Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair.

Nephrotoxicity is a major side effect of platinum-based antineoplastic drugs, and there is currently no available therapeutic intervention. Our study suggests that targeting histone deacetylase 8 could be a potential treatment for cisplatin-induced acute kidney injury (AKI). In a murine model of AKI induced by cisplatin, the administration of PCI-34051, a selective inhibitor of HDAC8, resulted in significant improvement in renal function and reduction in renal tubular damage and apoptosis. Pharmacological inhibition of HDAC8 also decreased caspase-3 and PARP1 cleavage, attenuated Bax expression and preserved Bcl-2 levels in the injured kidney. In cultured murine renal epithelial cells (mRTECs) exposed to cisplatin, treatment with PCI-34051 or transfection with HDAC8 siRNA reduced apoptotic cell numbers and diminished expression of cleaved caspase-3 and PARP1; conversely, overexpression of HDAC8 intensified these changes. Additionally, PCI-34051 reduced p53 expression levels along with those for p21, p-CDK2 and γ-H2AX while preserving MRE11 expression in the injured kidney. Similarly, pharmacological and genetic inhibition of HDAC8 reduced γ-H2AX and enhanced MRE11 expression; conversely, HDAC8 overexpression exacerbated these changes in mRTECs exposed to cisplatin. These results support that HDAC8 inhibition attenuates cisplatin-induced AKI through a mechanism associated with reducing DNA damage and promoting its repair.

Effects of rootstocks and developmental time on the dynamic changes of main functional substances in 'Orah' (Citrus reticulata Blanco) by HPLC coupled with UV detection.

Introduction: Citrus fruit is rich in important functional constituents such as flavonoids, phenolic acids terpenes and other functional substances that play an important role for treating clinical diseases or controlling major agricultural diseases and pests. Plant secondary metabolites have become one of the most important resources of novel lead compounds, especially young citrus fruits contain multiple functional substances. 'Orah', a type of citrus reticulata, is known for its fine appearance, productivity, delicious sweetness, late-maturing characteristics, and is widely cultivated in China. Fruit thinning and rootstock selection are commonly used agronomic measures in its production to ensure its quality and tree vigor. However, few studies have demonstrated the effects of these agronomic measures on the functional substances of 'Orah'. Methods: In this study, we used HPLC coupled with UV to detect the dynamic changes of fruit quality, 13 main flavonoids, 7 phenolic acids, 2 terpenes, synephrine and antioxidant capacity in both peel and pulp of citrus fruits grafted on four rootstocks (Red orange Citrus reticulata Blanco cv. red tangerine, Ziyang xiangcheng Citrus junos Sieb. ex Tanaka, Trifoliate orange Poncirus trifoliata L. Raf, and Carrizo citrange Citrus sinensis Osb.×P.trifoliate Raf) at six different developmental stages (from 90 DAF to 240 DAF). Results: The results indicated that rootstock can significantly affect the contents of functional constituents and antioxidant capacity in 'Orah'. Additionally, it was found that pruning at either 90 DAF (days after flowering) or 150 DAF produced the most favorable outcomes for extracting functional substances. We also identified rootstock 'Trifoliate orange' has the highest total soluble solids (TSS) and 'Ziyang xiangcheng' to be the optimal in terms of comprehensive sensory of fruit quality, while 'Red orange' and 'Ziyang xiangcheng' are optimal in terms of functional substance quality, and 'Red orange' excels in antioxidant capacity. Discussion: Overall, the findings demonstrate the important role of rootstocks and developmental stage in shaping fruit sensory quality and functional substance synthesis, providing valuable insights for guiding rootstock selection, determining thinning time, and utilizing pruned fruits in a more informed manner.

Combined Metabolomics and Network Pharmacology Analysis Reveal the Effect of Rootstocks on Anthocyanins, Lipids, and Potential Pharmacological Ingredients of Tarroco Blood Orange (Citrus sinensis L. Osbeck).

