Factors influencing physical activity levels in elderly community-dwelling convalescent stroke survivors: A cross-sectional study.

AIM: This study aimed to investigate factors affecting physical activity (PA) among elderly stroke survivors living in the community and assess the mediating role of exercise planning in the relationship between exercise self-efficacy and PA. METHODS: 300 participants were surveyed using questionnaires and scales, with data analyzed using SPSS 26.0. RESULTS: Univariate analysis identified sociological, disease-related factors, exercise self-efficacy, and exercise planning as influencing PA. Ordered logistic regression showed significant associations between PA, exercise self-efficacy (OR 1.093, 95 % CI 1.055-1.133, P < 0.001), and exercise planning (OR 1.296, 95 % CI 1.202-1.398, P < 0.001). Exercise planning partially mediated the relationship between exercise self-efficacy and PA, accounting for 64.86 % of the total effect. CONCLUSIONS: Multiple factors, including sociological and disease-related ones, as well as exercise self-efficacy and planning, influence PA in elderly stroke survivors. Exercise planning partially mediates the relationship between exercise self-efficacy and PA.

Sodium Houttuyfonate Ameliorates DSS-induced Colitis Aggravated by Candida albicans through Dectin-1/NF-κB/miR-32-5p/NFKBIZ Axis Based on Intestinal microRNA Profiling.

Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1ß, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1ß, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.

Treatment of bone-cartilage defects with dual-layer tissue-engineered scaffolds loaded with icariin and quercetin.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

Major pathological response obtained after neoadjuvant chemotherapy combined with dual immunotherapy for malignant pleural mesothelioma: a case report.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.

Impacts of Tumor Stage at Diagnosis and Adjuvant Therapy on Long-Term Survival Outcomes in Patients With Triple-Negative Breast Cancer Achieving Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.

Integrative transcriptome-proteome approach reveals key hypoxia-related features involved in the neuroprotective effects of Yang Xue oral liquid on Alzheimer's and Parkinson's disease.

Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action.

Proteogenomic insights into the biology and treatment of pan-melanoma.

Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Exosomes derived from tendon stem/progenitor cells enhance tendon-bone interface healing after rotator cuff repair in a rat model.

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.

Development of a 1-step multiplex PCR assay for the detection of S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis associated with poultry production.

Salmonellosis in poultry is detrimental to the advancement of the breeding industry and poses hazards to human health. Approximately 2,600 Salmonella varieties exist, among which S. Enteritidis, S. Pullorum, S. Typhimurium, and S. Infantis are prevalent serotypes in the poultry industry in recent years. They can also infect humans by contaminating poultry eggs and meat. Therefore, identifying these serotypes is crucial for successful preventive and control interventions. The White-Kauffmann-Le Minor scheme is time-consuming and requires expensive reagents. Whole-genome sequencing (WGS) and other molecular biology techniques require skilled technical staff. In comparison, the polymerase chain reaction (PCR) is more accurate, rapid, and inexpensive, thus proving suitable for widespread application in the poultry industry. Here, we selected 4 specific primers: lygD, mdh, ipaJ, and SIN_02055, which correspond to detecting S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, respectively. They were integrated into a 1-step multiplex PCR method. We optimized the PCR method by utilizing specificity test results to determine the optimal annealing temperature (57°C). The PCR method exhibited excellent sensitivity for genomic DNA and bacterial cultures. We used the developed method to determine 157 clinical Salmonella isolates from various stages of the poultry production chain. The results aligned with serotype data generated via WGS analysis, demonstrating the method's excellent accuracy. In conclusion, this study developed a 1-step multiplex PCR method that simultaneously identifies S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Infantis, allowing routine mass detection in the grass-root poultry industry.

Histone lactylation-related genes correlate with the molecular patterns and functions of cancer-associated fibroblasts and have significant clinical implications in clear cell renal cell carcinoma.

