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The microstructure and materials performance of Laser Powder Bed Fusion-fabricated (LPBFed) NiTi shape memory alloys (SMAs) varies depending on the laser parameters and building directions. This study initially optimized the laser processing parameters (laser power and scanning speed) for LPBFed NiTi SMAs to enhance their printing quality and mechanical properties. We determined that with fixed hatch spacing of 80 μm and layer thickness of 30 μm, the laser power of 105 W, and scanning speed of 600 mm/s produced the best results. Subsequently, the corrosion behavior of LPBFed NiTi SMAs built in three different building directions (0°, 45°, 90°) was investigated in 0.9 wt% NaCl solution at 37 °C. The electrochemical data revealed that the corrosion current density (Icorr) decreased with increasing building direction angle (Icorr-90° < Icorr-45° < Icorr-0°). The corrosion resistance followed the order of 0° sample < 45° sample < 90° sample. These findings were attributed to the difference in the grain size and boundary density. Higher boundary densities enhanced the electron activity capacity and the element diffusion rates, facilitating the rapid formation of a protective film and thus improving the corrosion resistance. This new insight into the anisotropy of corrosion behavior relative to building directions can inform the design of NiTi-SMA products and improve their reliability in tissue engineering applications.

Summary: Background: Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder affecting numerous females worldwide. Dysbiosis of gut microbiota has been linked to the occurrence of PCOS; however, research into the characteristics of gut microbiota in PCOS patients, especially those from different regions and with different testosterone level, remains limited. Additionally, it is still unclear whether gut microbiota helps to distinguish different PCOS subtypes. Methods: We searched four electronic databases (PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov) from Jan 1, 2010 to May 1, 2024. This combined analysis included studies providing the raw data of gut microbiota in PCOS patients. We reanalyzed the characteristics of gut microbiota in PCOS patients from different regions and with different testosterone level. Findings: Fourteen publications satisfying the inclusion criteria were included in the combined analysis. Based on data from 948 individuals, we found alpha-diversity was not significantly different between PCOS and healthy control (HC) groups. However, gut microbiota composition was distinct in PCOS patients compared with healthy individuals. Specifically, Fusobacterium, Ruminococcus_gnavus_group, and Escherichia-Shigella increased, while Dysosmobacter, Schaedlerella, Merdimonas, Clostridiisalibacter, Flintibacter et al. decreased in PCOS women. Regionally, Alistipes was enriched in primarily European patients, while Blautia and Roseburia were more abundant in Chinese patients. Subtype analysis revealed that the gut microbiota of PCOS patients with higher testosterone level (PCOS-HT) differed significantly from those with lower testosterone level (PCOS-LT). Prevotella, Blautia, Dialister, Ruminococcus_torques_group and UCG-002 were enhanced in PCOS-HT patients, while Alistipes, Dysosmobacter, Phocaeicola and Faecalibacterium were diminished. Importantly, a set of eight genera effectively differentiated PCOS-HT patients from PCOS-LT patients with an AUC of 0.95. Interpretation: This systematic anatomization of gut microbiota revealed the microbial characteristics of PCOS patients, particularly those with different testosterone level, thus laying the foundations for further research into pathogenesis of PCOS, and the development of effective diagnostic, treatment, and intervention strategies. Funding: This work was supported by the National Natural Science Foundation of China (No. 81973217, 82260304), the Hainan Province Clinical Medical Center (QWYH202175), and the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202311).

PD-1/PD-L1 is an important signaling pathway in the adaptive immune system. The CD47/SIRPα signaling pathway is a crucial “do not eat me” signal for innate immunity. This study evaluated the anti-tumor mechanism of IMM2520 in vitro and in vivo. IMM2520 was generated using the “mab-trap” platform. IMM2520 showed high affinity to PD-L1 and relatively lower affinity to CD47, displaying preferential binding to PD-L1 on tumor cells. IMM2520 had the potent ability to inhibit the PD-1/PD-L1 and CD47/SIRPα signaling pathways and killed tumor cells through ADCC and ADCP. Importantly, IMM2520 did not bind to human red blood cells or induce erythrocyte agglutination. IMM2520 demonstrated a tendency to bind to CD47+/PD-L1+ tumor cells, reducing its binding to CD47 single-positive cells. In mouse transplantation models, compared with the first-generation CD47/PD-L1 BsAb (IMM2505), IMM2520 exhibited stronger and dose-dependent antitumor activity. These findings imply that IMM2520 may offer a novel therapeutic alternative for cancer patients.