The benefits of citrus fruits are strongly associated with their secondary metabolites. In this study, we conducted widely targeted metabolomics analyses to compare the variability of the ingredients in four scion-rootstock combinations. A total of 376 differential metabolites were obtained by a multivariate statistical analysis, and a KEGG pathway analysis showed that the enriched metabolic pathways were mainly related to the biosynthesis of flavonoids as well as lipid metabolism. The anthocyanin-targeted metabolomic features showed that cyanidin 3-O-glucoside, cyanidin 3-O-(6-O-malonyl-beta-D-glucoside), cyanidin 3-O-sophoroside, and cyanidin 3-O-xyloside were the pigments responsible for the red color of Tarocco. A lipid metabolomics analysis revealed that when Tarocco was hetero-grafted with rootstock H, there was an increase in the content of each lipid subclass, accompanied by an increase in the levels of unsaturated fatty acids, including polyunsaturated linoleic and linolenic acids, thus impacting the ratio of unsaturated fatty acids to saturated fatty acids. Additionally, we determined their antioxidant capacity ('Trifoliate orange' (Z) > 'Citrange' (ZC) > 'Hongju' (H) > 'Ziyang Xiangcheng' (X)) using in vitro assays. Finally, we utilized a network pharmacology analysis to explore the antioxidant mechanisms and potential pharmacological ingredients; we obtained 26 core targets proteins and 42 core metabolites associated with oxidative damage, providing a basis for future preventive and therapeutic applications of these metabolites.

Digital mobile fronthaul scheme based on diff-delta-sigma modulation and OCT precoding.

In this Letter, we experimentally demonstrate digital mobile fronthaul (MFH) for 65536 quadrature amplitude modulation (65536-QAM) signals based on a diff-delta-sigma modulation (D-DSM) scheme with orthogonal circulant matrix transform (OCT) precoding. By combining the D-DSM scheme with OCT precoding, we successfully solved the problem of uneven distribution of in-band quantization noise (IBN) while bringing about a quantization SNR gain of about 1.5 dB. In addition, we compare two signal combination schemes, Gray coding and power superposition, in the D-DSM scheme. The results show that the power superposition scheme can achieve similar performance to Gray coding with lower computational complexity. At the same time, the power superposition scheme is less affected by the saturation effect. Therefore, the D-DSM solution combined with OCT precoding and power superposition provides an effective solution for future 6 G digital mobile fronthaul.

Low-rank prior-based Fast-RPCA for clutter filtering and noise suppression in non-contrast ultrasound microvascular imaging.

Accurate and real-time separation of blood signal from clutter and noise signals is a critical step in clinical non-contrast ultrasound microvascular imaging. Despite the widespread adoption of singular value decomposition (SVD) and robust principal component analysis (RPCA) for clutter filtering and noise suppression, the SVD's sensitivity to threshold selection, along with the RPCA's limitations in undersampling conditions and heavy computational burden often result in suboptimal performance in complex clinical applications. To address those challenges, this study presents a novel low-rank prior-based fast RPCA (LP-fRPCA) approach to enhance the adaptability and robustness of clutter filtering and noise suppression with reduced computational cost. A low-rank prior constraint is integrated into the non-convex RPCA model to achieve a robust and efficient approximation of clutter subspace, while an accelerated alternating projection iterative algorithm is developed to improve convergence speed and computational efficiency. The performance of the LP-fRPCA method was evaluated against SVD with a tissue/blood threshold (SVD1), SVD with both tissue/blood and blood/noise thresholds (SVD2), and the classical RPCA based on the alternating direction method of multipliers algorithm through phantom and in vivo non-contrast experiments on rabbit kidneys. In the slow flow phantom experiment of 0.2 mm/s, LP-fRPCA achieved an average increase in contrast ratio (CR) of 10.68 dB, 9.37 dB, and 8.66 dB compared to SVD1, SVD2, and RPCA, respectively. In the in vivo rabbit kidney experiment, the power Doppler results demonstrate that the LP-fRPCA method achieved a superior balance in the trade-off between insufficient clutter filtering and excessive suppression of blood flow. Additionally, LP-fRPCA significantly reduced the runtime of RPCA by up to 94-fold. Consequently, the LP-fRPCA method promises to be a potential tool for clinical non-contrast ultrasound microvascular imaging.

The miR-199a-5p/HIF1α dual-regulatory axis participates in hypoxia-induced aggressive phenotypes of oral squamous cell carcinoma (OSCC) cells.

