Fluorescence imaging-guided surgery: current status and future directions.

Surgery is one of the most important paradigms for tumor therapy, while fluorescence imaging (FI) offers real-time intraoperative guidance, greatly boosting treatment prognosis. The imaging fidelity heavily relies on not only imaging facilities but also probes for imaging-guided surgery (IGS). So far, a great number of IGS probes with emission in visible (400-700 nm) and near-infrared (NIR 700-1700 nm) windows have been developed for pinpointing disease margins intraoperatively. Herein, the state-of-the-art fluorescent probes for IGS are timely updated, with a special focus on the fluorescent probes under clinical examination. For a better demonstration of the superiority of NIR FI over visible FI, both imaging modalities are critically compared regarding signal-to-background ratio, penetration depth, resolution, tissue autofluorescence, photostability, and biocompatibility. Various types of fluorescence IGS have been summarized to demonstrate its importance in the medical field. Furthermore, the most recent progress of fluorescent probes in NIR-I and NIR-II windows is summarized. Finally, an outlook on multimodal imaging, FI beyond NIR-II, efficient tumor targeting, automated IGS, the use of AI and machine learning for designing fluorescent probes, and the fluorescence-guided da Vinci surgical system is given. We hope this review will stimulate interest among researchers in different areas and expedite the translation of fluorescent probes from bench to bedside.

Coding-complete genome sequence of a bovine viral diarrhea virus isolate NX2023 from a calf in China.

The coding-complete genome sequence of bovine viral diarrhea virus (BVDV) isolate NX2023 that originated from a calf in China was determined. Phylogenetic analysis showed that the NX2023 strain belongs to the BVDV-1d subgenotype.

Arctigenin derivative A-1 ameliorates motor dysfunction and pathological manifestations in SOD1G93A transgenic mice via the AMPK/SIRT1/PGC-1α and AMPK/SIRT1/IL-1ß/NF-κB pathways.

AIM: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by progressive death of upper and lower motor neurons, leading to generalized muscle atrophy, paralysis, and even death. Mitochondrial damage and neuroinflammation play key roles in the pathogenesis of ALS. In the present study, the efficacy of A-1, a derivative of arctigenin with AMP-activated protein kinase (AMPK) and silent information regulator 1 (SIRT1) activation for ALS, was investigated. METHODS: A-1 at 33.3 mg/kg was administrated in SOD1G93A transgenic mice orally from the 13th week for a 6-week treatment period. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes, and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl, and immunohistochemistry staining. Protein expression was detected with proteomics analysis, Western blotting, and ELISA. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. RESULTS: A-1 administration in SOD1G93A mice enhanced mobility, decreased skeletal muscle atrophy and fibrosis, mitigated loss of spinal motor neurons, and reduced glial activation. Additionally, A-1 treatment improved mitochondrial function, evidenced by elevated ATP levels and increased expression of key mitochondrial-related proteins. The A-1 treatment group showed decreased levels of IL-1ß, pIκBα/IκBα, and pNF-κB/NF-κB. CONCLUSIONS: A-1 treatment reduced motor neuron loss, improved gastrocnemius atrophy, and delayed ALS progression through the AMPK/SIRT1/PGC-1α pathway, which promotes mitochondrial biogenesis. Furthermore, the AMPK/SIRT1/IL-1ß/NF-κB pathway exerted neuroprotective effects by reducing neuroinflammation. These findings suggest A-1 as a promising therapeutic approach for ALS.

The effect of injectable platelet-rich fibrin and platelet-rich fibrin in regenerative endodontics: a comparative in vitro study.

