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Steroidal glycoalkaloids (SGAs) such as α-solanine found in solanaceous food plants— as, for example, potato— are antinutritional factors for humans. Comparative coexpression analysis between tomato and potato coupled with chemical profiling revealed an array of 10 genes that partake in SGA biosynthesis. We discovered that six of them exist as a cluster on chromosome 7, whereas an additional two are adjacent in a duplicated genomic region on chromosome 12. Following systematic functional analysis, we suggest a revised SGA biosynthetic pathway starting from cholesterol up to the tetrasaccharide moiety linked to the tomato SGA aglycone. Silencing GLYCOALKALOID METABOLISM 4 prevented accumulation of SGAs in potato tubers and tomato fruit. This may provide a means for removal of unsafe, antinutritional substances present in these widely used food crops.

This study aimed to evaluate the clinical application of different myopia correction methods in the prevention and control of myopia in adolescents. A total of 145 myopic adolescents aged 8 to 15 years were included, and their eyes were divided into four groups based on the treatment modality: wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses alone (Group A), orthokeratology (OK) lenses alone (Group B), DIMS spectacle lenses combined with racemic anisodamine eye drops (Group C), and OK lenses combined with racemic anisodamine eye drops (Group D). The primary outcomes, including axial length and refractive error (expressed as spherical equivalent refraction, SER), were measured at baseline and at the 12-month follow-up. The clinical effects of each group were compared. The results showed significant differences in myopia progression across the groups, with Group D showing the least axial elongation. OK lenses were more effective than DIMS spectacle lenses in controlling myopia progression, and the combination of racemic anisodamine eye drops further enhanced the correction effect. This study provides important clinical evidence for myopia control interventions in adolescents.

Postoperative nausea and vomiting (PONV) frequently occur in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) under general anesthesia. Glycopyrronium bromide, an anticholinergic medication, is believed to not only relieve gastrointestinal spasms but also effectively prevent PONV. To compare the incidence of nausea and vomiting and the effect of relieving spasm between patients administered glycopyrronium bromide and those given anisodamine hydrobromide following endoscopic retrograde cholangiopancreatography (ERCP). This is a monocentric prospective study. Patients eligible for ERCP were randomly assigned to two groups. One group received 0.2 mg glycopyrronium bromide (Group G) intravenously, while the other group received 10 mg anisodamine hydrobromide (Group A) intramuscularly for anesthesia induction. The study assessed duodenal motility during ERCP and the incidence of PONV within 24 hours. The study included 130 patients. Nausea and vomiting within 24 hours post-surgery occurred in nine patients (13.8%) in Group G and 19 patients (29.2%) in Group A, with statistical significance (relative risk (RR), 0.47; 95% confidence interval (CI) [0.02-0.29];  = 0.033). Vomiting specifically was observed in three patients (4.6%) in Group G and 12 patients (18.5%) in Group A, showing statistical significance (RR 0.25; 95% CI [0.03-0.25];  = 0.028). There was no significant difference in duodenal peristalsis between the groups (Group G: 10.9 ± 3.1 times/min; Group A: 11.6 ± 3.1 times/min;  = 0.174). For patients undergoing ERCP under general anesthesia, a subcutaneous injection of 0.2 mg glycopyrronium bromide significantly reduces PONV and provides similar anti-spasmodic effects to 10 mg intramuscular anisodamine hydrobromide.

Background Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. Methods In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ 2 test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. Results Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p  = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p  = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). Conclusions There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Sepsis, marked by hyperinflammation and subsequent immunosuppression, lacks effective phase-specific therapies. Although anisodamine hydrobromide (Ani HBr) reduced 28-day mortality in our prior trial, its mechanisms remained unclear. Here, we integrated network pharmacology, machine learning, immunological profiling, molecular simulations, and single-cell transcriptomics to elucidate Ani HBr’s multi-target actions. Among 30 cross-species targets, ELANE and CCL5 emerged as core regulators via protein interaction networks, survival modeling (AUC: 0.72–0.95), and statistical significance (p < 0.05). Ani HBr inhibited ELANE-driven NET formation (HR = 1.176), associated with immunosuppression and endothelial damage, while enhancing CCL5-related cytotoxic T-cell recruitment (HR = 0.810). Docking and dynamics simulations showed Ani HBr binds ELANE’s catalytic cleft, suggesting direct inhibition of its enzymatic activity, and interacts stably with CCL5 at potential receptor-binding interfaces, indicating a modulatory role. Single-cell analysis revealed ELANE upregulation in CCI-phase neutrophils and widespread yet stage-specific CCL5 expression. These findings support Ani HBr as a phase-tailored agent that targets ELANE in early hyperinflammation while preserving CCL5-mediated immunity. The ELANE/CCL5 prognostic model offers a framework for precision immunotherapy in sepsis.

