Nuciferine, an active ingredient derived from lotus leaf, lights up the way for the potential treatment of obesity and obesity-related diseases.

Obesity, is an increasingly global public health problem associated complications. However, the proven anti-obesity agents are inefficient with adverse side effects; hence attention is being paid to novel drugs from natural resources to manage obesity and obesity-related diseases. Nuciferine (NF) is a high-quality aporphine alkaloid present in lotus leaf. Unlike the chemical drugs, NF elicits anti-obesity, anti-dyslipidemia, anti-hyperglycemic, anti-hypouricemic, anti-inflammatory, and anti-tumor effects, and affinity to neural receptors, and protection against obesity-related diseases. The underlying mechanism of NF includes the regulation of targeted molecules and pathways related to metabolism, inflammation, and cancer and modulation of Ca2+ flux, gut microbiota, and ferroptosis. Besides, the clinical application, availability, pharmacokinetics, pharmaceutics, and security of NF have been established, highlighting the potential of developing NF as an anti-obesity agent. Therefore, this review provides a comprehensive summarization, which sheds light on future research in NF.

Therapeutic potential of dietary flavonoid hyperoside against non-communicable diseases: targeting underlying properties of diseases.

Non-communicable diseases (NCDs) are a global epidemic with diverse pathogenesis. Among them, oxidative stress and inflammation are the most fundamental co-morbid features. Therefore, multi-targets and multi-pathways therapies with significant anti-oxidant and anti-inflammatory activities are potential effective measures for preventing and treating NCDs. The flavonol glycoside compound hyperoside (Hyp) is widely found in a variety of fruits, vegetables, beverages, and medicinal plants and has various health benefits, especially excellent anti-oxidant and anti-inflammatory properties targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. In this review, we summarize the pathogenesis associated with oxidative stress and inflammation in NCDs and the biological activity and therapeutic potential of Hyp. Our findings reveal that the anti-oxidant and anti-inflammatory activities regulated by Hyp are associated with numerous biological mechanisms, including positive regulation of mitochondrial function, apoptosis, autophagy, and higher-level biological damage activities. Hyp is thought to be beneficial against organ injuries, cancer, depression, diabetes, and osteoporosis, and is a potent anti-NCDs agent. Additionally, the sources, bioavailability, pharmacy, and safety of Hyp have been established, highlighting the potential to develop Hyp into dietary supplements and nutraceuticals.

Combined effect of nanoscale zero-valent iron and linear alkylbenzene sulfonate (LAS) to the freshwater algae Scenedesmus obliquus.

With wide use of nanoparticles, co-exposure of aquatic organisms to nanoparticles and organic pollutants often takes place in the environment. However, the combined effects are still rarely understood. In this study, in order to study the interaction and biological effects of nanoscale zero-valent iron (nZVI) and linear alkylbenzene sulfonate (LAS), which acts as a typical surfactant, the freshwater algae Scenedesmus obliquus was exposed to nZVI and LAS individually and in combination for 96 h. According to the inhibition rate of the algae, the toxic effects were investigated by dose-response analysis. Then the combined effect of nZVI and LAS was evaluated using three evaluation models including toxicity unit (TU), additional index (AI), and mixture toxicity index (MTI). The results showed that the 96 h IC50 of nZVI and LAS to Scenedesmus obliquus was 2.464 mmol L-1 and 0.332 mmol L-1, respectively. When nZVI coexisted with LAS at toxic ratio 1:1, the 96 h IC50 value was 1.658 mmol L-1 (shown with nZVI), and the partly additive effect of nZVI mixed with LAS was confirmed. However, when the toxic ratio of nZVI:LAS was 4:1, it showed synergistic effect. In addition, when nZVI mixed with LAS at toxic ratio 1:4, the joint effect is antagonistic effect. In addition, the content of chorophyll in Scenedesmus obliquus, especially the content of chlorophyll a, was decreased with the increase of mixture dose. However, the protein levels did not show significant changes at different mixture doses.

Sub-regional Radiomics Analysis for Predicting Metastasis Risk in Clear Cell Renal Cell Carcinoma: A Multicenter Retrospective Study.

