Characterization and removal mechanism of fluoroquinolone-bioremediation by fungus Cladosporium cladosporioides 11 isolated from aquacultural sediments.

Antibiotics have been widely detected in aquatic environments, and fungal biotransformation receives considerable attention for antibiotic bioremediation. Here, a fungus designated Cladosporium cladosporioides 11 (CC11) with effective capacity to biotransform fluoroquinolones was isolated from aquaculture pond sediments. Enrofloxacin (ENR), ciprofloxacin (CIP) and ofloxacin (OFL) were considerably abated by CC11, and the antibacterial activities of the fluoroquinolones reduced significantly after CC11 treatment. Transcriptome analysis showed the removal of ENR, CIP and OFL by CC11 is a process of enzymatic degradation and biosorption which consists well with ligninolytic enzyme activities and sorption experiments under the same conditions. Additionally, CC11 significantly removed ENR in zebrafish culture water and reduced the residue of ENR in zebrafish. All these results evidenced the potential of CC11 as a novel environmentally friendly process for the removal of fluoroquinolones from aqueous systems and reduce fluoroquinolone residues in aquatic organisms.

Origin of Interfacial Orbital Reconstruction in Perovskite Superlattices.

The competition between on-site electronic correlation and local crystal field stands out as a captivating topic in research. However, its physical ramifications often get overshadowed by influences of strong periodic potential and orbital hybridization. The present study reveals this competition may become more pronounced or even dominant in two-dimensional systems, driven by the combined effects of dimensional confinement and orbital anisotropy. This leads to electronic orbital reconstruction in certain perovskite superlattices or thin films. To explore the emerging physics, we investigate the interfacial orbital disorder-order transition with an effective Hamiltonian and how to modulate this transition through strains.

PGC1α-Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D-Overexpressing Cell Membranes for Intervertebral Disc Degeneration.

Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence-associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D-overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D-mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator-activated receptor-É£ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH-responsive drug release. Moreover, SP@NNPm effectively induces PGC1α-mediated mitochondrial biogenesis and mitigates senescence-associated markers induced by oxidative stress and the SASP, thereby alleviating puncture-induced senescence and disc degeneration. This dual-targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

Increased stress hyperglycemia ratio at hospital admission in stroke patients are associated with increased in-hospital mortality and length of stay.

OBJECTIVE: Recently, the stress hyperglycemia ratio (SHR) has been introduced as a metric to signify relative hyperglycemia. This study aimed to investigate the relationship between SHR and in-hospital mortality and length of stay occurring during hospitalization in stroke patients. METHODS: The retrospective cohort study comprised a total of 4,018 patients diagnosed with acute stroke. The SHR is expressed by the formula: SHR = ABG (mmol/L) / [1.59 × HbA1c (%) - 2.59]. Outcomes included in-hospital mortality and length of stay. Multivariable logistic and linear regression analyses were conducted. Receiver operating characteristic (ROC) analysis was performed to distinguish between the variables, and the area under the ROC curve (AUC) was compared. RESULTS: In this analysis, a total of 4,018 individuals participated, including 2,814 male patients, accounting for 70.0%. Overall, in-hospital mortality and length of stay tended to rise as SHR increased. A higher prevalence of in-hospital mortality was observed with each standard deviation (SD) increase of the SHR (odds ratio [OR]: 1.26, 95% confidence interval [CI]: 1.05-1.52). Moreover, after considering the confounders, a significant positive association between SHR levels and length of stay was observed (ß = 0.70, 95% CI: 0.40-1.00). ROC analysis showed that among stroke patients, SHR (AUC = 0.693) was more effective than admission blood glucose (ABG) (AUC = 0.646) and glycosylated hemoglobin (HbA1c) (AUC = 0.523), which were more predictive of in-hospital mortality. CONCLUSIONS: Elevated SHR levels are associated with increased in-hospital mortality and prolonged length of stay in stroke patients.

