ACSL4 accelerates osteosarcoma progression via modulating TGF-ß/Smad2 signaling pathway.

Osteosarcoma (OS) is a malignant bone sarcoma arising from mesenchymal stem cells. The biological role of Acyl-CoA synthetase long-chain family member 4 (ACSL4), recently identified as an oncogene in numerous tumor types, remains largely unclear in OS. In this study, we investigated the expression of ACSL4 in OS tissues using immunohistochemistry staining (IHC) staining of a human tissue microarray and in OS cells by qPCR assay. Our findings revealed a significant up-regulation of ACSL4 in both OS tissues and cells. To further understand its biological effects, we conducted a series of loss-of-function experiments using ACSL4-depleted MNNG/HOS and U-2OS cell lines, focusing on OS cell proliferation, migration, and apoptosis in vitro. Our results demonstrated that ACSL4 knockdown remarkably suppressed OS cell proliferation, arrested cells in the G2 phase, induced cell apoptosis, and inhibited cell migration. Additionally, a subcutaneous xenograft mice model was established to validate the in vivo impact of ACSL4, revealing ACSL4 silencing impaired tumor growth in the OS xenograft mice. Additionally, we discovered that ACSL4 could regulate the phosphorylation level of Smad2 through cooperative interactions, and treatment with a TGF-ß inhibitor weakened the promoting effects of ACSL4 overexpression. In short, ACSL4 regulated OS progression by modulating TGF-ß/Smad2 signaling pathway. These findings underscore ACSL4 as a promising therapeutic target for OS patients and contribute novel insights into the pathogenesis of OS.

Ultralow Thermal Conductivity and Very High Seebeck Coefficient in Two-Dimensional TeSe2 Semiconductor.

Emerging chalcogenide-based two-dimensional (2D) materials possess various unique yet fully explored properties and are thus considered promising candidates for next-generation optoelectronic and energy conversion applications. Here, TeSe2 crystals with interesting thermoelectric features were synthesized using a simple solid-state reaction. High-resolution transmission electron microscopy reveals that TeSe2 stabilizes in a 2D atomic structure with helical chains, resembling 2D tellurene. The thermoelectric properties were measured from 2 to 390 K in a polycrystalline pellet, showing an ultralow thermal conductivity below 0.25 W m-1 K-1 and a very high positive Seebeck coefficient of up to 865 µV K-1. Particularly, the thermal conductivity shows a hysteresis effect upon temperature cycling, which is tentatively explained as cracks opening and partially closing. Optical measurements indicate that TeSe2 is a semiconductor with two bandgaps at 1.43 and 1.65 eV. These results highlight that TeSe2 is an intriguing 2D semiconductor with complex thermoelectric properties, which provides a platform to further study the interplay of emerging 2D structure, thermal, and electronic properties.

Integrated multi-omics analyses reveal microbial community resilience to fluctuating low oxygen in the East China sea.

Climate change and eutrophication are accelerating ocean deoxygenation, leading to a global decline in oxygen levels. The East China Sea, frequently experiencing deoxygenation events, harbors diverse microbial communities. However, the response of these communities to the changing deoxygenation dynamics remains poorly understood. Here, we explored the composition and function of microbial communities inhabiting seawaters of the Changjiang Estuary and offshore areas. Our findings suggested that neutral processes significantly influenced the assembly of these communities. The overall bacterial composition demonstrated remarkable high stability across the oxygen gradient. Salinity exhibited a significantly stronger correlation with bacterial community structure than dissolved oxygen. Both metagenomics and metaproteomics revealed that all of the samples exhibited similar functional community structures. Heterotrophic metabolism dominated these sites, as evidenced by a diverse array of transporters and metabolic enzymes for organic matter uptake and utilization, which constituted a significant portion of the expressed proteins. O2 was the primary electron acceptor in bacteria even under hypoxic conditions, evidenced by expression of low- and high-affinity cytochrome oxidases. Proteins associated with anaerobic processes, such as dissimilatory sulfite reductases, were virtually undetectable. Untargeted liquid chromatography with tandem mass spectrometry analysis of seawater samples revealed a diverse range of dissolved organic matter (DOM) components in amino acids, lipids, organic acids, peptides, and carbohydrates, potentially fueling dominant taxa growth. Despite fluctuations in the abundance of specific genera, the remarkable similarity in community structure, function, and DOM suggests that this ecosystem possesses robust adaptive mechanisms that buffer against abrupt changes, even below the well-defined hypoxic threshold in marine ecosystem.

