Comparative analysis of the performance of hepatobiliary agents in depicting MRI features of microvascular infiltration in hepatocellular carcinoma.

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

Treatment-related adverse events of immune checkpoint inhibitors in clinical trials: a systematic review and meta-analysis.

Aim: This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites. Methods: We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023. Results: In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs. Conclusion: This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs. Systematic review registration: INPLASY platform, identifier INPLASY202380119.

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology.

Objective: Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP. Methods: Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays. Results: The M-RAP method had sensitivity rates of 1, 10, and 1 copies/µL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively ( P < 0.05). Conclusion: An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

A rare complex structural variant of novel intragenic inversion combined with reciprocal translocation t(X;1)(p21.2;p13.3) in Duchenne muscular dystrophy.

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

An Accelerated PETALUTE MRI Sequence for In Vivo Quantification of Sodium Content in Human Articular Cartilage at 3T.

In this work, we demonstrate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence. We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial-Matched Trajectories) and the other matching the total number of samples (Radial-Matched Samples) acquired in k-space. The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2× and 4× acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. Together, these results demonstrate improved scan time with equivalent performance of the PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.

Targeting tumor suppressor p53 for organ fibrosis therapy.

Fibrosis is a reparative and progressive process characterized by abnormal extracellular matrix deposition, contributing to organ dysfunction in chronic diseases. The tumor suppressor p53 (p53), known for its regulatory roles in cell proliferation, apoptosis, aging, and metabolism across diverse tissues, appears to play a pivotal role in aggravating biological processes such as epithelial-mesenchymal transition (EMT), cell apoptosis, and cell senescence. These processes are closely intertwined with the pathogenesis of fibrotic disease. In this review, we briefly introduce the background and specific mechanism of p53, investigate the pathogenesis of fibrosis, and further discuss p53's relationship and role in fibrosis affecting the kidney, liver, lung, and heart. In summary, targeting p53 represents a promising and innovative therapeutic approach for the prevention and treatment of organ fibrosis.

EFHD1 promotes osteosarcoma proliferation and drug resistance by inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP) by binding to ANT3.

Chemoresistance is the main obstacle in the clinical treatment of osteosarcoma (OS). In this study, we investigated the role of EF-hand domain-containing protein 1 (EFHD1) in OS chemotherapy resistance. We found that the expression of EFHD1 was highly correlated with the clinical outcome after chemotherapy. We overexpressed EFHD1 in 143B cells and found that it increased their resistance to cell death after drug treatment. Conversely, knockdown of EFHD1 in 143BR cells (a cisplatin-less-sensitive OS cell line derived from 143B cells) increased their sensitivity to treatment. Mechanistically, EFHD1 bound to adenine nucleotide translocase-3 (ANT3) and inhibited its conformational change, thereby inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP). This effect could maintain mitochondrial function, thereby favoring OS cell survival. The ANT3 conformational inhibitor carboxyatractyloside (CATR), which can promote mPTP opening, enhanced the chemosensitivity of EFHD1-overexpressing cells when combined with cisplatin. The ANT3 conformational inhibitor bongkrekic acid (BKA), which can inhibit mPTP opening, restored the resistance of EFHD1 knockdown cells. In conclusion, our results suggest that EFHD1-ANT3-mPTP might be a promising target for OS therapy in the future.

Improvement of physicochemical properties and quercetin delivery ability of fermentation-induced soy protein isolate emulsion gel processed by ultrasound.