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.

Objective: To analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). Methods: Patients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. Results: A total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5-82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF- group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. Conclusion: The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

Arthroscopic Repair of Rotator Cuff Tears Using a Suture Hook With Lasso Loop for Forward Suture Passing.

Rotator cuff injury is a common shoulder injury. Arthroscopic repair of rotator cuff tears has become a common way. Suture anchor is a commonly used fixation device. Threading the suture through the rotator cuff tendon is a key step in arthroscopic repair of rotator cuff tears. Common methods of passing suture through the rotator cuff tendon include using a suture hook or rotator cuff suture passer device. However, the suture using suture hook is a kind of reverse suture, and the operation is more troublesome. The rotator cuff suture passer device shows poor economy, which cannot be ignored at the risk of needle core breakage. We combined the advantages of the two suture passing methods to design an improved method by using a suture hook with the Lasso loop for forward suture passing. The key step of our improved technique is to deliver the end of the anchor suture 2-3 cm into the tip opening of suture hook, and ejecting the suture through pushing the Lasso loop after suture forward passing through the tendon. Our technique has achieved economy, safety, and simplicity, and has good clinical application value.

Renal function improvement correlates with 3D echocardiographic findings: Effect of surgical mitral valve repair.

BACKGROUND: The association between surgical treatment of mitral regurgitation (MR) and renal function is not sufficiently well-known. We tried to evaluate renal function before and after the procedure of surgical mitral valve repair (SMVR) in degenerative severe MR. METHODS: Patients with primary severe (4+) MR and normal left ventricular ejection fraction (LVEF) that underwent SMVR, examined by a cutting-edge 3-dimensional (3D) echocardiographic probe were enrolled in this study. We took three CKD-EPI equations to measure estimated glomerular filtration rate (eGFR) before SMVR and shortly before patients discharge. A total of 40 patients with baseline lower mean eGFR were evaluated. RESULTS: Measurements substantiated statistically significant improvements in eGFR (p < 0.001), multivariable linear regression modeling indicating prominent associations between increase in eGFR and decrease of MR (p = 0.003), decline of pulmonary arterial systolic pressure (p = 0.018), as well as increment of forward stroke volume (p = 0.02), in spite of LVEF reduction, left ventricular global longitudinal strain worsening and left atrial ejection fraction impairment. CONCLUSIONS: Renal function improves after SMVR in patients with degenerative significant MR and preserved LVEF, regardless of cardiac functional worsening.

Association of the trajectory of plasma aldosterone concentration with the risk of cardiovascular disease in patients with hypertension: a cohort study.

The purpose of this study was to determine the long-term pattern of plasma aldosterone concentration (PAC) trajectories and to explore the relationship between PAC trajectory patterns and cardiovascular disease (CVD) risk in patients with hypertension. Participants were surveyed three times between 2010 and 2016, and latent mixed modeling was employed to determine the trajectory of PAC over the exposure period (2010-2016). A Cox regression analysis was used to examine the association between PAC trajectory patterns and the risk of CVD (stroke and myocardial infarction). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated and reported. During a median follow-up of 4.10 (3.37-4.50) years, 82 incident CVD cases (33 myocardial infarction cases and 49 stroke cases) were identified. Among all three PAC models, the high-stability PAC pattern exhibited the highest risk of CVD. After full adjustment for all covariables, HRs were 2.19 (95% CI 1.59-3.01) for the moderate-stable pattern and 2.56 (95% CI 1.68-3.91) for the high-stable pattern in comparison to the low-stable pattern. Subgroup and sensitivity analyses verified this association. The presence of a high-stable PAC trajectory pattern is associated with an elevated risk of CVD in hypertensive patients. Nevertheless, more studies are warranted to confirm these findings.