BACKGROUND: The late-stage diagnosis and distant metastasis of oral squamous cell carcinoma (OSCC) remain a huge challenge to clinical treatment for OSCC. During the past decades, targeting glycolysis-inducing factors becomes an attractive new strategy in OSCC therapies. METHODS: OSCC cells were stimulated with hypoxia or transfected with agomir-199a-5p, antagomir-199a-5p, and siRNA for HIF1A, cell proliferation was detected by CCK-8 assay; HIF1α, GLUT1, HK2 and LDHA expression levels were examined with western blot; miR-199 expression was determined with RT-PCR; cell migratory and invasive abilities were examined using wound healing and transwell assays; the lactate and glucose in culture medium were also determined. Luciferase assay or CHIP assay was applied for confirm the binding between miR-199a-5p and HIF1A 3'UTR, or between HIF1α and miR-199a promoter. RESULTS: HIF1α showed to be abnormally up-regulated, and miR-199a-5p showed to be abnormally down-regulated within OSCC under hypoxia. Hypoxia considerably enhanced OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. MiR-199a-5p bound to HIF1A 3'-UTR and suppressed HIF1A expression; HIF1α targeted miR-199a-5p promoter region and downregulated miR-199a-5p expression. Under hypoxia, miR-199a-5p overexpression significantly repressed HIF1α up-regulation inresponse to hypoxia, OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. CONCLUSION: miR-199a-5p and HIF1α form a dual-regulatory axis in OSCC cells; the miR-199a-5p/HIF1α dual-regulatory axis contributes to hypoxia-induced aggressive OSCC phenotypes.

The safety and clinical outcomes of endovascular treatment versus microsurgical clipping of ruptured anterior communicating artery aneurysms: a 2-year follow-up, multicenter, observational study.

Background and objective: Current data on the optimal treatment modality for ruptured anterior communicating artery (AComA) aneurysms are limited. We conducted this multicenter retrospective study to evaluate the safety and clinical outcomes of endovascular treatment (EVT) and microsurgical clipping (MC) for the treatment of ruptured AComA patients. Methods: Patients with ruptured AComA aneurysms were screened from the Chinese Multicenter Cerebral Aneurysm Database. Propensity score matching (PSM) was used to adjust for baseline characteristic imbalances between the EVT and MC groups. The safety outcomes included total procedural complications, procedure-related morbidity/death and remedial procedure for complication. The primary clinical outcome was 2-year functional independence measured by the modified Rankin scale (mRS) score. Results: The analysis included 893 patients with ruptured AComA aneurysms (EVT: 549; MC: 346). PSM yielded 275 pairs of patients in the EVT and MC cohorts for comparison. Decompressive craniectomy being more prevalent in the MC group (19.3% vs. 1.5%, p < 0.001). Safety data revealed a lower rate of total procedural complications (odds ratio [OR] = 0.62, 95% CI 0.39-0.99; p = 0.044) in the EVT group and similar rates of procedure-related morbidity/death (OR = 0.91, 95% CI 0.48-1.73; p = 0.880) and remedial procedure for complication (OR = 1.35, 95% CI 0.51-3.69, p = 0.657) between the groups. Compared with that of MC patients, EVT patients had a greater likelihood of functional independence (mRS score 0-2) at discharge (OR = 1.68, 95% CI 1.14-2.50; p = 0.008) and at 2 years (OR = 1.89, 95% CI 1.20-3.00; p = 0.005), a lower incidence of 2-year all-cause mortality (OR = 0.54, 95% CI 0.31-0.93; p = 0.023) and a similar rate of retreatment (OR = 1.00, 95% CI 0.23-4.40; p = 1.000). Conclusion: Clinical outcomes after treatment for ruptured AComA aneurysms appear to be superior to those after treatment with MC, with fewer overall procedure-related complications and no increase in the retreatment rate. Additional studies in other countries are needed to verify these findings.

High-order QAM NANF transmission utilizing MIMO equalizer integrated with low-complexity decision-directed carrier phase estimation.

We experimentally realized a high-speed nested anti-resonant nodeless fiber (NANF) transmission with the assistance of the polarization division multiplexing (PDM) and probabilistic shaping (PS) technology. In this system, a low-complexity multiple-input multiple-output (MIMO) real-valued equalizer (RVE) is integrated with decision-directed carrier phase estimation (DDCPE), which is robust against the IQ cross talk and a tiny phase disturbance between PS symbols. By using the proposed MIMO-RVEDDCPE, the 60-Gbaud PDM-PS-256QAM signal has been delivered through 2-km NANF satisfying the soft-decision forward error correction (SD-FEC) threshold.

Photonic-assisted high-order vector millimeter-wave signal generation enabled by DSM.

