The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

CDCA5 accelerates progression of breast cancer by promoting the binding of E2F1 and FOXM1.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women. Cell division cycle associated 5 (CDCA5), a master regulator of sister chromatid cohesion, was reported to be upregulated in several types of cancer. Here, the function and regulation mechanism of CDCA5 in breast cancer were explored. METHODS: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms. RESULTS: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/ß-catenin signaling pathway was required for CDCA5 induced progression of breast cancer. CONCLUSIONS: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment.

Scutellarin inhibits the glioma cell proliferation by downregulating BIRC5 to promote cell apoptosis.

The expression changes of baculovirus inhibitor of apoptosis repeat-containing protein5 in brain glioma after administration of Scutellarin was detected. To explore the effort of scutellarin on anti-glioma by downregulating BIRC5.The effect of scutellarin on tumour growth and animal survival was detected by administering scutellarin to nude mice subcutaneous tumour formation and SD rats in situ tumour formation models. A significantly different gene BIRC5 was found by using the combination of TCGA databases and network pharmacology. And then qPCR was performed to detect the expression of BIRC5 in glioma tissues, cells and normal brain tissues and glial cells. CCK-8 was used to detect the IC50 of scutellarin on glioma cells. The wound healing assay, flow cytometry and MTT test were used to detect the effect of scutellarin on the apoptosis and proliferation of glioma cells. The expression of BIRC5 in glioma tissues was significantly higher than that in normal brain tissues. Scutellarin can significantly reduce tumour growth and improve animal's survival. After scutellarin was administered, the expression of BIRC5 in U251 cells was significantly reduced. And after same time, apoptosis increased and cell proliferation was inhibited. This original research showed that scutellarin can promote the apoptosis of glioma cells and inhibit the proliferation by downregulating the expression of BIRC5.

Analysis of hemi-uterus pregnancy outcomes in uterine malformations: a retrospective observational study.

BACKGROUND: The association between uterine malformations and adverse pregnancy outcomes is well recognized. However, studies on adverse pregnancy outcomes based on one kind of anatomical commonality between different uterine anomalies have not been reported. This study aimed to investigate pregnancy outcomes in pregnancies with uterine malformations when the pregnancy is confined to a hemi-uterus. METHODS: A retrospective observational study of 336 women who gave birth at our hospital from 2015 to 2021 was performed. Women (n = 112) with a unicornuate, complete bicornuate, or didelphic uterus were set as the study group, and women (n = 224) with a normal uterus were set as the reference group. Maternal and neonatal outcomes were evaluated and compared between the two groups using Student's t-test, one-way ANOVA, Chi-squared test, Yates correction for continuity, or Fisher's exact test. Modified Poisson regression analyses were used to estimate the relationships between the hemi-uterus pregnancy and preterm birth, preterm premature rupture of membranes, and cesarean section rates by adjusting for potential confounders. A P value < 0.05 was considered significant. RESULTS: Women in the study group had a higher history of spontaneous abortion (24.1% vs. 10.7%, P = 0.002) and intrauterine fetal death (5.4% vs. 0.4, P = 0.006). Compared with the reference group, the study group had significantly higher rates of assisted reproductive technology (9.4% vs. 2.2%, P = 0.001) and cord-around-the neck (54.5% vs. 29.9%, P = 0.000). Modified Poisson regression analyses showed that the study group was at higher risk for preterm birth (aRR, 6.8; 95% CI 2.7-16.7), preterm premature rupture of membranes (aRR, 14.1; 95% CI 3.2-62.5), malpresentation (aRR, 13.2; 95% CI 6.3-27.7), and cesarean section (aRR, 4.4; 95% CI 3.3-5.7). CONCLUSION: Women with a unicornuate, didelphic, or complete bicornuate uterus are at higher risk for some adverse pregnancy outcomes than those with a normal uterus.

Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients.

INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

[Scoping review of acupuncture-moxibustion treatment for non-specific low back pain].

