Recruitment of HAB1 and SnRK2.2 by C2-domain protein CAR1 in plasma membrane ABA signaling.

Plasma membrane (PM)-associated abscisic acid (ABA) signal transduction is an important component of ABA signaling. The C2-domain ABA-related (CAR) proteins have been reported to play a crucial role in recruiting ABA receptor PYR1/PYL/RCAR (PYLs) to the PM. However, the molecular details of the involvement of CAR proteins in membrane-delimited ABA signal transduction remain unclear. For instance, where this response process takes place and whether any additional members besides PYL are taking part in this signaling process. Here, the GUS-tagged materials for all Arabidopsis CAR members were used to comprehensively visualize the extensive expression patterns of the CAR family genes. Based on the representativeness of CAR1 in response to ABA, we determined to use it as a target to study the function of CAR proteins in PM-associated ABA signaling. Single-particle tracking showed that ABA affected the spatiotemporal dynamics of CAR1. The presence of ABA prolonged the dwell time of CAR1 on the membrane and showed faster lateral mobility. Surprisingly, we verified that CAR1 could directly recruit hypersensitive to ABA1 (HAB1) and SNF1-related protein kinase 2.2 (SnRK2.2) to the PM at both the bulk and single-molecule levels. Furthermore, PM localization of CAR1 was demonstrated to be related to membrane microdomains. Collectively, our study revealed that CARs recruited the three main components of ABA signaling to the PM to respond positively to ABA. This study deepens our understanding of ABA signal transduction.

Cortical Microhemorrhage Presentation of Small Vessel Primary Angiitis of the Central Nervous System.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). METHODS: This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. RESULTS: We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. INTERPRETATION: The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.

Central vein sign and trigeminal lesions of multiple sclerosis visualised by 7T MRI.

BACKGROUND: Although trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site specificity of trigeminal nerve injury is still unclear. We aim to determine the prevalence of trigeminal nerve involvement in patients with MS in a consecutive 7T brain MRI cohort. METHODS: This observational cohort originates from an ongoing China National Registry of Neuro-Inflammatory Diseases. Inclusion criteria were the following: age 18 years or older, diagnosis of MS according to the 2017 McDonald criteria and no clinical relapse within the preceding 3 months. Each participant underwent 7T MAGNETOM Terra scanner (Siemens, Erlangen, Germany), using a 32-channel phased array coil at Beijing Tiantan Hospital. T1-weighted magnetisation-prepared rapid acquisition gradient echoes, fluid-attenuated inversion recovery (FLAIR) and fluid and white matter suppression images were used to identify lesions. FLAIR* and T2* weighted images were used to identify central vein sign (CVS) within the trigeminal lesions. RESULTS: 120 patients underwent 7T MRI scans between December 2021 and May 2023. 19/120 (15.8%) patients had a total of 45 trigeminal lesions, of which 11/19 (57.9%) were bilateral. The linear lesions extended along the trigeminal nerve, from the root entry zone (REZ) (57.8%, 26/45) to the pontine-medullary nucleus (42.2%, 19/45). 26.9% (7/26) of the lesions in REZ showed a typical central venous sign. CONCLUSION: In this 7T MRI cohort, the prevalence of trigeminal nerve involvement was 15.8%. Characteristic CVS was detected in 26.9% of lesions in REZ. This suggests an inflammatory demyelination mechanism of trigeminal nerve involvement in MS.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing.

BACKGROUND: Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. METHODS: RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. RESULTS: In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. CONCLUSIONS: We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Association of body mass index and waist-to-height ratio with outcomes in ischemic stroke: results from the Third China National Stroke Registry.

BACKGROUND AND PURPOSE: Conflicting reports of obesity paradox have led to confusion about weight management strategies for post-stroke patients. The main purpose of this study is to determine whether the obesity paradox measured by body mass index (BMI) or by waist-to-height ratio (WHtR) is real. METHODS: We evaluated the association of general obesity measured by BMI, and abdominal obesity measured by WHtR with 1-year all-cause mortality, recurrence of stroke and combined vascular events of acute ischemic stroke (AIS) patients in a cohort -- the Third China National Stroke Registry (CNSR-III). Cox proportional hazards models and restricted cubic splines were performed to investigate the association between obesity and clinical outcomes. RESULTS: A total of 14,146 patients with ischemic stroke were included. When BMI was used as a measure of obesity, compared to the normal weight patients, mortality decreased in overweight patients (hazard ratio [HR] 0.74 [95% confidence interval (CI) 0.61-0.91], P = 0.0035) and obese patients (HR 0.54 [0.40-0.73], P < 0.0001); and increased in underweight patients (HR 2.55 [1.75-3.73], P < 0.0001). After adjustment for confounding factors, the protective effect of obesity and overweight disappeared. BMI had no association with recurrence of stroke or combined vascular events. When WHtR was used as a measure of obesity, obese patients had lower 1-year all-cause mortality (HR 0.64 [0.43-0.97], P = 0.0357). After adjustment for confounding factors, this difference disappeared; overweight patients still had lower all-cause mortality (adjusted hazard ratio [aHR] 0.42 [0.26-0.67], P = 0.0003), recurrence of stroke (aHR 0.77 [0.60-0.99], P = 0.0440) and combined vascular events (aHR 0.75 [0.58-0.95], P = 0.0198). CONCLUSIONS: Among Chinese patients with AIS, our study does not support the BMI paradox; overweight patients measured by WHtR had a more favorable prognosis. TOAST subtypes did not modify the association.