OBJECTIVE: To explore the feasibility of injectable platelet-rich fibrin (i-PRF) in regenerative endodontics by comparing the effect of i-PRF and platelet-rich fibrin (PRF) on the biological behavior and angiogenesis of human stem cells from the apical papilla (SCAPs). METHODOLOGY: i-PRF and PRF were obtained from venous blood by two different centrifugation methods, followed by hematoxylin-eosin (HE) staining and scanning electron microscopy (SEM). Enzyme-linked immunosorbent assay (ELISA) was conducted to quantify the growth factors. SCAPs were cultured with different concentrations of i-PRF extract (i-PRFe) and PRF extract (PRFe), and the optimal concentrations were selected using the Cell Counting Kit-8 (CCK-8) assay. The cell proliferation and migration potentials of SCAPs were then observed using the CCK-8 and Transwell assays. Mineralization ability was detected by alizarin red staining (ARS), and angiogenesis ability was detected by tube formation assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of genes related to mineralization and angiogenesis. The data were subjected to statistical analysis. RESULTS: i-PRF and PRF showed a similar three-dimensional fibrin structure, while i-PRF released a higher concentration of growth factors than PRF ( P <.05). 1/4× i-PRFe and 1/4× PRFe were selected as the optimal concentrations. The cell proliferation rate of the i-PRFe group was higher than that of the PRFe group ( P <.05), while no statistical difference was observed between them in terms of cell mitigation ( P >.05). More importantly, our results showed that i-PRFe had a stronger effect on SCAPs than PRFe in facilitating mineralization and angiogenesis, with the consistent result of RT-qPCR ( P <.05). CONCLUSION: This study revealed that i-PRF released a higher concentration of growth factors and was superior to PRF in promoting proliferation, mineralization and angiogenesis of SCAPs, which indicates that i-PRF could be a promising biological scaffold for application in pulp regeneration.

Research on drought stress in Medicago sativa L. from 1998 to 2023: a bibliometric analysis.

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. Drought is recognized as a major challenge limiting alfalfa production and threatening food security. Although some literature reviews have been conducted in this area, bibliometric reviews based on large amounts of published data are still lacking. In this paper, a bibliometric analysis of alfalfa drought stress from 1998-2023 was conducted using the Web of Science Core Collection database in order to assess global trends in alfalfa drought stress research and to provide new directions for future research. The results showed that the annual publication output maintained an increase in most years, with China and the United States contributing significantly to the field. Most of the journals published are specialized journals in botany, environmental science, soil science and crop science, as well as related agribusiness journals. "plant growth" and "yield" were the most frequently used keywords, reflecting the important purpose of research in this field. And two main research directions were identified: research on drought response mechanism of alfalfa and exploration of drought-resistant technology. In addition, physiological, biochemical, and molecular responses of drought tolerance and high yield in alfalfa, transgenics, and microbial fertilizer research have been hot research topics in recent years and may continue in the future. The ultimate goal of this paper is to provide a foundational reference for future research on alfalfa's drought resistance and yield optimization mechanisms, thereby enhancing the crop's application in agricultural production.

The interaction effect of metals exposure and dietary habit on cognitive function in Chinese older adult cohort.

BACKGROUND: As the important factors in cognitive function, dietary habits and metal exposures are interactive with each other. However, fewer studies have investigated the interaction effect of them on cognitive dysfunction in older adults. METHODS: 2,445 registered citizens aged 60-85 years from 51 community health centers in Luohu District, Shenzhen, were recruited in this study based on the Chinese older adult cohort. All subjects underwent physical examination and Mini-cognitive assessment scale. A semi quantitative food frequency questionnaire was used to obtain their food intake frequency, and 21 metal concentrations in their urine were measured. RESULTS: Elastic-net regression model, a machine learning technique, identified six variables that were significantly associated with cognitive dysfunction in older adults. These variables included education level, gender, urinary concentration of arsenic (As) and cadmium (Cd), and the frequency of monthly intake of egg and bean products. After adjusting for multiple factors, As and Cd concentrations were positively associated with increased risk of mild cognitive impairment (MCI) in the older people, with OR values of 1.19 (95% CI: 1.05-1.42) and 1.32 (95% CI: 1.01-1.74), respectively. In addition, older adults with high frequency of egg intake (≥30 times/month) and bean products intake (≥8 times/month) had a reduced risk of MCI than those with low protein egg intake (<30 times/month) and low bean products intake (<8 times/month), respectively. Furthermore, additive interaction were observed between the As exposure and egg products intake, as well as bean products. Cd exposure also showed additive interactions with egg and bean products intake. CONCLUSIONS: The consumption of eggs and bean products, as well as the levels of exposure to the heavy metals Cd and As, have been shown to have a substantial influence on cognitive impairment in the elderly population.

Developing a nomogram based on SEER database for predicting prognosis in choroid plexus tumors.

