Functional trait-based phytoplankton biomass and assemblage analyses in the pre-growing season for comprehensive algal bloom risk assessment.

Algal bloom (AB) risk assessment is critical for maintaining ecosystem health and human sustainability. Previous AB risk assessments have focused on the potential occurrence of ABs and related factors in the growing season, whereas their hazards, especially in the pre-growing season, have attracted less attention. Here, we performed a comprehensive AB risk assessment, including water trophic levels, phytoplankton biomass, functional trait-based assemblages, and related environmental factors, in the pre-growing season in Dongting Lake, China. Although mesotrophic water and low phytoplankton biomass suggested low AB potential, toxic taxa, which constituted 13.28% of the phytoplankton biomass, indicated non-negligible AB hazards. NH4+ and water temperature were key factors affecting phytoplankton motility and toxicity. Our study establishes a new paradigm for quantitative AB risk assessment, including both potential AB occurrence and hazards. We emphasize the importance of phytoplankton functional traits for early AB warning and NH4+ reduction for AB control in the pre-growing season.

Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.

Modification and completion of geological structure knowledge graph based on pattern matching.

As a knowledge representation method, knowledge graph is widely used in intelligent question answering systems and recommendation systems. At present, the research on knowledge graph mainly focuses on information query and retrieval based on knowledge graph. In some domain knowledge graphs, specific subgraph structures (patterns) have specific physical meanings. Aiming at this problem, this paper proposes a method and framework of knowledge graph pattern mining based on gat. Firstly, the patterns with specific physical meaning were transformed into subgraph structures containing topological structures and entity attributes. Secondly, the subgraph structure of the pattern is regarded as the query graph, and the knowledge graph is regarded as the data graph, so that the problem is transformed into an approximate subgraph matching problem. Then, the improved relational graph attention network is used to fuse the adaptive edge deletion mechanism to realize the approximate subgraph matching of subgraph structure and attribute, so as to obtain the best matching subgraph. The proposed method is trained in an end-to-end manner. The approximate subgraph matching is realized on the existing data set, and the research work of key pattern mining of complex geological structure knowledge graph is carried out.

Construction of knowledge constraints: a case study of 3D structural modeling.

The uncertainty of structural interpretation complicates the practical production and application of data-driven complex geological structure modeling technology. Intelligent structural modeling excavates and extracts structural knowledge from structural interpretation through human-machine collaboration and combines structural interpretation to form a new model of complex structural modeling guided by knowledge. Specifically, we focus on utilizing knowledge rule reasoning technology to extract topological semantic knowledge from interpretive data and employ knowledge inference to derive structural constraint information from complex geological structure models, thus effectively constraining the 3D geological structure modeling process. To achieve this, we develop a rule-based knowledge inference system that derives theoretical models consistent with expert cognition from interpretive data and prior knowledge. Additionally, we represent the extracted knowledge as a topological semantic knowledge graph, which facilitates computer recognition and allows estimation of intersection lines during 3D geological modeling, resulting in the creation of accurate models. The applicability of our proposed method to various complex geological structures is validated through application tests using real-world data. Furthermore, our method effectively supports the realization of intelligent structure modeling in real working area.

In Situ Nanomechanics: Opportunities Based on Superplastic Nanomolding.

In situ nanomechanics, referring to the real-time monitoring of nanomechanical deformation during quantitative mechanical testing, is a key technology for understanding the physical and mechanical properties of nanoscale materials. This perspective reviews the progress of in situ nanomechanics from the aspects of preparation and testing of nanosamples, with a major focus on one-dimensional (1D) nanostructures and discussions of their challenges. We highlight the opportunities provided by in situ nanomechanics combined with the superplastic nanomolding technique, especially in the aspects of regulating physical and chemical properties which are highly exploitable for mechanoelectronics, mechanoluminescence, piezoelectronics, piezomagnetism, piezothermography, and mechanochemistry.

The effect of the bgs13 mutation on the structure of the reporter protein beta-lactoglobulin: Influence on folding and aggregation in Pichia pastoris.