Spin-selectivity effect of G-quadruplex DNA molecules.

Chirality-induced spin selectivity has been attracting extensive interest in recent years and is demonstrated in a variety of chiral molecules, all of which arise from inherent molecular chirality. Here, we first propose a theoretical model to study the spin-dependent electron transport along guanine-quadruplex (G4) DNA molecules, connected to two nonmagnetic electrodes, by considering the molecule-electrode contact and weak spin-orbit coupling. Our results indicate that the G4-DNA molecular junctions exhibit pronounced spin-selectivity effect, and the asymmetric contact-induced external chirality, instead of the inherent molecular chirality, dominates their spin filtration efficiency. Furthermore, the spin-selectivity effect is robust against the disorder and hold in a wide range of model parameters. These results could be checked by charge transport measurements and provide an alternative way to improve the spin-selectivity effect of chiral nanodevices.

Efficiency and safety of optic canal unroofing in tuberculum sellae meningiomas: a meta-analysis and systematic review.

Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733-0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803-0.965, p < 0.01) and 0.788 (95% CI: 0.700-0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739-0.969), Type II:2-4 cm was 0.844(95% CI: 0.755-0.910), Type III: > 4 cm was 0.500(95% CI: 0.068-0.932) and the total was 0.853(95% CI: 0.779-0.927 p < 0.01) with low heterogeneity of I2 = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848-0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817-0.986), Type II:2-4 cm was 0.880(95% CI: 0.800-0.936), Type III: > 4 cm was 0.600(95% CI: 0.147-0.947). The total was 0.897(95% CI: 0.830-0.965 p < 0.01) with low heterogeneity of I2 = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041-0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019-0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM.

Associations between obesity, diabetes mellitus, and cardiovascular disease with progression states of knee osteoarthritis (KOA).

BACKGROUND: Data on common comorbidities targeting at different progression states of knee osteoarthritis (KOA) in continuous time are limited. AIMS: To examine the associations between obesity, diabetes mellitus (DM), and cardiovascular disease (CVD) with the progression of KOA. METHODS: Data were obtained from the Osteoarthritis Initiative for up to 48 months. Progression states of KOA were defined as (1) normal; (2) asymptomatic radiographic KOA (RKOA, Kellgren-Lawrence grade ≥ 2 in at least one knee); (3) only knee symptoms; (4) symptomatic KOA (SxKOA, a combination of RKOA and knee symptoms in the same knee). A multi-state Markov model was used to investigate the associations while accounting for potential confounders. RESULTS: Participants with obesity had an increased risk of developing RKOA [normal to asymptomatic RKOA, adjusted hazard ratio (aHR) 1.55, 95% confidence interval (95% CI) (1.07, 2.24); only knee symptoms to SxKOA, aHR 2.25, 95% CI (1.60, 3.18)], and an increased risk of developing knee symptoms [normal to only knee symptoms, aHR 1.45, 95% CI (1.15, 1.83); asymptomatic RKOA to SxKOA, aHR 1.33, 95% CI (1.16, 1.52)]. DM was also significantly associated with development of RKOA or knee symptoms [normal to asymptomatic RKOA, aHR 1.92, 95% CI (1.12, 3.30); normal to only knee symptoms, aHR 1.78, 95% CI (1.12, 2.84)]. Knee symptoms were less likely to be relieved among participants with CVD, compared with those without [only knee symptoms to normal, aHR 0.60, 95% CI (0.38, 0.94)]. CONCLUSIONS: Obesity, DM and CVD are associated with an increased risk for SxKOA progression. Common comorbidities should be considered to prevent KOA development.

Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

RESEARCH QUESTION: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity? DESIGN: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo. RESULTS: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%). CONCLUSIONS: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway.