Choroid plexus tumors (CPT) are rare and highly vascularized neoplasms that have three histologically confirmed diagnoses, including choroid plexus papilloma, atypical choroid plexus papilloma, and choroid plexus carcinoma (CPC). This study aimed to determine the epidemiology and survival of patients with CPTs and develop a nomogram to quantify the prognosis of the patients with CPT. Data of 808 patients who were diagnosed as CPT between 2000 and 2020 was obtained from the surveillance, epidemiology, and end results database. Descriptive analysis was used to assess the distribution and tumor-related characteristics of the patients with CPT. Independent prognostic factors for patients with CPT were identified by univariate and multivariate Cox regression analysis. The nomogram was established and evaluated by receiver operating characteristic curve, and decision curve analysis (DCA), calibration curves. The independent prognostic factors for patients with CPT are age, tumor size, surgery, chemotherapy, tumor number, pathologies, and race. For the prognostic nomogram, the area under the curve (AUC) of 60-, 120-, and 180-months were 0.855, 0.869 and 0.857 in the training set and 0.836, 0.864 and 0.922 in the test set. The DCA and calibration curve indicated the good performance of the nomogram. Patients with CPTs can be diagnosed at any age. Among the three histopathological tumors, patients with CPC had the worst prognosis. The nomogram was established to predict the prognosis of patients with CPT, which had satisfactory accuracy, and clinical utility may benefit for clinical decision-making.

Plasminogen degrades α-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson's disease.

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis. We investigated the functional roles of plasminogen in vitro in an okadaic acid-induced Tau hyperphosphorylation NSC34 cell model, ex vivo using brains from normal controls and methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and in vivo in a widely used MPTP-induced PD mouse model and an α-syn overexpression mouse model. The in vitro, ex vivo and in vivo results showed that the administered plasminogen crossed the blood‒brain barrier (BBB), entered cells, and migrated to the nucleus, increased plasmin activity intracellularly, bound to α-syn through lysine binding sites, significantly promoted α-syn, Tau and TDP-43 clearance intracellularly and even intranuclearly in the brain, decreased dopaminergic neurodegeneration and increased the tyrosine hydroxylase levels in the substantia nigra and striatum, and improved motor function in PD mouse models. These findings indicate that plasminogen plays a wide range of pivotal protective roles in PD and therefore may be a promising drug candidate for PD treatment.

Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient: A case report.

BACKGROUND: Infections by non-tuberculous mycobacteria (NTM) have become more common in recent years. Mycobacterium canariasense (M. canariasense) was first reported as an opportunistic pathogen in 2004, but there have been very few case reports since then. Nocardia is a genus of aerobic and Gram-positive bacilli, and these species are also opportunistic pathogens and in the Mycobacteriales order. Conventional methods for diagnosis of NTM are inefficient. Metagenomic next-generation sequencing (mNGS) can rapidly detect many pathogenic microorganisms, even rare species. Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms. There are no previous reports of infection by M. canariasense and Nocardia farcinica (N. farcinica), especially in immunocompetent patients. This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M. canariasense, N. farcinica, and Candida parapsilosis (C. parapsilosis) based on mNGS. CASE SUMMARY: A 52-year-old woman presented with a productive cough and chest pain for 2 wk, and recurrent episodes of moderate-grade fever for 1 wk. She received antibiotics for 1 wk at a local hospital, and experienced defervescence, but the productive cough and chest pain persisted. We collected samples of a lung lesion and alveolar lavage fluid for mNGS. The lung tissue was positive for M. canariasense, N. farcinica, and C. parapsilosis, and the alveolar lavage fluid was positive for M. canariasense. The diagnosis was pneumonia, and application of appropriate antibiotic therapy cured the patient. CONCLUSION: Etiological diagnosis is critical for patients with infectious diseases. mNGS can identify rare and novel pathogens, and does not require a priori knowledge.

Natural Pyrethrin-Induced Oxidative Damage in Human Liver Cells through Nrf-2 Signaling Pathway.

Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs' induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration.

Genetically determined metabolites in allergic conjunctivitis: A Mendelian randomization study.