This study systematically searched and sorted out randomized controlled trial(RCT) of acupuncture-moxibustion treatment for non-specific low back pain by scoping review, so as to demonstrate the current state of the research evidence and provide a reference point for future clinical research and healthcare decision-making. Eight commonly used Chinese and English databases were searched, and the search time was from the establishment of the databases to July 7, 2023, so as to analyze the characteristics of the current status of the current research through visualization methods. A total of 50 studies were included, including 23 studies in Chinese and 27 studies in English. The overall number of studies showed an increasing trend. The percentage of studies published in Chinese non-core journals was 42.0%. The disease subtypes of interest were mainly chronic non-specific low back pain, accounting for 68.0% of the studies. The sample sizes of the studies were mainly concentrated in the range of 50-100 cases. A total of 15 types of interventions were categorized, with acupuncture interventions being the most studied. Duration of treatment did not exceed one month in 80.0% of the studies. Only 8.0% of the studies used minimal clinical important difference(MCID) as a basis for judgment. The follow-up period was set within 3 months in 28.0% of the studies, and 82.0% of the studies concluded that acupuncture-moxibustion was effective in the treatment of non-specific lower back pain. Adverse events were reported in 20.0% of the studies. The risk of bias in the included studies was dominated by low risk of bias and uncertain risk of bias, with fewer studies focusing on high risks of bias. In most of the studies, acupuncture-moxibustion was significantly more effective than the control group. The research on acupuncture-moxibustion treatment for non-specific low back pain is developing rapidly, but there are still insufficient studies on psychological state, safety, and other indicators, and there are still some studies with uncertain risks of bias, which is not conducive to the generalization and application of the findings. Therefore, future studies should improve and refine these shortcomings.

Reassigning the Pressure-Induced Phase Transitions of Methylammonium Lead Bromide Perovskite.

The high-pressure crystal structure evolution of CH3NH3PbBr3 (MAPbBr3) perovskite has been investigated by single-crystal X-ray diffraction and synchrotron-based powder X-ray diffraction. Single-crystal X-ray diffraction reveals that the crystal structure of MAPbBr3 undergoes two phase transitions following the space-group sequence: Pm3̅m → Im3̅ → Pmn21, unveiling the occurrence of a nonpolar/polar transition (Im3̅ → Pmn21). The transitions take place at around 0.8 and 1.8 GPa, respectively. This result contradicts the previously reported phase transition sequence: Pm3̅m → Im3̅ →Pnma. In this work, the crystal structures of each of the three phases are determined from single-crystal X-ray diffraction analysis, which is later supported by Rietveld refinement of powder X-ray diffraction patterns. The pressure dependence of the crystal lattice parameters and unit-cell volumes are determined from the two aforementioned techniques, as well as the bulk moduli for each phase. The bandgap behavior of MAPbBr3 has been studied up to around 4 GPa, by means of single-crystal optical absorption experiments. The evolution of the bandgap has been well explained using the pressure dependence of the Pb-Br bond distance and Pb-Br-Pb angles as determined from single-crystal X-ray diffraction experiments.

Upconversion under Photon Trapping in ZnO/BN Nanoarray: An Ultrahigh Responsivity Solar-Blind Photodetecting Paper.

Solar-blind photodetectors (PDs) are widely applicable in special, military, medical, environmental, and commercial fields. However, high performance and flexible PD for deep ultraviolet (UV) range is still a challenge. Here, it is demonstrated that an upconversion of photon absorption beyond the energy bandgap is achieved in the ZnO nanoarray/h-BN heterostructure, which enables the ultrahigh responsivity of a solar-blind photodetecting paper. The direct growth of ultralong ZnO nanoarray on polycrystalline copper paper induced by h-BN 2D interlayer is obtained. Meanwhile, strong photon trapping takes place within the ZnO nanoarray forest through the cyclic state transition of surface oxygen ions, resulting in an extremely high absorption efficiency (> 99.5%). A flexible photodetecting paper is fabricated for switchable detections between near UV and deep UV signals by critical external bias. The device shows robust reliability, ultrahigh responsivity up to 700 A W-1 @ 265-276 nm, and high photoconductive gain of ≈2 × 103 . A negative differential resistance effect is revealed for driving the rapid transfer of up-converted electrons between adjacent energy valleys (Γ to A) above the critical bias (3.9 V). The discovered rationale and device structure are expected to bring high-efficiency deep UV detecting and future wearable applications.

LukS-PV inhibits hepatocellular carcinoma cells migration by downregulating HDAC6 expression.