Natural Variation in the Promoter of GmSPL9d Affects Branch Number in Soybean.

The branch number is a crucial factor that influences density tolerance and is closely associated with the yield of soybean. However, its molecular regulation mechanisms remain poorly understood. This study cloned a candidate gene GmSPL9d for regulating the soybean branch number based on the rice OsSPL14 homologous gene. Meanwhile, the genetic diversity of the GmSPL9d was analyzed using 3599 resequencing data and identified 55 SNP/InDel variations, which were categorized into seven haplotypes. Evolutionary analysis classified these haplotypes into two groups: GmSPL9d H-I and GmSPL9d H-II. Soybean varieties carrying the GmSPL9d H-II haplotype exhibited a significantly lower branch number compared with those carrying the GmSPL9d H-I haplotype. Association analysis between the variation sites and branch number phenotypes revealed a significant correlation between the promoter variations and the branch number. Promoter activity assays demonstrated that the GmSPL9d H-II promoter displayed significantly higher activity than the GmSPL9d H-I promoter. Transgenic experiments confirmed that the plants that carried the GmSPL9d H-II promoter exhibited a significantly lower branch number compared with those that carried the GmSPL9d H-I promoter. These findings indicate that the variation in the GmSPL9d promoter affected its transcription level, leading to differences in the soybean branch number. This study provides valuable molecular targets for improving the soybean plant structure.

MicroRNA-203 mediates Porphyromonas gingivalis LPS-induced inflammation and differentiation of periodontal ligament cells.

AIM: In this study, we aimed to explore the effects of microRNA-203 (miR-203) on Porphyromonas gingivalis lipopolysaccharide (P.g. LPS)-stimulated periodontal ligament cells (PDLCs) and identify potential molecular targets for periodontitis treatment. METHODS: Periodontal ligament cells were stimulated by P.g. LPS, followed by quantification of miR-203 and AP-1 expression. Next, loss- and gain-of-function experiments were applied in P.g. LPS-induced PDLCs. The proliferation, apoptosis, and differentiation of PDLCs were determined, and mineralized nodule numbers were counted. Functional assays were used to identify interactions among miR-203, activator protein-1 (AP-1), and intercellular adhesion molecule-1 (ICAM-1). In addition, expression of osteogenesis-related genes and release of proinflammatory factors were analyzed. RESULTS: miR-203 was found to be downregulated while AP-1 was upregulated in PDLCs stimulated by P.g. LPS. The overexpression of miR-203 promoted P.g. LPS-stimulated PDLC proliferation and differentiation, inhibited apoptosis, and increased the number of mineralized nodules. miR-203 was verified to downregulate AP-1/ICAM-1 axis. miR-203 overexpression reduced the secretion of proinflammatory factors while increasing the expression of osteogenesis-related genes in P.g. LPS-stimulated PDLCs, which was reversed by overexpressing AP-1 and ICAM-1. CONCLUSION: These experimental data demonstrated the potential inhibitory effects of overexpressed miR-203 on periodontitis development by promoting PDLC differentiation and suppressing inflammatory responses through AP-1/ICAM-1 axis.

Evaluation of effects of 3% diquafosol ophthalmic solution on preocular tear film stability after trabeculectomy.

