Systematic characterization of the influence of petroleum spill on terpene metabolism in Suaeda salsa (L.) Pall from coastal wetland: Implication by compound-specific stable isotope.

With the increasing industrialization and urbanization, the ecological environment is suffering from severe deterioration in Liaohe coastal wetland, and petroleum spill is one of the pollution sources. Suaeda salsa (L.) Pall (S. salsa), one of the predominant plants in Liaohe coastal wetland, is facing the increasing degradation. Terpenes are a class of inherent compounds in plants, and play key role in maintain the growth of plants. However, the environmental stress on the terpene metabolism remained unclear in the plants. In the present study, the influence of petroleum spill on terpene metabolism in S. salsa was systematically investigated by analysis of concentrations, compositions and stable carbon isotope. Under the stress of petroleum spill, terpene concentrations showed the decreasing trend, indicating the inhibition effect of petroleum spill on terpene synthesis in S. salsa. The proportions of Sabinene and A-humulene showed the obviously increased with the influence of petroleum spill, implying that these congeners were more sensitive to petroleum spills. The significant changes in stable carbon isotope compositions were observed for Borneol, Dl-menthol, A-humulene and (-) -@-bisabolol, with the enrichment in heavier isotopes in residual fractions. This result indicated that the heavier 13C was preferentially fixed on terpene by S. salsa under the petroleum stress. The similar change trends along the incubation time was observed for A-humulene and (-) - trans caryophyllene, which might imply that A-humulene was one of the products of (-) - trans caryophyllene in S. salsa. Overall, the findings of present study verified the influence of petroleum spill on terpene metabolism in S. salsa, and were meaningful for protecting the plants in the petroleum-pollution wetlands.

Effects of Naikan-Mindfulness Therapy on Psychiatric Rehabilitation for Chronic Schizophrenia.

Objective: To explore the effect of Naikan mindfulness therapy on psychiatric rehabilitation for chronic schizophrenia. Methods: 100 chronic schizophrenic patients in a third-class psychiatric hospital from July 2020 to August 2021 were selected as the research object. The following criteria were adopted: a clinician clearly diagnosed chronic schizophrenia, the patient was between 18 and 65 years old, and the patient agreed to participate in the study and signed an informed consent form.The random mathematical table method divided them into the control group (50 cases treated with Naikan therapy) and the experimental group (50 cases treated with Naikan mindfulness therapy). The LSIA(Life Satisfaction Index in Schizophrenia) score, SSFPI (Social Satisfaction and Functioning in Patients with Schizophrenia)score and satisfaction of psychiatric rehabilitation nursing were compared between the two groups. Result: In terms of LSIA score, there was no significant difference in baseline score between the two groups (P > .05). At 6 and 12 weeks after the intervention, the scores of the two groups increased, but the scores of the experimental group at 6 and 12 weeks after the intervention were higher than those of the control group, the difference was statistically significant (P < .05). In terms of SSFPI score, there was no significant difference in baseline score between the two groups (P < .05); At 6 and 12 weeks after the intervention, the scores of the two groups increased, but the scores of the experimental group at 6 and 12 weeks after the intervention were higher than those of the control group, the difference was statistically significant (P < .05). In terms of satisfaction with psychiatric rehabilitation nursing, there was no significant difference between the experimental group and the control group 6 weeks after intervention (P > .05); 12 weeks after the intervention, the satisfaction scores of the two groups increased significantly, and the scores of the experimental group were significantly higher than those of the control group (P < .05). Naikan mindfulness therapy led to significant improvements in LSIA scores, SSFPI scores, and satisfaction with psychiatric rehabilitation nursing at both 6 and 12 weeks. Conclusion: The life satisfaction, social function, and the satisfaction of psychiatric rehabilitation nursing of the chronic schizophrenics can be improved by the combination of Naikan mindfulness therapy. This study found that by using Naikan therapy, we can improve life satisfaction, social functioning, and satisfaction with psychiatric rehabilitation care in patients with chronic schizophrenia. This has important practical implications for patient treatment and care, including improving quality of life, enhancing social integration, improving rehabilitation outcomes, and reducing the burden on medical staff. This research provides a useful method for comprehensive care of patients with schizophrenia and is expected to have a positive impact on improving patients' lives and recovery in the future.