We propose an optical dual-single-sideband (dual-SSB) modulated 16384-quadrature amplitude modulation (QAM) photonic vector millimeter-wave (mm-wave) signal generation scheme based on delta-sigma modulation (DSM). With the aid of the DSM, the severe nonlinear distortion of envelope detection for high-order QAM modulation signals in wireless communication can be effectively resolved. For the validation of our proposed scheme, we experimentally demonstrate the generation of a 40 GHz 16384-QAM orthogonal frequency division multiplexing (OFDM) photonic vector mm-wave signal and transmission over a 25-km standard single-mode fiber (SSMF), and a 1-m wireless link with the bit error ratio (BER) reaches the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.

Toxicology study profile of Nicotinamide mononucleotide after acute and 90-day sub chronic dosing in Wistar rats and mutagenicity tests.

Nicotinamide mononucleotide (NMN) is an intermediate in biosynthesis pathway of Nicotinamide adenine dinucleotide (NAD+), an essential cofactor in all living cells involved in fundamental biological processes. Evidence stemming from recent studies have unveiled numerous roles of NAD+ metabolism on aging, longevity, delaying the progression of age-related diseases. A three-study genetic toxicity (genetox) battery (bacterial mutagenesis, in vitro cytogenetics, and in vivo mammalian test) is usually required to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time. The acute oral LD50 of NMN was greater than 2000 mg/kg body weight with 5000 mg/kg body weight as LD50 cut-off value and was classified under "Category 5 or Unclassified" as per Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Based on 90 days repeated dose toxicity test the NOAEL was considered to be NLT 800 mg NMN/kg body weight in Wistar rats. The bacterial reverse mutation test, the in vitro and in vivo chromosomal aberration test, found NMN to be non-mutagenic. In the mammalian bone marrow chromosomal aberration test, it was concluded that NMN is non clastogenic at and up to 2,000 mg/kg body weight in all the animals tested to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time.

K-means non-uniform-quantization digital-analog radio-over-fiber scheme for THz-band photonics-aided wireless fronthaul.

We propose a non-uniform-quantization digital-analog radio-over-fiber (NUQ-DA-RoF) scheme based on an advanced K-means NUQ algorithm and demonstrate it experimentally in a 2-m 300-GHz photonics-aided wireless fronthaul system. Results show that the NUQ-DA-RoF scheme achieves a SNR gain of ∼1.9 dB compared to the uniform-quantization DA-RoF (UQ-DA-RoF) at an equivalent Common Public Radio Interface equivalent data rate (CPRI-EDR). Remarkably, the NUQ-DA-RoF scheme exhibits an ∼1.6-dB power sensitivity enhancement over the UQ-DA-RoF at the 256-QAM SNR threshold. These findings highlight the advantages of the NUQ-DA-RoF scheme over UQ-DA-RoF in terms of power budget and SNR improvement, suggesting promising prospects for future radio access networks and wireless fronthaul.

Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Widely Targeted Metabolomic Analysis Provides New Insights into the Effect of Rootstocks on Citrus Fruit Quality.

The use of different rootstocks has a significant effect on the content of flavor components and overall fruit quality. However, little information is available about the metabolic basis of the nutritional value of citrus plants. In this study, UPLC-MS/MS (ultra-performance liquid chromatography-tandem mass spectrometry) was performed to analyze the metabolites of three late-maturing hybrid mandarin varieties ('Gold Nugget', 'Tango' and 'Orah') grafted on four rootstocks ('Trifoliate orange', 'Carrizo citrange', 'Red tangerine' and 'Ziyang Xiangcheng'). A total of 1006 metabolites were identified through OPLS-DA (Orthogonal Partial Least Squares-Discriminant Analysis) analysis. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed the most critical pathways among the different pathways associated with genes grafted on the four rootstocks that were differentially activated, including tryptophan metabolism and sphingolipid metabolism in 'Gold Nugget'; tryptophan metabolism, phenylpropanoid biosynthesis and sphingolipid metabolism in 'Tango'; and pantothenate and CoA biosynthesis- and photosynthesis-related biosynthesis in 'Orah'. A considerable difference between the different rootstocks was also observed in the accumulation of lipids, phenolic acids and flavonoids; further analysis revealed that the rootstocks regulated specific metabolites, including deacetylnomylinic acid, sudachinoid A, amoenin evodol, rutaevin, cyclo (phenylalanine-glutamic acid), cyclo (proline-phenylalanine), 2-hydroxyisocaproic acid, and 2-hydroxy-3-phenylpropanoic acid. The results of this study provide a useful foundation for further investigation of rootstock selection for late-maturation hybrid mandarin varieties.

Delta-sigma modulation supporting the 4194304QAM dual polarization signal at the W-band transmission over a 4.6†km wireless distance.

