Three nonconventional starch: Comparison of physicochemical properties and in vitro digestibility.

Extraction of starch from waste is also an effective way to recover resources and provide new sources of starch. In this study, starch was isolated from white kidney bean residue, chickpea residue, and tiger nut meal after protein or oil extraction, and the morphology of starch particles was observed to determine their physicochemical properties and in vitro digestibility. All these isolated starches had unique properties, among which white kidney bean starch (KBS) had a high amylose content (43.48%), and its structure was better ordered. Scanning electron microscopy revealed distinct granular morphologies for the three starches. KBS and chickpea starch (CHS) were medium-granular starches, whereas tiger nut starch was a small granular starch. Fourier transform infrared spectroscopy analysis confirmed the absence of significant differences in functional groups and chemical bonds among the three starch molecules. In vitro digestibility studies showed that CHS is more resistant to enzymatic degradation. Overall, these results will facilitate the development of products based on the separation of nonconventional starches from waste.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

BACKGROUND AND OBJECTIVES: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes. METHODS: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China. Longitudinal postoperative seizures were classified by Engel class, and Engel class I was regarded as seizure-free outcome. Functional (motor and cognitive) outcomes were evaluated using the SWS neurologic score, and improved or unchanged scores between baseline and follow-up were considered to have stable outcomes. Outcomes were analyzed using Kaplan-Meier analyses. Multivariate Cox regression was used to identify factors associated with outcomes. RESULTS: A total of 214 patients with a median age of 2.0 (interquartile range 1.2-4.6) years underwent surgery (focal resection, FR [n = 87]; hemisphere surgery, HS [n = 127]) and completed a median of 3.5 (1.7-5.0) years of follow-up. The overall estimated probability for being seizure-free postoperatively at 1, 2, and 5 years was 86.9% (95% CI 82.5-91.6), 81.4% (95% CI 76.1-87.1), and 70.7% (95% CI 63.3-79.0), respectively. The overall estimated probability of being motor stable at the same time post operatively was 65.4% (95% CI 58.4-71.2), 80.2% (95% CI 73.8-85.0), and 85.7% (95% CI 79.5-90.1), respectively. The overall probability for being cognition stable at 1, 2, and 5 years was 80.8% (95% CI 74.8-85.5), 85.1% (95% CI 79.3-89.2), and 89.5% (95% CI 83.8-93.2), respectively. Both FR and HS were effective at ensuring seizure control. For different HS techniques, modified hemispherotomy had comparable outcomes but improved safety compared with anatomical hemispherectomy. Regarding FR, partial resection (adjusted hazard ratio [aHR] 11.50, 95% CI 4.44-29.76), acute postoperative seizure (APOS, within 30 days of surgery; aHR 10.33, 95% CI 3.94-27.12), and generalized seizure (aHR 3.09, 95% CI 1.37-6.94) were associated with seizure persistence. For HS, seizure persistence was associated with APOS (aHR 27.61, 9.92-76.89), generalized seizure (aHR 7.95, 2.74-23.05), seizure frequency ≥30 times/month (aHR 4.76, 1.27-17.87), and surgical age ≥2 years (aHR 3.78, 1.51-9.47); motor stability was associated with severe motor defects (aHR 5.23, 2.27-12.05) and postoperative seizure-free status (aHR 3.09, 1.49-6.45); and cognition stability was associated with postoperative seizure-free status (aHR 2.84, 1.39-5.78) and surgical age <2 years (aHR 1.76, 1.13-2.75). DISCUSSION: FR is a valid option for refractory epilepsy in patients with SWS and has similar outcomes to those of HS, with less morbidity associated with refractory epilepsy. Early surgical treatment (under the age of 2 years) leads to better outcomes after HS, but there is insufficient evidence that surgical age affects FR outcomes. These findings warrant future prospective multicenter cohorts with international cooperation and prolonged follow-up in better exploring more precise outcomes and developing prognostic predictive models. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SWS and refractory seizures, surgical resection-focal, hemispherectomy, or modified hemispherotomy-leads to improved outcomes.

The Chinese medaka (Oryzias sinensis) dmrt1 gene converts females to males in medaka (Oryzias latipes).