OBJECTIVES: To determine the potential effects of 3% diquafosol (DQS) on tear film stability after glaucoma surgery. METHODS: We retrospectively reviewed consecutive patients who underwent glaucoma surgery at the glaucoma division of the Henan Eye Institute from January 2020 to January 2021. Clinical parameters, including age, sex, intraocular pressure, and number of glaucoma medications, were tested. Tear film parameters, such as tear meniscus height (TMH), first and average noninvasive tear break-up time (FBUT and ABUT, respectively), and tear film lipid layer grade (TFLL), were evaluated using the Oculus Keratograph 5M. We investigated the differences in clinical and tear film parameters pre- and postoperatively. We compared the baseline and different time points after surgery between the DQS and HA groups and identified the factors associated with changes in the tear film at 8 weeks postoperatively. RESULTS: A total of 101 eyes were included. Early administration of DQS increased TMH, FBUT, ABUT, and TFLL after trabeculectomy (all p < 0.05). In addition, the DQS group showed significantly higher ABUT than the HA group (p < 0.05). DQS use served as an associated parameter for better TMH, FBUT, ABUT, and the TFLL (p < 0.05). DQS and preoperative FBUT were significant independent parameters of postoperative FBUT (p < 0.05). CONCLUSIONS: The present study showed that postoperative TMH, FBUT, ABUT, and TFLL significantly increased after early application of DQS, and the efficacy of ABUT was better than that of HA at the early stage in 8 weeks after trabeculectomy (p < 0.05).

GmWRI1c Increases Palmitic Acid Content to Regulate Seed Oil Content and Nodulation in Soybean (Glycine max).

Soybean (Glycine max) is an important oil crop, but the regulatory mechanisms underlying seed oil accumulation remain unclear. We identified a member of the GmWRI1s transcription factor family, GmWRI1c, that is involved in regulating soybean oil content and nodulation. Overexpression of GmWRI1c in soybean hairy roots increased the expression of genes involved in glycolysis and de novo lipogenesis, the proportion of palmitic acid (16:0), and the number of root nodules. The effect of GmWRI1c in increasing the number of root nodules via regulating the proportion of palmitic acid was confirmed in a recombinant inbred line (RIL) population. GmWRI1c shows abundant sequence diversity and has likely undergone artificial selection during domestication. An association analysis revealed a correlation between seed oil content and five linked natural variations (Hap1/Hap2) in the GmWRI1c promoter region. Natural variations in the GmWRI1c promoter were strongly associated with the GmWRI1c transcript level, with higher GmWRI1c transcript levels in lines carrying GmWRI1cHap1 than in those carrying GmWRI1cHap2. The effects of GmWRI1c alleles on seed oil content were confirmed in natural and RIL populations. We identified a favourable GmWRI1c allele that can be used to breed new varieties with increased seed oil content and nodulation.

Effect of lentivirus-mediated miR-182 targeting FGF9 on hallux valgus.

The pathogenesis of hallux valgus is not clearly understood. However, genetics research about hallux valgus is rare. Therefore, the present study aimed to explore the pathogeny of hallux valgus from the perspective of genetics. Human samples were collected from normal bone tissue and hallux valgus region bone tissue. The bone samples were studied using real time-PCR, western blot and immunohistochemical. Lentivirus-mediated miR-182 transfected osteoblasts and tested the expression of FGF9 mRNA with real time-PCR. To test alkaline phosphatase activity, number of calcium nodules and proliferation of osteoblast with enzymatic activity analysis, calcium nodules stained and MTT assay. We found that (1) FGF9 expressed in hallux valgus region bone tissue was significantly higher than normal bone tissue. (2) miR-182 expression levels in hallux valgus region bone tissue were notably lower than those of normal bone tissue. (3) miR-182 could negatively regulate the expression of FGF9 in osteoblasts. (4) FGF9 may enhance osteoblasts proliferation. We have demonstrated that miR-182 promotes the formation of bone by targeting FGF9, implicating an essential role of miR-182 in the etiology of hallux valgus. Moreover, miR-182 might potentially be a therapeutic target for hallux valgus treatment.

Soil water-stable aggregates and microbial community under long-term tillage in black soil of Northern China.

