Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Phthalide derivative CD21 attenuates tissue plasminogen activator-induced hemorrhagic transformation in ischemic stroke by enhancing macrophage scavenger receptor 1-mediated DAMP (peroxiredoxin 1) clearance.

BACKGROUND: Hemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke. The present study explored the effects and underlying mechanism of action of CD21 on tissue plasminogen activator (tPA)-induced HT in a mouse model of transient middle cerebral artery occlusion (tMCAO) and cultured primary microglial cells. METHODS: The tMCAO model was induced by 2 h occlusion of the left middle cerebral artery with polylysine-coated sutures in wildtype (WT) mice and macrophage scavenger receptor 1 knockout (MSR1-/-) mice. At the onset of reperfusion, tPA (10 mg/kg) was intravenously administered within 30 min, followed by an intravenous injection of CD21 (13.79 mg/kg/day). Neuropathological changes were detected in mice 3 days after surgery. The effect of CD21 on phagocytosis of the DAMP peroxiredoxin 1 (Prx1) in lysosomes was observed in cultured primary microglial cells from brain tissues of WT and MSR1-/- mice. RESULTS: Seventy-two hours after brain ischemia, CD21 significantly attenuated neurobehavioral dysfunction and infarct volume. The tPA-infused group exhibited more severe brain dysfunction and hemorrhage. Compared with tPA alone, combined treatment with tPA and CD21 significantly attenuated ischemic brain injury and hemorrhage. Combined treatment significantly decreased Evans blue extravasation, matrix metalloproteinase 9 expression and activity, extracellular Prx1 content, proinflammatory cytokine mRNA levels, glial cells, and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway activation and increased the expression of tight junction proteins (zonula occludens-1 and claudin-5), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, and MSR1. MSR1 knockout significantly abolished the protective effect of CD21 against tPA-induced HT in tMCAO mice. Moreover, the CD21-induced phagocytosis of Prx1 was MSR1-dependent in cultured primary microglial cells from WT and MSR1-/- mice, respectively. CONCLUSION: The phthalide derivative CD21 attenuated tPA-induced HT in acute ischemic stroke by promoting MSR1-induced DAMP (Prx1) clearance and inhibition of the TLR4/NF-κB pathway and neuroinflammation.

Structure-activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure-activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 µM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.

Role of OXCT1 in ovine adipose and preadipocyte differentiation.

3-oxoacid CoA-transferase 1 (OXCT1) is a key enzyme in ketone body metabolism that is expressed in adipose and other tissues. The present study addressed the function of OXCT1 in adipose tissue from Tan sheep. The 1563 bp ovine OXCT1 coding sequence was cloned from ovine adipose tissue. The OXCT1 protein sequence was highly homologous to OXCT1 from other species. OXCT1 was highly expressed in kidney and at lower levels in small intestine, lung, spleen, heart, stomach, liver, tail adipose, and cartilage, but not in longissimus muscle. OXCT1 was expressed at higher levels in perirenal and tail adipose tissues than in subcutaneous adipose tissue. OXCT1 expression levels increased during the in vitro differentiation of adipocytes, but decreased dramatically at day 8. OXCT1 knockdown in ovine adipocytes promoted lipid accumulation, whereas overexpression did the converse. This study demonstrates that OXCT1 may play a role in adipogenesis and provides new insight on adipose deposition in sheep.

Face Recognition Using the SR-CNN Model.

In order to solve the problem of face recognition in complex environments being vulnerable to illumination change, object rotation, occlusion, and so on, which leads to the imprecision of target position, a face recognition algorithm with multi-feature fusion is proposed. This study presents a new robust face-matching method named SR-CNN, combining the rotation-invariant texture feature (RITF) vector, the scale-invariant feature transform (SIFT) vector, and the convolution neural network (CNN). Furthermore, a graphics processing unit (GPU) is used to parallelize the model for an optimal computational performance. The Labeled Faces in the Wild (LFW) database and self-collection face database were selected for experiments. It turns out that the true positive rate is improved by 10.97⁻13.24% and the acceleration ratio (the ratio between central processing unit (CPU) operation time and GPU time) is 5⁻6 times for the LFW face database. For the self-collection, the true positive rate increased by 12.65⁻15.31%, and the acceleration ratio improved by a factor of 6⁻7.

Automated assessment of thigh composition using machine learning for Dixon magnetic resonance images.