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high-fat diet (HFD). Increases in muscle atrophy markers (FOXO-3, Atrogin-1, MuRF-1) were abrogated by FGF19 in palmitic acid (PA)-treated C2C12 myotubes and in the skeletal muscle of HFD-fed mice. FGF19 not only reduced HFD-induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC-1α, UCP-1, PPAR-γ) in brown adipose tissue (BAT). FGF19 treatment restored PA- and HFD-induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS-1, GLUT-4) and mitigated the PA- and HFD-induced decrease in FNDC-5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT-1 and PGC-1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT-1/PGC-α signalling pathway, which might be a potential therapeutic target for obesity and SO.

Design of bovine lactoferricin-derived peptide and its expression and activity in Pichia pastoris.

Bovine lactoferrin peptide has been shown to be a broad-spectrum antimicrobial peptide. Based on the relationship between the structure and function of antimicrobial peptides, the antimicrobial peptide databases and protein analysis software were used to optimize the design of bovine lactoferricin peptide (LfcinB). The designed bovine lactoferricin-derived peptide (LfcinBD) gene fragment was inserted into a pPIC9K-His plasmid to construct a recombinant expression vector. After linearization of the Recombinant plasmid, Pichia pastoris GS115 cells were transfected with linearized recombinant plasmid by using electroporation and LfcinBD gene expression was induced with methanol. After the fermentation, supernatant was separated by low-temperature high-speed centrifugation. Ultrafiltration and freeze drying of the fermentation supernatant were performed, purified. Experimental results showed that the LfcinBD had stronger bacteriostatic activity against Staphylococcus aureus than the natural bovine lactoferrin peptide (LfcinB) produced under the same fermentation conditions. The effective expression of the optimized bovine lactoferricin-derived peptide was detected using SDS-PAGE electrophoresis. This study lays the foundation for further exploration to improve the biological activities of antimicrobial peptides.

Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis.

Fibrosis is a key pathological event during muscle aging that accelerates the development of sarcopenia. We show that sarcolipin (SLN) is highly expressed during aging, promotes intracellular calcium overload and participates in impaired myogenic differentiation. d-Galactose (D-gal) was used to induce senescence in C2C12 myoblasts. Conventional AAV-mediated SLN knockdown cells were used to study the role of SLN in muscle physiology and pathophysiology. C2C12 cells were treated with D-gal, which promoted fibrosis and SLN upregulation. The expression of TGF-ß1 and α-SMA, which participate in myogenic transdifferentiation, were also elevated. C2C12 cells with reduced sarcolipin expression produced decreased amounts of collagen. Our study identified an unrecognized role of SLN in regulating myogenic transdifferentiation during aging-associated skeletal muscle cell fibrosis. Targeting SLN may be a novel therapeutic strategy to relieve sarcopenia-associated muscle fibrosis.

Association between changes in hip-knee-ankle angle and hindfoot alignment after total knee arthroplasty for varus knee osteoarthritis.

BACKGROUND: The change in hip-knee-ankle (HKA) angle after total knee arthroplasty (TKA) may cause an adjustment in hindfoot alignment (HFA). However, the relationship between the changes in HKA angle and HFA is still not well studied. This study aimed to investigate the association between HKA angle and hindfoot alignment changes after TKA for varus knee osteoarthritis. METHODS: A prospective study was carried out in which 108 patients with varus knee deformities were radiographically and clinically evaluated before and 3 months after TKA. The relationship of change in HFA with correction in HKA angle was investigated. RESULTS: The results showed that the HFA was adjusted significantly by 3 months after TKA (p < 0.001), along with improved American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score (p < 0.001). Next, a univariate correlation and linear regression analysis showed that the change in HFA was weakly correlated with the change in HKA angle (r=-0.262, ß=-0.14, 95 % CI: -0.23 to -0.04, P = 0.006). Further stratified analysis and interaction tests revealed that age has a distinct effect on the correlation between the changes in HFA and HKA angle. The correlation was dramatically greater in the group under 65 years (r=-0.474, ß=-0.26, 95 % CI: -0.41 to -0.12, P = 0.001), whilst, no correlation was observed in those above 65 years old (r=-0.036, ß=-0.02, 95 % CI: -0.14 to 0.11, P = 0.779). CONCLUSIONS: Our findings indicated that correction of HKA after TKA tend to promote adjustment in the hindfoot alignment toward re-balance of the whole lower limb weight-bearing axis. However, this mechanism obviously weakens in elderly patients. Therefore, if apparent hindfoot deformity exists in these patients before TKA, more perioperative intervention is required for hindfoot adjustment, and even HKA undercorrection may be considered.

Graphene-PtPd nanocomposite for low-potential-driven electrochemiluminescent determination of carcinoembryonic antigen using Ru(bpy)32.