Pichia pastoris, a methylotrophic yeast used for recombinant protein expression, has the capability of performing many eukaryotic post-translational modifications, growing to high cell densities, and producing proteins in a cost-effective manner. However, P. pastoris's secretion properties are not always efficient, and its secretory pathway mechanisms have not been thoroughly elucidated. A previously identified mutant strain, bgs13, was found to efficiently secrete most recombinant proteins tested, raising the possibility that this bgs13 mutant is a universal super secreter. In this study, we used a reporter protein, ß-lactoglobulin (b-LG), to perform structural analysis of the protein secreted from wild type and mutant bgs13 strains to investigate the secretory mechanism. Primary, secondary, and tertiary structures of b-LG were examined using Edman sequencing, circular dichroism, tryptophan fluorescence, and temperature induced aggregation analysis. Our results demonstrate that the bgs13 produced more b-LG than the wt strain and that this protein was functionally folded similar to the wt. Surprisingly, we also found that the bgs13 b-LG was more resistant to aggregation, providing another example of the superior qualities of this strain for enhanced secreted protein production.

Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A.

Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treatment. We demonstrate that a benzonaphthopyranone glycoside, chrysomycin A (ChryA), is a rapid bactericide that is highly active against S. aureus persisters, robustly eradicates biofilms in vitro, and shows a sustainable killing efficacy in vivo. ChryA was suggested to target multiple critical cellular processes. A wide range of genetic and biochemical approaches showed that ChryA directly binds to GlmU and DapD, involved in the biosynthetic pathways for the cell wall peptidoglycan and lysine precursors, respectively, and inhibits the acetyltransferase activities by competition with their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining multiple MoAs onto a single small molecule for treatments of S. aureus persistent infections.

Longitudinal surveillance of three biomarkers to predict recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha- fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. METHODS: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-II, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-II, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The generalized estimation equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) and overall survival (OS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Multivariate logistic regression models were used to analyze potential risk factors for recurrence. RESULTS: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-II and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-II, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-II, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5% respectively. The sensitivity in predicting recurrence for PIVKA-II, AFP, AFP-L3 and combination were 75.0, 54.7, 57.8 and 79.7% respectively. The RFS and the OS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers ( P  < 0.001). Multivariate analysis showed that any of the biomarkers elevated was the independent risk factor of recurrence. CONCLUSION: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.

Liquid metal for high-entropy alloy nanoparticles synthesis.

High-entropy alloy nanoparticles (HEA-NPs) show great potential as functional materials1-3. However, thus far, the realized high-entropy alloys have been restricted to palettes of similar elements, which greatly hinders the material design, property optimization and mechanistic exploration for different applications4,5. Herein, we discovered that liquid metal endowing negative mixing enthalpy with other elements could provide a stable thermodynamic condition and act as a desirable dynamic mixing reservoir, thus realizing the synthesis of HEA-NPs with a diverse range of metal elements in mild reaction conditions. The involved elements have a wide range of atomic radii (1.24-1.97 Å) and melting points (303-3,683 K). We also realized the precisely fabricated structures of nanoparticles via mixing enthalpy tuning. Moreover, the real-time conversion process (that is, from liquid metal to crystalline HEA-NPs) is captured in situ, which confirmed a dynamic fission-fusion behaviour during the alloying process.

Mechanisms of conservation tillage on nitrogen-fertilizer reduction and maize grain improvement in Mollisols of Northeast China: Insights from a 15N tracing study.

Conservation tillage is an important management practice to guarantee soil fertility in degraded Mollisols. It is still unclear, however, whether the improvement and stability of crop yield under conservation tillage can be sustainable with increasing soil fertility and reducing fertilizer-N application. Based on a long-term tillage experiment initiated in Lishu Conservation Tillage Research and Development Station by Chinese Academy of Sciences, we conducted a 15N tracing field micro-plot experiment to investigate the effects of reducing nitrogen application on maize yield and fertilizer-N transformation under long-term conservation tillage agroecosystem. There were four treatments, including conventional ridge tillage (RT), no-tillage with 0% (NT0), 100% (NTS) maize straw mul-ching, and 20% reduced fertilizer-N plus 100% maize stover mulching (RNTS). The results showed that after a complete cultivation round, the average percentages of fertilizer N recovery in soil residues, crop usage, and gaseous loss were 34%, 50%, and 16%, respectively. Compared with conventional ridge tillage, no-tillage with maize straw mulching (NTS and RNTS) significantly increased the use efficiency of fertilizer N in current season by 10% to 14%. From the perspective of N sourcing analysis, the average percentage of fertilizer N absorbed by crop parts (including seeds, straws, roots, and cobs) to the total N uptake reached nearly 40%, indicating that soil N pool was the main source of N for crop uptakes. In comparison with conventional ridge tillage, conservation tillage significantly increased total N storage in 0-40 cm by reducing soil disturbance and increasing organic inputs, and thus ensured the expansion and efficiency increment of soil N pool in degraded Mollisols. Compared with conventional ridge tillage, NTS and RNTS treatments significantly increased the maize yield from 2016 to 2018. In all, by improving fertilizer nitrogen utilization efficiency and maintaining the continuous supply of soil nitrogen, long-term management of no-tillage with maize straw mulching could achieve a stable and increasing maize yield in three consecutive growing seasons and simultaneously reduce environmental risks derived by fertilizer-N losses, even under the condition of 20% reduction of fertilizer-N application, and thus actualize the sustainable development of agriculture in Mollisols of Northeast China.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