Long-term frequent tillage would cause black soil degradation and serious soil erosion as soil microbial communities and soil structure are extremely sensitive to tillage process. However, there is no unified conclusion on the relationship between the distribution of soil water-stable aggregates (WSAs), and microbial community construction and diversity under long-term tillage in black soil during different seasons. In this study, we used wet-sieving method to evaluate the composition and stability of soil WSAs and employed Illumina MiSeq high-throughput sequencing technology to study the diversity, taxonomic composition and co-occurrence network properties of microbial community, comparing outcomes between uncultivated soil and long-term cultivated soil for 60 years in Keshan farm of Heilongjiang Province. The results showed that after long-term tillage, the proportion of larger than 1 mm WSAs reduced by 34.17-51.37%, and the stability of WSAs, soil pH, organic matter (OM), total nitrogen (TN) contents decreased significantly in all seasons (P < 0.05), while soil available phosphorus (AP) and available potassium (AK) contents increased remarkably (P < 0.05). The diversity of bacteria increased, while that of fungi decreased. Soil fungal communities were more susceptible to long-term tillage than bacterial and archaeal communities. Actinobacteria mainly exist in large WSAs (˃1 mm), and when their relative abundance is high, it is beneficial to improve the water-stability of black soil; while Proteobacteria and Gemmatimonadetes may exist in small WSAs (˂1 mm), whose high relative abundance will weaken the water-stability of black soil. The experimental results provide a scientific theoretical basis for sustainable utilization of black soil.

GmMs1 encodes a kinesin-like protein essential for male fertility in soybean (Glycine max L.).

The application of heterosis is a promising approach for greatly increasing yield in soybean (Glycine max L.). Nuclear male sterility is essential for hybrid seed production and the utilization of heterosis. Here we report the cloning of the gene underlying the soybean male-sterile mutant ms-1, which has been widely used for recurrent selection in soybean breeding programs. We initially delimited the ms1 locus to a 16.15 kb region on chromosome 13, based on SLAF_BSA sequencing followed by genotyping of an F2 population segregating for the locus. Compared with the same region in fertile plants, the mutant region lacks a sequence of approximately 38.7 kb containing five protein-coding genes, including an ortholog of the kinesin-like protein gene NACK2, named GmMs1. The GmMs1 knockout plants generated via CRISPR/Cas-mediated gene editing displayed a complete male-sterile phenotype. Metabolic profiling showed that fertile anthers accumulated starch and sucrose normally, whereas sterile anthers had higher anthocyanin levels and lower flavonoid levels and lower antioxidant enzyme activities. These results provide insights into the molecular mechanisms governing male sterility and demonstrate that GmMs1 could be used to create male-sterile lines through targeted mutagenesis. These findings pave the way for designing seed production technology and an intelligent male-sterile line system to utilize heterosis in soybean.

IgH translocation with undefined partners is associated with superior outcome in multiple myeloma patients.

BACKGROUND: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored. METHODS: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%). RESULTS: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort. CONCLUSION: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.

The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells.

BACKGROUND: Oxidative stress results in cell apoptosis/death and plays a detrimental role in disease development and progression. Stressors alter the miRNA expression profile and miRNAs play a role in the cell response to stress. We previously showed that miR-711 is significantly over-expressed in extended cold ischemia reperfusion injured hearts in heart transplant. In this study, we aimed to investigate the role of miR-711 in cardiac cell damage in response to oxidative stress and how miR-711 is regulated. METHODS: Rat cardiac cell line H9c2 cells were cultured and exposed to oxidative conditions (Antimycin A (AA), H2O2, CoCl2, or cold hypoxia/reoxygenation (H/R)) in vitro. H9c2 cells were transfected with miR-711 mimics, miR-711 inhibitors, or small interference RNA, using transfection reagents. The expression of miR-711 was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell apoptosis/death was detected by flow cytometry and an IncuCyte system. Mitochondrial damage was detected by measuring the mitochondria membrane potential by flow cytometry. Gene expression was detected by qRT-PCR at the mRNA level and Western blotting and immunocytochemistry staining at the protein level. RESULTS: We found that miR-711 was significantly up-regulated in cells treated with H2O2, AA, CoCl2, and cold H/R. Over-expression of miR-711 increased cell apoptosis/death induced by AA and H/R whereas cell death was reduced by miR-711 inhibitors. MiR-711 induced cell death through negative regulation of angiopoietin 1 (Ang-1), fibroblast growth factor 14 (FGF14) and calcium voltage-gated channel subunit alpha1C (Cacna1c) genes. Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. CONCLUSION: Oxidative stress increases the expression of miR-711. Over-expression of miR-711 induces cell apoptosis/death. HIF-1α and NFКB regulate miR-711 in H9c2 cells during oxidative stress. miR-711 is a new target for preventing oxidative stress.

