Activity and safety evaluation of natural preservatives.

Synthetic preservatives are widely used in the food industry to control spoilage and growth of pathogenic microorganisms, inhibit lipid oxidation processes and extend the shelf life of food. However, synthetic preservatives have some side effects that can lead to poisoning, cancer and other degenerative diseases. With the improvement of living standards, people are developing safer natural preservatives to replace synthetic preservatives, including plant derived preservatives (polyphenols, essential oils, flavonoids), animal derived preservatives (lysozyme, antimicrobial peptide, chitosan) and microorganism derived preservatives (nisin, natamycin, ε-polylysine, phage). These natural preservatives exert antibacterial effects by disrupting microbial cell wall/membrane structures, interfering with DNA/RNA replication and transcription, and affecting protein synthesis and metabolism. This review summarizes the natural bioactive compounds (polyphenols, flavonoids and terpenoids, etc.) in these preservatives, their antioxidant and antibacterial activities, and safety evaluation in various products.

Blood-supplementing effect of low molecular weight peptides of E-Jiao on chemotherapy-induced myelosuppression: evaluation of pharmacological activity and identification of bioactive peptides released in vivo.

Background: Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao's blood-supplementing effect and to explore the specific peptides contributing to its efficacy. Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms. Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao's efficacy. Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.

Extraction, physicochemical properties, bioactivities and application of natural sweeteners: A review.

Natural sweeteners generally refer to a sweet chemical component directly extracted from nature or obtained through appropriate modifications, mainly secondary metabolites of plants. Compared to the first-generation sweeteners represented by sucrose and the second-generation sweeteners represented by sodium cyclamate, natural sweeteners usually have high sweetness, low-calorie content, good solubility, high stability, and rarely toxic side effects. Historically, researchers mainly focus on the function of natural sweeteners as substitutes for sugars in the food industry. This paper reviews the bioactivities of several typical natural sweeteners, including anti-cancer, anti-inflammatory, antioxidant, anti-bacterial, and anti-hyperglycemic activities. In addition, we have summarized the extraction, physicochemical properties, and application of natural sweeteners. The article aimed to comprehensively collate vital information about natural sweeteners and review the potentiality of tapping bioactive compounds from natural products. Hopefully, this review provides insights into the further development of natural sweeteners as therapeutic agents and functional foods.

Chromene meroterpenoids from Rhododendron dauricum L. and their anti-inflammatory effects.

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.

Myositis as a prominent manifestation of primary skeletal muscle peripheral T-cell lymphoma: a case report and literature review.

The patient presented to the clinic with painful muscle swelling in the right lower extremity, which improved with immunosuppressive therapy. Initially, the condition was diagnosed as polymyositis but recurred soon after. After imaging and biopsy, the final diagnosis was primary skeletal muscle peripheral T-cell lymphoma, not otherwise specified (PSM-PTCL, NOS). In this report, we discuss the challenges in diagnosing and treating this aggressive malignancy and review the literature on PSM-PTCL, NOS. Key Points • To date, there are few reports of PSM-PTCL, NOS, and our case is the tenth. • It is crucial to consider PSM-PTCL, NOS, when presenting with localized muscle edema and unexplained pain. • Histopathological examination is likely the most effective method for diagnosing this rare disease.

CXCL10 and IL15 co-expressing chimeric antigen receptor T cells enhance anti-tumor effects in gastric cancer by increasing cytotoxic effector cell accumulation and survival.

Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.

Multifunctional Biomimetic Liposomes with Improved Tumor-Targeting for TNBC Treatment by Combination of Chemotherapy, Antiangiogenesis and Immunotherapy.

Triple negative breast cancer (TNBC) featuring high relapses and metastasis shows limited clinical therapeutic efficiency with chemotherapy for the extremely complex tumor microenvironment, especially angiogenesis and immunosuppression. Combination of antiangiogenesis and immunotherapy holds promise for effective inhibition of tumor proliferation and invasion, while it remains challenging for specific targeting drug delivery to tumors and metastatic lesions. Here, a multifunctional biomimetic liposome loading Gambogic acid (G/R-MLP) is developed using Ginsenoside Rg3 (Rg3) to substitute cholesterol and cancer cell membrane coating, which is designed to increase long-circulating action by a low immunogenicity and specifically deliver gambogic acid (GA) to tumor site and metastatic lesions by homologous targeting and glucose transporter targeting. After G/R-MLP accumulates in the primary tumors and metastatic nodules, it synergistically enhances the antitumor efficacy of GA, effectively suppressing the tumor growth and lung metastasis by killing tumor cells, inhibiting tumor cell migration and invasion, achieving antiangiogenesis and improving the antitumor immunity. All in all, the strategy combining chemotherapy, antiangiogenesis, and immunotherapy improves therapeutic efficiency and prolonged survival, providing a new perspective for the clinical treatment of TNBC.