A Cadaveric Limb Analysis of the Posterior Tibial Musculotendinous Junction to determine the feasibility of Interosseous Membrane Tendon Transfer.

The transfer of the posterior tibial tendon through the interosseous membrane is potentially an effective treatment to correct the deformity of the foot and ankle. Our study aimed to evaluate the anatomical feasibility of anterior transfer of the posterior tibial tendon through the interosseous membrane route using the musculotendinous junction (MTJ). Eighteen adult cadavers were used. The width and thickness of the tibial posterior MTJ, width of the interosseous membrane at the corresponding level, and the window size of the interosseous membrane were measured. Additionally, the distance between the distal end of the MTJ and the tip of the medial malleolus were recorded. The mean length of the posterior tibial tendon was 83.60 mm, the mean distance of the posterior tibial MTJ to medial malleolus tip was 45.48 mm and the mean length of MTJ was 31.74 mm. The mean width of distal end of MTJ was 7.76 mm, thickness of distal end of MTJ was 4.07 mm and the mean width of the interosseous membrane at the distal end of MTJ was 4.76 mm. We found the mean width of the proximal end of MTJ was 20.68 mm, the mean thickness of proximal end of MTJ was 5.52 mm, and mean width of interosseous membrane at the proximal end of MTJ was 8.76 mm. Our study has demonstrated that a 31 mm length incision made at approximately 45 mm from the proximal end of the medial malleolus can safely reach the MTJ. We recommend an opening length of the interosseous membrane of at least 20 mm.

Effect of acupoint stimulation assisted anesthetics on the agitation during recovery and the levels of serum opioids and amyloid A in elderly patients after hip fracture surgery / 中国医师进修杂志

Objective:To investigate the effect of acupoint stimulation assisted anesthesia on the agitation during recovery and the levels of serum opioids (Opiorphin) and amyloid A (SAA) in elderly patients after hip fracture surgery.Methods:Eighty-six older patients who underwent hip fracture surgery in Shaoxing Second Hospital from February 2020 to September 2021 were randomly divided into the routine group and the research group, each with 43 patients. They were given acupoint sham stimulation and acupoint stimulation respectively, and the general indexes of the two groups, recovery quality, cognitive function and changes in serum Opiorphin and SAA levels were compared.Results:There were no differences in operation time, anesthesia time, recovery time and intraoperative blood transfusion between the two groups ( P>0.05). The dosage of remifentanil in the research group was significantly lower than that in the routine group: (270.64 ± 17.62) μg vs. (291.82 ± 23.34) μg, P<0.05. The incidence of agitation during the recovery period in the research group was significantly lower than that in the routine group: 13.95% (6/43) vs. 48.84% (21/43), P<0.05. The mini-mental state examination (MMSE) scores in the research group at 12, 24 and 48 h after operation were significantly higher than those in the routine group: (22.80 ± 2.04) scores vs. (19.31 ± 3.61) scores, (24.92 ± 2.44) scores vs. (21.49 ± 3.58) scores, (26.73 ± 2.57) scores vs. (24.23 ± 3.95) scores, there were statistical differences ( P<0.05). The serum Opiorphin level at 24 h after operation in the research group was higher than that in the routine group: (32.74 ± 8.57) mg/L vs. (25.40 ± 6.36) mg/L; and the SAA level was lower than that in the routine group: (157.36 ± 10.24) mg/L vs. (204.37 ± 15.56) mg/L, there were statistical differences ( P<0.05). Conclusions:Acupoint stimulation adjuvant anesthesia can reduce the occurrence of agitation during the recovery period of elderly patients with hip fracture, reduce the dosage of anesthetics, reduce postoperative cognitive impairment, regulate serum Opiorphin and SAA levels, and help early postoperative recovery.