This study aimed to investigate the effects of ultrasonic treatment at different powers on the physicochemical properties, microstructure and quercetin delivery capacity of fermentation-induced soy protein isolate emulsion gel (FSEG). The FSEG was prepared by subjecting soy protein isolate (SPI) emulsion to ultrasonic treatment at various powers (0, 100, 200, 300, and 400 W), followed by lactic acid bacteria fermentation. Compared with the control group (0 W), the FSEG treated with ultrasound had higher hardness, water holding capacity (WHC) and rheological parameters. Particularly, at an ultrasonic power of 300 W, the FSEG had the highest hardness (101.69 ± 4.67 g) and WHC (75.20 ± 1.07%) (p < 0.05). Analysis of frequency sweep and strain scanning revealed that the storage modulus (G') and yield strains of FSEG increased after 300 W ultrasonic treatment. Additionally, the recovery rate after creep recovery test significantly increased from 18.70 ± 0.49% (0 W) to 58.05 ± 0.54% (300 W) (p < 0.05). Ultrasound treatment also resulted in an increased ß-sheet content and the formation of a more compact micro-network structure. This led to a more uniform distribution of oil droplets and reduced mobility of water within the gel. Moreover, ultrasonic treatment significantly enhanced the encapsulation efficiency of quercetin in FSEG from 81.25 ± 0.62 % (0 W) to 90.04 ± 1.54% (300 W). The bioaccessibility of quercetin also increased significantly from 28.90 ± 0.40% (0 W) to 42.58 ± 1.60% (300 W) (p < 0.05). This study enriches the induction method of soy protein emulsion gels and provides some references for the preparation of fermented emulsion gels loaded with active substances.

Structural basis of a small monomeric Clivia fluorogenic RNA with a large Stokes shift.

RNA-based fluorogenic modules have revolutionized the spatiotemporal localization of RNA molecules. Recently, a fluorophore named 5-((Z)-4-((2-hydroxyethyl)(methyl)amino)benzylidene)-3-methyl-2-((E)-styryl)-3,5-dihydro-4H-imidazol-4-one (NBSI), emitting in red spectrum, and its cognate aptamer named Clivia were identified, exhibiting a large Stokes shift. To explore the underlying molecular basis of this unique RNA-fluorophore complex, we determined the tertiary structure of Clivia-NBSI. The overall structure uses a monomeric, non-G-quadruplex compact coaxial architecture, with NBSI sandwiched at the core junction. Structure-based fluorophore recognition pattern analysis, combined with fluorescence assays, enables the orthogonal use of Clivia-NBSI and other fluorogenic aptamers, paving the way for both dual-emission fluorescence and bioluminescence imaging of RNA molecules within living cells. Furthermore, on the basis of the structure-based substitution assay, we developed a multivalent Clivia fluorogenic aptamer containing multiple minimal NBSI-binding modules. This innovative design notably enhances the recognition sensitivity of fluorophores both in vitro and in vivo, shedding light on future efficient applications in various biomedical and research contexts.

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

Influencing factors of effective lens position in patients with Marfan syndrome and ectopia lentis.

AIMS: The aim of this study was to analyse the effective lens position (ELP) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). METHODS: Patients with MFS undergoing lens removal and primary intraocular lens (IOL) implantation were enrolled in the study. The back-calculated ELP was obtained with the vergence formula and compared with the theoretical ELPs. The back-calculated ELP and ELP error were evaluated among demographic and biometric parameters, including axial length (AL), corneal curvature radius (CCR) and white-to-white (WTW). RESULTS: A total of 292 eyes from 200 patients were included. The back-calculated ELP was lower in patients undergoing scleral-fixated IOL than those receiving in-the-bag IOL implantation (4.54 (IQR 3.65-5.20) mm vs 4.98 (IQR 4.56-5.67) mm, p<0.001). The theoretical ELP of the SRK/T formula exhibited the highest accuracy, with no difference from the back-calculated ELP in patients undergoing in-the-bag IOL implantation (5.11 (IQR 4.83-5.65) mm vs 4.98 (IQR 4.56-5.67) mm, p=0.209). The ELP errors demonstrated significant correlations with refraction prediction error (PE): a 1 mm ELP error led to PE of 2.42D (AL<22 mm), 1.47D (22 mm≤AL<26 mm) and 0.54D (AL≥26 mm). Multivariate analysis revealed significant correlations of ELP with AL (b=0.43, p<0.001), CCR (b=-0.85, p<0.001) and WTW (b=0.41, p=0.004). CONCLUSION: This study provides novel insights into the origin of PE in patients with MFS and EL and potentially refines existing formulas.

