. Researchers screen them according to the inclusion criteria and invite them to participate in this study. If they meet the requirements, participants will answer the research questionnaire face to face after signing the informed consent form.

Regulating Effect of Exogenous α-Ketoglutarate on Ammonium Assimilation in Poplar.

Extensive industrial activities and anthropogenic agricultural practices have led to substantial ammonia release to the environment. Although croplands can act as ammonia sinks, reduced crop production under high concentrations of ammonium has been documented. Alpha-ketoglutarate (AKG) is a critical carbon source, displaying pleiotropic physiological functions. The objective of the present study is to disclose the potential of AKG to enhance ammonium assimilation in poplars. It showed that AKG application substantially boosted the height, biomass, and photosynthesis activity of poplars exposed to excessive ammonium. AKG also enhanced the activities of key enzymes involved in nitrogen assimilation: glutamine synthetase (GS) and glutamate synthase (GOGAT), elevating the content of amino acids, sucrose, and the tricarboxylic acid cycle (TCA) metabolites. Furthermore, AKG positively modulated key genes tied to glucose metabolism and ATP synthesis, while suppressing ATP-depleting genes. Correspondingly, both H+-ATPase activity and ATP content increased. These findings demonstrate that exogenously applying AKG improves poplar growth under a high level of ammonium treatment. AKG might function through sufficient carbon investment, which enhances the carbon-nitrogen balance and energy stability in poplars, promoting ammonium assimilation at high doses of ammonium. Our study provides novel insight into AKG's role in improving poplar growth in response to excess ammonia exposure.

Study on the applicability of FAI linear fitting model in the extraction of cyanobacterial blooms.

Currently, more and more lakes around the world are experiencing outbreaks of cyanobacterial blooms, and high-precision and rapid monitoring of the spatial distribution of algae in water bodies is an important task. Remote sensing technology is one of the effective means for monitoring algae in water bodies. Studies have shown that the Floating Algae Index (FAI) is superior to methods such as the Standardized Differential Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) in monitoring cyanobacterial blooms. However, compared to the NDVI method, the FAI method has difficulty in determining the threshold, and how to choose the threshold with the highest classification accuracy is challenging. In this study, FAI linear fitting model (FAI-L) is selected to solve the problem that FAI threshold is difficult to determine. Innovatively combine FAI index and NDVI index, and use NDVI index to find the threshold of FAI index. In order to analyze the applicability of FAI-L to extract cyanobacterial blooms, this paper selected multi-temporal Landsat8, HJ-1B, and Sentinel-2 remote sensing images as data sources, and took Chaohu Lake and Taihu Lake in China as research areas to extract cyanobacterial blooms. The results show that (1) the accuracy of extracting cyanobacterial bloom by FAI-L method is generally higher than that by NDVI and FAI. Under different data sources and different research areas, the average accuracy of extracting cyanobacterial blooms by FAI-L method is 95.13%, which is 6.98% and 18.43% higher than that by NDVI and FAI respectively. (2) The average accuracy of FAI-L method for extracting cyanobacterial blooms varies from 84.09 to 99.03%, with a standard deviation of 4.04, which is highly stable and applicable. (3) For simultaneous multi-source image data, the FAI-L method has the highest average accuracy in extracting cyanobacterial blooms, at 95.93%, which is 6.77% and 13.26% higher than NDVI and FAI methods, respectively. In this paper, it is found that FAI-L method shows high accuracy and stability in extracting cyanobacterial blooms, and it can extract the spatial distribution of cyanobacterial blooms well, which can provide a new method for monitoring cyanobacterial blooms.

Proteome and phosphoproteome profiling of non-small cell lung cancer cell line A549 treated with TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is recognized for its promising therapeutic effects against cancer. However, mechanisms underlying the effect of TRAIL on protein expression, signal transduction, and apoptosis induction remain unclear. We surmised that a systematic analysis of the proteome and phosphoproteome associated with TRAIL signaling may help elucidate the mechanisms involved and facilitate the development of therapeutics. Therefore, we investigated the proteome and phosphoproteome of non-small cell lung cancer cell line A549 treated with TRAIL. Our results indicated that 126 proteins and 1684 phosphosites were markedly differentially expressed between the phosphate-buffered saline- and TRAIL-treated groups. The expression at protein and phosphosite levels were not completely consistent. Gene ontology functional analysis revealed that metal ion (zinc) binding was highly affected by TRAIL treatment. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that almost all pathways that involved differentially expressed phosphosites were associated with apoptosis. We also identified an important kinase, AKT1, and its series of substrates in TRAIL signaling. The results of this study may provide guidance for future research on tumor therapy using TRAIL.