[Screening of small molecule inhibitors of IL-15Rα using molecular docking and surface plasmon resonance technology].

The study aims to explore the active molecules of traditional Chinese medicine that specifically bind to interleukin-15 receptor α (IL-15Rα) using molecular docking and surface plasmon resonance (SPR) technology. AutoDock molecular docking software was used to perform simulated docking of more than 3 000 compounds from 48 traditional Chinese medicines at IL-15Rα and screen the specific binding compounds. Then Biocore T200 biomolecular interaction analysis system of SPR was used to confirm the binding specificity of the selected target compounds. Finally, the biological effects of the target compounds on IL-15Rα were verified by cell biological experiments. The results showed that neoprzewaquinone A (Neo) possessed the highest specific binding affinity among the active molecules from traditional Chinese medicine, and the dissociation constant (KD) value was (0.62 ± 0.20) µmol/L. The results of cell experiment showed that Neo significantly inhibited the proliferation of Mo7e cells induced by IL-15, and the IC50 was 1.075 µmol/L, approximately 1/120 of the IC50 of Cefazolin (IL-15 specific antagonist). These results suggest that Neo is a specific inhibitor of IL-15Rα and may be a potential active drug for the treatment of diseases related to the dysfunction of the IL-15Rα signaling.

Network pharmacology and molecular docking to explore the mechanism of Sheng Xue Bao mixture against iron deficiency anemia.

Based on network pharmacology and molecular docking, we investigated the mechanism of action of Sheng Xue Bao mixture (SXBM) in treating iron deficiency anemia (IDA). We screened the HERB and traditional Chinese medicine systems pharmacology database and analysis platform databases to identify the active ingredients and targets of SXBM. The targets associated with "iron deficiency anemia" were collected from GeneCards, TTD, and OMIM databases. A component-target interaction network was constructed using Cytoscape 3.8.2. The protein-protein interaction network of candidate targets was generated using the STRING database and visualized with Cytoscape 3.8.2 software. Core modules obtained from clustering analysis were subjected to Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, molecular docking validation of key targets and active components was performed using Autodock Vina software. A total of 174 active components and 111 genes were identified as potential active components and targets for IDA treatment, including quercetin, kaempferol, luteolin, beta-sitosterol, and other flavonoids as main active components. Gene Ontology enrichment analysis show that interleaved genes are enriched in 2328 biological processes, 71 cellular component expression processes, and 157 molecular function processes. Kyoto encyclopedia of genes and genomes analysis mainly envolved Prostate cancer, Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Endocrine resistance, Lipid and atherosclerosis, Central carbon metabolism in cancer, Human cytomegalovirus infection and HIF-1 signaling pathway. STAT3, SRC, PIK3R1, and GRB2 were selected as core targets. The molecular docking results demonstrated strong interactions between key components and their respective target proteins. Network pharmacological analysis suggested that SXBM could treat IDA by regulating various biological processes and related signaling pathways. It laid the foundation for further elucidating the molecular mechanism of SXBM treatment of IDA.

Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.

As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic-co-glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.

Effect of vitamin D supplementation on glucose control in mid-late gestation: A randomized controlled trial.