Background: Allergic conjunctivitis (AC) afflicts a significant portion of the global populace. Yet, its metabolic foundations remain largely unexplored. Methods: We applied Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC) to scrutinize a cohort comprising 20 958 AC cases and 356 319 controls. Data were amalgamated from the metabolomics GWAS server and the FinnGen project, under strict quality control protocols. Results: Using two-sample MR analysis, 486 blood metabolites were investigated in relation to AC. The IVW approach highlighted 18 metabolites as closely tied to AC risk; of these, 16 retained significance post sensitivity assessments for heterogeneity and horizontal pleiotropy. LDSC analysis, adopted to bolster our findings and negate confounders from shared genetic markers, revealed 8 metabolites with marked heritability, including: palmitate (OR = 0.614), 3-methoxytyrosine (OR = 0.657), carnitine (OR = 1.368), threonate (OR = 0.828), N-[3-(2-Oxopyrrolidin-1-yl)propyl]acetamide (OR = 1.257), metoprolol acid metabolite (OR = 0.982), oleoylcarnitine (OR = 0.635), and 2-palmitoylglycerophosphocholine (OR = 1.351). Conclusion: AC is precipitated by ocular responses to environmental allergens. Our study unveils a causal link between 8 blood metabolites and AC. This insight accentuates the role of metabolites in AC onset, suggesting novel avenues for its early prediction, targeted prevention, and tailored therapeutic interventions.

Associations between Geriatric Nutrition Risk Index, bone mineral density and body composition in type 2 diabetes patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a fast-growing issue in public health, is one of the most common chronic metabolic disorders in older individuals. Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities. In people with T2DM, the association between nutrition, sarcopenia, and osteoporosis has rarely been explored. AIM: To evaluate the connections among nutrition, bone mineral density (BMD) and body composition in patients with T2DM. METHODS: We enrolled 689 patients with T2DM for this cross-sectional study. All patients underwent dual energy X-ray absorptiometry (DXA) examination and were categorized according to baseline Geriatric Nutritional Risk Index (GNRI) values calculated from serum albumin levels and body weight. The GNRI was used to evaluate nutritional status, and DXA was used to investigate BMD and body composition. Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index. RESULTS: Of the total patients, 394 were men and 295 were women. Compared with patients in tertile 1, those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c, higher BMD at all bone sites, and higher appendicular skeletal muscle index (ASMI). These important trends persisted even when the patients were divided into younger and older subgroups. The GNRI was positively related to ASMI (men: r = 0.644, P < 0.001; women: r = 0.649, P < 0.001), total body fat (men: r = 0.453, P < 0.001; women: r = 0.557, P < 0.001), BMD at all bone sites, lumbar spine (L1-L4) BMD (men: r = 0.110, P = 0.029; women: r = 0.256, P < 0.001), FN-BMD (men: r = 0.293, P < 0.001; women: r = 0.273, P < 0.001), and hip BMD (men: r = 0.358, P < 0.001; women: r = 0.377, P < 0.001). After adjustment for other clinical parameters, the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck. Additionally, a low lean mass index and higher ß-collagen special sequence were associated with low BMD at all bone sites. Age was negatively correlated with ASMI, whereas weight was positively correlated with ASMI. CONCLUSION: Poor nutrition, as indicated by a low GNRI, was associated with low levels of ASMI and BMD at all bone sites in T2DM patients. Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.

Development of Polymethine Dyes for NIR-II Fluorescence Imaging and Therapy.

Fluorescence imaging in the second near-infrared window (NIR-II) is burgeoning because of its higher imaging fidelity in monitoring physiological and pathological processes than clinical visible/the second near-infrared window fluorescence imaging. Notably, the imaging fidelity is heavily dependent on fluorescence agents. So far, indocyanine green, one of the polymethine dyes, with good biocompatibility and renal clearance is the only dye approved by the Food and Drug Administration, but it shows relatively low NIR-II brightness. Importantly, tremendous efforts are devoted to synthesizing polymethine dyes for imaging preclinically and clinically. They have shown feasibility in the customization of structure and properties to fulfill various needs in imaging and therapy. Herein, a timely update on NIR-II polymethine dyes, with a special focus on molecular design strategies for fluorescent, photoacoustic, and multimodal imaging, is offered. Furthermore, the progress of polymethine dyes in sensing pathological biomarkers and even reporting drug release is illustrated. Moreover, the NIR-II fluorescence imaging-guided therapies with polymethine dyes are summarized regarding chemo-, photothermal, photodynamic, and multimodal approaches. In addition, artificial intelligence is pointed out for its potential to expedite dye development. This comprehensive review will inspire interest among a wide audience and offer a handbook for people with an interest in NIR-II polymethine dyes.

