Review on toxicology and activity of tomato glycoalkaloids in immature tomatoes.

Owing to the lack of selection and limited intelligence in mechanical picking, some immature tomatoes that contain alkaloids are thrown away. Tomatine alkaloids are steroidal alkaloids naturally present in Solanaceae plants, which are distributed in small amounts in immature tomato fruits and decrease as the fruits ripen. Tomato glycoalkaloids are harmful to human health. However, in small quantities, there is some evidence that these compounds might be beneficial, as other non-antioxidant bioactivities. This article considers recent research on the biological effects of tomato glycoalkaloids in immature tomatoes, providing reference value for the potential development of these compounds.

Research Progress in Modifications, Bioactivities, and Applications of Medicine and Food Homologous Plant Starch.

Starchy foods are an essential part of people's daily diet. Starch is the primary substance used by plants to store carbohydrates, and it is the primary source of energy for humans and animals. In China, a variety of plants, including edible medicinal plants, such as Pueraria root, yam tuber and coix seed, are rich in starch. However, limited by their inherent properties, kudzu starch and other starches are not suitable for the modern food industry. Natural starch is frequently altered by physical, chemical, or biological means to give it superior qualities to natural starch as it frequently cannot satisfy the demands of industrial manufacturing. Therefore, the deep processing market of modified starch and its products has a great potential. This paper reviews the modification methods which can provide excellent functional, rheological, and processing characteristics for these starches that can be used to improve the physical and chemical properties, texture properties, and edible qualities. This will provide a comprehensive reference for the modification and application of starch from medicinal and edible plants.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation.

The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.

[Prediction of global potential growth areas for Panax ginseng based on GMPGIS system and MaxEnt model].

The suitable habitat for the endangered and valuable medicinal herb Panax ginseng is gradually decreasing. It is crucial to investigate its suitable growing areas in China for global protection and sustainable utilization of P. ginseng. In this study, 371 distribution points of P. ginseng were collected, and 21 environmental factors were used as ecological indicators. The geographic information system for global medicinal plants(GMPGIS) system, MaxEnt model, and Thiessen polygon method were used to analyze the potential suitable areas for P. ginseng globally. The results showed that the key environmental variables affecting P. ginseng were precipitation in the hottest quarter(Bio18) and the coefficient of temperature seasonality(Bio4). The suitable habitats for P. ginseng were mostly located in the "One Belt, One Road" countries such as China, Japan, South Korea, North Korea, and Russia. The highly suitable habitats were mainly distributed along mountain ranges in southeastern Shandong, southern Shanxi and Shaanxi, northern Jiangsu, and northwestern Henan of China. Data analysis indicated that the current P. ginseng planting sites were all in high suitability zones, and the Thiessen polygon results showed that the geographic locations of P. ginseng production companies were unbalanced and urgently needed optimization. This study provides data support for P. ginseng planting site selection, scientific introduction, production layout, and long-term development planning.

The lower He-sea points playing a significant role in postoperative ileus in colorectal cancer treated with acupuncture: based on machine-learning.

Background: Postoperative ileus (POI) is a common complication following abdominal surgery, which can lead to significant negative impacts on patients' well-being and healthcare costs. However, the efficacy of current treatments is not satisfactory. The purpose of this study was to evaluate the therapeutic effects of acupuncture intervention and explore the regulation of acupoint selection for treating POI in colorectal cancer (CRC) patients. Methods: We searched eight electronic databases to identify randomized controlled trials (RCTs) on acupuncture for POI in CRC and conducted a meta-analysis. Subsequently, we utilized the Apriori algorithm and the Frequent pattern growth algorithm, in conjunction with complex network and cluster analysis, to identify association rules of acupoints. Results: The meta-analysis showed that acupuncture led to significant reductions in time to first defecation (MD=-20.93, 95%CI: -25.35, -16.51; I2 = 93.0%; p < 0.01; n=2805), first flatus (MD=-15.08, 95%CI: -18.39, -11.76; I2 = 96%; p < 0.01; n=3284), and bowel sounds recovery (MD=-10.96, 95%CI: -14.20, -7.72; I2 = 94%; p < 0.01; n=2043). A subgroup analysis revealed that acupuncture not only reduced the duration of POI when administered alongside conventional care but also further expedited the recovery of gut function after colorectal surgery when integrated into the enhanced recovery after surgery (ERAS) pathway. The studies included in the analysis reported no instances of serious adverse events associated with acupuncture. We identified Zusanli (ST36), Shangjuxu (ST37), Neiguan (PC6), Sanyinjiao (SP6), Xiajuxu (ST39), Hegu (LI4), Tianshu (ST25), and Zhongwan (RN12) as primary acupoints for treating POI. Association rule mining suggested potential acupoint combinations including {ST37, ST39}≥{ST36}, {PC6, ST37}≥{ST36}, {SP6, ST37}≥{ST36}, and {ST25, ST37}≥{ST36}. Conclusion: Meta-analysis indicates acupuncture's safety and superior effectiveness over postoperative care alone in facilitating gastrointestinal recovery. Machine-learning approaches highlight the importance of the lower He-sea points, including Zusanli (ST36) and Shangjuxu (ST37), in treating POI in CRC patients. Incorporating additional acupoints such as Neiguan (PC6) (for pain and vomiting) and Sanyinjiao (SP6) (for abdominal distension and poor appetite) can optimize treatment outcomes. These findings offer valuable insights for refining treatment protocols in both clinical and experimental settings, ultimately enhancing patient care.