BACKGROUND & AIMS: It is unclear whether vitamin D supplementation contributes to gestational glucose control and whether the specific effects vary in individuals with diverse genetic and metabolic contexts. The study aimed to assess the effect of vitamin D supplementation during pregnancy on subsequent glucose levels and to identify factors modulating the response to vitamin D3 intake. METHODS: We conducted a multicenter randomized controlled trial, 1720 pregnant women recruited from the three antenatal clinics of Hefei city, China, who were allocated to receive either 1600 IU/d vitamin D3 (n = 858) or 400 IU/d vitamin D3 (n = 862) for 2 months at 24-28 weeks' gestation. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D) and fasting plasma glucose (FPG) levels from baseline, 32-36 weeks' gestation to delivery (37-41 weeks) quantified using a linear mixed model. RESULTS: After 2 months, FPG levels of the control group significantly increased by 0.22 mmol/L (from 4.6 [0.4] mmol/L to 4.8 [1.2] mmol/L, P < 0.001) at delivery, but that of the intervention group had no significant variation (from 4.6 [0.4] mmol/L to 4.7 [1.1] mmol/L; between-group difference in changes, -0.2 mmol/L, 95% CI, -0.3 to -0.08, P = 0.015). And differences in FPG variation were found in participants with the ApaI SNP CC genotype, or BsmI-CC, TaqI-AA, FokI-AA, respectively. Pregnant women with basal 25(OH)D concentrations higher than 50 nmol/L subgroup showed the greatest decline in FPG levels (between-group difference, -0.3 mmol/L; 95% CI, -0.5 to -0.1, P < 0.001). Moreover, pregnant women with GDM, multiple pregnancies or who were overweight were more likely to have FPG decline from vitamin D treatment. CONCLUSIONS: Vitamin D supplementation significantly protected glucose homeostasis in mid-late gestation, and glycemic response to vitamin D may be dependent on basal 25(OH)D status, VDR gene polymorphism or their metabolic profiles. TRIAL REGISTRATION NUMBER: ChiCTR2100051914. URL OF REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=134700.

Selenium treatment promotes anthocyanin accumulation in radish sprouts (Raphanus sativus L.) by its regulation of photosynthesis and sucrose transport.

Red radish sprout become a popular dietary vegetable because of its unique flavor, abundant nutrients and short production cycle. As a cruciferous plant, it has strong ability to absorb and assimilate Se which can promote the content of anthocyanin in plants. However, the mechanisms of Se on anthocyanin accumulation are still unclear. In this study, we explored that appropriate Se promoted growth, antioxidant system and nutrients in radish sprouts. The enhancement of photosynthesis by Se treatment resulted in more sucrose synthesis in radish sprouts. And the transport of sucrose from cotyledon to hypocotyl promoted by Se through up-regulating the gene expression of sucrose transporters, and more sucrose increased the expression of anthocyanin biosynthesis genes to promote anthocyanin accumulation in hypocotyl. These results reveal the beneficial effect of Se on radish sprouts quality, and provide a new insight into the function of Se on sucrose-induced anthocyanin accumulation in radish sprouts.

[Ginkgo biloba Ketone Ester Tablets with different release rates prepared by fused deposition modeling 3D printing technology].

The present study prepared a new type of Ginkgo biloba ketone ester(GBE50) preparation from polyethylene glycol and croscarmellose sodium with good biocompatibility and a certain viscosity by fused deposition modeling(FDM)-type 3D printing technique. Firstly, a cylindrical 3D printing model with a diameter of 9.00 mm and a height of 4.50 mm was established. Subsequently, the 3D-GBE50 preparations with three paths(concentric, zigzag, and grid), different layer heights, and different filling gaps were designed and prepared after the optimization of the proportions of excipients. The morphology, size, chemical properties, and dissolution activity of the 3D-GBE50 preparations were fully characterized and investigated. The results showed that 3D-GBE50 preparations had smooth appearance, clear texture, standard friability, good thermal stability, and stable chemical properties. Moreover, the printing path, layer height, and filling gap were directly related to the release rate of 3D-GBE50 preparations. The dissolution of 3D-GBE50 tablets with zigzag printing path was the fastest, while the dissolution rates of 3D-GBE50 tablets with concentric circle and grid-shaped printing paths were slower than that of commercially available G. biloba Ketone Ester Tablets. In addition, the dissolution of 3D-GBE50 tablets was faster with higher layer height and wider filling gap. As revealed by the results, th FDM-type 3D printing technique can flexibly regulate the drug release activity via controlling the printing parameters, providing effective ideas and methods for the pre-paration of personalized pharmaceutical preparations.