Numerical and Field Investigations of Acoustic Emission Laws of Coal Fracture under Hydro-Mechanical Coupling Loading.

Taking coal under hydro-mechanical coupling as the research object, the discrete element software PFC3D (particle flow code) was used to analyze the relationships among the force, acoustic emission (AE), and energy during coal fracture. Based on the moment tensor (MT) inversion, we revealed the AE event distribution and source type during crack initiation and propagation until the final failure of coal. Meanwhile, we examined the relationships among the stress, number and type of cracks, magnitude, KE, and b value of AE under different water and confining pressures. The results show that the numerical simulation can effectively determine the microscopic damage mechanism of coal under different conditions. Moreover, the rupture type of the numerical simulation is consistent with the field investigations, which verifies the rationality of the simulation. These research results can provide reference for safety production evaluation of water inrush mines.

Predictive Value of the TP53 p.G245S Mutation Frequency for the Short-Term Recurrence of Hepatocellular Carcinoma as Detected by Pyrophosphate Sequencing.

Aims: We explored the relationship between the mutation at the p.G245S site in TP53 and the short-term recurrence of hepatocellular carcinoma (HCC). Materials and Methods: 101 HCC patients were included in this study. The TP53 p.G245S mutation frequency spectrum was examined by direct sequencing of genomic DNA from tissue specimens of HCC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the independent prognostic factors of tumor recurrence. ROC curve analysis was applied to determine the cut-off value for the p.G245S mutation frequency and to verify the predictive ability of the Cox model compared with single risk factor indices. Results: A multivariate Cox regression analysis showed that TP53 p.G245S mutation frequency (HR = 1.231, 95% CI: 1.006-1.505, p = 0.043), AFP (HR = 2.432, 95% CI: 1.297-4.561, p = 0.006), MTM (HR = 2.656, 95% CI: 0.930-7.583, p = 0.068), and PVTT (HR = 14.297, 95% CI: 3.085-66.243, p = 0.001) were independent prognostic factors for short-term recurrence. The cut-off value for the TP53 p.G245S mutation frequency (18.5%) was determined by ROC analysis. A predictive model integrating the TP53 p.G245S mutation frequency with PVTT, MTM, and AFP values appears to an excellent predictive indicator of short-term recurrence in HCC patients (AUC = 0.849, 95% CI = 0.748-0.950, p = 0.000001). Survival analysis indicated that the probability of short-term recurrence-free survival was significantly different among different TP53 p.G245S mutation frequency, MTM, PVTT, and AFP risk groups (p < 0.05). Conclusion: The mutation frequency of the p.G245S site is a novel prognostic risk factor for the short-term recurrence of HCC.

Indirect herbivore biomanipulation may halt regime shift from clear to turbid after macrophyte restoration.

Eutrophication transforms clear water into turbid water in shallow lakes. Current restoration techniques focus on re-establishing the clear-water state rather than on its maintenance. We investigated the response of submerged macrophytes to temporary grass carp (Ctenopharyngodon idella) and scraping snail (Bellamya aeruginosa) introductions. We also explored the impacts of herbivores on underwater light conditions to identify their long- and short-term potential to halt regime shift from clear to turbid after clear-water state reestablishment. Herbivores reduced both the biomass of submerged macrophytes and accumulated nutrients in the tissue of submerged macrophytes. This potentially avoided the pulse of endogenous nutrient release which would have exceeded the threshold required for the regime shift from clear to turbid. However, herbivores had a non-significant impact on submerged macrophyte-reduced light attenuation coefficient, which has a positive linear relationship with water chlorophyll a. Further, grass carp and snails enhanced the inhibition ratio of submerged macrophytes to phytoplankton by 3.96 and 2.13 times, respectively. Our study provides novel findings on the potential of herbivore introduction as an indirect biomanipulation tool for halting the regime shift of shallow lakes from clear to turbid after the restoration of submerged macrophytes.

Research on instability characteristics and precursory effect of coal-rock parting-coal structures.