Effects of Endurance Exercise and Vitamin D Supplementation on Insulin Resistance and Plasma Lipidome in Middle-Aged Adults with Type 2 Diabetes.

(1) Background: We investigated the effects of a 12-week exercise intervention with or without vitamin D supplementation on insulin resistance and the plasma lipidome of participants with type 2 diabetes. We further explored whether the effects of the intervention on glycemic parameters could be associated with the baseline lipidome. (2) Methods: Sixty-one participants were randomly allocated to control (Con), exercise (EX), vitamin D (VD), and EX + VD groups. Multiple glycemic and anthropometric parameters were evaluated before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) was the primary outcome. The plasma lipidome was analyzed before, after, and at an additional 12-week follow-up. Machine learning was applied to establish prediction models for responsiveness of glycemic control. (3) Results: Our interventions failed to improve the HOMA-IR index while fasting glucose was reduced in the EX + VD group (change%, -11.9%; effect size, 0.65; p < 0.05). Both EX and VD interventions altered the plasma lipidome, with EX + VD intervention considerably affecting levels of lyso-phosphatidylcholines and triglycerols containing long-chain unsaturated fatty acids. Such effects could last until 12 weeks after intervention. Notably, there was high inter-individual variability in glycemic parameters including HOMA-IR in response to the interventions, which could be predicted with great accuracy using an optimal panel of baseline lipid predictors alone or in combination with clinical indices, as assessed by an area under the receiver operating characteristic curve value of over 0.9. (4) Conclusions: Although substantial alterations were observed in the plasma lipidome related to glycemic control, our intervention failed to improve HOMA-IR scores, which may have been predominately due to the large inter-individual variability in responses. Basal plasma lipid levels could potentially predict an individual's response to intervention, highlighting the necessity of personalized nutrition.

[Research progress on chemical constituents and pharmacological effects of Ajania plants].

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

A new sesquiterpene synthase catalyzing the formation of (R)-ß-bisabolene from medicinal plant Colquhounia coccinea var. mollis and its anti-adipogenic and antibacterial activities.

The sesquiterpene ß-bisabolene possessing R and S configurations is commonly found in plant essential oils with antimicrobial and antioxidant activities. Here, we report the cloning and functional characterization of a (R)-ß-bisabolene synthase gene (CcTPS2) from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. The biochemical function of CcTPS2 catalyzing the cyclization of farnesyl diphosphate to form a single product (R)-ß-bisabolene was characterized through an engineered Escherichia coli producing diverse polyprenyl diphosphate precursors and in vitro enzyme assay, indicating that CcTPS2 was a high-fidelity (R)-ß-bisabolene synthase. The production of (R)-ß-bisabolene in an engineered E. coli strain harboring the exogenous mevalonate pathway, farnesyl diphosphate synthase and CcTPS1 genes was 17 mg/L under shaking flask conditions. Ultimately, 120 mg of purified (R)-ß-bisabolene was obtained from the engineered E. coli, and its structure was elucidated by detailed spectroscopic analyses (including 1D and 2D NMR, and specific rotation). Four chimeric enzymes were constructed through domain swapping, which altered the product outcome, indicating the region important for substrate and product specificity. In addition, (R)-ß-bisabolene exhibited anti-adipogenic activity in the model organism Caenorhabditis elegans and antibacterial activity selectively against Gram-positive bacteria.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber ­ gut microbiota (Anaerostipes)­constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

[Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology].

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

[Traditional Chinese medicine microbiomics and its research strategies].

The tight relationships between microbiome and traditional Chinese medicine(TCM)have been widely recognized. New technologies, results, and theories are emerging in the field of microbiomics in recent years with the advances in high-throughput sequencing and multi-omics technologies. Based on the previous research, the present study has proposed the concept of TCM microbiomics(TCMM), which is an interdisciplinary subject aiming at elucidating the functions and applications of microbiome in the areas of herb resources, herb processing, herb storage, and clinical effects by using modern technology of biology, ecology, and informatics. This subject essentially contains the structures, functions, interactions, molecular mechanisms, and application strategies of the microbiome associated with the quality, safety, and efficacy of TCM. Firstly, the development of the TCMM concept was summarized, with the profound understanding of TCMM on the complexity and entirety of microbiome being emphasized. Then, the research contents and applications of TCMM in promoting the sustainable development of herb resources, improving the standardization and diversification of herb fermentation, strengthening the safety of herb storage, and resolving the scientific connotation of theories and clinical efficacy of TCM are reviewed. Finally, the research strategies and methods of TCM microbiomics were elaborated from basic research, application research, and system research. TCMM is expected to promote the integrative development of TCM with frontier science and technology, thereby expanding the depth and scope of TCM study and facilitating TCM modernization.