Hyaluronan degradation by HYAL2 is essential for odontoblastic differentiation and migration of mouse dental papilla cells.

The coordination between odontoblastic differentiation and directed cell migration of mesenchymal progenitors is necessary for regular dentin formation. The synthesis and degradation of hyaluronan (HA) in the extracellular matrix create a permissive niche that directly regulates cell behaviors. However, the role and mechanisms of HA degradation in dentin formation remain unknown. In this work, we present that HA digestion promotes odontoblastic differentiation and cell migration of mouse dental papilla cells (mDPCs). Hyaluronidase 2 (HYAL2) is responsible for promoting odontoblastic differentiation through degrading HA, while hyaluronidase 1 (HYAL1) exhibits negligible effect. Silencing Hyal2 generates an extracellular environment rich in HA, which attenuates F-actin and filopodium formation and in turn inhibits cell migration of mDPCs. In addition, activating PI3K/Akt signaling significantly rescues the effects of HA accumulation on cytodifferentiation. Taken together, the results confirm the contribution of HYAL2 to HA degradation in dentinogenesis and uncover the mechanism of the HYAL2-mediated HA degradation in regulating the odontoblastic differentiation and migration of mDPCs.

Promoting the healing of diabetic wounds with an antimicrobial gel containing AgNPs with anti-infective and anti-inflammatory properties.

Diabetic wounds are prone to develop chronic wounds due to bacterial infection and persistent inflammatory response. However, traditional dressings are monofunctional, lack bioactive substances, have limited bacterial inhibition as well as difficulties in adhesion and retention. These limit the therapeutic efficacy of traditional dressings on diabetic wounds. Therefore, finding and developing efficient and safe wound dressings is currently an urgent clinical need. In this study, an antimicrobial gel loaded with silver nanoparticles (AgNPs) (referred to as AgNPs@QAC-CBM) was prepared by crosslinking quaternary ammonium chitosan (QAC) with carbomer (CBM) as a gel matrix. AgNPs@QAC-CBM exhibited a reticulated structure, strong adhesion, good stability, and remarkable bactericidal properties, killing 99.9% of Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa within 1 min. Furthermore, AgNPs@QAC-CBM improved the wound microenvironment and accelerated wound healing in diabetic mice by promoting tissue production and collagen deposition, inducing M2 macrophages, reducing pro-inflammatory factor secretion and increasing anti-inflammatory factor levels. Moreover, AgNPs@QAC-CBM was proven to be safe for use through skin irritation and cytotoxicity tests, as they did not cause any irritation or toxicity. To summarize, AgNPs@QAC-CBM showed promising potential in enhancing the diabetic wound healing process.

Edaravone dexborneol protects against cerebral ischemia/reperfusion-induced blood-brain barrier damage by inhibiting ferroptosis via activation of nrf-2/HO-1/GPX4 signaling.

PURPOSE: Ferroptosis has recently been recognized as a mechanism of cerebral ischemia-reperfusion (I/R) injury, attributed to blood-brain barrier (BBB) disruption. Edaravone dexboneol (Eda.B) is a novel neuroprotective agent widely employed in ischemic stroke, which is composed of edaravone (Eda) and dexborneol. This study aimed to investigate the protective effects of Eda.B on the BBB in cerebral I/R and explore its potential mechanisms. METHODS: Transient middle cerebral artery occlusion (tMCAO) Sprague-Dawley-rats model was used. Rats were randomly assigned to sham-operated group (sham, n = 20), model group (tMCAO, n = 20), Eda.B group (Eda.B, n = 20), Eda group (Eda, n = 20) and dexborneol group (dexborneol, n = 20), and Eda.B + Zinc protoporphyria group (Eda.B + ZnPP, n = 5). Infarct area, cellular apoptosis and neurofunctional recovery were accessed through TTC staining, TUNEL staining, and modified Garcia scoring system, respectively. BBB integrity was evaluated via Evans blue staining. Nuclear factor E2 related factor 2 (Nrf-2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling were qualified by Western blot. Transmission electron microscopy (TEM) revealed alterations in ipsilateral brain tissue among groups. Glutathione (GSH) and malondialdehyde (MDA) levels, and Fe2+ tissue content determination were detected. RESULTS: Eda.B effectively improved neurological deficits, diminished infarct area and cellular apoptosis, as well as ameliorated BBB integrity in tMCAO rats. Further, Eda.B significantly inhibited ferroptosis, as evidenced by ameliorated pathological features of mitochondria, down-regulated of MDA and Fe2+ levels and up-regulated GSH content. Mechanistically, Eda.B attenuated BBB disruption via Nrf-2-mediated ferroptosis, promoting nuclear translocation of Nrf-2, increasing HO-1, GPX4 expression, alleviating the loss of zonula occludens 1 (ZO-1) and occludin as well as decreasing 4-hydroxynonenal (4-HNE) level. CONCLUSIONS: This study revealed for the first time that Eda.B safeguarded the BBB from cerebral I/R injury by inhibiting ferroptosis through the activation of the Nrf-2/HO-1/GPX4 axis, providing a novel insight into the neuroprotective effect of Eda.B in cerebral I/R.