Conservative Interventions for Urinary Incontinence on Postpartum Women: A Systematic Review and Meta-Analysis.

INTRODUCTION: Urinary incontinence (UI) is common in postpartum women and can lead to a reduced quality of life and withdrawal from fitness and exercise activities. Conservative management interventions such as pelvic floor muscle training (PFMT), use of vaginal cones, and biofeedback have been recommended as first-line treatment. We aimed to explore the effects of conservative interventions on UI rate, severity, and incontinence-specific quality of life in postpartum women with UI. METHODS: Nine databases were searched from inception to August 2022: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, Wanfang, China National Knowledge Infrastructure, China Biological Medicine, and VIP Journal Integration Platform. Randomized controlled trials examining the effects of conservative interventions on postpartum UI were included. RESULTS: Initial searches produced 1839 results, of which 17 studies were eligible. All included studies had a low to moderate risk of bias. Supervised PFMT and use of a vaginal cone were more effective than individual PFMT in decreasing rates of UI (odds ratio, 0.29; 95% CI, 0.14-0.61). Individual PFMT combined with acupuncture (mean difference, -1.91; 95% CI, -2.46 to -1.37) or electroacupuncture and supervised PFMT combined with moxibustion were more effective than individual supervised PFMT alone in improving the severity of symptoms. Furthermore, electrical stimulation and biofeedback combined with acupoint stimulation or core training were more effective than electrical stimulation and biofeedback alone. For improving the incontinence-specific quality of life, supervised PFMT was more efficacious than individual PFMT; electrical stimulation and biofeedback plus core training were more beneficial than electrical stimulation and biofeedback alone. DISCUSSION: Supervised PFMT and use of a vaginal cone were more beneficial in decreasing rates of UI compared with individual PFMT. Superior effects in decreasing UI severity may be achieved by combining PFMT or electrical simulation and biofeedback with other therapies. Electrical stimulation and biofeedback plus core training, as well as supervised PFMT, are most effective in improving incontinence-specific quality of life. Further research is required to provide more evidence on the efficacy of these therapies.

Dual circulation strategy, regional healthcare development, and medical collaborative innovation efficiency: evidence from Chinese cities.

This study analyzes panel data of Chinese cities from 2003 to 2018 as a sample in the context of the dual circulation strategy in China to ascertain the impact of urban healthcare development on medical collaborative innovation efficiency by using the GS2SLS method. Furthermore, it empirically examines the influence mechanism of regional healthcare development on medical collaborative innovation efficiency by using a threshold regression model. Additionally, we identified the heterogeneity of this impact in different cities. The results show the following: (1) There is a significant positive spatial correlation between regional healthcare development and medical collaborative innovation efficiency; (2) Under the dual circulation strategy, the regional investment level in international circulation has the most significant role in the overall strategy, and domestic circulation has been significantly improved after the launch of the innovation-driven strategy; (3) The results of the threshold test show that while domestic and international circulation promote the efficiency of collaborative innovation by 0.83, the promotion effect is more obvious under a higher regional healthcare development level. The research in this paper can provide specific guidance for the development of China's healthcare industry under the background of dual-cycle strategy, and can also provide valuable reference for developing countries in the world.

Natural products with potential hypoglycemic activity in T2DM: 2019-2023.

As currently the most common metabolic disease, type 2 diabetes mellitus (T2DM) has shown a continuous increase in the number of patients in recent decades. Most anti-T2DM drugs tend to cause some side effects. Given the pathogenesis of T2DM, natural products have emerged as an important source of anti-T2DM drugs. This article reviews natural products with potential hypoglycemic activity from 2019 to 2023. A total of 200 previously natural products were discovered on SciFinder, PubMed and Web of Science. These products were categorized based on their structural frameworks and their biological activities were summarized. Although the mechanisms of action of most compounds are unclear, these compounds could still serve as candidates for the development of lead compounds. Therefore, further structure and activity research of natural products will significantly contribute to the development of potential anti-T2DM drugs.

