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The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure. [Display omitted] • XBB.1.5, EG.5.1, and BA.2.86 exhibit similar but high resistance to neutralization • Nearly 60% of individuals were reinfected during periods of XBB/EG.5.1 predominance • Antibody wanes within 6 months, but additional infection improves the antibody response • Similar binding and neutralizing antibody responses are induced in older and younger adults Jiang et al. assess antibody binding and neutralization against BA.5, XBB.1.5, EG.5.1, and BA.2.86 after four vaccination doses, reinfection, and breakthrough infection. They observe decreased antibody levels and less neutralization of XBB.1.5, EG.5.1, and BA.2.86 6 months after exposure. Approximately 60% of individuals experienced reinfection, which elicited increased antibody responses. [ABSTRACT FROM AUTHOR]

• The Lushan earthquake occurred at the boundary zone between the high- and low-resistivity bodies. • The crustal structure of the southern Longmen Shan thrust belt matches the multiunit combination seismogenic model. • The seismogenic potential of the southern segment of Longmen Shan is weaker than that of the central segment. Since the Ms 7.0 earthquake occurred in Lushan on April 20, 2013, five years after the Wenchuan Ms 8.0 earthquake, the seismogenic potential of southern Longmen Shan has been a considerable concern. Comparative studies of active faults and deep structures of the Lushan and Wenchuan earthquakes are important to evaluate Longmen Shan potential. Terrace measurements, geophysical surveys and borehole drilling reveal that late Quaternary fault activity in the southern segment of the Longmen Shan thrust belt is weaker than that along the central segment. Magnetotelluric data across the southern segment of the Longmen Shan thrust belt show that the central fault and the front-range fault are the electrical boundaries of the crust and that the Longmen Shan thrust belt is a high-resistivity body. The Lushan earthquake occurred at the boundary zone between the high- and low-resistivity bodies, and the crustal structure of the southern Longmen Shan thrust belt matches the multiunit combination seismogenic model, indicating a potential large earthquake in Longmen Shan. Compared to conditions along the central segment, the low-resistivity layer of the upper and lower crust on the western side of the Songpan-Ganzi block develops along the Xianshuihe fault, which may reduce the strain accumulated from the Songpan-Ganzi block to the southern Longmen Shan thrust belt. This interpretation suggests that the main crustal shortening is accommodated by foreland thin fold structures, whereas the structural deformation accommodated by the thrust belt accounts for only a small proportion; thus, the seismogenic potential of southern Longmen Shan is weaker than that of the central segment. [ABSTRACT FROM AUTHOR]

