Structure and activation mechanism of the rice Salt Overly Sensitive 1 (SOS1) Na+/H+ antiporter.

Salinity is one of the most severe abiotic stresses that adversely affect plant growth and agricultural productivity. The plant Na+/H+ antiporter Salt Overly Sensitive 1 (SOS1) located in the plasma membrane extrudes excess Na+ out of cells in response to salt stress and confers salt tolerance. However, the molecular mechanism underlying SOS1 activation remains largely elusive. Here we elucidate two cryo-electron microscopy structures of rice (Oryza sativa) SOS1, a full-length protein in an auto-inhibited state and a truncated version in an active state. The SOS1 forms a dimeric architecture, with an NhaA-folded transmembrane domain portion in the membrane and an elongated cytosolic portion of multiple regulatory domains in the cytoplasm. The structural comparison shows that SOS1 adopts an elevator transport mechanism accompanied by a conformational transition of the highly conserved Pro148 in the unwound transmembrane helix 5 (TM5), switching from an occluded conformation in the auto-inhibited state to a conducting conformation in the active state. These findings allow us to propose an inhibition-release mechanism for SOS1 activation and elucidate how SOS1 controls Na+ homeostasis in response to salt stress.

[Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism]. / ç¯ç›èŠ±ç´ å¯¹å®«å† ç‚Žç—‡è‡´æ—©äº§å¤§é¼ è„‘æŸä¼¤çš„ä¿æŠ¤ä½œç”¨åŠå ¶æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. METHODS: A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. RESULTS: Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1ß, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1ß, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). CONCLUSIONS: Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Glomangiomatosis - immunohistochemical study: A case report.

BACKGROUND: Glomangiomatosis (also known as diffuse glomus tumor) is extremely rare, accounting for only 5% of glomus tumors. The prevalence of glomus tumors is only 2% of soft tissue tumors. Lesions can recur after resection. Although growth may be diffuse or infiltrating and invasive, definitive identifying standards for malignant glomus tumors are lacking. This article describes a case of glomangiomatosis with many nodular masses in the soft tissues of the right foot and calf. A review of the Chinese and English-language literature is included. CASE SUMMARY: A case of glomangiomatosis in a 55-year-old Chinese woman who presented clinically with many nodular masses in the soft tissues of the right foot and calf. The tumor was examined histologically and immunostaining was performed. CONCLUSION: Glomangiomatosis occurs most often in young people, in the distal extremities, but is rare. Multiple nodules are even rarer. Only 15 clinicopathological analyses of glomangiomatosis have been reported in the combined Chinese- and English-language literature. In the present case, microscopically, nested vascular globular cells were observed around the blood vessel wall. Immunohistochemistry revealed diffuse immunoreactivity for smooth muscle actin, vimentin, type IV collagen, and Bcl-2. Caldesmon, CD34, and calponin were weakly, partially, and slightly positive, respectively. There was no recurrence 1 year after resection.

Discovery of cyclooxygenase-2 inhibitors from Kadsura coccinea by affinity ultrafiltration mass spectrometry and the anti-inflammatory activity.

The medicinal plant Kadsura coccinea distributing in South China, was widely used for reducing inflammation and relieving pain. Previous study in our laboratory had proved the significant therapeutic effects of K. coccinea extract on adjuvant arthritis rats. To explore the responsible components and possible mechanisms, an AUF-HPLC-Q-TOF/ MS method was employed for screening and characterizing COX-2 ligands from K. coccinea stems for the first time. Meanwhile, the molecular docking was performed to simulate the binding modes for ligands and COX-2, the cell-free enzyme activity assay was applied to verify the direct COX-2 inhibition of potential inhibitors, and the cell-based study on COX-2 expression was to evaluate the anti-inflammatory effect of (+)-Anwulignan. As a result, the potential COX-2 inhibitor (+)-Anwulignan significantly suppressing COX-2 expressions in LPS signaling pathways might be a good candidate for anti-inflammation and analgesia. In conclusion, AUF mass spectrometry combining the molecular docking and bioassays in vitro was an efficient approach for discovering enzyme inhibitors from traditional herbs.

Dynamics, thermodynamics, and mechanism of perfluorooctane sulfonate (PFOS) sorption to various soil particle-size fractions of paddy soil.

Soil is an important sink for perfluorooctane sulfonate (PFOS) that is a typical persistent organic pollutant with high toxicity. Understanding of PFOS sorption to various particle-size fractions of soil provides an insight into the mobility and bioavailability of PFOS in soil. This study evaluated kinetics, isotherms, and mechanisms of PFOS sorption to six soil particle-size fractions of paddy soil at environmentally relevant concentrations (0.01-1 µg/mL). The used soil particle-size fractions included coarse sand (120.4-724.4 mm), fine sand (45.7-316.2 mm), coarse silt (17.3-79.4 mm), fine silt (1.9-39.8 mm), clay (0.5-4.4 mm), and humic acid fractions (8.2-83.7 mm) labeled as F1~F6, respectively. PFOS sorption followed pseudo-second-order kinetics related to film diffusion and intraparticle diffusion, with speed-limiting phase acted by the latter. PFOS sorption isotherm data followed Freundlich model, with generally convex isotherms in larger size fractions (F1~F3) but concave isotherms in smaller size fractions (F4 and F5) and humic acid fraction (F6). Increasing organic matter content, Brunner-Emmet-Teller surface area, and smaller size fractions were conducive to PFOS sorption. Hydrophobic force, divalent metal ion-bridging effect, ligand exchange, hydrogen bonding, and protein-like interaction played roles in PFOS sorption. But hydrophobic force controlled the PFOS sorption, because its relevant organic matter governed the contribution of the soil fractions to the overall PFOS sorption. The larger size fractions dominated the PFOS sorption to the original soil because of their high mass percentages (~80%). This likely caused greater potential risks of PFOS migration into groundwater and bioaccumulation in crops at higher temperatures and ce values, based on their convex isotherms with an exothermic physical process.