Identification of G-quadruplex-interacting proteins in living cells using an artificial G4-targeting biotin ligase.

G-quadruplexes (G4s) are noncanonical nucleic acid structures pivotal to cellular processes and disease pathways. Deciphering G4-interacting proteins is imperative for unraveling G4's biological significance. In this study, we developed a G4-targeting biotin ligase named G4PID, meticulously assessing its binding affinity and specificity both in vitro and in vivo. Capitalizing on G4PID, we devised a tailored approach termed G-quadruplex-interacting proteins specific biotin-ligation procedure (PLGPB) to precisely profile G4-interacting proteins. Implementing this innovative strategy in live cells, we unveiled a cohort of 149 potential G4-interacting proteins, which exhibiting multifaceted functionalities. We then substantiate the directly binding affinity of 7 candidate G4-interacting-proteins (SF3B4, FBL, PP1G, BCL7C, NDUV1, ILF3, GAR1) in vitro. Remarkably, we verified that splicing factor 3B subunit 4 (SF3B4) binds preferentially to the G4-rich 3' splice site and the corresponding splicing sites are modulated by the G4 stabilizer PDS, indicating the regulating role of G4s in mRNA splicing procedure. The PLGPB strategy could biotinylate multiple proteins simultaneously, which providing an opportunity to map G4-interacting proteins network in living cells.

Effect of Infusion Set Replacement Intervals on Central Line-Associated Bloodstream Infection in the Intensive Care Unit: Study Protocol of the INSPIRATION Study.

INTRODUCTION: The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. METHODS: This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. PLANNED OUTCOME: The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. CONCLUSION: This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05359601.

Ultrathin and Biodegradable Bismuth Oxycarbonate Nanosheets with Massive Oxygen Vacancies for Highly Efficient Tumor Therapy.

Nanomaterials doped with high atom number elements can improve the efficacy of cancer radiotherapy, but their clinical application faces obstacles, such as being difficult to degrade in vivo, or still requiring relatively high radiation dose. In this work, a bismuth oxycarbonate-based ultrathin nanosheet with the thickness of 2.8 nm for safe and efficient tumor radiotherapy under low dose of X-ray irradiation is proposed. The high oxygen content (62.5% at%) and selective exposure of the facets of ultrathin 2D nanostrusctures facilitate the escape of large amounts of oxygen atoms on bismuth nanosheets from surface, forming massive oxygen vacancies and generating reactive oxygen species that explode under the action of X-rays. Moreover, the exposure of almost all atoms to environmental factors and the nature of oxycarbonates makes the nanosheets easily degrade into biocompatible species. In vivo studies demonstrate that nanosheets could induce apoptosis in cancer cells after low dose of X-ray irradiation without causing any damage to the liver or kidney. The tumor growth inhibition effect of radiotherapy increases from 49.88% to 90.76% with the help of bismuth oxycarbonate nanosheets. This work offers a promising future for nanosheet-based clinical radiotherapies of malignant cancers.

A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013-2020.

BACKGROUND: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. METHODS: The National Health and Nutrition Examination Survey (2013-2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were the specific diagnostic criteria for DKD. RESULTS: In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably (P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. CONCLUSIONS: A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.