Abstract Metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) pose an emerging threat to public health worldwide. An effective inhibitor of MBLs is therefore urgently needed for clinical use. In this study, two acyclic pyridine-containing ligands, H 2 dedpa and compound 8, were discovered with excellent activities when combined with meropenem (MEM) against MBL (bla NDM and bla IMP)-producing clinical isolates, including Escherichia coli , Citrobacter freundii, Proteus mirabilis , Enterobacter cloacae and Klebsiella pneumoniae. In particular, these two compounds improved the activity of MEM against E. coli harboring the bla NDM-4 gene by nearly 40,960 times. H 2 dedpa (IC 50 = 0.17 ± 0.04 μM) and compound 8 (IC 50 = 0.04 ± 0.02 μM) showed higher inhibitory activity against bla NDM-1 enzyme than the positive control ethylenediaminetetraacetic acid (EDTA, IC 50 = 28.84 ± 0.70 μM). A sterilization kinetics experiment showed that H 2 dedpain combined with MEM could kill 99.9% of bacteria within 24 h H 2 dedpa and compound 8 are therefore promising MBL inhibitors. Graphical abstract Image 1 Highlights • Two non-cyclic pyridine ligands, H 2 dedpa and compond 8 , were synthesized. • H 2 dedpa combined with MEM could kill 99.9% of bacteria which containing NDM-4 whithin 24h. • The two compouds could inhibit the growth of various strains containing NDM-1 and IMP-4 under low toxicity conditions. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The activity of β-lactam antibiotics is compromised by metallo-β-lactamases (MBLs). Herein, a series of dithiocarbamate derivatives were designed and synthesized. Their antibacterial activities were tested in combination with meropenem (MEM) against several MBL (NDM and IMP type)-producing clinical isolates. Clinical isolates harboring NDM-1 and IMP-4 became susceptible to MEM when it was combined with dithiocarbamate compounds 4a , 4b or 4f synthesized in this work. Compounds 4a and 4b increased the effectiveness of MEM by up to 2560 times against strains. In vitro bactericidal dynamics tests showed that bacteria died within 24 h when they were treated with compound 4f + MEM. Compounds 4a , 4b and 4f were non-hemolytic and exhibited low toxicity toward HeLa cells in vitro. These data show that compounds containing dithiocarbamate functional group may be helpful in the development of MBL inhibitors. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic drug (like carbapenem) resistance is being a global crisis. Among those resistance factors of the β-lactam antibiotics, the metallo-β-lactamases (MBLs) is one of the most important reasons. In this paper, a series of cyclic dithiocarbamate compounds were synthesized and their inhibition activities against MBLs were initially tested combined with meropenem (MEM) by in vitro antibacterial efficacy tests. Sodium 1,4,7-triazonane-1,4,7-tris(carboxylodithioate) (compound 5 ) was identified as the most active molecule to restore the activity of MEM. Further anti-bacterial effectiveness assessment, compound 5 restored the activity of MEM against Escherichia coli , Citrobacter freundii , Proteus mirabilis and Klebsiella pneumonia , which carried resistance genes of bla NDM-1 . The compound 5 was non-hemolytic, even at a concentration of 1000 µg/mL. This compound was low toxic toward mammalian cells, which was confirmed by fluorescence microscopy image and the inhibition rate of HeLa cells. The Ki value of compounds 5 against NDM-1 MBL was 5.63 ± 1.27 μM. Zinc ion sensitivity experiments showed that the inhibitory effect of compound 5 as a MBLs inhibitor was influenced by zinc ion. The results of the bactericidal kinetics displayed that compound 5 as an adjuvant assisted MEM to kill all bacteria. These data validated that this NOTA dithiocarbamate analogue is a good inhibitor of MBLs. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Panax quinquefolium saponin (PQS) is the active component extracted from traditional Chinese medicine Panax quinquefolius L. and has been widely used as a supplement to dual antiplatelet drugs (DA) for treatment of coronary artery disease (CAD) for two decades; however, the efficacy of PQS combined with DA against platelet adhesion to endothelial cells (ECs), an essential step in thrombosis, remains unclear. Aim of the study To compare PQS combined with DA and DA alone in inhibiting platelet adhesion to injured human umbilical vein endothelial cells (HUVECs) and to explore the possible mechanisms focusing on PI3K/AKT, COX-2/6-keto-PGF 1α , and COX-1/TXB 2 pathways. Methods HUVECs injured by oxidized low-density lipoprotein (ox-LDL) were randomly allocated into control, model, DA, PQS+DA (P+DA), LY294002 (a PI3K inhibitor)+DA (L+DA), and LY294002+PQS+DA (LP+DA) groups. HUVEC apoptosis, platelet adhesion to injured HUVECs, and platelet CD62p expression were assayed by fluorescence activated cell sorting (FACS). The concentrations of 6-keto-PGF 1α and TXB 2 in the supernatant were measured by radioimmunoassay. Protein expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT, AKT, COX-1, and COX-2 in both platelets and HUVECs was evaluated by western blot. Results Compared to DA alone, PQS combined with DA reduced platelet adhesion to HUVECs and HUVEC apoptosis more potently, increased the concentration of supernatant 6-keto-PGF 1α and up-regulated phospho-AKT protein in HUVECs. LY294002 mitigated the effects of PQS on HUVEC apoptosis and platelet adhesion. Conclusions These findings show that PQS as a powerful supplement to DA, attenuated HUVEC apoptosis and improved the DA-mediated reduction of platelet adhesion to injured HUVECs and the underlying mechanisms may be associated with PI3K/AKT and COX pathways in HUVECs and platelets. PQS might provide a new complementary approach to improve the prognosis of thrombotic diseases in future. [ABSTRACT FROM AUTHOR]