KLF5 inhibits the migration and invasion in cervical cancer cell lines by regulating SNAI1.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important biological process by which malignant tumor cells to acquire migration and invasion abilities. This study explored the role of KLF5 in the EMT process of in cervical cancer cell lines. OBJECTIVE: Krüpple-like factor 5 (KLF5) is a basic transcriptional factor that plays a key role in cell-cycle arrest and inhibition of apoptosis. However, the molecular mechanism by which KLF5 mediates the biological functions of cervical cancer cell lines has not been elucidated. Here, we focus on the potential function of ELF5 in regulating the EMT process in in vitro model of cervical cancer cell lines. METHOD: Western-blot and real-time quantitative PCR were used to detect the expression of EMT-related genes in HeLa cells. MTT assays, cell scratch and Transwell assays were used to assess HeLa cells proliferation and invasion capability. Using the bioinformatics tool JASPAR, we identified a high-scoring KLF5-like binding sequence in the SNAI1 gene promoter. Luciferase reporter assays was used to detect transcriptional activity for different SNAI1 promoter truncates. RESULT: After overexpressing the KLF5 gene in HeLa cells, KLF5 not only significantly inhibited the invasion and migration of HeLa cells, but also increased the expression of E-cadherin and decreased the expression of N-cadherin and MMP9. In addition, the mRNA expression of upstream regulators of E-cadherin, such as SNAI1, SLUG, ZEB1/2 and TWIST1 was also decreased. Furthermore, KLF5 inhibiting the expression of the SNAI1 gene via binding its promoter region, and the EMT of Hela cells was promoted after overexpression of the SNAI1 gene. CONCLUSION: These results indicate that KLF5 can downregulate the EMT process of HeLa cells by decreasing the expression of the SNAI1 gene, thereby inhibiting the migration and invasion of HeLa cervical cancer cells.

Circulating miR-423-5p levels are associated with carotid atherosclerosis in patients with chronic kidney disease.

BACKGROUND AND AIMS: Carotid atherosclerosis is associated with an elevated risk of stroke in patients with chronic kidney disease. However, the molecular basis for the incidence of carotid atherosclerosis in patients with CKD is poorly understood. Here, we investigated whether circulating miR-423-5p is a crucial link between CKD and carotid atherosclerosis. METHODS AND RESULTS: We recruited 375 participants for a cross-sectional study to examine the occurrence of carotid plaque and plaque thicknesses. Levels of miR-423-5p were determined by qPCR analysis. We found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels, and dialysis-dependent patients had lower miR-423-5p levels than non-dialysis CKD patients. After excluding for the influence of dialysis patients, linear regression analysis indicated that levels of circulating miR-423-5p are negatively correlated with eGFR (P < 0.001). Higher plasma miR-423-5p levels were associated with the incidence and severity of carotid plaques. In parallel, we constructed a murine model of CKD with a 5/6 nephrectomy protocol and performed RNA sequencing studies of aortic tissues. Consistent with these findings in CKD patients, circulating exosomal miR-423-5p levels in CKD mice were elevated. Furthermore, our RNA-seq studies indicated that the putative target genes of miR-423-5p were related to oxidative stress functions for aorta of CKD mice. CONCLUSION: Levels of miR-423-5p are associated with the presence and severity of carotid plaque in CKD. Data from our mouse model suggests that miR-423-5p likely influences gene expression programs related to oxidative stress in aorta of CKD mice.

Bamboo-Inspired Porous Scaffolds for Advanced Orthopedic Implants: Design, Mechanical Properties, and Fluid Characteristics.