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. OBJECTIVES: To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. METHODS: Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. RESULTS: Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. CONCLUSIONS: iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.

Crosstalk between autophagy and ferroptosis mediate injury in ischemic stroke by generating reactive oxygen species.

Stroke represents a significant threat to global human health, characterized by high rates of morbidity, disability, and mortality. Predominantly, strokes are ischemic in nature. Ischemic stroke (IS) is influenced by various cell death pathways, notably autophagy and ferroptosis. Recent studies have increasingly highlighted the interplay between autophagy and ferroptosis, a process likely driven by the accumulation of reactive oxygen species (ROS). Post-IS, either the inhibition of autophagy or its excessive activation can escalate ROS levels. Concurrently, the interaction between ROS and lipids during ferroptosis further augments ROS accumulation. Elevated ROS levels can provoke endoplasmic reticulum stress-induced autophagy and, in conjunction with free iron (Fe2+), can trigger ferroptosis. Moreover, ROS contribute to protein and lipid oxidation, endothelial dysfunction, and an inflammatory response, all of which mediate secondary brain injury following IS. This review succinctly explores the mechanisms of ROS-mediated crosstalk between autophagy and ferroptosis and the detrimental impact of increased ROS on IS. It also offers novel perspectives for IS treatment strategies.

[Spatial-temporal Variation and Spatial Differentiation Geographic Detection of PM2.5 Concentration in the Shandong Province Based on Spatial Scale Effect].

PM2.5 remote sensing data was applied in this study, and Theil-Sen Median trend analysis and the Mann-Kendall significance test were utilized to analyze the temporal and spatial variation in PM2.5 in the Shandong Province from 2000 to 2021. The influencing power of the influencing factors on the spatial differentiation of PM2.5 concentration in the Shandong Province was detected at the provincial-city-county levels based on Geo-detector data. The results showed that:① on the temporal scale, the mean ρ(PM2.5)in the Shandong Province ranged from 38.15 to 88.63 µg·m-3 from 2000 to 2021, which was slightly higher than the secondary limit of inhalable particulate matter (35 µg·m-3) in the Ambient Air Quality Standards. On the interannual scale, 2013 was the peak year for the variation in ρ(PM2.5) with a value of 83.36 µg·m-3, according to which the trend of PM2.5 concentrations in the Shandong Province was divided into two phases:a continuous increase and a rapid decrease. On the seasonal scale, PM2.5 concentration presented the distribution characteristics of "low in summer and high in winter and moderate in spring and autumn" and the U-shaped change rule of first decreasing and then increasing. ② On the spatial scale, the PM2.5 concentration in the Shandong Province presented a spatial distribution pattern of "high in the west and low in the east." The areas with high PM2.5 concentration were distributed in the western area of the Shandong Province, whereas the areas with low PM2.5 concentration were distributed in the eastern peninsula region. The spatial variation in the changing trend of PM2.5 concentration showed significant spatial heterogeneity, and the extremely significant decrease was mainly distributed in the eastern peninsula region. ③ The results of factor detection showed that climate factor was an important factor affecting the spatial differentiation of PM2.5 concentration in the Shandong Province. Mean temperature had the highest influence on the spatial differentiation of PM2.5 concentration in the Shandong Province, with a q value of 0.512. Provincial-city-county multi-scale detection results showed that the influencing factors affecting the spatial differentiation of PM2.5 concentration and their influencing power differed at different spatial scales. At the provincial scale, mean temperature, sunshine duration, and slope were the main factors affecting the spatial differentiation of PM2.5 concentration. At the city level, precipitation, elevation, and relative humidity were the main factors affecting the spatial differentiation of PM2.5. At the county level, precipitation, mean temperature, and sunshine duration were the main factors affecting the spatial variation in PM2.5 concentration.

Regulation of cardiomyocyte t-tubule structure by preload and afterload: Roles in cardiac compensation and decompensation.