Baeckeins L and M, two novel C-methylated triflavonoids from the roots of Baeckea frutescens L.

Baeckea frutescens is a medicinal plant distributing from Southeast Asia to Australia. A pair of novel diastereomeric C-methylated triflavonoids named baeckeins L (1) and M (2) were isolated from the roots of B. frutescens. The structures of these isolates were elucidated by analysis of the 1D (1H/13C) and 2D NMR (HSQC/HMBC/NOESY) and HR-ESI-MS spectroscopic data, and the absolute configurations of chiral carbons (C-2/C-3/C-2°/C-3°) were established by CD spectrometry combined with quantum chemical calculations.

Impact of perioperative blood transfusion on immune function and prognosis in colorectal cancer patients.

OBJECTIVE: To investigate the impacts of perioperative blood transfusion on the immune function and prognosis in colorectal cancer (CC) patients. METHODS: A retrospective analysis was conducted in 1404 CC patients, including 1223 sporadic colorectal cancer (SCC) patients and 181 hereditary colorectal cancer (HCC) patients. Among them, 701 SCC and 102 HCC patients received perioperative blood transfusion. The amount of T lymphocyte subsets and natural killer (NK) cells was measured. All patients received a 10-year follow-up and relapse, metastasis and curative conditions were recorded. RESULTS: In SCC group, mortality, local recurrence and distant metastasis rate of transfused patients were significantly higher than non-transfused patients (all P <0.05). In HCC group, mortality was apparently higher in transfused patients than non-transfused patients (P = 0.002). SCC patients transfused with ≥3 U of blood had significantly higher mortality than patients transfused with <3 U (P = 0.006). The amount of T lymphocyte subsets and NK cells showed statistical differences before and after perioperative blood transfusion in SCC and HCC patients (all P <0.05). Also, there existed statistical differences in CD4+/CD8+ ratio among SCC patients before and after the perioperative blood transfusion (P <0.05). CC patients who received perioperative blood transfusion had markedly lower 10-year survival rates as compared with those who did not receive (both P <0.05). SCC patients transfused with ≥3 U of blood had remarkably lower survival rates compared with SCC patients transfused with <3 U (P = 0.002). CONCLUSIONS: Perioperative blood transfusion could impact immune function, increased postoperative mortality, local recurrence rate and distant metastasis rate in CC patients; and survival rate of CC patients is negatively related to blood transfusion volume.

Chemical constituents of Allophylus longipes.

AIM: To investigate the chemical constituents of Allophylus longipes. METHODS: Compounds were isolated and purified by various chromatographic techniques and their structures were elucidated by physicochemical characteristics and spectral data. RESULTS: Twenty-five compounds were isolated and identified as cycloart-24-en-3ß, 26-diol (1), 3-oxotrirucalla-7, 24-dien-21-oic acid (2), zizyberenalic acid (3), colubrinic acid (4), ent-4(15)-eudesmene-1ß, 6α-diol (5), 4(15)-eudesmene-1ß, 8α-diol (6), 4(15)-eudesmene-1ß, 5α-diol (7), methyl asterrate (8), betulin (9), betulinic aldehyde (10), betulinic acid (11), 3ß-hydroxy-5α, 8α-epidioxyergosta-6, 22-dien (12), 3-oxo-19α-hydroxyurs-12-en-28-oic acid (13), ursolic acid (14), scopoletin (15), fraxidin (16), cleomiscosin A (17), 4-hydroxy-3-methoxybenzaldehyde (18), 4-hydroxy-3-methoxycinnamaldehyde (19), 2',6'-dihydroxy-4'-methoxyacetophenone (20), p-(aminoalkyl)-benzoic acid (21), 4-hydroxy-3-methoxybenzoic acid (22), 1-O-p-coumaroylglucose (23), ß-sitosterol (24), and poriferast-5-ene-3ß, 4ß-diol (25). CONCLUSION: All the compounds were isolated from Allophylus longipes for the first time.

Tirucallane-type alkaloids from the bark of Dysoxylum laxiracemosum.

Eight novel tirucallane-type alkaloids (1-8) and 11 known compounds were isolated from a methanol extract of the bark of Dysoxylum laxiracemosum. The structures of 1-8 were elucidated using extensive NMR spectrometric and mass spectroscopic methods. Compounds 1 and 5, named laxiracemosins A and E, showed significant cytotoxicity against five human cancer cell lines.

Monoterpenoid indole alkaloids from Alstonia yunnanensis.

Eight new monoterpenoid indole alkaloids, alstoyunines A-H (1-8), along with 17 known analogues, were isolated from Alstonia yunnanensis. The structures of the new alkaloids were established by means of extensive spectroscopic methods. Alstoyunines C (3), E (5), and F (6) showed selective inhibition of Cox-2 (>75%). Alstoyunine F (6) showed weak cytotoxicity against the human myeloid leukemia HL-60 (IC50 = 3.89 microM) and hepatocellular carcinoma SMMC-7721 (IC50 = 21.73 microM) cell lines.