Recent research emphasised the indispensable role of histone lactylation in the activation of hepatic stellate cells. The VHL mutation is extremely common in clear cell renal cell carcinoma, which normally causes a metabolic shift in cancer cells and increases lactate production, eventually creating a lactate-enriched tumour microenvironment. Cancer-associated fibroblasts (CAFs) promote tumour progression, which is also vital in clear cell renal cell carcinoma. Therefore, this study investigated histone lactylation in CAFs and its impact on patient survival. Multiomics technology was employed to determine the role of histone lactylation-related genes in the evolution of CAFs which correlated with the function and molecular signatures of CAFs. The results suggested that TIMP1 was the hub gene of histone lactylation-related genes in clear cell renal cell carcinoma.

Comparative analysis of the short and medium-term efficacy of the Da Vinci robot versus laparoscopic total mesangectomy for rectal cancer.

BACKGROUND: The Da Vinci robot-assisted surgery technique has been widely used in laparoscopic mesangectomy for rectal cancer. However, the short-term efficacy of these procedures compared to traditional laparoscopic surgery remains controversial. The purpose of this study was to compare and analyze the short- and medium-term efficacy of Da Vinci robot and laparoscopic surgery in total mesangectomy (TME) for rectal cancer, so as to provide guidance and reference for clinical practice. AIM: To investigate the safety and long-term efficacy of robotic and laparoscopic total mesorectal resection for the treatment of rectal cancer. METHODS: The clinicopathologic data of 240 patients who underwent TME for rectal cancer in the Anorectal Department of People's Hospital of Xinjiang Uygur Autonomous Region from August 2018 to March 2023 were retrospectively analyzed. Among them, 112 patients underwent laparoscopic TME (L-TME) group, and 128 patients underwent robotic TME (R-TME) group. The intraoperative, postoperative, and follow-up conditions of the two groups were compared. RESULTS: The conversion rate of the L-TME group was greater than that of the R-TME group (5.4% vs 0.8%, χ 2 = 4.417, P = 0.036). The complication rate of the L-TME group was greater than that of the R-TME group (32.1% vs 17.2%, χ 2 = 7.290, P = 0.007). The percentage of positive annular margins in the L-TME group was greater than that in the R-TME group (7.1% vs 1.6%, χ 2 = 4.658, P = 0.031). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate of the L-TME group were lower than those of the R-TME group (74.1% vs 85.2%, χ 2 = 4.962, P = 0.026; 81.3% vs 91.4%, χ 2 = 5.494, P = 0.019); in patients with American Joint Committee on Cancer stage III DFS rate and OS rate in the L-TME group were significantly lower than those in the R-TME group (52.5% vs 76.1%, χ 2 = 5.799, P = 0.016; 65.0% vs 84.8%, χ 2 = 4.787, P = 0.029). CONCLUSION: Compared with the L-TME group, the R-TME group had a better tumor prognosis and was more favorable for patients with rectal cancer, especially for patients with stage III rectal cancer.

Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.

Therapeutic effectiveness of Donepezil hydrochloride in combination with butylphthalide for post-stroke cognitive impairment.

OBJECTIVE: To study the therapeutic effectiveness of donepezil hydrochloride (DPZ) in combination with butylphthalide (BP) for the treatment of post-stroke cognitive impairment (PSCI). METHODS: In this retrospective study, the clinical data of 125 PSCI patients treated at the First Affiliated Hospital of Harbin Medical University from December 2019 to December 2023 were collected and analyzed. The patients were grouped into a joint group (n=75, receiving DPZ + BP) and a control group (n=50, receiving DPZ alone) according to their treatment regimen. Inter-group comparisons were then carried out from the perspectives of therapeutic effectiveness, safety (constipation, abdominal distension and pain, and gastrointestinal reactions), cognitive function (Montreal Cognitive Assessment Scale [MoCA], Chinese Stroke Scale [CSS]), Activities of Daily Living Scale (ADL), and serum biochemical indexes (neuron-specific enolase [NSE], high-sensitivity C-reactive protein [hs-CRP], nitric oxide [NO], and malondialdehyde [MDA]). In addition, a univariate analysis was carried out to identify factors affecting therapeutic effectiveness in PSCI patients. RESULTS: The joint group showed significantly better therapeutic effectiveness compared to the control group (P<0.05). There was a significant correlation between the type of stroke, treatment method, and therapeutic effectiveness in PSCI patients (P<0.05). There was no significant difference in the total incidence of adverse reactions (P>0.05). After the treatment, compared to the control group, the joint group demonstrated significant improvements in MoCA and ADL scores (all P<0.05) and reductions in CSS scores and levels of NSE, hs-CRP, NO, and MDA (all P<0.05). CONCLUSIONS: DPZ in combination with BP is highly effective for the treatment of PSCI. It positively affects cognitive function and ADL, alleviates neurological deficits, and reduces abnormal serum biochemical indices without increasing the risk of adverse reaction.