Bacterial resistance is a growing threat to public health and a significant barrier to anti-infective treatment. Consequently, the development of novel antibacterial strategies to address this issue is critical. Herein, we developed a series of chalcone-alkyl-lysine compounds by mimicking the chemical structure and antibacterial properties of cationic antimicrobial peptides. Most of the compounds showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. Compound 6d displayed potent antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), with MICs of 1–4 μg/mL. In addition, 6d exhibited excellent antibacterial activity against clinical MRSA and NDM-positive isolates, bactericidal properties, low resistance frequency. The mechanism studies revealed that compound 6d destroys bacterial cell membranes by interacting with phosphatidylglycerol (PG), causing the production of reactive oxygen species (ROS) and the leakage of nucleic acids, resulting in bacterial death. Furthermore, compound 6d did not exhibit any observable toxicity in HeLa and HEK293 cells at 8 × MIC. As a result, the findings suggest that compound 6d has potential therapeutic effects against bacterial infections and could be a promising drug candidate for future research. [Display omitted] • Cationic chalcone peptide mimics 6d displayed excellent antibacterial activity. • 6d showed difficulty in inducing bacterial resistance. • 6d exhibited low toxicity to mammalian cells at 8 × MIC. • 6d can act on the PG in the bacterial cell membrane to cause membrane breakage. [ABSTRACT FROM AUTHOR]

Objective This study was designed to investigate the effect of Panax notoginseng saponin (PNS) on platelet adhesion to injured endothelial cells (ECs) and platelet activation induced by injured ECs, and to explore its underlying mechanisms. Methods Human umbilical vein endothelial cells (HUVECs) pretreated with aspirin (ASA,15 μg/mL) or PNS (160 μg/mL), or neither, were exposed to oxidized low-density lipoprotein (ox-LDL,80 mg/L) for 16 h. Platelets were then added and co-cultured with HUVECs for 5 min. Platelet adhesion to ECs, platelet CD62p expression, and HUVEC apoptosis were assessed by fluorescence activated cell sorting (FACS)·Supernatant concentration of 6-keto-PGF1α and thromboxane 2 (TXB 2 ) were measured by radioimmunoassay. Cyclooxygenase-1 (COX-1) and COX-2 protein expression were measured by western blotting. Results The inhibitory effect of PNS on platelet activation was similar to ASA, but the inhibitory effect of PNS on platelet adhesion to ECs was superior to ASA. PNS modulated COX-2 expression, and increased 6-keto-PGF1α concentration in HUVECs, while down-regulated COX-1 expression and decreased supernatant TXB 2 concentration in platelets. Co-culturing of injured HUVECs with platelets increased HUVEC apoptosis induced by ox-LDL compared with HUVECs cultured without platelets; ASA increased HUVEC apoptosis induced by ox-LDL when cultured without platelets, while decreased the apoptosis when co-cultured with platelets. Conclusions EC protection by ASA is closely associated with its inhibitory effect on platelet activation. PNS is superior to ASA in protecting ECs and in inhibiting platelet adhesion to injured ECs, and the regulation of COX pathway in both ECs and platelets might be the underlying mechanisms of PNS. [ABSTRACT FROM AUTHOR]