The skeleton of tropane alkaloids is derived from ornithine-derived N -methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N -methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), Aa PYKS, Ds PYKS, and Ab PYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of Aa PYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N -methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N -methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation. Tropane alkaloids are medicinally significant plant metabolites generated by an unusual condensation of ornithine-derived and malonyl-CoA precursors. Here, Huang et al. show that pyrrolidine ketide synthase catalyzes a single round of condensation, which is followed by a non-enzymatic Mannich-like condensation.

Summary Transient expression in Nicotiana benthamiana offers a powerful and versatile platform for rapid production of complex specialized metabolites. Steroidal glycoalkaloids (SGAs) and steroidal saponins produced by members of the Solanaceae family are known for their diverse structures and activities including antimicrobial, anticancer, antiviral, and anti‐inflammatory. Attempts to reconstitute their complete biosynthetic pathway have been unsuccessful to date. In this study, we identified a different tomato (Solanum lycopersicum) GLYCOALKALOID METABOLISM2 (SlGAME2‐NEW) enzyme as a xylosyltransferase in the penultimate step of α‐tomatine and dehydrotomatine biosynthesis. The discovery of SlGAME2‐NEW facilitated the engineering of tomato SGAs and steroidal saponin biosynthesis in N. benthamiana. Expressing from 9 to 15 genes in combination we efficiently engineered a total of 20 steroidal ‘end products’ (both alkaloids and saponins) typically produced by tomato and eggplant and ones merely found in wild tomato species. Furthermore, we engineered the biosynthetic pathway of the steroidal saponins uttroside B, dehydrouttroside B, and their stereoisomers [25(S)‐uttroside B and 25(S)‐dehydrouttroside B]. Production of these metabolites in N. benthamiana opens broad possibilities for examining and exploring their therapeutic potential. This study therefore makes a significant contribution to the application of synthetic biology for producing high‐value steroidal metabolites in heterologous plant hosts.

Fe3O4-magnetic liposome (MLP) can deliver drugs to target tissues and can increase drug efficacy. The present study aimed to investigate the effects of solamargine (SM) and Fe3O4-SM in pancreatic cancer (PC). Cell viability was detected using a Cell Counting kit-8 assay. Apoptosis and cell cycle progression was tested using a flow cytometry assay. A scratch assay was used to examine cell metastasis. Quantitative polymerase chain reaction, western blot analysis or immunohistochemical analysis were performed to determine the expression of target factors. Magnetic resonance imagining (MRI) and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling were conducted to detect tumor growth and apoptosis in vivo, respectively. It was demonstrated that Fe3O4-SM inhibited cancer cell growth via a slow release of SM over an extended period of time. SM was revealed to induce apoptosis and cell cycle arrest. Furthermore, SM decreased the expression of X-linked inhibitor of apoptosis, Survivin, Ki-67, proliferating cell nuclear antigen and cyclin D1, but increased the activity of caspase-3. It was also observed that SM inhibited tumor cell metastasis by modulating the expression of matrix metalloproteinase (MMP)-2 and TIMP metallopeptidase inhibitor-2. Furthermore, the phosphorylation of protein kinase B and mechanistic target of rapamycin was suppressed by SM. Notably, the effect of SM was enhanced by Fe3O4-SM. The malignant growth of PC was decreased by SM in vivo. Furthermore, the expression of Ki-67 was decreased by SM and Fe3O4-SM. Additionally, cell apoptosis was increased in the Fe3O4-SM group, compared with the SM group. The present study illustrated the antitumor effect and action mec hanism produced by SM. Additionally, it was demonstrated that Fe3O4-SM was more effective than SM in protecting against PC.

Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP −/− and NLRP3 −/− (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1β, and IL-18) were detected. The knock down of TXNIP or NLRP3 expression in mice showed protective effect against RIAKI pathogenesis, as compared with the RIAKI mice. The expression of Caspase-1, ASC, and interleukins, renal injury, renal tubular cells apoptosis in TXNIP-KD and LNPR3-KD mice were significantly inhibited in comparison with the RIAKI mice. Moreover, anisodamine treatment reduced expression of ER stress markers IRE-1α, CHOP, and ATF4, TXNIP and NLRP3, as well as ACS, Caspase-1, IL-1α, IL-1β, and IL-18, showing moderate protective effect on the changes of above factors comparing with TXNIP or NLRP3 knock down. This study declared that anisodamine showed protective effect on RIAKI model may by inhibiting ER stress associated TXNIP/NLRP3 inflammasome.

Increasing evidences have revealed that solasodine, isolated from fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied. To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay. Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3β signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased. Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.