Traditional Chinese Medicine Formula Jian Pi Tiao Gan Yin Reduces Obesity in Mice by Modulating the Gut Microbiota and Fecal Metabolism.

The current study employed the high-fat diet (HFD) induced murine model to assess the relationship between the effect of Jian Pi Tiao Gan Yin (JPTGY) and the alterations of gut microbiota and fecal metabolism. C57BL/6 mice were used to establish an animal model of obesity via HFD induce. Serum biochemical indicators of lipid metabolism were used to evaluate the pharmacodynamics of JPTGY in obese mice. Bacterial communities and metabolites in the feces specimens from the controls, the Group HFD, and the JPTGY-exposed corpulency group were studied by 16s rDNA genetic sequence in combination with liquid chromatography-mass spectrometry (LC-MS) based untargeted fecal metabolomics techniques. Results revealed that JPTGY significantly decreased the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and elevated high-density lipoprotein cholesterol (HDL-C). Moreover, JPTGY could up-regulate the abundance and diversity of fecal microbiota, which was characterized by the higher phylum of proteobacteria. Consistently, at the genus levels, JPTGY supplementation induced enrichments in Lachnospiraceae NK4A136 group, Oscillibacter, Turicibacter, Clostridium sensu stricto 1, and Intestinimonas, which were intimately related to 14 pivotal fecal metabolins in respond to JPTGY therapy were determined. What is more, metabolomics further analyses show that the therapeutic effect of JPTGY for obesity involves linoleic acid (LA) metabolism paths, alpha-linolenic acid (ALA) metabolism paths, glycerophospholipid metabolism paths, arachidonic acid (AA) metabolism paths, and pyrimidine metabolism paths, which implied the potential mechanism of JPTGY in treating obesity. It was concluded that the linking of corpulency phenotypes with intestinal flora and fecal metabolins unveils the latent causal link of JPTGY in the treatment of hyperlipidemia and obesity.

Effective co-treatment of synthetic acid mine drainage and domestic sewage using multi-unit passive treatment system supplemented with silage fermentation broth as carbon source.

A multi-unit passive treatment system was constructed for co-treatment of synthetic acid mine drainage (AMD) and domestic sewage supplemented with silage fermentation broth as carbon source. AMD and domestic sewage mixing pretreatment (unit 1) improved influent quality with pH increase, metals removal and nutrients supplement. The generated metal-rich sludge in unit 1 retained the metals (69.95% of Fe, 97.36% of Cu, 96.53% of Cd, 72.52% of Zn, and 8.59% of Mn) of influent prior to entering subsequent bioreactors. Silage fermentation broth performed well to promote bacterial sulfate reduction in sulfate reducing bioreactor system (unit 2). Residual metals (Mn) and organic/nutrient pollutants were further polished in surface-flow aerobic wetland (unit 3), where relatively high pH (7.4-8.6), aerobic condition, potential Mn-oxidizing bacteria, limestone layer and low concentrations of Fe(II) (0.04-3.5 mg/L) favored the efficient removal of Mn. After 210-day continuous flow-through experiment, this passive treatment system demonstrated the efficient performance, increasing pH from 2.5 to 8.0 with removal of metals (99%), sulfate and organic/nutrient pollutants. Diverse sulfate reducing bacteria including complete organic oxidizers (e.g. Desulfobacter) and incomplete organic oxidizers (e.g. Desulfovibrio) promoted sulfate reduction and organic/nutrient pollutants removal. Ammonia oxidizing bacteria (e.g. Nitrosomonas) and nitrite oxidizing bacteria (e.g. unidentified_Nitrospiraceae) were the potential nitrifiers for ammonia removal. Collaboration of anaerobic denitrifiers (e.g. Denitratisoma) and potential heterotrophic nitrifying and aerobic denitrifiers (HN-AD) achieved effective nitrate removal. This multi-unit treatment system with domestic sewage and silage fermentation broth as stimulation substrates provided an attractive option for AMD treatment.