OBJECTIVES: To develop and validate a machine learning based automated segmentation method that jointly analyzes the four contrasts provided by Dixon MRI technique for improved thigh composition segmentation accuracy. MATERIALS AND METHODS: The automatic detection of body composition is formulized as a three-class classification issue. Each image voxel in the training dataset is assigned with a correct label. A voxel classifier is trained and subsequently used to predict unseen data. Morphological operations are finally applied to generate volumetric segmented images for different structures. We applied this algorithm on datasets of (1) four contrast images, (2) water and fat images, and (3) unsuppressed images acquired from 190 subjects. RESULTS: The proposed method using four contrasts achieved most accurate and robust segmentation compared to the use of combined fat and water images and the use of unsuppressed image, average Dice coefficients of 0.94 ± 0.03, 0.96 ± 0.03, 0.80 ± 0.03, and 0.97 ± 0.01 has been achieved to bone region, subcutaneous adipose tissue (SAT), inter-muscular adipose tissue (IMAT), and muscle respectively. CONCLUSION: Our proposed method based on machine learning produces accurate tissue quantification and showed an effective use of large information provided by the four contrast images from Dixon MRI.

CT differentiation of malignant peritoneal mesothelioma and tuberculous peritonitis.

OBJECTIVE: The aim of this study was to determine which computed tomography (CT) findings were useful in differentiating malignant peritoneal mesothelioma (MPM) and tuberculous peritonitis (TBP). METHODS: CT scans performed in 53 patients with MPM and 27 patients with TBP confirmed by pathology were retrospectively reviewed. The CT findings were evaluated for the morphologic appearance of ascites, peritoneum, mesenterium and omentum involvement, enlarged lymph nodes, solid abdominal viscera infiltration and metastases, and thoracic changes. The Pearson χ (2) test was used to compare differences between groups. RESULTS: Patients in both groups displayed a high proportion of peritoneum and mesenterium thickening. However, there were no obvious differences observed for ascites or swollen lymph nodes. There were significant differences in the following aspects between the two groups: (1) smooth peritoneal thickening was more frequent in patients with TBP, while irregular thickening was more frequently observed in patients with MPM; (2) caked omentum stratification was more common in patients with MPM; (3) mesentery involvement was less commonly observed in patients with TBP; (4) abdominal viscera infiltration and pleural plaques were more common in patients with MPM (46/53 and 48/53, respectively) than in those with TBP (0/27 and 0/27); and (5) more patients in the TBP group (14/27) displayed pleural effusion, and extraperitoneal tuberculosis was more common in patients with TBP (20/27). CONCLUSION: Although most CT findings analyzed are observed in both diseases, each disease has its own several unique characteristics. Therefore, using a combination of CT findings may increase our ability to distinguish TBP from MPM.

Recent Advances and Multiple Strategies of Monoterpenoid Overproduction in Saccharomyces cerevisiae and Yarrowia lipolytica.

Monoterpenoids are an important subclass of terpenoids that play important roles in the energy, cosmetics, pharmaceuticals, and fragrances fields. With the development of biotechnology, microbial synthesis of monoterpenoids has received great attention. Yeasts such Saccharomyces cerevisiae and Yarrowia lipolytica are emerging as potential hosts for monoterpenoids production because of unique advantages including rapid growth cycles, mature gene editing tools, and clear genetic background. Recently, advancements in metabolic engineering and fermentation engineering have significantly enhanced the accumulation of monoterpenoids in cell factories. First, this review introduces the biosynthetic pathway of monoterpenoids and comprehensively summarizes the latest production strategies, which encompass enhancing precursor flux, modulating the expression of rate-limited enzymes, suppressing competitive pathway flux, mitigating cytotoxicity, optimizing substrate utilization, and refining the fermentation process. Subsequently, this review introduces four representative monoterpenoids. Finally, we outline the future prospects for efficient construction cell factories tailored for the production of monoterpenoids and other terpenoids.