Mechanical load is a potent regulator of cardiac structure and function. Although high workload during heart failure is associated with disruption of cardiomyocyte t-tubules and Ca2+ homeostasis, it remains unclear whether changes in preload and afterload may promote adaptive t-tubule remodelling. We examined this issue by first investigating isolated effects of stepwise increases in load in cultured rat papillary muscles. Both preload and afterload increases produced a biphasic response, with the highest t-tubule densities observed at moderate loads, whereas excessively low and high loads resulted in low t-tubule levels. To determine the baseline position of the heart on this bell-shaped curve, mice were subjected to mildly elevated preload or afterload (1 week of aortic shunt or banding). Both interventions resulted in compensated cardiac function linked to increased t-tubule density, consistent with ascension up the rising limb of the curve. Similar t-tubule proliferation was observed in human patients with moderately increased preload or afterload (mitral valve regurgitation, aortic stenosis). T-tubule growth was associated with larger Ca2+ transients, linked to upregulation of L-type Ca2+ channels, Na+-Ca2+ exchanger, mechanosensors and regulators of t-tubule structure. By contrast, marked elevation of cardiac load in rodents and patients advanced the heart down the declining limb of the t-tubule-load relationship. This bell-shaped relationship was lost in the absence of electrical stimulation, indicating a key role of systolic stress in controlling t-tubule plasticity. In conclusion, modest augmentation of workload promotes compensatory increases in t-tubule density and Ca2+ cycling, whereas this adaptation is reversed in overloaded hearts during heart failure progression. KEY POINTS: Excised papillary muscle experiments demonstrated a bell-shaped relationship between cardiomyocyte t-tubule density and workload (preload or afterload), which was only present when muscles were electrically stimulated. The in vivo heart at baseline is positioned on the rising phase of this curve because moderate increases in preload (mice with brief aortic shunt surgery, patients with mitral valve regurgitation) resulted in t-tubule growth. Moderate increases in afterload (mice and patients with mild aortic banding/stenosis) similarly increased t-tubule density. T-tubule proliferation was associated with larger Ca2+ transients, with upregulation of the L-type Ca2+ channel, Na+-Ca2+ exchanger, mechanosensors and regulators of t-tubule structure. By contrast, marked elevation of cardiac load in rodents and patients placed the heart on the declining phase of the t-tubule-load relationship, promoting heart failure progression. The dependence of t-tubule structure on preload and afterload thus enables both compensatory and maladaptive remodelling, in rodents and humans.

Diversity Analysis of Intestinal Bifidobacteria in the Hohhot Population.

(1) Background: Bifidobacterium plays a pivotal role within the gut microbiota, significantly affecting host health through its abundance and composition in the intestine. Factors such as age, gender, and living environment exert considerable influence on the gut microbiota, yet scant attention has been directed towards understanding the specific effects of these factors on the Bifidobacterium population. Therefore, this study focused on 98 adult fecal samples to conduct absolute and relative quantitative analyses of bifidobacteria. (2) Methods: Using droplet digital PCR and the PacBio Sequel II sequencing platform, this study sought to determine the influence of various factors, including living environment, age, and BMI, on the absolute content and biodiversity of intestinal bifidobacteria. (3) Results: Quantitative results indicated that the bifidobacteria content in the intestinal tract ranged from 106 to 109 CFU/g. Notably, the number of bifidobacteria in the intestinal tract of the school population surpassed that of the off-campus population significantly (p = 0.003). Additionally, the group of young people exhibited a significantly higher count of bifidobacteria than the middle-aged and elderly groups (p = 0.041). The normal-weight group displayed a significantly higher bifidobacteria count than the obese group (p = 0.027). Further analysis of the relative abundance of bifidobacteria under different influencing factors revealed that the living environment emerged as the primary factor affecting the intestinal bifidobacteria structure (p = 0.046, R2 = 2.411). Moreover, the diversity of bifidobacteria in the intestinal tract of college students surpassed that in the out-of-school population (p = 0.034). This was characterized by a notable increase in 11 strains, including B. longum, B. bifidum, and B. pseudolongum, in the intestinal tract of college students, forming a more intricate intestinal bifidobacteria interaction network. (4) Conclusions: In summary, this study elucidated the principal factors affecting intestinal bifidobacteria and delineated their characteristics of intestinal bifidobacteria in diverse populations. By enriching the theory surrounding gut microbiota and health, this study provides essential data support for further investigations into the intricate dynamics of the gut microbiota.