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1–3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

Background: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. Methods: We retrospectively analysed patients with stage IIIA–IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. Findings: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. Interpretation: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

Introduction: Zearalenone-14-glucoside (Z14G) is a modified mycotoxin that widely contaminates food across the world. Our preliminary experiment showed that Z14G degrades to zearalenone (ZEN) in the intestine exerting toxicity. Notably, oral administration of Z14G in rats induces intestinal nodular lymphatic hyperplasia. Objectives: To investigate the mechanism of Z14G intestinal toxicity and how it differs from ZEN toxicity. We conducted a precise toxicology study on the intestine of rats exposed to Z14G and ZEN using multi-omics technology. Methods: Rats were exposed to ZEN (5 mg/kg), Z14G-L (5 mg/kg), Z14G-H (10 mg/kg), and pseudo germ free (PGF)-Z14G-H (10 mg/kg) for 14 days. Histopathological studies were performed on intestines from each group and compared. Metagenomic, metabolomic, and proteomic analyses were performed on rat feces, serum, and intestines, respectively. Results: Histopathological studies showed that Z14G exposure resulted in dysplasia of gut-associated lymphoid tissue (GALT) compared to ZEN exposure. The elimination of gut microbes in the PGF-Z14G-H group alleviated or eliminated Z14G-induced intestinal toxicity and GALT dysplasia. Metagenomic analysis revealed that Z14G exposure significantly promoted the proliferation of Bifidobacterium and Bacteroides compared to ZEN. Metabolomic analysis showed that Z14G exposure significantly reduced bile acid, while proteomic analysis found that Z14G exposure significantly reduced the expression of C-type lectins compared to ZEN. Conclusions: Our experimental results and previous research suggest that Z14G is hydrolyzed to ZEN by Bifidobacterium and Bacteroides promoting their co-trophic proliferation. This leads to inactivation of lectins by hyperproliferative Bacteroides when ZEN caused intestinal involvement, resulting in abnormal lymphocyte homing and ultimately GALT dysplasia. It is noteworthy that Z14G is a promising model drug to establish rat models of intestinal nodular lymphatic hyperplasia (INLH), which is of great significance for studying the pathogenesis, drug screening and clinical application of INLH.

Canavan disease (CD, OMIM# 271900) is an autosomal recessive neurodegenerative disorder caused by homozygous or compound heterozygous mutations in ASPA gene, which result in catalytic deficiency of the aspartoacylase enzyme and the accumulation of N-acetylaspartic acid (NAA). Clinical presentation varies according to the age of disease onset. Here, we generated a human induced pluripotent stem cell line (hiPSCs) SDQLCHi064-A from a 5-month old boy with CD carrying two novel frame shift mutations c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) of the ASPA gene, in order for us to better understanding the disease.

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, #615075), a rare autosomal dominant genetic disorder caused by heterozygous mutation in the CTNNB1 gene, is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Here, we established an iPSC line (SDQLCHi055-A) from a patient with NEDSDV carrying a heterozygote mutation (c.854 T > A, p.L285*) in the CTNNB1 gene. The iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.