The technology of Zn extraction from sphalerite concentrate by using electro-oxidation in weak alkaline sodium chloride solution has been investigated in this paper. The effects of several parameters on Zn recovery during the electro-oxidation have been investigated, and the optimized conditions are listed as follows : pH in the range of 8.5–8.8, NaCl concentration = 3 mol/L, reaction time = 1 h, solid–liquid ratio ≥ 0.03 g/ml, anodic current density = 1342 A/m 2 , stirring speed = 800 rpm. Under these experimental conditions, sphalerite concentrate can be oxidized efficiently. Furthermore, the electro-oxidation mechanism of sphalerite in weak alkaline NaCl solution has been studied. It was found that the elemental sulfur and the SO 4 2 − were the major existing forms of S from sphalerite and Zn would precipitate in the form of Na 2 Zn 3 (CO 3 ) 4 in the case where Na 2 CO 3 served as electrolyte pH regulator. To prevent SO 4 2 − from accumulating in the electrolyte and precipitate Zn as Zn(OH) 2 instead of Na 2 Zn 3 (CO 3 ) 4 , Na 2 CO 3 was replaced by Ca(OH) 2 to stabilize the pH of electrolyte, and the effect of the addition of Ca(OH) 2 on Zn recovery was investigated. [ABSTRACT FROM AUTHOR]

The flotation separation is the general method to recover molybdenite from a concentration containing molybdenite and bismuthinite, although the whole circuit could be long and complicated. In this paper, a novel selective electro-oxidation of molybdenite process has been introduced and systematically investigated for bismuthinite purification. It was found that Mo could be selectively separated by the electro-oxidation method under the conditions of pH not less than 9.0 and the applied potential at between 3.0 V and 4.0 V, by this circumstance Bi was hard to extract. The effects of NaCl concentration, liquid/solid ratio and stirring speed on electro-oxidation leaching were investigated. Optimum leaching conditions were found as follows: operated at room temperature, leaching time = 2.5 h, NaCl concentration = 4 mol/L, pH = 9–10, applied potential = 3.4 V, liquid/solid ratio = 30 mL/g, stirring speed = 400 rpm. Under these conditions, Mo extraction yield was obtained at 98.4% and 99.3% of Bi remained in the residue. The chlorine evolution reaction at the anode which was effected by leaching pH was studied by linear scan voltammetry. Mechanism of electro-oxidation leaching of Mo was studied by cyclic voltammetry. Furthermore, the mass transfer of Mo from leachate to organic phase was introduced, and the two phase transfer could obtain as high as 99.6%. [ABSTRACT FROM AUTHOR]

To explore the incidence and prognosis trends for high-grade cervical neuroendocrine tumor (HGCNET) and construct a nomogram to predict prognosis for HGCNET. Annual age-adjusted incidence of HGCNET from 1975 to 2015 was retrieved from the Surveillance, Epidemiology, and End Results program, the linear regression, poisson regression and annual percentage changes were used to assess the incidence trend. Also, trends for relative survival (RS) and overall survival (OS) in HGCNET patients from 1975 to 2015 were evaluated. From 1988 to 1975, 514 HGCNET patients were selected and divided into two cohorts with a ratio of 7:3. Nomogram to predict OS for these patients was constructed and validated. The incidence trend for HGCNET was unchanged in the past four decades (P = 0.734), but the proportion of HGCNET in diagnosed cervical cancer slightly increased from 0.9% in 1975 to 1.9% in 2015 (P < 0.001). The 5-year RS and OS for HGCNET in the study periods decreased steadily (RS: P = 0.009; OS: P = 0.008). Nomogram incorporating age, T stage, lymph-node positive, distant metastasis and surgery was constructed. The C-index of the nomogram was 0.716 (0.680-0.752), which was higher than the FIGO staging system. The incidence of HGCNET remained unchanged in the past four decades but the proportion of HGCNET has slightly increased. Besides, a steadily decreasing survival for HGCNET was observed in the study periods. A nomogram was constructed to better predict prognosis for HGCNET. [ABSTRACT FROM AUTHOR]