RATIONALE AND OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm affecting the kidney, exhibiting a dismal prognosis in metastatic instances. Elucidating the composition of ccRCC holds promise for the discovery of highly sensitive biomarkers. Our objective was to utilize habitat imaging techniques and integrate multimodal data to precisely predict the risk of metastasis, ultimately enabling early intervention and enhancing patient survival rates. MATERIAL AND METHODS: A retrospective analysis was performed on a cohort of 263 patients with ccRCC from three hospitals between April 2013 and March 2021. Preoperative CT images, ultrasound images, and clinical data were comprehensively analyzed. Patients from two campuses of Qilu Hospital of Shandong University were assigned to the training dataset, while the third hospital served as the independent testing dataset. A robust consensus clustering method was used to classify the primary tumor space into distinct sub-regions (i.e., habitats) using contrast-enhanced CT images. Radiomic features were extracted from these tumor sub-regions and subsequently reduced to identify meaningful features for constructing a predictive model for ccRCC metastasis risk assessment. In addition, the potential value of radiomics in predicting ccRCC metastasis risk was explored by integrating ultrasound image features and clinical data to construct and compare alternative models. RESULTS: In this study, we performed k-means clustering within the tumor region to generate three distinct tumor subregions. We quantified the Hounsfiled Unit (HU) value, volume fraction, and distribution of high- and low-risk groups in each subregion. Our investigation focused on 252 patients with Habitat1 + Habitat3 to assess the discriminative power of these two subregions. We then developed a risk prediction model for ccRCC metastasis risk classification based on radiomic features extracted from CT and ultrasound images, and clinical data. The Combined model and the CT_Habitat3 model showed AUC values of 0.935 [95%CI: 0.902-0.968] and 0.934 [95%CI: 0.902-0.966], respectively, in the training dataset, while in the independent testing dataset, they achieved AUC values of 0.891 [95%CI: 0.794-0.988] and 0.903 [95%CI: 0.819-0.987], respectively. CONCLUSION: We have identified a non-invasive imaging predictor and the proposed sub-regional radiomics model can accurately predict the risk of metastasis in ccRCC. This predictive tool has potential for clinical application to refine individualized treatment strategies for patients with ccRCC.

Healthcare providers' perceived barriers to providing breastfeeding support in Northwest rural China.

BACKGROUND: Healthcare providers play important roles in supporting breastfeeding. Although there has been insufficient actual breastfeeding support from healthcare providers in China, little research has been conducted to understand Chinese healthcare providers' perceived barriers to providing breastfeeding support, especially in rural China. This study aims to identify these perceived barriers to providing breastfeeding support in Northwestern rural China. METHODS: This study was conducted during the period from March 2018 to December 2018. Forty-one healthcare providers were recruited through purposive sampling in two rural counties in Northwest China that are in close proximity to each other and share similar demographic features. Participants included obstetrician-gynecologists, midwives, nurses, "village doctors", and township and village maternal and child health workers. Qualitative data were collected through one-on-one in-depth semi-structured interviews and focus group discussions. Transcripts were thematically analyzed. RESULTS: Analysis of interview data resulted in four themes that the participants perceived as barriers to supporting breastfeeding: (1) lack of medical resources, within which inadequate staffing, and lack of financial incentives were discussed, (2) lack of clear and specific responsibility assignment, within which no one takes the lead, and mutual buck-passing were discussed, (3) healthcare providers' lack of relevant expertise, within which lack of knowledge and skills, and low prestige of village healthcare providers were discussed, (4) difficulties in accessing mothers, within which medical equipment shortages reduce services utilization, mothers' housing situation, mothers' mobility, and cultural barriers were discussed. CONCLUSIONS: The study identified HCPs perceived barriers to providing breastfeeding support. Unique to China's Tri-Level Healthcare System, challenges like staffing and financial incentives are hard to swiftly tackle. Recommendations include mHealth enhancement and clarified responsibilities with incentives and tailored training. Further research is crucial to evaluate these strategies in rural Northwestern China and comparable underdeveloped areas nationwide.

New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Vasorelaxant Activities and its Underlying Mechanisms of Magnolia Volatile Oil on Rat Thoracic Aorta Based on Network Pharmacology.