BACKGROUND: Chinese medaka (Oryzias sinensis) is widely distributed in freshwater rivers in China. Similar to the medaka (Oryzias latipes), Chinese medaka has the characteristics of small size, rapid reproductive cycle, and strong adaptability, which makes it suitable as a model organism for studies in basic biology and environmental toxicology. Chinese medaka exhibits distinct sexual dimorphism. However, due to the lack of complete genomic information, the regulation of sex determination and differentiation-related genes in Chinese medaka remains unclear. METHODS: Chinese medaka dmrt1 (Osdmrt1) was cloned by PCR, and transgenic individuals of medaka [Tg(CMV:Osdmrt1)] overexpressing Osdmrt1 were generated to investigate the role of Osdmrt1 in sex determination. Western blot was used to validate the integration of the Osdmrt1 into the medaka genome. Tissue sectioning and HE staining were used to identify Tg(CMV:Osdmrt1) physiological gender and phenotype. qRT-PCR was used to analyze the expression of gonad-specific genes. RESULTS: Osdmrt1 was cloned and identified, and it shared similar evolutionary relationships with medaka dmrt1. Tg(CMV:Osdmrt1) exhibited partial sex reversal from female to male in the F2 generation, with genetically female individuals developing testes and producing functional sperm. Additionally, the secondary sexual characteristics of the transgenic females also changed to males. CONCLUSION: The Chinese medaka dmrt1 gene could convert females to males in medaka. GENERAL SIGNIFICANCE: These results not only elucidate the function of Chinese medaka dmrt1, but also accumulate knowledge for studying the function of economically important fish genes in model fish by transgenic technology.

Perfluoropolyether-Based Gut-Liver-on-a-Chip for the Evaluation of First-Pass Metabolism and Oral Bioavailability of Drugs.

In the evolving field of drug discovery and development, multiorgans-on-a-chip and microphysiological systems are gaining popularity owing to their ability to emulate in vivo biological environments. Among the various gut-liver-on-a-chip systems for studying oral drug absorption, the chip developed in this study stands out with two distinct features: incorporation of perfluoropolyether (PFPE) to effectively mitigate drug sorption and a unique enterohepatic single-passage system, which simplifies the analysis of first-pass metabolism and oral bioavailability. By introducing a bolus drug injection into the liver compartment, hepatic extraction alone could be evaluated, further enhancing our estimation of intestinal availability. In a study on midazolam (MDZ), PFPE-based chips showed more than 20-times the appearance of intact MDZ in the liver compartment effluent compared to PDMS-based counterparts. Notably, saturation of hepatic metabolism at higher concentrations was confirmed by observations when the dose was reduced from 200 µM to 10 µM. This result was further emphasized when the metabolism was significantly inhibited by the coadministration of ketoconazole. Our chip, which is designed to minimize the dead volume between the gut and liver compartments, is adept at sensitively observing the saturation of metabolism and the effect of inhibitors. Using genome-edited CYP3A4/UGT1A1-expressing Caco-2 cells, the estimates for intestinal and hepatic availabilities were 0.96 and 0.82, respectively; these values are higher than the known human in vivo values. Although the metabolic activity in each compartment can be further improved, this gut-liver-on-a-chip can not only be used to evaluate oral bioavailability but also to carry out individual assessment of both intestinal and hepatic availability.

Evaluating the beam shape coefficients of Bessel-Gauss beams with radial quadrature: a comparison with angular spectrum decomposition and finite series methods.

The Bessel-Gauss beam (BGB) stands as a physically realizable beam extensively employed in applications such as micromanipulation and optical trapping. In these contexts, the assessment of beam shape coefficients (BSCs) becomes imperative. Previous research reveals that the BSCs of the BGBs obtained with different methods deviate from each other under certain circumstances. In this paper, the formulation of BSCs employs the radial quadrature method, and a comparative analysis is conducted with counterparts formulated using the angular spectrum decomposition and the finite series technique. Contributions stemming from evanescent waves and the situation of the BSC blowing-ups are discussed, offering a deep insight of pertinent BSC evaluation methods. The paper provides an alternative approach for calculating the BSCs of the BGBs.

Advances and applications of biomimetic biomaterials for endogenous skin regeneration.

Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential for self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials for inducing endogenous skin regeneration are simplistic in their structure and function, lacking the ability to accurately mimic the intricate tissue structure and regulate the disordered microenvironment. Novel biomimetic biomaterials with precise structure, chemical composition, and biophysical properties offer a promising avenue for achieving perfect endogenous skin regeneration. Here, we outline the recent advances in biomimetic materials induced endogenous skin regeneration from the aspects of structural and functional mimicry, physiological process regulation, and biophysical property design. Furthermore, novel techniques including in situ reprograming, flexible electronic skin, artificial intelligence, single-cell sequencing, and spatial transcriptomics, which have potential to contribute to the development of biomimetic biomaterials are highlighted. Finally, the prospects and challenges of further research and application of biomimetic biomaterials are discussed. This review provides reference to address the clinical problems of rapid and high-quality skin regeneration.

Changes of microbial communities and metabolites in the fermentation of persimmon vinegar by bioaugmentation fermentation.