In orthopedic implant development, incorporating a porous structure into implants can reduce the elastic modulus to prevent stress shielding but may compromise yield strength, risking prosthesis fracture. Bamboo's natural structure, with its exceptional strength-to-weight ratio, serves as inspiration. This study explores biomimicry using bamboo-inspired porous scaffolds (BISs) resembling cortical bone, assessing their mechanical properties and fluid characteristics. The BIS consists of two 2D units controlled by structural parameters α and ß. The mechanical properties, failure mechanisms, energy absorption, and predictive performance are investigated. BIS exhibits mechanical properties equivalent to those of natural bone. Specifically, α at 4/3 and ß at 2/3 yield superior mechanical properties, and the destruction mechanism occurs layer by layer. Besides, the Gibson-Ashby models with different parameters are established to predict mechanical properties. Fluid dynamics analysis reveals two high-flow channels in BISs, enhancing nutrient delivery through high-flow channels and promoting cell adhesion and proliferation in low-flow regions. For wall shear stress below 30 mPa (ideal for cell growth), α at 4/3 achieves the highest percentage (99.04%), and ß at 2/3 achieves 98.46%. Permeability in all structural parameters surpasses that of human bone. Enhanced performance of orthopedic implants through a bionic approach that enables the creation of pore structures suitable for implants.

Association between white matter hyperintensities and altered cerebral blood flow in maintenance hemodialysis patients: a longitudinal study.

OBJECTIVES: To explore changes in cerebral blood flow (CBF) and white matter in hemodialysis patients. METHODS: Thirty-three hemodialysis patients who underwent two brain MRI at an interval of three years and 33 age- and sex-matched healthy controls (HC) underwent structural and arterial spin-labeling MRI examinations. Intergroup differences in CBF in the gray matter, white matter, and whole matter, and regional white matter hyperintensities (WMH) were analyzed. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups: an increased CBF group and a decreased CBF group. Differences in CBF and WMH between the subgroups and HC were analyzed. RESULTS: Patients undergoing hemodialysis exhibited increased cerebral watershed (CW) WMH, deep WMH, and periventricular WMH (P < 0.01). The CBF of patients with decreased CBF was higher than that of HC at baseline (,P < 0.01) and lower than that of HC at follow-up (P < 0.01). Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter (P < 0.01). CONCLUSIONS: WMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and CW, and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration. ADVANCES IN KNOWLEDGE: These findings provide a basis for exploring neuropathological changes of hemodialysis patients.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

Changes in iron load in specific brain areas lead to neurodegenerative diseases of the central nervous system.

The causes of neurodegenerative diseases remain largely elusive, increasing their personal and societal impacts. To reveal the causal effects of iron load on Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis and multiple sclerosis, we used Mendelian randomisation and brain imaging data from a UK Biobank genome-wide association study of 39,691 brain imaging samples (predominantly of European origin). Using susceptibility-weighted images, which reflect iron load, we analysed genetically significant brain regions. Inverse variance weighting was used as the main estimate, while MR Egger and weighted median were used to detect heterogeneity and pleiotropy. Nine clear associations were obtained. For AD and PD, an increased iron load was causative: the right pallidum for AD and the right caudate, left caudate and right accumbens for PD. However, a reduced iron load was identified in the right and left caudate for multiple sclerosis, the bilateral hippocampus for mixed vascular dementia and the left thalamus and bilateral accumbens for subcortical vascular dementia. Thus, changes in iron load in different brain regions have causal effects on neurodegenerative diseases. Our results are crucial for understanding the pathogenesis and investigating the treatment of these diseases.

Zeolite enhanced iron-modified biocarrier drives Fe(II)/Fe(III) cycle to achieve nitrogen removal from eutrophic water.