Objective: Magnolia volatile oil (MVO) is a mixture mainly containing eudesmol and its isomers. This study was to investigate the vasorelaxant effects and the underlying mechanism of MVO in rat thoracic aortas. Method: The present study combined gas chromatography-mass spectrometry (GC-MS) and network pharmacology analysis with in vitro experiments to clarify the mechanisms of MVO against vessel contraction. A compound-target network, compound-target-disease network, protein-protein interaction network, compound-target-pathway network, gene ontology, and pathway enrichment for hypertension were applied to identify the potential active compounds, drug targets, and pathways. Additionally, the thoracic aortic rings with or without endothelium were prepared to explore the underlying mechanisms. The roles of the PI3K-Akt-NO pathways, neuroreceptors, K+ channels, and Ca2+ channels on the vasorelaxant effects of MVO were evaluated through the rat thoracic aortic rings. Results: A total of 29 compounds were found in MVO, which were identified by GC-MS, of which 21 compounds with a content of more than 0.1% were selected for further analysis. The network pharmacology research predicted that beta-caryophyllene, palmitic acid, and (+)-ß-selinene might act as the effective ingredients of MVO for the treatment of hypertension. Several hot targets, mainly involving TNF, CHRM1, ACE, IL10, PTGS2, REN, and F2, and pivotal pathways, such as the neuroactive ligand-receptor interaction, the calcium signaling pathway, and the PI3K-Akt signaling, were responsible for the vasorelaxant effect of MVO. As expected, MVO exerted a vasorelaxant effect on the aortic rings pre-contracted by KCl and phenylephrine in an endothelium-dependent and non-endothelium-dependent manner. Importantly, a pre-incubation with indomethacin (Indo), N-nitro-L-arginine methyl ester, methylene blue, wortmannin, and atropine sulfate as well as 4-aminopyridione diminished MVO-induced vasorelaxation, suggesting that the activation of the PI3K-Akt-NO pathway and KV channel were involved in the vasorelaxant effect of MVO, which was consistent with the results of the Kyoto Encyclopedia of Genes and the Genomes. Additionally, MVO could significantly inhibit Ca2+ influx resulting in the contraction of aortic rings, revealing that the inhibition of the calcium signaling pathway exactly participated in the vasorelaxant activity of MVO as predicted by network pharmacology. Conclusion: MVO might be a potent treatment of diseases with vascular dysfunction like hypertension. The underlying mechanisms were related to the PI3K-Akt-NO pathway, KV pathway, as well as Ca2+ channel, which were predicted by the network pharmacology and verified by the experiments in vitro. This study based on network pharmacology provided experimental support for the clinical application of MVO in the treatment of hypertension and afforded a novel research method to explore the activity and mechanism of traditional Chinese medicine.

Ginsenoside CK, rather than Rb1, possesses potential chemopreventive activities in human gastric cancer via regulating PI3K/AKT/NF-κB signal pathway.

Ginsenoside Rb1, a main component of ginseng, is often transformed into ginsenoside CK by intestinal flora to exert various pharmacological activity. However, it remains unclear whether ginsenoside CK is responsible for the anti-gastric cancer effect of ginsenoside Rb1 in vivo. In this study, network pharmacology was applied to predict the key signal pathways of ginsenoside Rb1 and ginsenoside CK when treating gastric cancer. The anti-proliferative effects of ginsenoside Rb1 and ginsenoside CK and the underlying mechanism in gastric cancer cells were explored by MTT, Hoechst3328 staining, ELISA, RT-qPCR and Western blotting. The results showed that PI3K-AKT/NF-κB signal pathway was the common important pathway of ginsenoside Rb1 and CK in the treatment of gastric cancer. The results of MTT assay showed that ginsenoside Rb1 could hardly inhibit the proliferation of HGC-27 cells, whereas ginsenoside CK could inhibit the proliferation of HGC-27 cells. Hoechst3328 staining showed that cells in the ginsenoside CK group were densely stained bright blue and nuclear fragmented, indicating that apoptosis occurred. ELISA results showed that ginsenoside CK could effectively downregulate the levels of cyclin CyclinB1 and CyclinD1, but ginsenoside Rb1 had no significant effect. Also, the results of Western blot and RT-qPCR showed that ginsenoside CK inhibited the expressions of anti-apoptosis-related protein Bcl-2 and apoptosis-related pathway PI3K/AKT/NF-κB, and promoted the expression of pro-apoptosis proteins Bax and Caspase 3, whereas ginsenoside Rb1 exerted no effect. In short, ginsenoside Rb1 had no anti-gastric cancer cell activity in vitro, but ginsenoside CK could effectively inhibit cell proliferation and induce cell apoptosis in HGC-27 cells. The mechanism might relate to the inhibitory effect of ginsenoside CK on the PI3K/AKT/NF-κB pathway. These results suggest that ginsenoside CK might be the in vivo material basis for the anti-gastric cancer activity of ginsenosides.