Effect of electroacupuncture on proBDNF/mBDNF and synaptic plasticity in rats with learning and memory impairment after cerebral ischemia-reperfusion. / ç”µé’ˆå¯¹è„‘ç¼ºè¡€å†çŒæ³¨å­¦ä¹ è®°å¿†éšœç¢å¤§é¼ æµ·é©¬è„‘æºæ€§ç¥žç»è¥å »å› å­è½¬åŒ–å’Œçªè§¦å¯å¡‘æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.

3D ultra-short echo time 31P-MRSI with rosette k-space pattern: Feasibility and comparison with conventional weighted CSI.

Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) provides valuable non-invasive in vivo information on tissue metabolism but is burdened by poor sensitivity and prolonged scan duration. Ultra-short echo time (UTE) acquisitions minimize signal loss when probing signals with relatively short spin-spin relaxation time (T2), while also preventing first-order dephasing. Here, a three-dimensional (3D) UTE sequence with a rosette k-space trajectory is applied to 31P-MRSI at 3T. Conventional chemical shift imaging (CSI) employs highly regular Cartesian k-space sampling, susceptible to substantial artifacts when accelerated via undersampling. In contrast, this novel sequence's "petal-like" pattern offers incoherent sampling more suitable for compressed sensing (CS). These results showcase the competitive performance of UTE rosette 31P-MRSI against conventional weighted CSI with simulation, phantom, and in vivo leg muscle comparisons.

Medicinal cannabis oil improves anxiety-like and depressive-like behaviors in CCS mice via the BDNF/TRPC6 signaling pathway.

BACKGROUND: Post-traumatic stress disorder (PTSD) refers to a chronic impairing psychiatric disorder occurring after exposure to the severe traumatic event. Studies have demonstrated that medicinal cannabis oil plays an important role in neuroprotection, but the mechanism by which it exerts anti-PTSD effects remains unclear. METHODS: The chronic complex stress (CCS) simulating the conditions of long voyage stress for 4 weeks was used to establish the PTSD mice model. After that, behavioral tests were used to evaluate PTSD-like behaviors in mice. Mouse brain tissue index was detected and hematoxylin-eosin staining was used to assess pathological changes in the hippocampus. The indicators of cell apoptosis and the BDNF/TRPC6 signaling activation in the mice hippocampus were detected by western blotting or real-time quantitative reverse transcription PCR experiments. RESULTS: We established the PTSD mice model induced by CCS, which exhibited significant PTSD-like phenotypes, including increased anxiety-like and depression-like behaviors. Medicinal cannabis oil treatment significantly ameliorated PTSD-like behaviors and improved brain histomorphological abnormalities in CCS mice. Mechanistically, medicinal cannabis oil reduced CCS-induced cell apoptosis and enhanced the activation of BDNF/TRPC6 signaling pathway. CONCLUSIONS: We constructed a PTSD model with CCS and medicinal cannabis oil that significantly improved anxiety-like and depressive-like behaviors in CCS mice, which may play an anti-PTSD role by stimulating the BDNF/TRPC6 signaling pathway.

Risk factors and prediction score for new-onset diabetes mellitus after liver transplantation.

AIM: New-onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new-onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks. METHODS: We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database. RESULTS: A total of 468 patients met the outlined criteria and finished the follow-up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724-0.846) in the experimental population and 0.782 (95% CI: 0.708-0.856) in the validation population. CONCLUSIONS: Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.