The slip and instability mechanisms of coal-rock parting-coal structures under uniaxial loading conditions were investigated using experiments and case verification. The slip and the corresponding precursors were described by monitoring the displacement, strain, and acoustic emissions (AEs) of coal and rock parting blocks during testing, and the experimental results were verified by analyzing the microseismic (MS) effects during the working face advancing in a coal seam bifurcation area. The main conclusions were as follows: (1) each slip of the discontinuities sandwiched between coal and rock parting produced shear and tensile cracks, but the shear cracks was dominant; (2) for the instability mode that was characterized by low peak stress, high energy release, and a stable b value of AE, each slip corresponds to a peak frequency of AE, which can reveal the final instability mode; (3) the sudden drop in the fault total area of AE can be regarded as a precursor for the warning fracture or slip instability of a discontinuity; and (4) the MS events in the coal seam bifurcation area were mainly characterized by a wide frequency and high amplitude, especially near the coal bifurcation line, where there were obvious characteristics of low-frequency shear fracture for the MS events. This study is relevant for the early warning of coal-rock dynamic disasters triggered by the slip, fracture, and instability of coal-rock parting compound structures in coal mines.

Synthesis of multi-branched Au nanocomposites with distinct plasmon resonance in NIR-II window and controlled CRISPR-Cas9 delivery for synergistic gene-photothermal therapy.

Clinical implementation of photothermal therapy (PTT) is mainly hampered by limited tissue penetration, undesirable thermal damage to normal tissues, and thermotolerence induced by heat shock proteins (HSPs). To overcome these obstacles, we constructed a novel gene-photothermal synergistic therapeutic nanoplatform composed of a multi-branched Au nanooctopus (AuNO) core and mesoporous polydopamine (mPDA) shell, followed by CRISPR-Cas9 ribonucleoprotein (RNP) loading and then polyethylene glycol-folic acid (PEG-FA) coating. AuNO was simply synthesized by adjusting the ratio of cetyltrimethylammonium chloride (CTAC) and cetyltrimethylammonium bromide (CTAB), which showed significant localized surface plasmon resonances in the NIR-II window, and exhibited an excellent tissue penetration capability and high photothermal conversion efficiency (PCE, 47.68%). Even, the PCE could be further increased to 66.17% by mPDA coating. Furthermore, the sequential modification of AuNO@mPDA using RNP and PEG-FA can down-regulate HSP90α expression at tumor sites, enhance apoptosis and reduce the heat resistance of cancer cells. The synergistic effect of enhanced photothermal capacity and reduced thermoresistance addressed the multiple limitations of PTT, and presented excellent in vitro and in vivo antitumor efficacy, having great potential for the clinical application of PTT.

A New C22-Quassinoid with Anti-Pancreatic Adenocarcinoma Activity from Seeds of Brucea javanica.

An undescribed C22-quassinoid named sergeolide A (1) and fifteen known quassinoids (2-16) were obtained from the seeds of Brucea javanica (Simaroubaceae). All chemical structures were established based on spectroscopic data and X-ray diffraction analysis. Sergeolide A (1) is the first example of a naturally occurring C22-quassinoid bearing a butenolide group fused the A ring of the bruceolide skeleton from Brucea genus. And this is the first report of the NMR data for desmethyl-bruceines B (2) and C (3) and the crystal structure for bruceolide (11). In addition, all isolates were evaluated for their anti-pancreatic adenocarcinoma activity by measuring the growth inhibitory of the MIA PaCa-2 cell lines. Consequently, compounds 1, 7-10, and 12-16 exhibited potent anti-pancreatic cancer activity in vitro (IC50 =0.054∼0.357 µM).

High-fat diet promotes colorectal carcinogenesis through SERCA2 mediated serine phosphorylation of Annexin A2.

Colorectal cancer (CRC) is a highly common malignancy, being the third leading cause of cancer death worldwide. Recent epidemiological studies have indicated that carcinogenic effect of diet was mainly attributed to high-fat diets. To investigate the mechanism of high-fat diet-induced colorectal cancer, we systematically quantified the phosphoproteome in human HT-29 cells treated with sodium palmitate (PA). p-Annexin A2 (S26) was predicted to be specifically up-regulated by PA. We confirmed that PA-induced Annexin A2 phosphorylation at Ser26 in C57BL/6 J-ApcMin/J mice fed with high-fat diet. Phosphorylation of Annexin A2 at Ser26 promotes PA-induced proliferation of HT-29 cells. Moreover, PA suppressed SERCA activity and SERCA2 expression was compensatorily increased. Mechanistically, SERCA2 can partially reverse Annexin A2 phosphorylation at Ser26 caused by PA through intracellular calcium release. Finally, SERCA2 knockdown inhibited high-fat diet-induced tumor growth and Annexin A2 phosphorylation at Ser26 in SCID mice. In all, our studies demonstrate that high-fat diet promotes colorectal carcinogenesis through SERCA2 mediated serine phosphorylation of Annexin A2.