Exploring work readiness: A qualitative descriptive study of self-perceptions among new graduate nurses.

Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.

Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective Additive.

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.

A Novel Classification of Juvenile and Adolescent Idiopathic Scoliosis for Conservative Treatment.

BACKGROUND: The operative classification of scoliosis is well-developed but inadequate for guiding conservative treatment. The current conservative classification for juvenile and adolescent idiopathic scoliosis (JAIS) exhibits noticeable deficiencies. This study aimed to establish the Peking Union Medical College Hospital (PUMCH) classification and assess its clinical value in the conservative treatment of JAIS. METHODS: This study consisted of 2 parts. First, it involved a retrospective analysis of patients treated for JAIS in the Department of Rehabilitation Medicine, the ∗∗∗ Union Medical College Hospital, between January 2013 and June 2020. Second, it involved an ambispective cohort study that enrolled patients with JAIS in the above hospital between July and December 2020. RESULTS: A total of 989 patients with JAIS were enrolled, with 899 patients for establishing the PUMCH classification and 90 patients with JAIS for validating the PUMCH classification. The classification demonstrated an average reliability of 88.22% with a kappa coefficient of 0.862. After 1 week, the remeasured results presented a mean reproducibility of 92.78% and a kappa coefficient of 0.908. After 1-year follow-up, the Cobb angle decreased significantly from 16.61 ± 2.88° to 12.16°± 9.97° (P = 0.002) in 51 patients with PUMCH-scoliosis-specific exercise (SSE) treatment, while the Cobb angle increased significantly from 15.74 ± 2.75° to 17.64 ± 5.60° (P = 0.014) in 39 patients without PUMCH-SSE treatment. CONCLUSIONS: The PUMCH-SSE classification demonstrates good inter-observer reliability and intra-observer reproducibility. In addition, the classification may be used to guide the conservative treatment of JAIS in clinical settings.

The association between serum copper concentration and prevalence of diabetes among US adults with hypertension (NHANES 2011-2016).

The objective of this study was to examine the association between the serum copper concentration and the prevalence of diabetes among US adults with hypertension using the data from the National Health and Nutrition Examination Survey (NHANES). The study population was selected from adults aged over 20 years old in the three survey cycles of NHANES from 2011 to 2016. Logistic regression model analyses were applied to determine the independent risky effect of copper to the prevalence of diabetes. Also, a restricted cubic spline (RCS) model was performed to explore the potential nonlinear association between serum copper concentration and the prevalence of diabetes. A total of 1786 subjects (742 cases and 1044 controls) were included, and 924 were men (51.7%), and 742 (41.5%) were diabetic. Compared with non-diabetic individuals, the concentration of serum copper in diabetic patients with hypertension was higher. After adjusting for age, sex, race, education, marital status, body mass index (BMI), family poverty income ratio (PIR), smoking, alcohol drinking, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperlipidemia, the highest quartile of serum copper concentration significantly increased the risk of diabetes as compared with the lowest quartile (OR: 1.38, 95% CI: 1.01-1.92, ptrend = 0.036). The results of RCS analysis showed significant non-linear relationship between serum copper concentration and prevalence of diabetes (p-non-linear = 0.010). This study finds that serum copper concentration are significantly associated with risk of diabetes in hypertensive patients, which suggests copper as an important risk factor of diabetes development.

Antioxidant aromatic compounds from Amomum villosum and target prediction of active ingredients.

The dried fruit of Amomum villosum is an important spice and medicinal plant that has received great attention in recent years due to its high content of bioactive components and its potential for food additives and drug development. However, the stems and leaves of A. villosum are usually disposed of as waste. Based on the study of the fruits of A. villosum, we also systematically studied its stems and leaves. Fourteen aromatic compounds (1-14) were isolated and identified from A. villosum, including five new compounds (1-5) and nine known compounds (6-14). Among them, compounds 2-5, 8-10, 12-13 were obtained from the fruits of A. villosum, and compounds 1, 6-7,11, 14 were isolated from the stems and leaves of A. villosum. Based on chemical evidence and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds were tested for their effects on the survival rate of BV-2 cells in the presence of hydrogen peroxide. Among them, compound 5 showed antioxidant effects. Through network pharmacology screening and the cell thermal shift assay (CETSA), the Phosphoglycerate Mutase 5 (PGAM5) protein was identified as the antioxidant target of compound 5. Molecular docking results showed that compound 5 maintains binding to PGAM5 by forming hydrogen bond interactions with Lys93 and Agr214. In summary, A. villosum had potential medicinal and food values due to the diverse bioactive components.