A novel phthalein component ameliorates neuroinflammation and cognitive dysfunction by suppressing the CXCL12/CXCR4 axis in rats with vascular dementia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, a plant of the Umbelliferae family, is a genuine medicinal herb from Sichuan Province. Phthalides are one of its main active components and exhibit good protective effect against cerebrovascular diseases. However, the mechanism by which phthalides exert neuroprotective effects is still largely unclear. AIM OF THE STUDY: In this study, we extracted a phthalein component (named as QBT) from Ligusticum Chuanxiong, and investigated its neuroprotective effects against vascular dementia (VaD) rats and the underlying mechanism, focusing on the chemokine 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis. METHODS: A rat model of VaD was established, and treated with QBT. Cognitive dysfunction in VaD rats was assessed using the Y-maze, new object recognition, and Morris water maze tests. Neuronal damage and inflammatory response in VaD rats were examined through Nissl staining, immunofluorescence, enzyme-linked immunospecific assay, and western blotting analysis. Furthermore, the effects of QBT on CXCL12/CXCR4 axis and its downstream signaling pathways, Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB), were investigated in VaD rats and BV2 microglial cells exposed to oxygen glucose deprivation. RESULTS: QBT significantly alleviated cognitive dysfunction and neuronal damage in VaD rats, along with inhibition of VaD-induced over-activation of microglia and astrocytes and inflammatory response. Moreover, QBT exhibited anti-inflammatory effects by inhibiting the CXCL12/CXCR4 axis and its downstream JAK2/STAT3 and PI3K/AKT/NF-κB pathways, thereby attenuating the neuroinflammatory response both in vivo and in vitro. CONCLUSION: QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, exerting neuroprotective effects by suppressing neuroinflammatory response through inhibition of the CXCL12/CXCR4 axis.

Elevating sensing capability via dual-atom catalysts boosted luminol cathodic electrochemiluminescence.

BACKGROUND: The advancement of highly sensitive electrochemiluminescence (ECL) biosensors has garnered escalating interest over time. Owing to the distinctive physicochemical attributes, the signal amplification strategy facilitated by functional nanomaterials has achieved notable milestones. Single-atom catalysts (SACs), featuring atomically dispersed metal active sites, have garnered significant attention. SACs offer unprecedented control over active sites and surface structures at the atomic level. However, to fully harness their potential, ongoing efforts focus on strategies to enhance the catalytic performance of SACs, profoundly influencing both the sensitivity and selectivity of SACs-based sensing platforms. RESULTS: In this study, we focused on the synthesis and application of Fe-Co-PNC dual-atom catalysts (DACs) with the incorporation of phosphorus, aiming to enhance catalytic efficiency, particularly in the context of the oxygen reduction reaction (ORR) correlated cathodic luminol ECL. The synergistic effects arising from the combination of Fe and Co in DACs were explored by ECL emission. Comparative studies with Fe-PNC SACs highlighted the superior catalytic performance of Fe-Co-PNC DACs. The ECL sensing platform exhibited excellent sensitivity, which provided a fast detection of Trolox with a wide linear range (0.1 µM-1.0 mM) and a low detection limit (LOD) of 0.03 µM. The platform demonstrated remarkable reproducibility and long-term stability, showcasing its potential for practical biosensing applications. SIGNIFICANCE: This study introduced the novel concept of Fe-Co-PNC DACs. The demonstrated synergistic effects and enhanced catalytic efficiency of DACs offer new avenues for the rational design of advanced catalysts. The successful application in the sensitive detection of Trolox emphasizes their potential significance in biosensing. It not only expands our understanding of SACs but also opens doors for the development of efficient and stable catalysts with broader applications.

AI-assisted accelerated MRI of the ankle: clinical practice assessment.