Background: To estimate conditional survival (CS) for high-risk early-stage cervical cancer patients with lymph node metastasis after hysterectomy. Methods: 1964 T 1-2 N 1 M 0 cervical cancer patients who underwent primary hysterectomy from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Result (SEER) Program. Univariate and multivariate cox regression analysis were used to identify independent risk factors. 5-year conditional disease-specific survival (CDS5) and 5-year conditional relative survival (CRS5) were estimated. CDS5 and CRS5 stratified by risk factors were further calculated. Results: CDS5 and CRS5 increased from 71.0% and 73.7% at 0-year to 89.2% and 91.7% at 5-year, respectively. Inversely, the actuarial disease-specific survival and RS dropped from 71.0% and 73.7% at 5-year to 63.3% and 67.6% at 10-year, respectively. Patients with unfavorable factors had a bigger gap between actuarial survival and CS. Both CDS5 and CRS5 curves across stratas of each prognostic factor had a tendency to level off with time elapsing. Notably, CRS5 couldn't exceed 95% even after 5-year follow-up except for patients with grade I disease (CRS5 at 5-year: 100%) or tumor size less than 2 cm (CRS5 at 5-year: 96%). Conclusion: CS increased over time while actuarial survival decreased as time passed. Patients with unfavorable factors had bigger improvement in CS than those with favorable factors. Excess mortality still existed in these patients after 5-year follow-up compared to the general population except for patients with grade I disease or tumor size <2 cm, who might gradually decrease follow-up times after 5-year. [ABSTRACT FROM AUTHOR]

Autophagy has been reported to play protective and pathogenetic roles in cerebral ischemia/reperfusion (I/R)-induced neuronal injury. Our previous studies have shown that TP53-induced glycolysis and apoptosis regulator (TIGAR) ameliorates I/R-induced brain injury and reduces anti-cancer drug-induced autophagy activation. However, if TIGAR plays a regulatory role on autophagy in cerebral I/R injury is still unclear. The purpose of the present study is to investigate the role of TIGAR on I/R-induced autophagy activation and ischemic neuronal injury in vivo and in vitro stroke models using TIGAR-transgenic (tg-TIGAR) mice and TIGAR-knockout (ko-TIGAR) mice. The present study confirmed that autophagy was activated after I/R. Overexpression of TIGAR in tg-TIGAR mice significantly reduced I/R-induced autophagy activation and alleviated brain damage, while knockout of TIGAR in ko-TIGAR mice enhanced I/R-induced autophagy activation and exacerbated brain injury in vivo and in vitro. The different activity of autophagy in tg-TIGAR and ko-TIGAR primary neurons after OGD/R were largely reversed by knockdown or re-expression of TIGAR in these neurons. The autophagy inhibitor 3-methyladenine (3-MA) partly prevented exacerbation of brain damage induced by ko-TIGAR, whereas the autophagy inducer rapamycin partially abolished the neuroprotective effect of tg-TIGAR. Knockout of TIGAR reduced the levels of phosphorylated mTOR and S6KP70, which were blocked by 3-MA and NADPH after I/R and OGD/R in vivo and in vitro, respectively. Overexpression of TIGAR increased the levels of phosphorylated mTOR and S6KP70 under OGD/R condition, this enhancement effect was suppressed by rapamycin. In conclusion, our current data suggest that TIGAR protected against neuronal injury partly through inhibiting autophagy by regulating the mTOR-S6KP70 signaling pathway. Image 1 • Overexpression TIGAR in TIGAR transgenic mice is neuroprotective in ischemic stroke models. • The negative impact of TIGAR on I/R-induced autophagy activation partly contribute to its neuroprotection in ischemic stroke. • TIGAR regulates I/R-induced autophagy activation through the mTOR-S6KP70 signaling pathway and control of ROS. [ABSTRACT FROM AUTHOR]