Shengxuebao Mixture for Iron Deficiency Anemia: A Meta-Analysis and Systematic Review.

OBJECTIVE: Traditional Chinese medicine Shengxuebao Mixture (SXBM) has been approved for treating iron deficiency anemia (IDA) in China. This study aimed to collect evidence and quantify the effect of SXBM on IDA. METHODS: Seven online databases were surveyed up to July 13, 2021. Randomized controlled trials in which SXBM was combined with conventional therapies to treat IDA and compared with placebo or conventional therapies were included in the study. The red blood cell (RBC) count, hemoglobin (Hb) level, serum ferritin (SF) level, and adverse events rate (AER) were evaluated. RESULTS: A total of 1,108 patients from 8 trials were recruited. SXBM plus conventional therapy increased the Hb level (mean difference [MD] = 13.04, 95% confidence interval [CI] 8.37-17.7, p < 0.00001), RBC count (MD = 0.41, 95% CI 0.19-0.62, p = 0.002), SF level (MD = 6.25, 95% CI 2.88-9.62, p = 0.0003), and AER (risk ratio = 0.56, 95% CI 0.36-0.86; p = 0.008). CONCLUSIONS: SXBM combined with conventional treatment seemed to be beneficial for patients with IDA. However, the harmlessness of SXBM was not confirmed due to insufficient trials and low methodological quality. Follow-up clinical studies should be cautiously designed, and more research is needed.

Tenuifolin ameliorates chronic restraint stress-induced cognitive impairment in C57BL/6J mice.

The general consensus is that stress affects the central nervous system and can lead to cognitive problems. The root of Polygala tenuifolia (P. tenuifolia) is a well-known traditional Chinese medicine used for improving brain function. Tenuifolin (TEN) is the major constituent of P. tenuifolia and has a promising neuroprotective property. The purpose of this study was to investigate the alleviating effect of TEN on cognitive impairment induced by chronic restraint stress (CRS) and its mechanism. Our results showed that CRS exposure resulted in impaired cognitive performance in C57BL/6J mice, as indicated by decreased responses in Y-maze, novel objects recognition, and step-through passive avoidance tests. TEN treated daily orally (10 and 20 mg/kg) for 30 days reversed these behavior changes. Meanwhile, TEN could significantly regulate interleukin (IL)-6 and IL-10 levels in the hippocampus. TEN inhibited the toll-like receptor 4/nuclear factor-kappa B-mediated inflammation, as well as adrenocorticotropic hormone and corticosterone levels in serum. Most importantly, we found that TEN also upregulated the expressions of brain-derived neurotrophic factor, tropomyosin kinase B, glucocorticoid receptor, glutamate receptor 1, and synapse-associated proteins. Collectively, these data suggest that TEN has a potential improvement effect on memory loss caused by CRS.

A facile "turn-on" fluorescent aptasensor for simultaneous detection of dual mycotoxins in traditional Chinese medicine based on graphene oxide and FRET.

Mycotoxin is a common sort of harmful contaminant in traditional Chinese medicine (TCM), which is in a great demand of controlling. On this account, a facile "turn-on" fluorescent aptasensor based on fluorescence resonance energy transfer (FRET) for simultaneous detection of patulin (PAT) and zearalenone (ZEN) was developed. In this study, the aptamers of PAT and ZEN were labeled by FAM and Cy3, respectively, serving as fluorescence probes. Both aptamers could adsorb on the surface of graphene oxide (GO) via π-π stacking, which will consequently result in the occurrence of FRET between the fluorophores and GO. In the absence of the targets, the fluorescence would be quenched "off". In the presence of any of the dual mycotoxins, the corresponding aptamers would interact with the targets and release from GO due to the conformational variation, leading to a fluorescence "turn-on" effect. The limit of detection of this difunctional aptasensor was 2.29 nM for PAT and 0.037 nM for ZEN, respectively. This aptasensing platform exhibited satisfactory selectivity against interferents and reliability in real TCM sample detection. To our knowledge, it is the first aptasensor based on GO and FRET that realizes simultaneous detection of dual mycotoxin in TCM. Moreover, the measurement takes merely ∼60 min, does not need complicated pretreatment, and uses only inexpensive aptamer and GO as consuming materials. To sum up, this aptasensor exhibits great potential in fast, cost-effective and reliable simultaneous detection of multiple targets, and is expected to contribute to the quality and safety control of TCM.

Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 (S)-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one, by Fragment-Based Drug Design.

This publication details the successful use of FBDD (fragment-based drug discovery) principles in the invention of a novel covalent Bruton's tyrosine kinase inhibitor, which ultimately became the Takeda Pharmaceuticals clinical candidate TAK-020. Described herein are the discovery of the fragment 5-phenyl-2,4-dihydro-3H-1,2,4-triazol-3-one, the subsequent optimization of this hit molecule to the candidate, and synthesis and performance in pharmacodynamic and efficacy models along with direct biophysical comparison of TAK-020 with other clinical-level assets and the marketed drug Ibrutinib.

Evolutionarily distinct resistance proteins detect a pathogen effector through its association with different host targets.

Knowledge of the evolutionary processes which govern pathogen recognition is critical to understanding durable disease resistance. We determined how Phytophthora infestans effector PiAVR2 is recognised by evolutionarily distinct resistance proteins R2 and Rpi-mcq1. We employed yeast two-hybrid, co-immunoprecipitation, virus-induced gene silencing, transient overexpression, and phosphatase activity assays to investigate the contributions of BSL phosphatases to R2- and Rpi-mcq1-mediated hypersensitive response (R2 HR and Rpi-mcq1 HR, respectively). Silencing PiAVR2 target BSL1 compromises R2 HR. Rpi-mcq1 HR is compromised only when BSL2 and BSL3 are silenced. BSL1 overexpression increases R2 HR and compromises Rpi-mcq1. However, overexpression of BSL2 or BSL3 enhances Rpi-mcq1 and compromises R2 HR. Okadaic acid, which inhibits BSL phosphatase activity, suppresses both recognition events. Moreover, expression of a BSL1 phosphatase-dead (PD) mutant suppresses R2 HR, whereas BSL2-PD and BSL3-PD mutants suppress Rpi-mcq1 HR. R2 interacts with BSL1 in the presence of PiAVR2, but not with BSL2 and BSL3, whereas no interactions were detected between Rpi-mcq1 and BSLs. Thus, BSL1 activity and association with R2 determine recognition of PiAVR2 by R2, whereas BSL2 and BSL3 mediate Rpi-mcq1 perception of PiAVR2. R2 and Rpi-mcq1 utilise distinct mechanisms to detect PiAVR2 based on association with different BSLs, highlighting central roles of these effector targets for both disease and disease resistance.

Drought resistance mechanisms of Phedimus aizoon L.

Phedimus aizoon L. is a drought-resistant Chinese herbal medicine and vegetable. However, its drought tolerant limit and the mechanism of drought tolerance are unknown, which restricts the promotion of water-saving cultivation of Phedimus aizoon L. in arid areas. To solve the above problem, we carried out a 30-day-long drought stress experiment in pots that presented different soil water contents and were divided into four groups: control check, 75-80% of the maximum water-holding capacity (MWHC); mild drought, 55-60%; moderate drought, 40-45%; and severe drought, 20-25%. The dynamic changes in both plant physiological indexes from 10 to 30 days and leaf anatomical structure on the 30th day of stress were recorded. The results show that Phedimus aizoon L. grew normally under mild drought stress for 30 days, but the growth of the plants became inhibited after 20 days of severe drought and after 30 days of moderate drought. At the same time, Phedimus aizoon L. physiologically responded to cope with drought stress: the growth of the root system accelerated, the waxy layer of the leaves thickened, and the dark reactions of the plants transformed from those of the C3 cycle to CAM. The activity of antioxidant enzymes (SOD, POD and CAT) continuously increased to alleviate the damage caused by drought stress. To ensure the relative stability of the osmotic potential, the contents of osmoregulatory substances such as proline, soluble sugars, soluble protein and trehalose increased correspondingly. Although Phedimus aizoon L. has strong drought stress resistance, our experimental results show that the soil available water content should not be less than 27% during cultivation.