As well known, the electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) heavily relies on highly positive or negative triggered voltage, prejudicing the detection toward the bio-molecules. In this work, Ru(bpy)32+ could generate enhanced and stable ECL at a low potential of 0.05 V (vs. Ag/AgCl) on graphene-PtPd hybrid, attributing to its excellent electrocatalysis from the synergistic effect between Pt and Pd. The obtained low-potential-driven ECL could be quenched by MoS2 nanoflowers. Based on the quenching effect, a sandwich "signal-off" ECL immunosensor was fabricated to sensitively detect carcinoembryonic antigen (CEA). A linear calibration curve from 1 fg mL-1 to 1 ng mL-1 was obtained along with a low detection limit of 0.54 fg mL-1 (S/N = 3) under optimal conditions. The sensor showed satisfactory specificity, stability, and reproducibility and was successfully applied to determine CEA in actual samples. The recoveries ranged from 98.80 to 100.23%, and the relative standard deviation (RSD) was lower than 5%. Above all, this work explored new materials in low-potential-driven ECL system and provided a reliable sensing strategy for clinical applications.

Single-Molecule Imaging in Living Plant Cells: A Methodological Review.

Single-molecule imaging is emerging as a revolutionary approach to studying fundamental questions in plants. However, compared with its use in animals, the application of single-molecule imaging in plants is still underexplored. Here, we review the applications, advantages, and challenges of single-molecule fluorescence imaging in plant systems from the perspective of methodology. Firstly, we provide a general overview of single-molecule imaging methods and their principles. Next, we summarize the unprecedented quantitative details that can be obtained using single-molecule techniques compared to bulk assays. Finally, we discuss the main problems encountered at this stage and provide possible solutions.

Distribution of Linezolid in Tuberculosis Lesions in Patients with Spinal Multidrug-Resistant Tuberculosis.

Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study was to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples, and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography-tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, and 14.08 ± 10.61 mg/liter, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t = -2.810, P = 0.015; t = -4.901, P = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB-infected tissues in patients with spinal MDR-TB.

Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle.

Obesity-induced fat ectopic deposition results in mitochondrial dysfunction and oxidative stress in skeletal muscle, which could impair the quality and function of the skeletal muscle. Human fibroblast growth factor 19 (FGF19) acts as a vital metabolic regulator of bile acid synthesis and metabolic homeostasis. Recent studies have shown that FGF19 regulates skeletal muscle mass through the enlargement of muscle fiber size and protects muscles from atrophy. However, the role of FGF19 in regulating mitochondrial function and the antioxidant response in skeletal muscle remains unknown. Therefore, we investigated the effect of FGF19 on palmitic acid (PA)-induced mitochondrial dysfunction and oxidative stress in C2C12 cells. In this study, we found that FGF19 can increase the mRNA and protein expression levels of mitochondrial biogenesis regulators (PGC-1α, Nrf-1, and TFAM) and antioxidant response regulators (Nrf-2 and HO-1), alleviating PA-induced mitochondrial dysfunction and oxidative stress. However, the regulatory effect of FGF19 was blocked by Compound C, an AMP-activated protein kinase (AMPK) inhibitor, and siRNA knockdown of PGC-1a. Taken together, these findings indicate that FGF19 might promote mitochondrial biogenesis and antioxidant response via the AMPK/PGC-1α pathway, attenuating the effect of PA on mitochondrial dysfunction and oxidative stress; therefore, FGF19 might be a potential therapeutic target for the effects of obesity on skeletal muscle.

MRI-based Bosniak Classification of Cystic Renal Masses, Version 2019: Interobserver Agreement, Impact of Readers' Experience, and Diagnostic Performance.

Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

Multiparametric MRI Radiomic Model for Preoperative Predicting WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Percutaneous microwave ablation of renal cell carcinoma: practice guidelines of the ultrasound committee of Chinese medical association, interventional oncology committee of Chinese research hospital association.

Imaging-guided percutaneous microwave ablation (MWA) with high thermal efficiency comprises rapid, successful management of small renal cell carcinomas (RCCs) in selected patients. Ultrasound Committee of Chinese Medical Association, Interventional Oncology Committee of Chinese Research Hospital Association developed evidence-based guidelines for MWA of RCCs after systematically reviewing the 1969-2019 literature. Systematic reviews, meta-analyses, randomized controlled trials, cohort, and case-control studies reporting MWA of RCCs were included and levels of evidence assessed. Altogether, 146 articles were identified, of which 35 reported percutaneous MWA for T1a RCCs and 5 articles for T1b RCCs. Guidelines were established based on indications, techniques, safety, and effectiveness of MWA for RCCs, with the goal of standardizing imaging-guided percutaneous MWA treatment of RCCs. Key points Microwave ablation is recommended for managing small renal cell carcinoma in selected patients. Imaging protocols are tailored based on the procedural plan, guidance, and evaluation. Patient's selection evaluation, updated technique information, clinical efficacy, and complications are recommended to standardize management. A joint task force (multidisciplinary team) summarized the key elements of the standardized report.