In this Letter, we propose a dual-polarized coherent millimeter-wave system based on differential delta-sigma modulation (D-DSM) intended for long-distance wireless transmission in the W-band. The proposed system can transmit polarization-division-multiplexed (PDM) D-DSM signals with modulation orders up to 4194304QAM over a wireless channel for 4.6 km at a signal baud rate of 20 G. After 4.6 km of wireless transmission, we successfully achieve a bit error rate (BER) lower than the hard-decision forward error correction (HD-FEC) of 3.8 × 10-3 for 34.51 Gbit/s PDM-524288QAM and a BER lower than the soft-decision forward error correction (SD-FEC) of 4.2 × 10-2 for 32.23 Gbit/s PDM-4194304QAM.

Conditional chemoconnectomics (cCCTomics) as a strategy for efficient and conditional targeting of chemical transmission.

Dissection of neural circuitry underlying behaviors is a central theme in neurobiology. We have previously proposed the concept of chemoconnectome (CCT) to cover the entire chemical transmission between neurons and target cells in an organism and created tools for studying it (CCTomics) by targeting all genes related to the CCT in Drosophila. Here we have created lines targeting the CCT in a conditional manner after modifying GFP RNA interference, Flp-out, and CRISPR/Cas9 technologies. All three strategies have been validated to be highly effective, with the best using chromatin-peptide fused Cas9 variants and scaffold optimized sgRNAs. As a proof of principle, we conducted a comprehensive intersection analysis of CCT genes expression profiles in the clock neurons, uncovering 43 CCT genes present in clock neurons. Specific elimination of each from clock neurons revealed that loss of the neuropeptide CNMa in two posterior dorsal clock neurons (DN1ps) or its receptor (CNMaR) caused advanced morning activity, indicating a suppressive role of CNMa-CNMaR on morning anticipation, opposite to the promoting role of PDF-PDFR on morning anticipation. These results demonstrate the effectiveness of conditional CCTomics and its tools created here and establish an antagonistic relationship between CNMa-CNMaR and PDF-PDFR signaling in regulating morning anticipation.

JMJD3 activation contributes to renal protection and regeneration following acute kidney injury in mice.

We have recently demonstrated that Jumonji domain-containing protein D3 (JMJD3), a histone demethylase of histone H3 on lysine 27 (H3K27me3), is protective against renal fibrosis, but its role in acute kidney injury (AKI) remains unexplored. Here, we report that JMJD3 activity is required for renal protection and regeneration in murine models of AKI induced by ischemia/reperfusion (I/R) and folic acid (FA). Injury to the kidney upregulated JMJD3 expression and induced expression of H3K27me3, which was coincident with renal dysfunction, renal tubular cell injury/apoptosis, and proliferation. Blocking JMJD3 activity by GSKJ4 led to worsening renal dysfunction and pathological changes by aggravating tubular epithelial cell injury and apoptosis in both murine models of AKI. JMJD3 inhibition by GSKJ4 also reduced renal tubular cell proliferation and suppressed expression of cyclin E and phosphorylation of CDK2, but increased p21 expression in the injured kidney. Furthermore, inactivation of JMJD3 enhanced I/R- or FA-induced expression of TGF-ß1, vimentin, and Snail, phosphorylation of Smad3, STAT3, and NF-κB, and increased renal infiltration by F4/80 (+) macrophages. Finally, GSKJ4 treatment caused further downregulation of Klotho, BMP-7, Smad7, and E-cadherin, all of which are associated with renal protection and have anti-fibrotic effects. Therefore, these data provide strong evidence that JMJD3 activation contributes to renal tubular epithelial cell survival and regeneration after AKI.