BACKGROUND: Hepatocellular carcinoma (HCC) is a clinically common malignant tumor worldwide. LukS-PV is the S component of Panton-Valentine leukocidin secreted by Staphylococcus aureus, which has shown anti-cancer activity. Based on previous findings, this study investigated the effects of LukS-PV on HCC migration and the potential molecular mechanisms involving acetylation pathways. METHODS: After treating HCC cells with different concentrations of LukS-PV, we used scratch assays to determine the mobility of the cancer cells. Western blots were used to determine the expression levels of migration-related proteins. Quantitative proteomic sequencing was used to evaluate proteomic changes in target proteins. Immunoprecipitation and liquid chromatography coupled with tandem mass spectrometry analyses were used to validate the binding of related target proteins. RESULTS: LukS-PV inhibited HCC cell migration in a concentration-dependent manner. In addition, LukS-PV attenuated the expression of histone deacetylase (HDAC)6, which is highly expressed in HCC cells. Further studies showed that LukS-PV increased the acetylation level of α-tubulin by down-regulating HDAC6, which resulted in the inhibition of HCC cell migration. CONCLUSION: Taken together, our data revealed a vital role of LukS-PV in suppressing HCC cell migration by down-regulating HDAC6 and increasing the acetylation level of α-tubulin.

Superconductivity and topological states in hexagonal TaC and NbC.

Materials with superconductivity and a nontrivial band structure near the Fermi level are promising candidates in realizing topological superconductivity. Using first-principles calculations, we systematically investigated the stability, mechanical properties, superconductivity, electronic structures, and topological states of hexagonal TaC and NbC. The results show that they are stable and have excellent mechanical properties. We predicted that these two carbides are strong electron-phonon coupling superconductors with superconducting transition temperatures of 14.8 and 17.1 K, respectively. Strong coupling is mainly dominated by in-plane Ta/Nb atomic vibrations and in-plane Ta/Nb-dxy/dx2-y2 electronic orbitals. The electronic structure calculations demonstrate that a nodal line and a triply degenerate point coexist when not including the spin-orbit coupling (SOC) effect. After including the SOC effect, the nodal line is gapped. The complicated surface states are also calculated and need further experiments to verify. The present results indicate that the hexagonal TaC and NbC are potential candidates as topological superconductors, and pave the way towards exploring the superconductivity and topological materials in condensed matter systems.

Evaluating the Functional Pore Size of Chloroplast TOC and TIC Protein Translocons: Import of Folded Proteins.

The degree of residual structure retained by proteins while passing through biological membranes is a fundamental mechanistic question of protein translocation. Proteins are generally thought to be unfolded while transported through canonical proteinaceous translocons, including the translocons of the outer and inner chloroplast envelope membranes (TOC and TIC). Here, we readdressed the issue and found that the TOC/TIC translocons accommodated the tightly folded dihydrofolate reductase (DHFR) protein in complex with its stabilizing ligand, methotrexate (MTX). We employed a fluorescein-conjugated methotrexate (FMTX), which has slow membrane transport rates relative to unconjugated MTX, to show that the rate of ligand accumulation inside chloroplasts is faster when bound to DHFR that is actively being imported. Stromal accumulation of FMTX is ATP dependent when DHFR is actively being imported but is otherwise ATP independent, again indicating DHFR/FMTX complex import. Furthermore, the TOC/TIC pore size was probed with fixed-diameter particles and found to be greater than 25.6 Å, large enough to support folded DHFR import and also larger than mitochondrial and bacterial protein translocons that have a requirement for protein unfolding. This unique pore size and the ability to import folded proteins have critical implications regarding the structure and mechanism of the TOC/TIC translocons.

[Platelet function tests and Chinese medicines with antiplatelet function:a review].