Nickel-titanium (NiTi) is the most ordinarily used shape memory alloy (SMAs), which has important implications in aerospace, medical devices and so on. However, NiTi parts were limited in their application scope and ability due to the difficulty of processing. Until the appearance of laser powder bed fusion (LPBF) technology, it overcame NiTi alloy preparation's multiple challenges and became the preferred method to fabricate NiTi alloy. Nevertheless, the NiTi parts fabricated by LPBF that have a great shortage still exist in corrosion resistance. Therefore, in this paper, a series of micro-nano structures with different characteristics were constructed in LPBF-NiTi by orthogonal experiment for the first time, which wants to explore the degree of influence of various parameters on the wettability of samples. After variance analysis, the nanolaser processing parameters which are most suitable for constructing lotus leaf structures on NiTi alloy surfaces are obtained. The surface morphology and composition were studied by SEM, XRD, EDS, and XPS, respectively. Finally, the corrosion resistance of samples was tested by electrochemical analysis. The results show that the laser power during processing has the greatest influence on the surface morphology of LPBF-NiTi alloy. And the wettability is affected by surface morphology and –CF/-CF2 adsorption. Furthermore, we compared the corrosion resistance of the superhydrophobic samples which was obtained based on the variance analysis with that of the substrate in 3.5 wt% NaCl solution. The result shows that the corrosion resistance and corrosion stability of superhydrophobic samples are brilliantly increased compared with the substrate.

Mulberry leaf has potential in lipid-lowering. Here, we compared the chemical composition and lipid-lowering effects of different mulberry leaf-derived teas, and investigated their underlying gut microbiome-related mechanisms. The main components of mulberry leaf-derived tea were flavonoids, phenolic acids and alkaloids, with green tea (0.60% polyphenols, 3.35% polysaccharides, 0.20% DNJ) containing higher levels than black tea (0.40% polyphenols, 2.95% polysaccharides, 0.15% DNJ). Accordingly, the lipid-lowering efficacy of green tea was superior to that of black tea in high-fat (HFD)-induced hyperlipidemic mice. Black tea increased 2 genera and 130 metabolites, decreased 6 genera and 90 metabolites, while green tea increased 5 genera and 127 metabolites, decreased 15 genera and 64 metabolites. Correlation analysis showed that the alterations of gut microbiota and metabolic profiles caused by mulberry leaf tea were tightly associated with its lipid-lowering effect. Altogether, this study provided a promising functional food targeting gut microbiota for the management of lipid metabolism.

AUTS2 syndrome is a neurodevelopmental disorder caused by pathogenic variants and deletions of the AUTS2 gene, resulting in intellectual disability, microcephaly, and other phenotypes. Here, we generated a human induced pluripotent stem cell (iPSC) line from a 21-month-old boy with AUTS2 syndrome caused by a heterozygous mutation (c.1486C > T, p.Q496X) in the AUTS2 gene. The iPSCs had normal morphology and karyotype, expressed pluripotency markers, showed differentiation potential in vitro, and carried the AUTS2 gene mutation.

Introduction: Acute myocardial infarction (AMI) accounts for the majority of deaths caused by coronary artery disease (CAD). Early warning of AMI, especially for patients with stable coronary artery disease (sCAD), is urgently needed. Our previous study showed that alterations in the gut microbiota were correlated with CAD severity. Objectives: Herein, we tried to discover accurate and convenient biomarkers for AMI by combination of gut microbiota and fecal/blood/urinary metabolomics. Methods: We recruited 190 volunteers including 93 sCAD patients, 49 AMI patients, and 48 subjects with normal coronary artery (NCA), and measured their blood biochemical parameters, 16S rRNA-based gut microbiota and NMR-based fecal/blood/urinary metabolites. We further selected 20 subjects from each group and analyzed their gut microbiota by whole-metagenome shotgun sequencing. Results: Multi-omic analyses revealed that AMI patients exhibited specific changes in gut microbiota and serum/urinary/fecal metabolites as compared to subjects with sCAD or NCA. Fourteen bacterial genera and 30 metabolites (11 in feces, 10 in blood, 9 in urine) were closely related to AMI phenotypes and could accurately distinguish AMI patients from sCAD patients. Some species belonging to Alistipes, Streptococcus, Ruminococcus, Lactobacillus and Faecalibacterium were effective to distinguish AMI from sCAD and their predictive ability was confirmed in an independent cohort of CAD patients. We further selected nine indicators including 4 bacterial genera, 3 fecal and 2 urinary metabolites as a noninvasive biomarker set which can distinguish AMI from sCAD with an AUC of 0.932. Conclusion: Combination of gut microbiota and fecal/urinary metabolites provided a set of potential useful and noninvasive predictive biomarker for AMI from sCAD.