Vertasile ferritin nanocages: Applications in detection and bioimaging.

Food safety and human health remain significant concerns in the food industry. Detecting food contaminants and diagnosing diseases are critical aspects. Ferritin, an iron storage protein widely found in nature, offers unique advantages. Its hollow protein nanocage structure, distinct interfaces, hydrophobic or hydrophilic channels, and B-C loop regions recognized by transferrin receptor 1 make ferritin versatile for detecting heavy metals, free radicals, and bioimaging both in vitro and in vivo. This review summarizes ferritin's general characteristics, its specific properties as biosensors, and its applications in food safety and in vivo imaging. It emphasizes not only ferritin's role in detecting heavy metals like mercury and chemical hazards but also its potential in early diagnosing chronic diseases such as tumors, macrophages, and kidney diseases. Further research into ferritin promises advancements in enhancing food safety and improving human health diagnostics.

Versatile Framework for Drug-Target Interaction Prediction by Considering Domain-Specific Features.

Predicting drug-target interactions (DTIs) is one of the crucial tasks in drug discovery, but traditional wet-lab experiments are costly and time-consuming. Recently, deep learning has emerged as a promising tool for accelerating DTI prediction due to its powerful performance. However, the models trained on limited known DTI data struggle to generalize effectively to novel drug-target pairs. In this work, we propose a strategy to train an ensemble of models by capturing both domain-generic and domain-specific features (E-DIS) to learn diverse domain features and adapt them to out-of-distribution data. Multiple experts were trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. E-DIS provides a comprehensive representation of proteins and ligands by capturing diverse features. Experimental results on four benchmark data sets in both in-domain and cross-domain settings demonstrated that E-DIS significantly improved model performance and domain generalization compared to existing methods. Our approach presents a significant advancement in DTI prediction by combining domain-generic and domain-specific features, enhancing the generalization ability of the DTI prediction model.

Feasibility of a modified hybrid glubran-supported single-proglide technique for access closure during endovascular aneurysm repair.

Objective: This study aimed to evaluate the feasibility of a hybrid Glubran-supported single-Proglide technique for large bore femoral access closure during percutaneous access endovascular aneurysm repair (EVAR). Methods: A retrospective cohort study was performed for all percutaneous EVARs at our center from January 2023 to June 2023. All patients received the hybrid Glubran-supported single-Proglide technique involving a mixture of surgical glue and Lipiodol injection after single suture placement for femoral access closure. Technical success was defined as achieving complete hemostasis without a bailout strategy. Vascular complications and bleeding were defined by Valve Academic Research Consortium-3 (VARC-3) criteria. Vascular access changes and 30-day mortality were recorded. Results: The technique success rate for the entire study population was 100% (55 femoral access in 37 patients; median age: 72; 78% males). The mean sheath size was 20.4 ± 2.3F. The mean manual compression time was 3.5 ± 1.4 min, the mean hemostasis time was 9.0 ± 2.5 min, and the mean procedural time was 103.9 ± 34.7 min. One patient (1.6%) developed an access site infection and recovered conservatively. No VARC-3 vascular complications and access changes were observed. No 30-day mortality happened. Conclusions: The hybrid Glubran-supported single-Proglide technique is feasible for large bore access closure during EVAR and may be a viable alternative; however, larger prospective studies are required to confirm its efficacy.

Finite element simulation of treatment with locking plate for distal fibula fractures.