Doppler Radar Vital Signs Detection Method Based on Higher Order Cyclostationary.

Due to the non-contact nature, using Doppler radar sensors to detect vital signs such as heart and respiration rates of a human subject is getting more and more attention. However, the related detection-method research meets lots of challenges due to electromagnetic interferences, clutter and random motion interferences. In this paper, a novel third-order cyclic cummulant (TOCC) detection method, which is insensitive to Gaussian interference and non-cyclic signals, is proposed to investigate the heart and respiration rate based on continuous wave Doppler radars. The k-th order cyclostationary properties of the radar signal with hidden periodicities and random motions are analyzed. The third-order cyclostationary detection theory of the heart and respiration rate is studied. Experimental results show that the third-order cyclostationary approach has better estimation accuracy for detecting the vital signs from the received radar signal under low SNR, strong clutter noise and random motion interferences.

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.

Effect of L-carnitine in Ameliorating Lipopolysaccharide-Induced Cardiomyocyte Injury via MAPK Signaling.

The present study aimed to elucidate whether L-carnitine (LC) protected H9c2 cells and its underlying mechanisms. Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability. Apoptosis, cell morphology, and lactate dehydrogenase (LDH) assessment were used to prove effects of lipopolysaccharide (LPS) and LC on H9c2 cells. RT-qPCR and western blot assays were hired to evaluate the mRNA and protein expression levels, respectively. ELISA assay was performed to determine the released protein levels. Reactive oxygen species (ROS) level was evaluated by immunofluorescence and flow cytometry. LC was revealed to protect H9c2 cells against LPS-induced injury as indicated by increased cell viability, reduced apoptosis ratio and LDH level. LC treatment also reduced BAX expression as well as up-regulated Bcl-2 expression under LPS treatment. Mechanically, LC reduced oxidative stress and ameliorated the mitochondrial injury through modulating extracellular signal-regulated kinase 1/2 and c-Jun N-terminal protein kinase c-Jun N-terminal protein kinase phosphorylation levels as indicated by decreased membrane potential, increased ATP production and mtDNA expression. We found that LC ameliorates LPS-induced cardiomyocyte injury by abrogating cell apoptosis ratio, ROS levels, as well as mitochondrial dysfunction via mitogen-activated protein kinase signaling. Our findings revealed a potential drug for sepsis or LPS-induced cardiomyocyte injury.

Revealing Strong Flexoelectricity and Optoelectronic Coupling in 2D Ferroelectric CuInP2S6 Via Large Strain Gradient.

The interplay between flexoelectric and optoelectronic characteristics provides a paradigm for studying emerging phenomena in various 2D materials. However, an effective way to induce a large and tunable strain gradient in 2D devices remains to be exploited. Herein, we propose a strategy to induce large flexoelectric effect in 2D ferroelectric CuInP2S6 by constructing a 1D-2D mixed-dimensional heterostructure. The strong flexoelectric effect is induced by enormous strain gradient up to 4.2 × 106 m-1 resulting from the underlying ZnO nanowires, which is further confirmed by the asymmetric coercive field and the red-shift in the absorption edge. The induced flexoelectric polarization efficiently boosts the self-powered photodetection performance. In addition, the improved photoresponse has a good correlation with the induced strain gradient, showing a consistent size-dependent flexoelectric effect. The mechanism of flexoelectric and optoelectronic coupling is proposed based on the Landau-Ginzburg-Devonshire double-well model, supported by density functional theory (DFT) calculations. This work provides a brand-new method to induce a strong flexoelectric effect in 2D materials, which is not restricted to crystal symmetry and thus offers unprecedented opportunities for state-of-the-art 2D devices.

Globally distributed marine Gemmatimonadota have unique genomic potentials.