D-chiro-inositol increases antioxidant capacity and longevity of Caenorhabditis elegans via activating Nrf-2/SKN-1 and FOXO/DAF-16.

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aß1-42, alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI.

[Early electroacupuncture intervention delays progression of disease in mice with amyotrophic lateral sclerosis by down-regulating TLR4/NF-κB signaling].

OBJECTIVE: To observe the effect of early electroacupuncture (EA) intervention on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in mice with amyotrophic lateral sclerosis (ALS), so as to explore its mechanisms underlying alleviation of ALS. METHODS: Fifty-four ALS (ALS-SOD1G93A) mice with SOD1G93A gene mutation identified by PCR were randomly divided into model group, 60 day(d) EA group and 90 d EA group(n=18 mice in each group), and other 18 ALS-SOD1G93A negative mice were used as the control group. At the age of 60 and 90 days, mice of the two EA groups received EA (2 Hz, 1 mA) stimulation of bilateral "Jiaji" (EX-B2) of L1-L2 and L5-L6 for 20 min, twice a week for 4 weeks,respectively. When being 60 days old, the mice in the model and control groups were subjected to the same binding as that in the two EA groups but without EA intervention. The tail suspension test was used to judge the onset time of disease and the survival period, and rotary rod fatigue test was used to evaluate the hind limb motor function. Nissl staining method was used to observe the content of Nissl bodies in the anterior horn of the lumbar spinal cord. Immunohistochemical staining was used to observe the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in the anterior horn of the lumbar spinal cord, and Western blot was used to detect the relative expression of TLR4, NF-κB and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord. RESULTS: The disease onset time apparently delayed in the 60 d EA group than in the model group (P<0.01). The survival time was apparently shorter in the model group than in the control group (P<0.01), and obviously prolonged in the 60 d EA and 90 d EA groups than in the model group (P<0.01). The rotatory rod time was obviously shorter in the model group than in the control group (P<0.05), and apparently longer in the 60 d EA group than in the model group and 90 d EA group (P<0.05). Compared with the control group, the model group had a decrease in the number of Nissl bodies in the anterior horn of the lumbar spinal cord (P<0.01), and an increase in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.01). In contrast to the model group, both 60 d EA and 90 d EA groups had an apparent increase in the number of Nissl bodies and a marked decrease in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.05, P<0.01). The therapeutic effects of 60 d EA group were evidently superior to those of 90 d EA group in delaying the onset time of disease, prolonging the survival time and rotatory rod time, increasing the number of Nissl bodies, and in down-regulating the expression of Iba-1, TLR4, NF-κB and TNF-α (P<0.05, P<0.01). CONCLUSION: The early intervention of EX-B2 EA is more effective in delaying the progression of ALS than post-onset intervention in ALS-SOD1G93A mice, which may be related to its functions in inhibiting the excessive activation of microglia, and down-regulating TLR4/NF-κB signaling.

Phosphorus Accumulation in Extracellular Polymeric Substances (EPS) of Colony-Forming Cyanobacteria Challenges Imbalanced Nutrient Reduction Strategies in Eutrophic Lakes.

Extracellular polymeric substances (EPS) are crucial for cyanobacterial proliferation; however, certain queries, including how EPS affects cellular nutrient processes and what are the implications for nutrient management in lakes, are not well documented. Here, the dynamics of cyanobacterial EPS-associated phosphorus (EPS-P) were examined both in a shallow eutrophic lake (Lake Taihu, China) and in laboratory experiments with respect to nitrogen (N) and phosphorus (P) availability. Results indicated that 40-65% of the total cyanobacterial aggregate/particulate P presented as EPS-P (mainly labile P and Fe/Al-P). Phosphorus-starved cyanobacteria rapidly replenished their EPS-P pools after the P was resupplied, and the P concentration in this pool was stable for long afterward, although the environmental P concentration decreased dramatically. A low-N treatment enhanced the EPS production alongside two-fold EPS-P accumulation (particularly labile P) higher than the control. Such patterns occurred in the lake where EPS and EPS-P contents were high under N limitation. EPS-P enrichment increased the P content in cyanobacteria; subsequently, it could hold the total P concentration higher for longer and make bloom mitigation harder. The findings outline a new insight into EPS functions in the P process of cyanobacterial aggregates and encourage consideration of both N and P reductions in nutrient management.