Unlocking the anticancer activity of gambogic acid: a shift towards ferroptosis via a GSH/Trx dual antioxidant system.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in ferroptosis by regulating the cellular antioxidant response and maintaining redox balance. However, compounds that induce ferroptosis through dual antioxidant pathways based on Nrf2 have not been fully explored. In our study, we investigated the impact of Gambogic acid (GA) on MCF-7 cells and HepG2 cells in vitro. The cytotoxicity, colony formation assay and cell cycle assay demonstrated potent tumor-killing ability of GA, while its effect was rescued by ferroptosis inhibitors. Furthermore, RNA sequencing revealed the enrichment of ferroptosis pathway mediated by GA. In terms of ferroptosis indicators detection, evidences for GA were provided including reactive oxygen species (ROS) accumulation, alteration in mitochondrial membrane potential (MMP), disappearance of mitochondrial cristae, lipid peroxidation induction, malondialdehyde (MDA) accumulation promotion, iron ion accumulation as well as glutathione (GSH)/thioredoxin (Trx) depletion. Notably, Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) successfully rescued GA-induced MDA accumulation. In terms of mechanism, Nrf2 was found to play a pivotal role in GA-induced ferroptosis by inducing protein alterations through the iron metabolism pathway and GSH/Trx dual antioxidant pathway. Furthermore, GA exerted good antitumor activity in vivo through GSH/Trx dual antioxidant pathway, and Fer-1 significantly attenuated its efficacy. In conclusion, our findings first provided new evidence for GA as an inducer of ferroptosis, and Nrf2-mediated GSH/Trx dual antioxidant system played an important role in GA-induced ferroptosis.

Associations of evening-type and insomnia symptoms with depressive symptoms among youths.

BACKGROUND: Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms. METHODS: Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023. Multivariate logistic regression models and additive interaction models were used to examine the independent and joint effects of chronotypes and insomnia symptoms on depressive symptoms, respectively. RESULTS: Of the 6145 eligible youths, the prevalence of evening-type and insomnia symptoms were 24.9 % and 29.6 %, respectively. Both evening-type (adjusted OR, [AdjOR]: 3.21, 95 % CI: 2.80-3.67) and insomnia symptoms (AdjOR: 10.53, 95 % CI: 9.14-12.12) were associated with an increased risk of depressive symptoms. In addition, the additive interaction models showed that there is an enhanced risk of depression related to interaction between evening-type and insomnia symptoms (relative excess risk due to interaction, [RERI]: 11.66, 95 % CI: 7.21-16.11). CONCLUSIONS: The present study provided additional evidence demonstrating the presence of interaction between evening-type and insomnia symptoms, which can lead to a higher risk of depressive symptoms. Our findings argue the need for addressing both sleep and circadian factors in the management of depressive symptoms in young people.

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis.

Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

The mechanism of UNC-51-like kinase 1 and the applications of small molecule modulators in cancer treatment.

Autophagy is a process of self-renewal in cells, which not only provides the necessary nutrients for cells, but also clears necrotic organelles. Autophagy disorders are closely related to diseases such as cancer. UNC-51-like kinase 1 (ULK1) is a serine/threonine protein kinase that plays a crucial role in receiving input from energy and nutrient sensors, activating autophagy to maintain cellular homeostasis under stressful conditions. In recent years, targeting ULK1 has become a highly promising strategy for cancer treatment. This review introduces the regulatory mechanism of ULK1 in autophagy through the AMPK/mTOR/ULK1 pathway and reviews the research progress of ULK1 activators and inhibitors and their applications in cancer treatment. In addition, we analyze the binding modes between ULK1 and modulators through virtual molecular docking, which will provide a reliable basis and theoretical guidance for the design and development of new therapeutic drugs targeting ULK1.

Simultaneous identification and enantioseparation of ofloxacin and duloxetine without the single standard and computational calculation of their inclusion complexes.

Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.