To evaluate the effects of bioaugmentation fermentation inoculated with one ester-producing strain (Wickerhamomyces anomalus ZX-1) and two strains of lactic acid bacteria (Lactobacillus plantarum CGMCC 24035 and Lactobacillus acidophilus R2) for improving the flavor of persimmon vinegar, microbial community, flavor compounds and metabolites were analyzed. The results of microbial diversity analysis showed that bioaugmentation fermentation significantly increased the abundance of Lactobacillus, Saccharomyces, Pichia and Wickerhamomyces, while the abundance of Acetobacter, Apiotrichum, Delftia, Komagataeibacter, Kregervanrija and Aspergillus significantly decreased. After bioaugmentation fermentation, the taste was softer, and the sensory irritancy of acetic acid was significantly reduced. The analysis of HS-SPME-GC-MS and untargeted metabolomics based on LC-MS/MS showed that the contents of citric acid, lactic acid, malic acid, ethyl lactate, methyl acetate, isocitrate, acetoin and 2,3-butanediol were significantly increased. By multivariate analysis, 33 differential metabolites were screened out to construct the correlation between the differential metabolites and microorganisms. Pearson correlation analysis showed that methyl acetate, ethyl lactate, betaine, aconitic acid, acetoin, 2,3-butanediol and isocitrate positively associated with Wickerhamomyces and Lactobacillus. The results confirmed that the quality of persimmon vinegar was improved by bioaugmentation fermentation.

Bridge-layered decompression technique for vertebral artery-involved hemifacial spasm: technical note.

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

Preparation of Polyaniline-Modified Cellulose/PDMS Composite Triboelectric Material and Application of Its Pretreatment in MOW Pulp.

Self-powered electronic equipment has rapidly developed in the fields of sensing, motion monitoring, and energy collection, posing a greater challenge to triboelectric materials. Triboelectric materials need to enhance their electrical conductivity and mechanical strength to address the increasing demand for stability and to mitigate unpredictable physical damage. In this study, polyaniline-modified cellulose was prepared by means of in situ polymerization and compounded with polydimethylsiloxane, resulting in a triboelectric material with enhanced strength and conductivity. The material was fabricated into a tubular triboelectric nanogenerator (TENG) (G-TENG), and an electrocatalytic pretreatment of mixed office waste paper (MOW) pulp was performed using papermaking white water as the flowing liquid to improve the deinking performance. The electrical output performance of G-TENG is highest at a flow rate of 400 mL/min, producing a voltage of 22.76 V and a current of 1.024 µA. Moreover, the deinking effect of MOW was enhanced after the electrical pretreatment. This study explores the potential application of G-TENG as a self-powered sensor power supply and emphasizes its prospect as an energy collection device.

Posterior cingulate epilepsy: Seizure semiology and intracranial electrical stimulation using SEEG.

PURPOSE: This study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). METHODS: This study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. RESULTS: Analysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. CONCLUSION: The manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC.

ADHD diagnosis guided by functional brain networks combined with domain knowledge.

Utilizing functional magnetic resonance imaging (fMRI) to model functional brain networks (FBNs) is increasingly prominent in attention-deficit/hyperactivity disorder (ADHD) research, revealing neural impact and mechanisms through the exploration of activated brain regions. However, current FBNs-based methods face two major challenges. The primary challenge stems from the limitations of existing modeling methods in accurately capturing both regional correlations and long-distance dependencies (LDDs) within the dynamic brain, thereby affecting the diagnostic accuracy of FBNs as biomarkers. Additionally, limited sample size and class imbalance also pose a challenge to the learning performance of the model. To address the issues, we propose an automated diagnostic framework, which integrates modeling, multimodal fusion, and classification into a unified process. It aims to extract representative FBNs and efficiently incorporate domain knowledge to guide ADHD classification. Our work mainly includes three-fold: 1) A multi-head attention-based region-enhancement module (MAREM) is designed to simultaneously capture regional correlations and LDDs across the entire sequence of brain activity, which facilitates the construction of representative FBNs. 2) The multimodal supplementary learning module (MSLM) is proposed to integrate domain knowledge from phenotype data with FBNs from neuroimaging data, achieving information complementarity and alleviating the problems of insufficient medical data and unbalanced sample categories. 3) An ADHD automatic diagnosis framework guided by FBNs and domain knowledge (ADF-FAD) is proposed to help doctors make more accurate decisions, which is applied to the ADHD-200 dataset to confirm its effectiveness. The results indicate that the FBNs extracted by MAREM perform well in modeling and classification. After with MSLM, the model achieves accuracy of 92.4%, 74.4%, and 80% at NYU, PU, and KKI, respectively, demonstrating its ability to effectively capture crucial information related to ADHD diagnosis. Codes are available at https://github.com/zhuimengxuebao/ADF-FAD.

Japanese medaka (Oryzias latipes) Nectin4 plays an important role against red spotted grouper nervous necrosis virus infection.