Platelet function tests have been increasingly used to assist in the diagnosis of platelet disorders and prethrombotic state, monitoring of the efficacy of antiplatelet therapies, and personalized treatment. On the basis of light transmission aggregometry, new methods for platelet function test have been developed successively. At present, the research and development of platelet function detector is in its infancy in China. The active constituents of antiplatelet Chinese medicines can be classified into terpenoids, flavonoids, saponins, organic acids, lignans, diketones, volatile oils, and stilbenes. The results of dose-antiplatelet effect relationship of Chinese medicines and the active constituents showed that the effective concentration of the extracts or monomers of Chinese medicines was at micromolar level(µmol·L~(-1)), among which salvianolic acid B and ginkgolide K, ginkgolide B, and ginkgolide A had the strongest antiplatelet effect. These results suggest that the antiplatelet effect of Chinese medicine may be weaker than that of chemical drugs and biological products. Therefore, it is necessary to explore the structure-activity relationship of the active constituents in existing Chinese medicines and further improve their efficacy through structure modification. The antiplatelet effect of Chinese medicines and the constituents involves multiple pathways and multiple targets. These research results provide a reference for clinical application of them. However, there is still a lack of large-scale multi-center clinical trials to confirm the efficacy and safety of them. The regularity of the relationship between the structures of various constituents and their corresponding functions is still unknown and the relevant signal transduction pathways and structure-activity relationship need to be further studied. This paper summarized and analyzed the determination methods of platelet functions and the research results of antiplatelet Chinese medicines, which is of reference value for the research of effective and safe antiplatelet Chinese medicines.

[Effects of Xueshuantong Injection on thrombosis formation and blood flow in rats].

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg~(-1)) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo®2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body's blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.

Anti-Phospholipase A2 Receptor (Anti-PLA2R) Antibody in Diagnosis and Treatment of Idiopathic Membranous Nephropathy: A Single-Center Observational Study in China.

BACKGROUND The aim of this study was to observe the concentration of serum anti-PLA2R antibody in idiopathic membranous nephropathy (IMN) patients and analyze its relationship with clinical and laboratory parameters. MATERIAL AND METHODS We treated 72 patients with idiopathic membranous nephropathy diagnosed by renal biopsy; all these patients who presented nephrotic syndrome were enrolled for investigation, and then underwent combination therapy with prednisone and cyclosporine A for 6 months. We collected data on 24-h total proteinuria (TUpro), creatinine clearance rate (Ccr), and serum albumin (Alb) levels before and after immunosuppressive treatment. Serum anti-PLA2R antibody was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Fifty-six out of 72 IMN patients presented positive serum anti-PLA2R antibody. The titer of anti-PLA2R antibody was significantly correlated with both TUpro and serum Alb levels of pre- and post-therapeutic values in IMN (P<0.05), but did not have a relationship with Ccr (P>0.05). In comparison with the anti-PLA2R antibody-negative group, there were significantly higher TUpro and lower Alb levels in the anti-PLA2R antibody-positive group (P<0.05). However, Ccr was comparatively lower in the anti-PLA2R antibody-positive group, but the difference was not statistically significant (P>0.05). There were 24 patients with negative anti-PLA2R antibody and 14 patients had complete remission in the positive anti-PLA2R antibody group, while anti-PLA2R antibody of all 14 patients became negative. Eight out of 16 patients without anti-PLA2R antibody went into complete remission. CONCLUSIONS Serum anti-PLA2R antibody, as determined by non-invasive technique, is a specific biomarker for diagnosis of IMN. Our results suggest that serum anti-PLA2R antibody has great potential to guide clinical diagnosis and treatment, as well as prognosis determination, in IMN patients.

Submucosal tunneling endoscopic resection for an unusually sized esophageal submucosal tumor protruding into the mediastinum.

A 50-year-old female came to our hospital with a 6-month history of upper abdominal discomfort. An upper endoscopy detected a protruding lesion that measured 3.0×2.0 cm at around 35-38 cm from the incisors located on the posterior wall. Endoscopic ultrasonography revealed a homogeneous hyperechoic mass located in the muscularis propria, with no malignant features. Contrast-enhanced CT was also performed. A submucosal tunneling endoscopic resection (STER) was performed. A longitudinal mucosal incision was made and a submucosal tunnel created, which uncovered an irregularly giant tumor. The size of the resected tumor was 3.0×4.0×1.5cm and the histopathological analysis identified leiomyomas. The patient was discharged 7 days after the procedure and 3 months after the surgery there was no recurrence on the CT scan. Meanwhile, the discomfort of the patient was relieved after STER and there were no severe complications during the 6-month follow-up. DISCUSSION Esophageal leiomyoma is a benign submucosal tumor derived from the muscularis propria layer of the esophagus [1]. STER has been demonstrated to be safe and effective for treating small (≤3.5 cm) and solitary esophageal leiomyoma with low complication rates [2-3]. Most esophageal leiomyoma grow into the lumen and their positions in the tunnel are relatively superficial and the entire surgery is comparatively safe. In this case, the tumor was very large and was close to the mediastinum, which greatly increases the difficulty of surgery. However, STER is recommended according to our experience, even in rare cases.