The problem of nitrogen removal in eutrophic water needs to be solved. Two new autotrophic nitrogen removal technologies, ammonia oxidation coupled with Fe(III) reduction (Feammox) and Nitrate-dependent Fe(II) oxidation (NDFO), have been shown to have the potential to treat eutrophic water. However, the continuous addition of iron sources not only costs more, but also leads to sludge mineralization. In this study, nano-sized iron powder was loaded on the surface of K3 filler as a solid iron source for the extracellular metabolism of iron-trophic bacteria. At the same time, due to the high selective adsorption of zeolite for ammonia can improve the low nitrogen metabolism rate caused by low nitrogen concentrations in eutrophic water, three kinds of modified functional biological carriers were prepared by mixing zeolite powder and iron powder in different proportions (Z1, Zeolite:iron = 1; Z2, Zeolite:iron = 2; Z3, Zeolite:iron = 3). Z3 exhibited the best performance, with removal efficiencies of 54.8% for total nitrogen during 70 days of cultivation. The chemical structure and state of iron compounds changed under microorganism activity. The ex-situ test detected high NDFO and Feammox activities, with values of 1.02 ± 0.23 and 0.16 ± 0.04 mgN/gVSS/h. The enrichment of NDFO bacteria (Gallionellaceae, 0.73%-1.43%-0.74%) and Feammox bacteria (Alicycliphilus, 1.51%-0.88%-2.30%) indicated that collaboration between various functional microorganisms led to autotrophic nitrogen removal. Hence, zeolite/iron-modified biocarrier could drive the Fe(II)/Fe(III) cycle to remove nitrogen autotrophically from eutrophic water without carbon and Fe resource addition.

A Modified Technique for All-Inside Anterior Cruciate Ligament Reconstruction (ACLR): True Femoral Socket.

Anterior cruciate ligament reconstruction (ACLR) performed via arthroscopy is the primary treatment for anterior cruciate ligament injury. In traditional ACLR, the surgeon must create bone tunnels in both the femur and tibia, which increases the risk of bleeding and pain. The advent of all-inside technology has introduced the concept of bone sockets. However, the femoral socket created by the traditional all-inside technique is not a true femoral socket since the tunnel ends are still connected to achieve suspensory fixation. We are dedicated to achieving a true femoral socket in the all-inside ACLR technique. The AperFix Implant fixation system offers the potential for a genuine femoral socket by securely holding the ligaments in place through compression fixation. In this report, we present an all-inside ACLR using the AperFix Implant fixation system, which allows for a single exit of the femur side tunnel. This technique effectively reduces "windshield wiper" effect, "bungee cord" effect, as well as surgical time and minimizes the risk of bleeding, pain, and local microfractures.

Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by rapid progression and poor prognosis. Understanding the genetic mechanisms that affect cancer properties and reprogram tumor immune microenvironment will develop new strategies to maximize the benefits for cancer therapies. METHODS: Gene signatures and biological processes associated with advanced cancer and unfavorable outcome were profiled using bulk RNA sequencing and spatial transcriptome sequencing, Caprin-1 was identified as an oncogenesis to expedite pancreatic cancer growth by activating autophagy. The mechanism of Caprin-1 inducing autophagy activation was further explored in vitro and in vivo. In addition, higher level of Caprin-1 was found to manipulate immune responses and inflammatory-related pathways. The immune profiles associated with increased levels of Caprin-1 were identified in human PDAC samples. The roles of CD4+T cells, CD8+T cells and tumor associated macrophages (TAMs) on clinical outcomes prediction were investigated. RESULTS: Caprin-1 was significantly upregulated in advanced PDAC and correlated with poor prognosis. Caprin-1 interacted with both ULK1 and STK38, and manipulated ULK1 phosphorylation which activated autophagy and exerted pro-tumorigenic phenotypes. Additionally, the infiltrated CD4+T cells and tumor associated macrophages (TAMs) were increased in Caprin-1High tissues. The extensive CD4+T cells determined poor clinical outcome in Caprin-1high patients, arguing that highly expressed Caprin-1 may assist cancer cells to escape from immune surveillance. CONCLUSIONS: Our findings establish causal links between the upregulated expression of Caprin-1 and autophagy activation, which may manipulate immune responses in PDAC development. Our study provides insights into considering Caprin-1 as potential therapeutic target for PDAC treatment.

Association of aberrant structural-functional network coupling with cognitive decline in patients with non-dialysis-dependent stage 5 chronic kidney disease.