Can aloin develop to medicines or healthcare products?

In folk medicine, Aloe, a genus of Aloaceae, is constantly developed into laxative drugs or products and skin remedies with tremendous popularity worldwide. However, almost all products of Aloe are in roughly processed form. Therefore, developing related products of the active ingredients derived from Aloe is of great medical value. Aloin is a quality standard compound based on the Chinese Pharmacopoeia (CHP). It has a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, anti-osteoporotic, organ-protective, anti-viral, anti-microbial, anti-parasitic, and laxative potentials. Moreover, it regulates blood lipids and glucose and improves neuropathic pain effects, depicting potential to be transformed into promising medicines and healthcare products. In addition to the functional cosmetics and health products of Aloe, the availability, pharmacological activities, pharmacokinetics, formulation studies, and toxicity of aloin were summarized after investigating the literature from PubMed, Google, and other databases. Moreover, significant attention had been paid to the development of aloin-derived medicines and healthcare products. Thus, the present review clarified the possibility of aloin as medicines and healthcare products to develop and utilize Aloe resources.

New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD is complex. One-targeted anti-AD drugs usually fail to delay AD progression. Traditional Chinese medicine records have documented the use of the roots of Panax ginseng (ginseng roots) and its prescriptions to treat dementia. Ginsenoside Rg1, the main ginsenoside component of ginseng roots, exhibits a certain therapeutic effect in the abovementioned diseases, suggesting its potential in the management of AD. Therefore, we combed the pathogenesis of AD and currently used anti-AD drugs, and reviewed the availability, pharmacokinetics, and pharmaceutic studies of ginsenoside Rg1. This review summarizes the therapeutic effects and mechanisms of ginsenoside Rg1 and its deglycosylated derivatives in AD in vivo and in vitro. The main mechanisms include improvement in Aß and Tau pathologies, regulation of synaptic function and intestinal microflora, and reduction of inflammation, oxidative stress, and apoptosis. The underlying mechanisms mainly involve the regulation of PKC, MAPK, PI3K/Akt, CDK5, GSK-3ß, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, and TLR4 signaling pathways. As the effects and underlying mechanisms of ginsenoside Rg1 on AD have not been systematically reviewed, we have provided a comprehensive review and shed light on the future directions in the utilization of ginsenoside Rg1 and ginseng roots as well as the development of anti-AD drugs.

Emerging Significance of Ginsenosides as Potentially Reversal Agents of Chemoresistance in Cancer Therapy.

Chemoresistance has become a prevalent phenomenon in cancer therapy, which alleviates the effect of chemotherapy and makes it difficult to break the bottleneck of the survival rate of tumor patients. Current approaches for reversing chemoresistance are poorly effective and may cause numerous new problems. Therefore, it is urgent to develop novel and efficient drugs derived from natural non-toxic compounds for the reversal of chemoresistance. Researches in vivo and in vitro suggest that ginsenosides are undoubtedly low-toxic and effective options for the reversal of chemoresistance. The underlying mechanism of reversal of chemoresistance is correlated with inhibition of drug transporters, induction of apoptosis, and modulation of the tumor microenvironment(TME), as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (NRF2)/AKT, lncRNA cancer susceptibility candidate 2(CASC2)/ protein tyrosine phosphatase gene (PTEN), AKT/ sirtuin1(SIRT1), epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/AKT, PI3K/AKT/ mammalian target of rapamycin(mTOR) and nuclear factor-κB (NF-κB). Since the effects and the mechanisms of ginsenosides on chemoresistance reversal have not yet been reviewed, this review summarized comprehensively experimental data in vivo and in vitro to elucidate the functional roles of ginsenosides in chemoresistance reversal and shed light on the future research of ginsenosides.