The Mw 6.1 2014 Ludian, Yunnan, China earthquake triggered numerous coseismic landslides that do not appear to be associated with any previously known seismogenic fault. Traditional models of triggering for seismically generated landslides do not provide a reasonable explanation for the landslide pattern observed here. Here the Newmark method is applied to a grid to calculate the minimum accelerations required for slope failures throughout the affected region. The results demonstrate that for much of the study area, the distribution of failure prone slopes is similar to the actual pattern of coseismic landslides, however there are some areas where the model predicts considerably fewer failures than occurred. We suggest that this is a result of the complex source faults that generated the Ludian earthquake, which produced a half-conjugate rupture on nearly EW- and NNW trending faults at depth. The rupture directed much of its seismic moment southeast of the epicenter, increasing ground shaking and the number of resulting landslides. [ABSTRACT FROM AUTHOR]

• Infection with BA.5 alone yielded moderate neutralization of D614G and its variants. • BA.5 breakthrough following heterologous booster increased neutralizing activity. • The antibody response to BA.5 was not affected by ancestral SARS-CoV-2 vaccination. • The effect of imprinting on the antibody response toward the ancestral strain. To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination. Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants. [ABSTRACT FROM AUTHOR]

Saline–alkaline stress is characterized by high salinity and high alkalinity (high pH); alkaline stress has been shown to be the primary factor inhibiting rice seedling growth. In this study, we investigated the potential priming effect of abscisic acid (ABA) on tolerance of rice seedlings to alkaline stress simulated by Na 2 CO 3 . Seedlings were pretreated with ABA at concentrations of 0 (control), 10, and 50 μM by root-drench for 24 h and then transferred to a Na 2 CO 3 solution that did not contain ABA. Compared to control treatment, pretreatment with ABA substantially improved the survival rate of rice seedlings and increased biomass accumulation after 7 days under the alkaline condition. ABA application at 10 μM also alleviated the inhibitory effects of alkaline stress on the total root length and root surface area. Physiologically, ABA increased relative water content (RWC) and decreased cell membrane injury degree (MI) and Na + /K + ratios. In contrast, fluridone (an ABA biosynthesis inhibitor) decreased the RWC and increased MI in shoots under the alkaline conditions. These data suggest that ABA has a potent priming effect on the adaptive response to alkaline stress in rice and may be useful for improving rice growth in saline–alkaline paddy fields. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Banxia (BX) is the dried tuber of Pinellia ternata (Thunb.) Breit., a commonly prescribed Chinese medicinal herb for the treatment of cough, phlegm, and vomiting in pregnant women. However, raw BX has been demonstrated to exert toxic effects on reproduction and the precise and comprehensive mechanisms remain elusive. Aim of the study We applied an iTRAQ (isobaric tags for relative and absolute quantitation, iTRAQ)-based proteomic method to explore the mechanisms of raw BX-induced fetal toxicity in mice. Materials and methods The mice were separated into two groups, control mice and BX-treated mice. From gestation days 6–8, the control group was treated with normal saline and the BX group was exposed to BX suspension (2.275 g/kg/day). Gastrulae were obtained and analyzed using the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multi-omics data analysis tool, OmicsBean ( http://www.omicsbean.cn ), was employed to conduct bioinformatic analysis of differentially abundant proteins (DAPs). Quantitative real-time PCR (qRT-PCR) and western blotting methods were applied to detect the protein expression levels and validate the quality of the proteomics. Results A total of 1245 proteins were identified with < 1% false discovery rate (FDR) and 583 protein abundance changes were confidently assessed. Moreover, 153 proteins identified in BX-treated samples showed significant differences in abundance. Bioinformatics analysis showed that the functions of 37 DAPs were predominantly related to nervous system development. The expression levels of the selected proteins for quantification by qRT-PCR or western blotting were consistent with the results in iTRAQ-labeled proteomics data. Conclusion The results suggested that oral administration of BX in mice may cause fetal abnormality of the nervous system. The findings may be helpful to elucidate the underlying mechanisms of BX-induced embryotoxicity. [ABSTRACT FROM AUTHOR]