Introduction: Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. Objectives: This study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. Methods: The correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. Results: Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. Conclusion: The gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

Selective laser melting (SLM)-fabricated NiTi alloys have attracted widespread interest because they can achieve high-precision preparation of implant materials with complex structures. However, as an implant material, SLM-NiTi alloy exhibits poor osteogenic and excessive release of Ni ions. In this investigation, a bioactive dicalcium phosphate dihydrate (DCPD) coating was prepared on the surface of SLM-NiTi alloy by electrodeposition for the first time to improve the biocompatibility and corrosion resistance of the SLM-NiTi alloys. The influence of coating preparation parameters (deposition current and deposition time) on morphology and corrosion resistance had been studied by SEM, electrochemical and immersion tests. The DCPD coating obtained when the deposition current was 3 mA and the deposition time was 30 min showed a uniform and dense morphology and had the best corrosion resistance, which the corrosion current density Icorr was three orders of magnitude lower than that of SLM-NiTi alloy. Moreover, as the precursor of hydroxyapatite (HA), DCPD effectively promoted the deposition of HA, thus improving the biomineralization property of the SLM-NiTi alloy. The in vitro cell experiments showed that the DCPD coating provided a good interface and microenvironment for the growth and adhesion of osteoblasts. Good corrosion resistance, biocompatibility and biomineralization properties render the DCPD coated SLM-NiTi alloys have great clinical application prospects as biomedical implants.

In this study, peripheral blood mononuclear cells were isolated from a young male patient bearing a histone deacetyl-lase 8 (HDAC8) mutation and suffering from Cornelia de Lange Syndrome verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, and expressed pluripotent stem cell markers at the mRNA and protein level. The iPSCs also showed differentiative capacity in vitro, and a normal karyotype. In addition, the established iPSCs still carried the HDAC8 mutation observed in the donor tissue.

Summary: Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE−/− mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.

Summary: Background: Tigecycline is one of the few last-resort antibiotics for the treatment of carbapenem-resistant Enterobacteriaceae infection, the incidence of which has been rapidly increasing. However, the emergence and spread of tigecycline resistance genes tet(X) (including tet(X3) and tet(X4)) has largely compromised the efficient usage of tetracyclines in the clinical settings. Methods: The synergistic effect was determined by a checkerboard minimum inhibitory concentration (MIC) assay, a time-killing assay and scanning electron microscopy (SEM) analysis. In-depth mechanisms were defined using an enzyme inhibition assay, western blotting, RT-PCR analysis, molecular dynamics (MD) simulations, biolayer interferometry (BLI) assay and metabolomics analysis. Findings: Herein, our work identified a natural compound, plumbagin, as an effective broad-spectrum inhibitor of Tet(X) (also known as monooxygenase) by simultaneously inhibiting the activity and the production of Tet(X3)/Tet(X4). Plumbagin in combination with tetracyclines showed a synergistic bactericidal effect against Tet(X3)/Tet(X4)-producing bacteria. Mechanistic studies revealed that direct engagement of plumbagin with the catalytic pocket of Tet(X3)/Tet(X4) induced an alternation in its secondary structure to inhibit the activity of these monooxygenases. As a consequence, monotherapy or combination therapy with plumbagin increases the oxidative stress and metabolism in bacteria. Moreover, in a mouse systemic infection model of tet(X4)-positive E. coli, the combination of plumbagin and methacycline exhibited remarkable treatment benefits, as shown by a reduced bacterial load and the alleviation of pathological injury. Interpretation: Plumbagin, as an inhibitor of Tet(X3)/Tet(X4), represents a promising lead drug, as well as an adjunct with tetracyclines to treat bacterial infections, especially for extensively drug-resistant bacteria harbouring Tet(X3)/Tet(X4). Funding: The National Natural Science Foundation of China.