BACKGROUND: High-spatial resolution magnetic resonance imaging (MRI) is essential for imaging ankle joints. However, the clinical application of fast spin-echo sequences remains limited by their lengthy acquisition time. Artificial intelligence-assisted compressed sensing (ACS) technology has been recently introduced as an integrative acceleration solution. We compared ACS-accelerated 3-T ankle MRI to conventional methods of compressed sensing (CS) and parallel imaging (PI) . METHODS: We prospectively included 2 healthy volunteers and 105 patients with ankle pain. ACS acceleration factors for ankle protocol of T1-, T2-, and proton density (PD)-weighted sequences were optimized in a pilot study on healthy volunteers (acceleration factor 3.2-3.3×). Images of patients acquired using ACS and conventional acceleration methods were compared in terms of acquisition times, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), subjective image quality, and diagnostic agreement. Shapiro-Wilk test, Cohen κ, intraclass correlation coefficient, and one-way ANOVA with post hoc tests (Tukey or Dunn) were used. RESULTS: ACS acceleration reduced the acquisition times of T1-, T2-, and PD-weighted sequences by 32-43%, compared with conventional CS and PI, while maintaining image quality (mostly higher SNR with p < 0.004 and higher CNR with p < 0.047). The diagnostic agreement between ACS and conventional sequences was rated excellent (κ = 1.00). CONCLUSIONS: The optimum ACS acceleration factors for ankle MRI were found to be 3.2-3.3× protocol. The ACS allows faster imaging, yielding similar image quality and diagnostic performance. RELEVANCE STATEMENT: AI-assisted compressed sensing significantly accelerates ankle MRI times while preserving image quality and diagnostic precision, potentially expediting patient diagnoses and improving clinical workflows. KEY POINTS: • AI-assisted compressed sensing (ACS) significantly reduced scan duration for ankle MRI. • Similar image quality achieved by ACS compared to conventional acceleration methods. • A high agreement by three acceleration methods in the diagnosis of ankle lesions was observed.

Structure-activity relationship and biological evaluation of xanthine derivatives as PCSK9 inhibitors for the treatment of atherosclerosis.

Developing non-statin small molecules for the treatment of hypercholesterolemia remains challenging. The proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapies have attracted considerable attentions. Forty-five 7030B-C5 derivatives were synthesized and evaluated for the PCSK9 repression activity, taking the PCSK9 transcriptional inhibitor 7030B-C5 as the lead. Structure-activity relationship (SAR) analysis at C8 and N7-position was carried out, and compound 3s and 5r exhibited comparable PCSK9 transcriptional inhibitory activity but much lower cytotoxicity with the therapeutic index (TI) values doubled of that of 7030B-C5. In the in vitro assay, both compounds significantly reduced the level of PCSK9 protein and increased LDL receptor (LDLR) protein level. What's more, both compounds promoted LDL cholesterol (LDL-C) clearance more efficiently than 7030B-C5 in HepG2 cells. Most importantly, compound 3s reduced the atherosclerotic plaque areas with promising lipid-lowing effects in ApoE KO mice with a higher in vivo activity and lower toxicity. The regulatory mechanism of 3s was explored that it might target the transcription factor HNF1α and/or HINFP upstream of PCSK9 transcription, similar to that of 7030B-C5. Thus, 3s was considered as a potential anti-atherosclerosis drug candidate as a novel PCSK9 down-regulatory agent, worthy of further investigations.

Single-atom boosted electrochemiluminescence via phosphorus doping of Fe-N/P-C catalysts.

Single-atom catalyst (SAC), one of the most attractive catalysts in the field of energy conversion and storage, was proven as efficient accelerator for luminol-dissolved oxygen electrochemiluminescence (ECL) via the catalysis of oxygen reduction reaction (ORR). In this work, we synthesized heteroatom doping SACs of Fe-N/P-C for the catalysis of cathodic luminol ECL. The doping of P could lower the reaction energy barrier of the OH* reduction, and promote catalytic efficiency toward ORR. The formation of reactive oxygen species (ROS) during ORR triggered cathodic luminol ECL. Greatly enhanced ECL emission catalyzed by SACs proved that Fe-N/P-C exhibited higher catalytic activity to ORR compared with Fe-N-C. Since the system was highly dependent on oxygen, an ultra-sensitive detection of a typical antioxidant, ascorbic acid, was achieved with detection limit of 0.03 nM. This study provides possibility to greatly enhance the performance of ECL platform through rational tailoring of SACs via heteroatom doping.