Saline-alkaline (SA) stress is one of the major constraints to crop production worldwide. It is characterized by high salinity and high alkalinity (high pH), with the latter being the primary inhibiting factor to rice growth. We previously reported that pretreatment with abscisic acid (ABA) primed rice seedlings for enhanced tolerance to alkaline stress. In the present study, we conducted a 3-year field experiment to further assess the ABA-priming effect on the stress tolerance of rice plants in two paddy fields with different SA levels (field-A: non-reclaimed field, pH = 10.13 ± 0.009, EC 1:5 = 0.50 ± 0.004; field-B: reclaimed field, pH = 9.74 ± 0.005, EC 1:5 = 0.48 ± 0.001). Rice seedlings were treated with ABA at concentrations of 0 (control), 1, and 10 μM by root-drenching for 24 h prior to transplanting to the two paddy fields with different SA levels. Compared to the control treatment, ABA application substantially reduced the occurrence of leaf withering by 22%–50% and seedling death by 11%–17%. Further, ABA application also significantly improved subsequent plant growth and the final grain yield by 8%–55%; a more profound effect was observed in the harder SA field. Expressions of the ABA-responsive genes SalT and OsWsi18 were highly induced by ABA treatment, and the induced levels were sustained until at least 8 d after transplanting. Collectively, these results suggest a potent priming effect of ABA on the SA stress tolerance of rice plants, providing an effective and practical approach to improving rice production in SA paddy fields. [ABSTRACT FROM AUTHOR]

A new azasugar (3S,4S)-3-((R)-1,2-dihydroxyethyl)pyrrolidine-3,4-diol ( 1 ) was obtained from commercially available d -glucose using one-pot reductive cyclization as a key step. The target product, i.e., the iminosugar isomer, was obtained in 10 steps and 24.3% overall yield. Only three column chromatography purifications were needed in this synthesis. The biological activity of the target molecule as glycosidase inhibitor was studied, but the inhibitory activity against four glycosidases was not good (IC 50 > 100 μM). [ABSTRACT FROM AUTHOR]

Metabolic bone diseases, such as rheumatoid arthritis (RA) and osteoporosis, are characterized as imbalance between bone formation and bone resorption, leading to bone microarchitecture damage and bone mineral density loss. Bone loss is huge threat for older people's health, which imposes a heavy financial burden on patients and their families. However, the effectiveness of bone loss treatment in clinical practice is limited. With the understanding of the molecular and cellular regulators and mediators of bone remodelling, we know that some signaling pathways and inflammatory cytokines play important roles in the development of RA and osteoporosis. The increasing evidence showed that tumor necrosis factor (TNF)-like weak inducer of apoptosis (Tweak)/fibroblast growth factor-inducible 14 (Fn14) signalling controls a variety of cellular activities in biological processes, such as proliferation, differentiation, and apoptosis and has diverse biological functions in pathological mechanisms like inflammation that are associated with the process of bone metabolism. Recent studies suggest that the interactions between Tweak/Fn14 play critical roles in osteoblast and osteoclast differentiation and apoptosis, especially in those rheumatoid arthritis patients. These findings suggest that interventions targeting Tweak/Fn14 signaling pathway to regulate osteoblast–osteoclast coupling according to its biological effects, which results in promoting osteoblast formation and inhibiting osteoclast resorption, may be a promising approach for bone loss prevention and treatment in the near future. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cytogenetic analysis in 16 years for mother and fetus after radiation accident. [•] Dicentric and centric rings, micronuclei frequencies are continually declined. [•] Translocation aberration yields also dropped along with time. [•] Biodose estimated for prenatal exposure using dose correction factor of mother. [Copyright &y& Elsevier]