An improved Finite Element Model(FEM) is applied to compare the biomechanical stability of plates with three different options in the treatment of distal fibula fractures in this study. The Computed Tomography(CT) scan of the knee to ankle segment of a volunteer was performed. A 3D fibula FEM was reconstructed based on the CT data. Three different loads (uni-pedal standing, torsion, and twisting) were applied, the same as in the experiments in the literature. The stresses and strains of the three options were compared under the same loads, using a 4-hole locking plate (Option A), a 5-hole locking plate (Option B), and a 6-hole locking plate (Option C) in a standard plate for lateral internal fixation. The simulation results show that all three options showed a stress masking effect. Option C had the best overall biomechanical performance and could effectively distribute the transferred weight. This is because option C has greater torsional stiffness and better biomechanical stability than options A and B, and therefore, option C is the recommended internal fixation method for distal fibula fractures. The Finite Element Analysis(FEA) method developed in this work applies to the stress analysis of fracture treatment options in other body parts.

Molecular features of uranium-binding natural organic matter in a riparian wetland determined by ultrahigh resolution mass spectrometry.

Tims Branch riparian wetland located in South Carolina, USA has immobilized 94 % of the U released >50 years ago from a nuclear fuel fabrication facility. Sediment organic matter (OM) has been shown to play an important role in immobilizing U. Yet, uranium-OM-mineral interactions at the molecular scale have never been investigated at ambient concentrations. The objectives of this study were to extract, purify, and concentrate U-bound sediment OM along the stream water pathway and perform molecular characterization using Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). Out of 9614 identified formulas, 715 contained U. These U-containing formulas were enriched with Fe, N, and/or S compared to the total OM. Lignin-like and protein-like molecules accounted for 40 % and 19 % of the U-containing formulas, respectively. Phosphorus-containing formulas were found to exert an insignificant influence on complexing U. U-containing formulas in the 'mobile' (groundwater extractable) OM fraction had lower (reduced) nominal oxidation states of carbon (NOSC); and less aromatic moieties than OM recovered from the 'immobile' (sodium pyrophosphate extractable) OM fraction. U-containing formulas in the redox interfacial zones (stream banks) compared to those in nearby up-slope zones tended to have smaller molecular weights; lower NOSC; higher contents of COO and/or CONO functional groups; and higher abundance of Fe-containing formulas. Fe was present in 38 % of the U-containing formulas but only 20 % of the total OM formulas. It is postulated that Fe played an important role in stabilizing the structure of sedimentary OM, especially U-containing compounds. The identification for the first time of hundreds of Fe-U-OM formulas demonstrates the complexity of such system is much greater than commonly believed and numerically predicting U binding behavior in OM-rich systems may require greater use of statistical or artificial intelligence approaches rather than deterministic approaches limited to measuring metal complexation with well-defined individual analogue organic ligands.

A clade of receptor-like cytoplasmic kinases and 14-3-3 proteins coordinate inositol hexaphosphate accumulation.

Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.

Harnessing the Potential of a Nitroreductase-Responsive Fluorescent Probe for the Diagnosis of Bacterial Keratitis.

Bacterial keratitis, an ocular emergency, is the predominant cause of infectious keratitis. However, diagnostic procedures for it are invasive, time-consuming, and expeditious, thereby limiting effective treatment for the disease in the clinic. It is imperative to develop a timely and convenient method for the noninvasive diagnosis of bacterial keratitis. Fluorescence imaging is a convenient and noninvasive diagnostic method with high sensitivity. In this study, a type of nitroreductase-responsive probe (NTRP), which responds to nitroreductase to generate fluorescence signals, was developed as an activatable fluorescent probe for the imaging diagnosis of bacterial keratitis. Imaging experiments both in vitro and in vivo demonstrated that the probe exhibited "turn-on" fluorescence signals in response to nitroreductase-secreting bacteria within 10 min. Furthermore, the fluorescence intensity reached its highest at 4 or 6 h in vitro and at 30 min in vivo when the excitation wavelength was set at 520 nm. Therefore, the NTRP has the potential to serve as a feasible agent for the rapid and noninvasive in situ fluorescence diagnosis of bacterial keratitis.