Effective and safe contrast agents for X-ray computed tomography (CT) imaging of the gastrointestinal (GI) tract are quite desirable for realizing high diagnostic accuracy and low toxicity in the clinic. Herein, we synthesize a series of silica-coated bismuth sulfide core-shell nanomaterials (Bi2S3@SiO2) of various sizes and systematically study their GI CT contrast performance and potential toxic effects in comparison with those of barium sulfate (BaSO4) in mice. The in vivo experimental results suggest that these Bi2S3@SiO2 core-shell nanomaterials display superior CT contrast performance and higher elimination efficacy than BaSO4 by single-dose exposure manner (10 ​mg/kg Bi element/b.w. for Bi2S3@SiO2 versus 30 ​mg/kg Ba element/b.w. for BaSO4). Furthermore, 28 days after exposure, Bi2S3@SiO2 core-shell nanomaterials show minimal toxic effects in vivo and nonsignificant influences on the structure and function of the gut microbiota in mice. This demonstrates that no adverse effects on the gut homeostasis are induced by Bi2S3@SiO2 core-shell nanomaterials and, thus, suggests that they can act as excellent and safe CT contrast agents for GI tract imaging.

In this study, peripheral blood monouclear cells (PBMCs) were donated from a boy suffering from familial combined hyperlipidemia confirmed by clinical and genetic diagnosis, which carried compound heterozygous mutations of lipoprotein lipase (LPL) gene. The induced pluripotent stem cell (iPSC) was generated with non-integrated episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The iPSCs presented the morphology of pluripotent cells, highly expressed mRNA and protein of pluripotent markers, excellent differentiation potency in vitro and normal karyotype, and bore LPL gene mutations.

Interactions between organic matter (OM) and metals in soils are important natural mechanisms that can mitigate metal bioaccumulation in terrestrial environments. A primary source of OM in soils is straw return, accounting for more than 65% of OM input. Straw-OM has long been believed to reduce metal bioaccumulation, e.g., by immobilizing metals in soils. However, there is growing evidence that straw return could possibly enhance bioavailability and thus risks (i.e., food safety) of some metals in crops, including Cd, Hg, and As. Poor understanding of straw return-induced increases in metal bioavailability would add uncertainty in assessing or mitigating risks of metals in contaminated farming soils. Here, 863 pieces of literature (2000–2019) that reported the effects of straw return on metal bioavailability and bioaccumulation were reviewed. Mechanisms responsible for the increased metal mobility and bioavailability under straw return are summarized, including the effects of dissolution, complexation, and methylation. Effects of straw return on the physiology and the absorption of metals in plants is also discussed (i.e., physiological effect). These mechanisms are then used to explain the observed increases in the mobility, bioavailability, and bioaccumulation of Cd, Hg, and As under straw amendment. Information summarized in this study highlights the importance to re-consider the current straw return policy, particularly in metal-contaminated farmlands.

Three new thionic compounds, (S)-2-(2-carboxyl-2-hydroxyethylthio)-ferulic acid (1), (E)-2-methoxy-4-(3-(methylsulfonyl)prop-1-en-1-yl)phenol (2), and thiosenkyunolide C (3), together with two new aromatic glycosides (4 and 5) were isolated from the rhizome of Ligusticum chuanxiong Hort. Two known compounds (6 and 7) were also obtained. Their structures were elucidated based on extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HR-ESI-MS). Furthermore the absolute configurations were established by comparison of their calculated and experimental circular dichroism spectra and by a dimolybdenum tetraacetate [Mo2(AcO)4]-induced circular dichroism procedure. All compounds were evaluated against lipopolysaccharide (LPS)-induced NO production in BV2 cells, and compounds 4 and 5 showed strong inhibitory activities with IC50 values of 2.03 and 3.09 µmol/L, respectively (positive control curcumin, IC50 = 6.17 µmol/L). In addition, compound 1 showed weak proteintyrosine phosphatase-1B (PTP1B) inhibitory activity. KEY WORDS: Ligusticum chuanxiong Hort., Thionic compounds, Aromatic glycosides, Anti-inflammatory, Natural products

Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2), along with seven known compounds, were isolated from the root bark of Lycium chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds 39 were isolated from this genus for the first time. In the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10 μmol/L.