Background: Cognitive decline exists in the chronic kidney disease (CKD) population and is particularly severe in patients with stage 5 CKD, but the mechanisms underlying this relationship are unclear. Structural-functional coupling, an integrated measure that combines functional and structural networks, offers the possibility of exploring changes in network relationships in patients with stage 5 CKD. This study aimed to investigate the brain network topology and structural-functional coupling characteristics in patients with non-dialysis-dependent stage 5 CKD (CKD 5ND) and the correlation between network changes and cognitive scores. Methods: We prospectively performed diffusion tensor and resting-state functional magnetic resonance (rs-fMRI) imaging on 40 patients with CKD 5ND disease and 47 healthy controls (HCs). Graph theory analysis of functional and structural connectivity (SC) was performed. Small-world properties and network efficiency properties were calculated, including characteristic path length (Lp), clustering coefficient (Cp), normalized clustering coefficient (Gamma), normalized characteristic path length (Lambda), small-worldness (Sigma), global efficiency (Eglob), and local efficiency (Eloc). The SC-functional connectivity (FC) coupling characteristics and the association between Montreal Cognitive Assessment (MoCA) scores and graph-theoretical features were analyzed. Results: For SC, the Sigma (P=0.009), Cp (P=0.01), Eglob (P<0.001), and Eloc (P=0.01) were significantly lower in patients with CKD 5ND than in HCs, while Lp (P<0.001) and Lambda (P<0.001) were significantly higher in the patients than in the HCs. For FC, the Sigma (P=0.008), Gamma (P=0.009), Eglob (P=0.04), and Eloc (P<0.0001) were lower in patients with CKD 5ND than in HCs; however, the Lp (P=0.02) was higher in the patients than in the HCs. SC-SC coupling (P<0.001) was greater in patients with CKD 5ND than in HCs. The structural (Cp, Eloc, Eglob) and functional network parameters (Sigma, Gamma, Eglob) of the patients with CKD 5ND were positively correlated with MoCA scores; however, the Lp of both structural and functional networks was negatively correlated with MoCA scores. Conclusions: All patients with CKD 5ND included in the study exhibited changes in their structural and functional brain network topology closely related to mild cognitive impairment. SC-SC coupling was elevated in the patients compared with that in the controls. This may provide vital information for understanding and revealing the underlying mechanisms of cognitive impairment in patients with CKD 5ND.

Identification of Whirly transcription factors in Triticeae species and functional analysis of TaWHY1-7D in response to osmotic stress.

Osmotic stress poses a threat to the production and quality of crops. Whirly transcription factors have been investigated to enhance stress tolerance. In this study, a total of 18 Whirly genes were identified from six Triticeae species, which were classified into Whirly1 and Whirly2. The exon-intron structure, conserved motif, chromosomal location, collinearity, and regulatory network of Whirly genes were also analyzed. Real-time PCR results indicated that TaWHY1 genes exhibited higher expression levels in leaf sheaths and leaves during the seedling stage, while TaWHY2 genes were predominantly expressed in roots. Under PEG stress, the expression levels of TaWHY1-7A, TaWHY2-6A, TaWHY2-6B, and TaWHY2-6D were increased, TaWHY1-7D was reduced, and TaWHY1-4A had no significant change. All TaWHY genes were significantly up-regulated in response to NaCl stress treatment. In addition, TaWHY1-7A and TaWHY1-7D mainly enhanced the tolerance to oxidative stress in yeast cells. TaWHY2s mainly improved NaCl stress tolerance and were sensitive to oxidative stress in yeast cells. All TaWHYs slightly improved the yeast tolerance to d-sorbitol stress. The heterologous expression of TaWHY1-7D greatly improved drought and salt tolerance in transgenic Arabidopsis. In conclusion, these results provide the foundation for further functional study of Whirly genes aimed at improving osmotic stress tolerance in wheat.