High-efficiency near-infrared enabled planar perovskite solar cells by embedding upconversion nanocrystals.

Integration of the upconversion effect in perovskite solar cells (PSCs) is a facile approach towards extending the spectral absorption from the visible to the near infrared (NIR) range and reducing the non-absorption loss of solar photons. However, the big challenge for practical application of UCNCs in planar PSCs is the poor compatibility between UCNCs and the perovskite precursor. Herein, we have subtly overcome the tough compatibility issue using a ligand-exchange strategy. For the first time, ß-NaYF4:Yb,Er UCNCs have been embedded in situ into a CH3NH3PbI3 layer to fabricate NIR-enabled planar PSCs. The CH3NH3I-capped UCNCs generated from the ligand-exchange were mixed with the perovskite precursor and served as nucleation sites for the UCNC-mediated heteroepitaxial growth of perovskite; moreover, the in situ embedding of UCNCs into the perovskite layer was realized during a spin-coating process. The resulting UCNC-embedded perovskite layer attained a uniform pinhole-free morphology with enlarged crystal grains and enabled NIR absorption. It also contributed to the energy transfer from the UCNCs to the perovskite and electron transport to the collecting electrode surface. The device fabricated using the UCNC-embedded perovskite film achieved an average power-conversion efficiency of 18.60% (19.70% for the best) under AM 1.5G and 0.37% under 980 nm laser, corresponding to 54% and 740-fold increase as compared to that of its counterpart without UCNCs.

Essential role of Gly33 in a novel organic solvent-tolerant lipase from Serratia marcescens ECU1010 as determined by site-directed mutagenesis.

A novel lipase lipB from Serratia marcescens ECU1010 is highly stable in the presence of organic solvents. By sequence and structure comparison with homologous lipase lipA, three amino acid residues were found to be different between them. To identify the residues which increase the organic solvent stability of lipB, residues that potentially provide this stability were mutated to the ones of lipA at equivalent positions. The replacement of Gly at position 33 by Asp obviously decreased its stability in organic solvents. Molecular modeling and structural analysis also suggested that the Gly33 residue is important for the organic solvent stability of lipB.

[Complications of CO2 laser surgery in the treatment of laryngeal carcinoma].

OBJECTIVE: To evaluate the complications of CO2 laser surgery in the treatment of laryngeal carcinoma, to analyze related factors and to propose preventive measures. METHODS: Retrospective analysis of 912 cases of laryngeal carcinoma (35 cases of supraglottic cancer and 877 cases of glottic cancer) treated only with laser surgery in Tongren Hospital was carried out. Among the glottic cancer, carcinoma in situ (Tis), T1, T2 and T3 were 53, 659, 158 and 7 cases. The follow-up period ranged from 2 to 18 years, with a median follow-up time of 9.3 years. RESULTS: Of 912 cases, 824 cases were still alive, 29 cases failed to be followed-up (taken into dead number), and 59 cases were dead. The recurrent rate was 9.4% (86/912). Three year survival rate was 95.6% (775/811) and five year survival rate was 87.9% (518/589). The incidence of surgery complications was 9.1% (83/912). Incidence of complications in supraglottic carcinoma and glottic carcinoma were 17.1%(6/35) and 8.8% (77/877), respectively, with no difference between the two groups (χ(2) = 2.85, P > 0.05). Incidence of complications of Tis, T1, T2 and T3 cases of glottic cancer were 5.7%(3/53), 7.8% (51/659), 13.3% (21/158) and 28.6% (2/7) respectively, with significant difference (χ(2) = 8.97, P < 0.05). Incidence of complications of glottic carcinoma with and without anterior commissure incision were 12.8%(31/242) and 7.2%(46/635) respectively, with significant difference between the two groups (χ(2) = 6.78, P < 0.05). Incidence of complications in the patients underwent type II, III, IV, V cordectomy were 3.8% (4/105), 7.0% (20/287), 9.7% (22/226) and 12.0% (31/259) respectively, with significant difference (χ(2) = 7.96, P < 0.05). CONCLUSIONS: There are some potential risks and complications intra- and post-operatively, according to the sites and extent of the primary tumors and the range and depth of removed tissues. It needs to take active preventive measures to reduce the incidence of complications.