Nectins are adhesion molecules that play a crucial role in the organization of epithelial and endothelial junctions and function as receptors for the entry of herpes simplex virus. However, the role of Nectin4 remains poorly understood in fish. In this study, nectin4 gene was cloned from medaka (OlNectin4). OlNectin4 was located on chromosome 18 and contained 11 exons, with a total genome length of 25754 bp, coding sequences of 1689 bp, coding 562 amino acids and a molecular weight of 65.5 kDa. OlNectin4 contained four regions, including an Immunoglobulin region, an Immunoglobulin C-2 Type region, a Transmembrane region and a Coiled coil region. OlNectin4 shared 47.18 % and 25.00 % identity to Paralichthys olivaceus and Mus musculus, respectively. In adult medaka, the transcript of nectin4 was predominantly detected in gill. During red spotted grouper nervous necrosis virus (RGNNV) infection, overexpression of OlNectin4 in GE cells significantly increased viral gene transcriptions. Meanwhile, Two mutants named OlNectin4△4 (+4 bp) and OlNectin4△7 (-7 bp) medaka were established using CRISPR-Cas9 system. Nectin4-KO medaka had higher mortality than WT after infected with RGNNV. Moreover, the expression of RGNNV RNA2 gene in different tissues of the Nectin4-KO were higher than WT medaka after challenged with RGNNV. The brain and eye of Nectin4-KO medaka which RGNNV mainly enriched, exhibited significantly higher expression of interferon signaling genes than in WT. Taken together, the OlNectin4 plays a complex role against RGNNV infection by inducing interferon responses for viral clearance.

AMPK deficiency inhibits fatty acid oxidation in endothelial progenitor cells to aggravate impaired angiogenesis after ischemic stroke in hyperlipidemic mice.

BACKGROUND: Hyperlipidemia is a risk factor for stroke, and worsens neurological outcome after stroke. Endothelial progenitor cells (EPCs), which become dysfunctional in cerebral ischemia, hold capacity to promote revascularization. OBJECTIVE: We investigated the role of dyslipidemia in impairment of EPC-mediated angiogenesis in cerebral ischemic mice. METHODS AND RESULTS: The high fat diet (HFD)-fed mice following by ischemic stroke exhibited increased infarct volumes and neurological severity scores, and poorer angiogenesis. Bone marrow-EPCs treated with palmitic acid (PA) showed impaired functions and inhibited activity of AMP-activated protein kinase (AMPK). Notably, AMPK deficiency aggravated EPC dysfunction, further decreased mitochondrial membrane potential, and increased reactive oxygen species level in EPCs with PA treatment. Furthermore, the expression of fatty acid oxidation (FAO)-related genes was remarkably reduced, and carnitine palmitoyltransferase 1A (CPT1A) protein expression was downregulated in AMPK-deficient EPCs. AMPK deficiency aggravated neurological severity scores and angiogenesis in ischemic brain of HFD-fed mice, accompanied by suppressed protein level of CPT1A. EPC transplantation corrected impaired neurological severity scores and angiogenesis in AMPK-deficient mice. CONCLUSION: Our findings suggest that AMPK deficiency aggravates poor angiogenesis in ischemic brain by mediating FAO and oxidative stress thereby inducing EPC dysfunction in hyperlipidemic mice.

RBM22 regulates RNA polymerase II 5' pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5.

BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

Effect of marine ecological compensation policy on coastal water pollution: Evidence from China based on a multiple period difference-in-differences approach.

With the development and utilization of marine resources, coastal water pollution has become increasingly prominent. The marine ecological compensation (MEC) is a key measure to balance the utilization of marine resources and the protection of marine environment. This paper attempts to explore the governance effect of MEC policy on coastal water pollution. Based on panel data of coastal cities in China from 2006 to 2020, a multiple period difference-in-differences (DID) model is used to estimate the impact of MEC policy on coastal water pollution. The research results show that the coastal water pollution has decreased significantly in the polit cities after implementing the MEC policy. The governance effect of MEC policy on coastal water pollution will last for three year and cover areas within a geographical distance of 200 km. The transmission mechanisms of MEC policy on coastal water pollution are the reduction of land-based sewage, marine technological progress and optimization of industrial structure. Further, this paper provides operational suggestions for strengthening the governance effect of MEC policy on coastal water pollution.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Lycorine inhibits Ang II-induced heart remodeling and inflammation by suppressing the PI3K-AKT/NF-κB pathway.

BACKGROUND: Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. METHODS: Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. RESULTS: LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. CONCLUSION: Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.

[Buyang Huanwu Decoction promotes arteriogenesis after hindlimb ischemia in mice by activating PDGF signaling pathway].

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.

Mechanistic insight into glioma through spatially multidimensional proteomics.

Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.