Bioinformatics analysis of ceRNA regulatory network of baicalin in alleviating pathological joint alterations in CIA rats.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovium, leading to cartilage damage, bone erosion, even joint destruction and deformity. The conventional treatment modalities in RA are associated with side effects, emphasizing the need for alternative therapeutic remedies. Baicalin possesses multiple pharmacological effects and the advantage of low toxicity. This study aimed to reveal the potential gene regulatory mechanisms underlying the alleviating effects of baicalin in joint pathological alterations in Collagen-Induced Arthritis (CIA) rat models. At 28 days after the primary immunization, 60 mg/kg/d of baicalin was administered via intraperitoneal injection once daily for 40 days, and the pathological alterations of hind paw joints were examined with X-ray imaging. Subsequently, the synovial tissue of knee joints was isolated, from which total RNA was extracted, and mRNA and miRNA sequencing libraries were established. Finally, High-throughput transcriptome sequencing(RNA-seq) technology was performed, and the lncRNAs/miRNAs/mRNAs competing endogenous RNA(ceRNA) regulatory network was analyzed. The CIA model was successfully established, and baicalin treatment significantly alleviated the destruction of distal joints of CIA rat models (p < 0.01). We found that 3 potential ceRNA regulatory networks of baicalin were established, including lncRNA ENSRNOT00000076420/miR-144-3p/Fosb, lncRNA MSTRG.1448.13/miR-144-3p/Atp2b2 and lncRNA MSTRG.1448.13/miR-144-3p/Shanks. The validation results from synovial tissue of CIA rats were consistent with the RNA-Seq results. Overall, this study revealed potentially important genes and ceRNA regulatory network that mediate the alleviating effects of baicalin on joint pathological alterations in CIA rats.

Evaluation of breast cancer malignancy, prognostic factors and molecular subtypes using a continuous-time random-walk MR diffusion model.

PURPOSE: To assess the continuous-time random-walk (CTRW) model's diagnostic value in breast lesions and to explore the associations between the CTRW parameters and breast cancer pathologic factors. METHOD: This retrospective study included 85 patients (70 malignant and 18 benign lesions) who underwent 3.0T MRI examinations. Diffusion-weighted images (DWI) were acquired with 16b-values to fit the CTRW model. Three parameters (Dm, α, and ß) derived from CTRW and apparent diffusion coefficient (ADC) from DWI were compared among the benign/malignant lesions, molecular prognostic factors, and molecular subtypes by Mann-Whitney U test. Spearman correlation was used to evaluate the associations between the parameters and prognostic factors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) based on the diffusion parameters. RESULTS: All parameters, ADC, Dm, α, and ß were significantly lower in the malignant than benign lesions (P < 0.05). The combination of all the CTRW parameters (Dm, α, and ß) provided the highest AUC (0.833) and the best sensitivity (94.3%) in differentiating malignant status. And the positive status of estrogen receptor (ER) and progesterone receptor (PR) showed significantly lower ß compared with the negative counterparts (P < 0.05). The high Ki-67 expression produced significantly lower Dm and ADC values (P < 0.05). Additionally, combining multiple CTRW parameters improved the performance of diagnosing molecular subtypes of breast cancer. Moreover, Spearman correlations analysis showed that ß produced significant correlations with ER, PR and Ki-67 expression (P < 0.05). CONCLUSIONS: The CTRW parameters could be used as non-invasive quantitative imaging markers to evaluate breast lesions.

Efficacy of Trastuzumab + Cisplatin Combined with Irinotecan on the Quality of Life of Patients with Advanced Her-2 Positive Gastric Cancer.

Objective: To observe the effect of trastuzumab and cisplatin combined with irinotecan in the treatment of advanced Her-2 positive gastric cancer and its influence on disease control rate. Methods: From January 2018 to January 2021, 120 patients with advanced Her-2 positive gastric cancer admitted to our hospital were selected as the research subjects. According to the treatment plan of the patients, they were divided into a control group and a joint group, with 60 cases in each group; the control group was given trastuzumab + cisplatin, the joint group was treated with irinotecan on this basis, and the clinical effects and disease control rate of the two groups were observed. Results: After treatment, there were 4 patients with CR in the joint group and 0 patients with CR in the control group. The ORR and DCR of the joint group were significantly higher than those of the control group (P < 0.05). The expression levels of CA199, CEA, and CA724 after treatment in the two groups were significantly reduced (P < 0.05), and the reduction in the joint group after treatment was more evident as compared with the control group (P < 0.05). The joint group witnessed better memory function, physical function, behavioral function, emotional function, and communication function than the control group (P < 0.05), and the scores of all dimensions of the two groups of patients after treatment were superior to those before treatment (P < 0.05). The occurrence of side effects was not statistically different between the two groups of patients (P > 0.05). The 1-year survival rate of the control group was 41.67%, the PFS was 6.33 ± 1.02 months, and the OS was 15.51 ± 2.16 months; the 1-year survival rate of the joint group was 43.33%, and the PFS was 8.05 ± 1.07 months, and OS was 16.03 ± 2.44 months; there was no significant difference in the 1-year survival rate between the two groups (P > 0.05), the difference in PFS between the groups was significant (t = 9.013, P < 0.001), and the difference in OS between the groups was not significant (t = 1.236, P=0.219). Conclusion: Trastuzumab + cisplatin combined with irinotecan yields a promising result in the treatment of advanced gastric cancer. It can effectively regulate the expression level of tumor markers, delay disease progression, and improve the quality of life of patients. Moreover, irinotecan will not bring more toxic side effects.