Calcium Positively Mediates Blue Light-Induced Anthocyanin Accumulation in Hypocotyl of Soybean Sprouts.

Soybean sprouts are a flavorful microgreen that can be eaten all year round and are widely favored in Southeast Asia. In this study, the regulatory mechanism of calcium on anthocyanin biosynthesis in soybean sprouts under blue light was investigated. The results showed that blue light, with a short wavelength, effectively induced anthocyanin accumulation in the hypocotyl of soybean sprout cultivar "Dongnong 690." Calcium supplementation further enhanced anthocyanin content, which was obviously inhibited by LaCl3 and neomycin treatment. Moreover, exogenous calcium changed the metabolism of anthocyanins, and seven anthocyanin compounds were detected. The trend of calcium fluorescence intensity in hypocotyl cells, as well as that of the inositol 1,4,5-trisphosphate and calmodulin content, was consistent with that of anthocyanins content. Specific spatial distribution patterns of calcium antimonate precipitation were observed in the ultrastructure of hypocotyl cells under different conditions. Furthermore, calcium application upregulated the expression of genes related to anthocyanin biosynthesis, and calcium inhibitors suppressed these genes. Finally, transcriptomics was performed to gain global insights into the molecular regulation mechanism of calcium-associated anthocyanin production. Genes from the flavonoid biosynthesis pathway were distinctly enriched among the differentially expressed genes, and weighted gene co-expression network analysis showed that two MYBs were related to the accumulation of anthocyanins. These results indicated that calcium released from apoplast and intracellular stores in specific spatial-temporal features promote blue light-induced anthocyanin accumulation by upregulation of the expression of genes related to anthocyanin synthesis of "Dongnong 690" hypocotyl. The findings deepen the understanding of the calcium regulation mechanism of blue light-induced anthocyanin accumulation in soybean sprouts, which will help growers produce high-quality foods beneficial for human health.

Iridoid compounds from the aerial parts of Swertia mussotii Franch. with cytotoxic activity.

One new secoiridoid compound swertiamarin B (1), along with a known compound lytanthosalin (2), were isolated from ethanol extract of the aerial parts of Swertia mussotii. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. All compounds were first isolated from the Swertia genus. Their antitumor activities were evaluated for four human tumor cell lines (HCT-116, HepG2, MGC-803 and A549). Compounds 1 and 2 showed excellent cytotoxic activities toward the MGC-803 cell lines with IC50 values 3.61 and 12.04 µM, respectively.

Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

3D Printed Bioceramic Scaffolds as a Universal Therapeutic Platform for Synergistic Therapy of Osteosarcoma.

The postoperative tumor recurrence and chemotherapy resistance in clinical osteosarcoma treatment have raised an imperative need to develop local implants for selectively killing residual tumor cells and simultaneously provide a scaffold for effectively filling the tumor resection-induced bone defects. Herein, a multifunctional platform is developed through successively coating TiN microparticles and doxorubicin (DOX) on the surface of tricalcium phosphate (TCP) scaffolds to achieve synergetic effects of photothermal therapy and chemotherapy for osteosarcoma. The content of TiN and DOX in the scaffolds can be flexibly adjusted by immersing the scaffolds into the solution containing different concentrations of TiN and DOX. The excellent therapeutic effect was achieved both in vitro and in vivo through the precise photothermal therapy and localized controlled-release chemotherapy. Moreover, the overall bulk scaffolds provide the mechanical support for bone tissue when implanting scaffolds into bone defects resulting from surgical removal of osteosarcoma. Importantly, using the poly(d,l-lactide) (PDLLA) as the medium, the scaffolds can be exploited as a universal platform for loading different kinds of therapeutic agents. This study may provide insights into designing multifunctional local implantation for eradicating tumors after surgical interventions with mitigated side effects.