[Modulation of drug-metabolizing enzymes and transporters under hypoxia environment].

Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and transporters. Studies have shown that hypoxia increases the release of a series of inflammatory cytokines which can modulate drug metabolism. Besides, both hypoxia inducible factor 1α (HIF-1α) and microRNA-mediated pathways play a role in regulating drug metabolism. This article reviewed the impact and single-factor modulating mechanisms of drug metabolism under hypoxia, and put forward the speculation and prospects of multi-factor modulating mechanisms.

Potential Medication Treatment According to Pathological Mechanisms in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a vascular disease with high mortality. Because of the lack of effective medications to stop or reverse the progression of AAA, surgical operation has become the most predominant recommendation of treatment for patients. There are many potential mechanisms, including inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, oxidative stress, and so on, involving in AAA pathogenesis. According to those mechanisms, some potential therapeutic drugs have been proposed and tested in animal models and even in clinical trials. This review focuses on recent advances in both pathogenic mechanisms and potential pharmacologic therapies of AAA.

Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration.

Sphingolipids typically have an 18-carbon (C18) sphingoid long chain base (LCB) backbone. Although sphingolipids with LCBs of other chain lengths have been identified, the functional significance of these low-abundance sphingolipids is unknown. The LCB chain length is determined by serine palmitoyltransferase (SPT) isoenzymes, which are trimeric proteins composed of two large subunits (SPTLC1 and SPTLC2 or SPTLC3) and a small subunit (SPTssa or SPTssb). Here we report the identification of an Sptssb mutation, Stellar (Stl), which increased the SPT affinity toward the C18 fatty acyl-CoA substrate by twofold and significantly elevated 20-carbon (C20) LCB production in the mutant mouse brain and eye, resulting in surprising neurodegenerative effects including aberrant membrane structures, accumulation of ubiquitinated proteins on membranes, and axon degeneration. Our work demonstrates that SPT small subunits play a major role in controlling SPT activity and substrate affinity, and in specifying sphingolipid LCB chain length in vivo. Moreover, our studies also suggest that excessive C20 LCBs or C20 LCB-containing sphingolipids impair protein homeostasis and neural functions.

[Complex enzyme combined with ultrasound extraction technology, physicochemical properties and antioxidant activity of Hedysarum polysaccharides].

In this study, complex enzymes combined with ultrasonic extraction technology（MC） were used, to select optimal extraction combinations by single factor and orthogonal test, with Hedysarum polysaccharides yield and content as the comprehensive indexes. The components, physicochemical properties and antioxidant activity of Hedysarum polysaccharides from complex enzyme combined with ultrasonic extraction（HPS-MC）and the Hedysarum polysaccharides from hot water extraction（HPS-R）were analyzed. The results showed that：complex enzymes had significant effect on the yield and content of Hedysarum polysaccharides, and the ultrasonic power could significantly improve the content of Hedysarum polysaccharides. The optimum technological parameters were as follows: complex enzyme ratio 1:1, ultrasonic power 105 W, ultrasonic time 60 min, and enzymatic hydrolysis pH 5, achieving （14.01±0.64）% and （92.45±1.47）% respectively for the yield and content of Polysaccharides. As compared with HPS-R, the molecular weight, absolute viscosity and protein content of HPS-MC were decreased, while the content of uronic acid was increased. In the antioxidant system, the concentration of polysaccharide was within the range of 1-7 g·L⁻¹; the antioxidant activity of HPS-MC was higher than that of HPS-R, and HPS-MC (80%) with the lowest molecular weight showed a significant dose effect relationship with the increase of the experimental concentration. In conclusion, MC is a simple, convenient, economical and environmentally friendly extraction technology, and the Hedysarum polysaccharides extracted by this method have obvious antioxidant activity.

Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90.

The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration-dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca2+ transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI-CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP-binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 µM. Araloside C also up-regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation-treated H9c2 cardiomyocytes, whereas the addition of 17-AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C-induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R-induced oxidative stress and [Ca2+ ]i overload, which was possibly related to its binding to the Hsp90 protein.