[Effects of bisphenol A exposure on proteins tyrosine phosphorylation in mammalian sperm]. / åŒé šAæš´éœ²å¯¹å“ºä¹³åŠ¨ç‰©ç²¾å­è›‹ç™½é ªæ°¨é ¸ç£·é ¸åŒ–çš„å½±å“.

Bisphenol A (BPA) is a synthetic estrogen compound, which widely exists in the environment, interferes with mammalian endocrine and affects the function of reproductive system of males. Taking fresh sperm of boar, 17 ℃ preservation boar sperm, and mouse sperm as test materials, we examined the effects of BPA (0, 0.1,1,10,100 µmol∙L-1) on proteins tyrosine phosphorylation in sperm and the molecular mechanism by using wes-tern blot (WB) and immunofluorescence techniques coupled to in vitro culture method. The results showed that low BPA concentration (0.1, 1 µmol∙L-1) markedly accelerated the protein tyrosine phosphorylation of fresh boar capacitated sperm. However, the tyrosine phosphorylation of boar sperm decreased in high BPA concentration (10, 100 µmol∙L-1). The tyrosine phosphorylation of the mouse sperm raised with the increases of BPA concentration. Moreover, BPA affected different kinds of proteins related to tyrosine phosphorylation modification of porcine and mouse sperm capacitation, suggesting that the effect of BPA exposure on mammalian sperm was species-specific. Furthermore, the results of immunofluorescence showed that the effects of BPA on protein tyrosine phosphorylation in sperm mainly occurred in the middle and principal piece of flagellum.

Complete chloroplast genome of Prunus fruticosa and its implications for the phylogenetic position within Prunus sensulato (Rosaceae).

Prunus fruticosa is a wild species of Prunus distributed across the central Eurasia. Here, we reported the complete chloroplast (cp) genome of P. fruticosa (GenBank accession number: MT916286). The cp genome was 158,217 bp long, with a large single-copy region (LSC) of 86,322 bp and a small single-copy region (SSC) of 19,153 bp separated by a pair of inverted repeats (IRs) of 26,371 bp. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. We also reconstructed the phylogeny of Prunus sensu lato using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that P. fruticosa is closely related with Prunus avium.

Phthalide derivative CD21 alleviates cerebral ischemia-induced neuroinflammation: Involvement of microglial M2 polarization via AMPK activation.

Microglia can be activated to become the classic phenotype (M1) or alternative phenotype (M2), which play an important role in regulating neuroinflammatory response and tissue repair after ischemic stroke. CD21, a novel phthalide derivative, is a potential neuroprotectant against ischemic brain injury. The present study further investigated the effects of CD21 on post-ischemic microglial polarization and the underlying mechanisms. Transient middle cerebral artery occlusion (tMCAO) was used as a mouse model of ischemic stroke, while BV2 cells stimulated with conditioned medium collected from oxygen-glucose deprivation-treated HT22 cells were used in in vitro ischemic studies. The current results showed that CD21 dose-dependently and significantly improved neurological outcomes in tMCAO mice. Biochemical analyses revealed that CD21 decreased the expression of M1 phenotype markers (CD86, interleukin-1ß and inducible nitric oxide synthase) and increased the expression of M2 phenotype markers (CD206, interleukin-10 and YM1/2) in both ischemic brain tissues and BV2 cells. Meanwhile, CD21 decreased the production of proinflammatory cytokines (interleukin-1ß, interleukin-6 and tumor necrosis factor-α), promoted the release of the antiinflammatory cytokine (interleukin-10), and enhanced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) in ischemic brain tissue and BV2 cells. Furthermore, the AMPK inhibitor (compound C) reversed these effects of CD21 in BV2 cells. These findings indicate that CD21 alleviates post-ischemic neuroinflammation through induction of microglial M2 polarization that is at least in part medicated by AMPK activation, suggesting that CD21 may be a promising candidate for protecting against ischemic brain injury.