BACKGROUND: Gemmatimonadota bacteria are widely distributed in nature, but their metabolic potential and ecological roles in marine environments are poorly understood. RESULTS: Here, we obtained 495 metagenome-assembled genomes (MAGs), and associated viruses, from coastal to deep-sea sediments around the world. We used this expanded genomic catalog to compare the protein composition and update the phylogeny of these bacteria. The marine Gemmatimonadota are phylogenetically different from those previously reported from terrestrial environments. Functional analyses of these genomes revealed these marine genotypes are capable of degradation of complex organic carbon, denitrification, sulfate reduction, and oxidizing sulfide and sulfite. Interestingly, there is widespread genetic potential for secondary metabolite biosynthesis across Gemmatimonadota, which may represent an unexplored source of novel natural products. Furthermore, viruses associated with Gemmatimonadota have the potential to "hijack" and manipulate host metabolism, including the assembly of the lipopolysaccharide in their hosts. CONCLUSIONS: This expanded genomic diversity advances our understanding of these globally distributed bacteria across a variety of ecosystems and reveals genetic distinctions between those in terrestrial and marine communities. Video Abstract.

Total synthesis of the indole alkaloid (±)- and (+)-methyl N-decarbomethoxychanofruticosinate.

All caged up: The first total synthesis of N-decarbomethoxychanofruticosinate is achieved by using a SmI2 -mediated intramolecular Reformatsky-like reaction to create the seven-membered ring, and an intramolecular oxidative coupling to install the caged and strained ring system.

Reduced nitrite accumulation at the primary nitrite maximum in the cyclonic eddies in the western North Pacific subtropical gyre.

Nitrite, an intermediate product of the oxidation of ammonia to nitrate (nitrification), accumulates in upper oceans, forming the primary nitrite maximum (PNM). Nitrite concentrations in the PNM are relatively low in the western North Pacific subtropical gyre (wNPSG), where eddies are frequent and intense. To explain these low nitrite concentrations, we investigated nitrification in cyclonic eddies in the wNPSG. We detected relatively low half-saturation constants (i.e., high substrate affinities) for ammonia and nitrite oxidation at 150 to 200 meter water depth. Eddy-induced displacement of high-affinity nitrifiers and increased substrate supply enhanced ammonia and nitrite oxidation, depleting ambient substrate concentrations in the euphotic zone. Nitrite oxidation is more strongly enhanced by the cyclonic eddies than ammonia oxidation, reducing concentrations and accelerating the turnover of nitrite in the PNM. These findings demonstrate a spatial decoupling of the two steps of nitrification in response to mesoscale processes and provide insights into physical-ecological controls on the PNM.

A novel rat model of cerebral small vessel disease and evaluation by super-resolution ultrasound imaging.

Cerebral small vessel disease (CSVD), which causes cognitive, functional and emotional decline, is related to stroke events, and it is a major cause of Alzheimer's disease. In the social context of an aging population, the incidence of CSVD is on the rise yearly, and the exact pathogenesis is still controversial and remains unclear. Exploring the pathological mechanism of CSVD on the histological level using animal models is important for the investigation of new clinical diagnostic methods and treatment options. The existing surgical CSVD model preparation methods are difficult to operate and cannot control the injury location or degree. This study used ultrasound combined with microbubbles (MBs) to induce an easy-to-operate and non-invasive animal model of CSVD with controllable location and degree. The rat model was evaluated from the perspective of histology, ethology, and imageology, respectively. In addition, we utilized super-resolution ultrasound imaging (SR-US) technology to directly observe the microvessels of the model. The histological results showed that the modeling was successful in the preset position, and neurology deficits were observed in 62.5% of 8 rats. The SR-US results of one rat showed that compared with the non-sonication region, the number of cerebral small blood vessels discovered in the sonication area was reduced (43 vs 11), the blood flow speed decreased significantly (p 0.001), and blood flow volume decreased (144.7 vs 11.7 µL/s) because of vasoconstriction. This study provides a new modeling method with controllable damage location and degree for the study of CSVD, and SR-US is found to be an effective evaluation method, which can directly assess the hemodynamic changes of CSVD in vivo.