Nanozyme-like single-atom catalyst combined with artesunate achieves photothermal-enhanced nanocatalytic therapy in the near-infrared biowindow.

Selectively generating active free radical (AFR) in tumor microenvironment (TME) can promote irreversible oxidation of biomolecules and damage tumor cells, resulting in effective tumor inhibition. However, therapeutic efficacy of AFR-based tumor suppression approaches is often limited by insufficient amount of H2O2 or O2 within TME. To overcome this obstacle, we design a pH/photothermal dual responsive nanosystem (PFeSA@AS) for combined photothermal and nanocatalytic therapy in the near-infrared biowindow. Here the Fe single-atom dispersed N, S-doped carbon nanosheets (FeSA) nanozyme is dispersed by phospholipid-polyethylene glycol-amine (DSPE-PEG-NH2), and further loads artesunate (AS) via an amide reaction. Upon 808-nm laser irradiation in TME, the AS is released and further be catalyzed by the FeSA nanozyme to produce cytotoxic C-centered AFRs, and further be accelerated due to the photothermal conversion performance of FeSA (23.35%). The nanocatalytic process of FeSA nanozyme is realized by density functional theory (DFT). The tumor inhibition rates of a CT26 xenograft model is 92% through a photothermal-enhanced nanocatalytic synergistic therapy, and negligible systematic toxicity is observed. This work offers a potential paradigm of multifunctional single atomic catalysts (SACs) for enhancing tumor nanocatalytic therapy. STATEMENT OF SIGNIFICANCE: We designed a pH/photothermal dual responsive nanosystem (PFeSA@AS) for nanocatalytic therapy: (1) the nanosystem responsively releases AS under 808-nm laser irradiation in TME; (2) FeSA in the nanosystem can act as heme mimetic to convert AS into high cytotoxic C-centered free radicals for nanocatalytic therapy; (3) the photothermal conversion performance of FeSA further enhances the catalytic process to yield abundant AFR. Both in vitro and in vivo results demonstrate that this nanosystem can efficiently inhibit tumor growth through a photothermal-enhanced nanocatalytic synergistic therapy.

Traditional Chinese medicine microbiomics and its research strategies / 中国中药杂志

The tight relationships between microbiome and traditional Chinese medicine(TCM)have been widely recognized. New technologies, results, and theories are emerging in the field of microbiomics in recent years with the advances in high-throughput sequencing and multi-omics technologies. Based on the previous research, the present study has proposed the concept of TCM microbiomics(TCMM), which is an interdisciplinary subject aiming at elucidating the functions and applications of microbiome in the areas of herb resources, herb processing, herb storage, and clinical effects by using modern technology of biology, ecology, and informatics. This subject essentially contains the structures, functions, interactions, molecular mechanisms, and application strategies of the microbiome associated with the quality, safety, and efficacy of TCM. Firstly, the development of the TCMM concept was summarized, with the profound understanding of TCMM on the complexity and entirety of microbiome being emphasized. Then, the research contents and applications of TCMM in promoting the sustainable development of herb resources, improving the standardization and diversification of herb fermentation, strengthening the safety of herb storage, and resolving the scientific connotation of theories and clinical efficacy of TCM are reviewed. Finally, the research strategies and methods of TCM microbiomics were elaborated from basic research, application research, and system research. TCMM is expected to promote the integrative development of TCM with frontier science and technology, thereby expanding the depth and scope of TCM study and facilitating TCM modernization.

Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology / 中国中药杂志

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

Research progress on chemical constituents and pharmacological effects of Ajania plants / 中国中药杂志

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

Quantitative fusion omics reveals that refrigeration drives methionine degradation through perturbing 5-methyltetrahydropteroyltriglutamate-homocysteine activity.

Postharvest senescence and quality deterioration of fresh tea leaves occurred due to the limitation of processing capacity. Refrigerated storage prolongs the shelf life of fresh tea. In this study, quantitative fusion omics delineated the translational landscape of metabolites and proteins in time-series (0-12 days) refrigerated tea by UHPLC-Q-Orbitrap HRMS. Accurate quantification results showed the content of amino acids, especially l-theanine, decreased with the lengthening of the storage duration (15.57 mg g-1 to 7.65 mg g-1) driven by theanine synthetase. Downregulation of enzyme 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase expression led to methionine degradation (6.29 µg g-1 to 1.78 µg g-1). Refrigerated storage inhibited serine carboxypeptidase-like acyltransferases activity (59.49 % reduction in 12 days) and induced the polymerization of epicatechin and epigallocatechin and generation of procyanidin dimer and δ-type dehydrodicatechin, causing the manifestation of color deterioration. A predictive model incorporating zero-order reaction and Arrhenius equation was constructed to forecast the storage time of green tea.