Mechanism of Tianma-Gouteng granules lowering blood pressure based on the bile acid-regulated Farnesoid X Receptor-Fibroblast Growth Factor 15- Cholesterol 7α-hydroxylase pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tianma-Gouteng granules (TGG) is a traditional Chinese medicine (TCM) compound that was first recorded by modern medical practitioner Hu Guangci in "New Meaning of the Treatment of Miscellaneous Diseases in Traditional Chinese Medicine". It is widely used to treat hypertensive vertigo, headache and insomnia. AIM OF STUDY: To investigate the antihypertensive effect of TGG and explore its mechanism. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHR) were prepared a model of the ascendant hyperactivity of liver yang syndrome (AHLYS), blood pressure and general state of rats were recorded. A series of experiments were performed by enzyme-linked immunosorbent assay (ELISA), ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), 16S rRNA sequencing, real-time fluorescence quantitative PCR (RT-qPCR), and enzymatic colorimetry. RESULTS: TGG can effectively lower blood pressure and improve related symptoms. TGG significantly reduced the levels of IL-1ß, IL-6, TNF-α, Renin and AngII. A total of 17 differential metabolites were found in plasma, with the two most potent metabolic pathways being glycerophospholipid metabolism and primary bile acid biosynthesis. After TGG intervention, 7 metabolite levels decreased and 10 metabolite levels increased. TGG significantly increased the relative abundance of Desulfovibio, Lachnoclostridium, Turicibacter, and decreased the relative abundance of Alluobaculum and Monoglobu. TGG also downregulated Farnesoid X Receptor (FXR) and Fibroblast Growth Factor 15 (FGF15) levels in the liver and ileum, upregulated Cholesterol 7α-hydroxylase (CYP7A1) levels, and regulated total bile acid (TBA) levels. CONCLUSION: TGG can regulate bile acid metabolism through liver-gut axis, interfere with related intestinal flora and plasma metabolites, decrease blood pressure, and positively influence the pathologic process of SHR with AHLYS. When translating animal microbiota findings to humans, validation studies are essential to confirm reliability and applicability, particularly through empirical human research.

Transcranial ultrasound estimation of viscoelasticity and fluidity in brain tumors aided by transcranial shear waves.

Cerebral diseases, such as brain tumors, are intricately linked to the mechanical properties of brain tissues. Estimating the mechanical properties of brain tumors using transcranial ultrasound is a promising approach. However, the complexity of cranial features introduces challenges, such as ultrasound attenuation and interference from multidirectional transcranial shear waves induced by impact vibrations. To address these issues, this study proposes a transcranial ultrasound estimation method assisted by transcranial shear vibrations. Transcranial vibrations apply shear forces on the parietal bone, inducing unidirectional transcranial shear waves within brain tissue, as validated through simulations. Shear waves at different frequencies were captured via transcranial ultrasound, which were used to assess the viscoelasticity and fluidity of brain tumors. Transcranial experimental validations were conducted in 3D-printed models with tumor phantoms and ex vivo animal tumors. Vibration safety assessments were also performed. The results demonstrate that transcranial ultrasound can detect micron displacements induced by transcranial shear waves. In phantom and ex vivo animal experiments, speed distribution maps were employed to determine the size and location of one or two tumors enclosed in the skull model. The results revealed that the proposed approach could detect tumors with a minimum diameter of 0.8 cm and an inter-tumor distance of 0.8 cm. Notably, significant differences in viscoelasticity and fluidity between normal brain tissue and brain tumors were found (p<0.001). The maximum assessment errors for the elasticity, viscosity, and fluidity using transcranial ultrasound were 11.90%, 4.82%, and 0.73%, respectively, indicating that fluidity was more robust than viscoelasticity. The maximum accelerations of the skull were only 3.21 ms-2.

Noninvasive assessment of pressure distribution and fractional flow in middle cerebral artery using microbubbles and plane wave in vitro.

Fractional flow has been proposed for quantifying the degree of functional stenosis in cerebral arteries. Herein, subharmonic aided pressure estimation (SHAPE) combined with plane wave (PW) transmission was employed to noninvasively estimate the pressure distribution and fractional flow in the middle cerebral artery (MCA) in vitro. Consequently, the effects of incident sound pressure (peak negative pressures of 86-653 kPa), pulse repetition frequency (PRF), number of pulses, and blood flow rate on the subharmonic pressure relationship were investigated. The radio frequency data were stored and beamformed offline, and the subharmonic amplitude over a 0.4 MHz bandwidth was extracted using a 12-cycle PW at 4 MHz. The optimal incident sound pressure was 217 kPa without skull (sensitivity = 0.09 dB/mmHg; r2 = 0.997) and 410 kPa with skull (median sensitivity = 0.06 dB/mmHg; median r2 = 0.981). The optimal PRF was 500 Hz, as this value affords the highest sensitivity (0.09 dB/mmHg; r2 = 0.976) and temporal resolution. In addition, the blood flow rate exhibited a lesser effect on the subharmonic pressure relationship in our experimental setup. Using the optimized parameters, the blood pressure distribution and fractional flow (FFs) were measured. As such, the FFs value was in high agreement with the value measured using the pressure sensor (FFm). The mean ± standard deviations of the FF difference (FFm - FFs) were 0.03 ± 0.06 without skull and 0.01 ± 0.05 with skull.