Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Active targeting tumor therapy using host-guest drug delivery system based on biotin functionalized azocalix[4]arene.

Host-guest drug delivery systems (HGDDSs) provided a facile method for incorporating biomedical functions, including efficient drug-loading, passive targeting, and controlled drug release. However, developing HGDDSs with active targeting is hindered by the difficult functionalization of popular macrocycles. Herein, we report an active targeting HGDDS based on biotin-modified sulfonated azocalix[4]arene (Biotin-SAC4A) to efficiently deliver drug into cancer cells for improving anti-tumor effect. Biotin-SAC4A was synthesized by amide condensation and azo coupling. Biotin-SAC4A demonstrated hypoxia responsive targeting and active targeting through azo and biotin groups, respectively. DOX@Biotin-SAC4A, which was prepared by loading doxorubicin (DOX) in Biotin-SAC4A, was evaluated for tumor targeting and therapy in vitro and in vivo. DOX@Biotin-SAC4A formulation effectively killed cancer cells in vitro and more efficiently delivered DOX to the lesion than the similar formulation without active targeting. Therefore, DOX@Biotin-SAC4A significantly improved the in vivo anti-tumor effect of free DOX. The facilely prepared Biotin-SAC4A offers strong DOX complexation, active targeting, and hypoxia-triggered release, providing a favorable host for effective breast cancer chemotherapy in HGDDSs. Moreover, Biotin-SAC4A also has potential to deliver agents for other therapeutic modalities and diseases.

Effects and mechanisms of anti-diabetic dietary natural products: an updated review.

Diabetes is a global public health issue, characterized by an abnormal level of blood glucose. It can be classified into type 1, type 2, gestational, and other rare diabetes. Recent studies have reported that many dietary natural products exhibit anti-diabetic activity. In this narrative review, the effects and underlying mechanisms of dietary natural products on diabetes are summarized based on the results from epidemiological, experimental, and clinical studies. Some fruits (e.g., grape, blueberry, and cherry), vegetables (e.g., bitter melon and Lycium barbarum leaves), grains (e.g., oat, rye, and brown rice), legumes (e.g., soybean and black bean), spices (e.g., cinnamon and turmeric) and medicinal herbs (e.g., Aloe vera leaf and Nigella sativa), and vitamin C and carotenoids could play important roles in the prevention and management of diabetes. Their underlying mechanisms include exerting antioxidant, anti-inflammatory, and anti-glycation effects, inhibiting carbohydrate-hydrolyzing enzymes, enhancing insulin action, alleviating insulin resistance, modulating the gut microbiota, and so on. This review can provide people with a comprehensive knowledge of anti-diabetic dietary natural products, and support their further development into functional food to prevent and manage diabetes.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Invited review: Camel milk and gut health-Understanding digestibility and the effect on gut microbiota.

Camel milk (CM), known for its immune-regulatory, anti-inflammatory, antiapoptotic, and antidiabetic properties, is a natural healthy food. It is easily digestible due to the high levels of ß-casein and diverse secreted antibodies, exhibiting superior antibacterial and antiviral activities compared with bovine milk. ß-casein is less allergic and more digestible because it is more susceptible to digestive hydrolysis in the gut; therefore, higher levels of ß-casein make CM advantageous for human health. Furthermore, antibodies help the digestive system by destroying the antigens, which are then overwhelmed and digested by macrophages. The connection between the gut microbiota and human health has gained substantial research attention, as it offers potential benefits and supports disease treatment. The gut microbiota has a vital role in regulating the host's health because it helps in several biological functions, such as protection against pathogens, immune function regulation, energy harvesting from digested foods, and reinforcement of digestive tract biochemical barriers. These functions could be affected by the changes in the gut microbiota profile, and gut microbiota differences are associated with several diseases, such as inflammatory bowel disease, colon cancer, irritable bowel disorder, mental illness, allergy, and obesity. This review focuses on the digestibility of CM components, particularly protein and fat, and their influence on gut microbiota modulation. Notably, the hypoallergenic properties and small fat globules of CM contribute to its enhanced digestibility. Considering the rapid digestion of its proteins under conditions simulating infant gastrointestinal digestion, CM exhibits promise as a potential alternative for infant formula preparation due to the high ß-/αs-casein ratio and protective proteins, in addition to the absence of ß-lactoglobulin.

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps.

Objective: To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Methods: The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. Results: The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve. Conclusion: These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

Antioxidant Activities, Phenolic Compounds, and Sensory Acceptability of Kombucha-Fermented Beverages from Bamboo Leaf and Mulberry Leaf.

Kombucha is traditional drink made from the fermentation of a black tea infusion, and is believed to offer a variety of health benefits. Recently, exploring kombucha made from alternative substrates has become a research hotspot. In this paper, two novel kombucha beverages were produced with bamboo leaf or mulberry leaf for the first time. Moreover, the effects of fermentation with leaf residues (infusion plus residues) or without leaf residues (only infusion) on the antioxidant properties of kombucha were compared. The ferric-reducing antioxidant power assay, Trolox equivalent antioxidant capacity assay, Folin-Ciocalteu method, and high-performance liquid chromatography were utilized to measure the antioxidant capacities, total phenolic contents, as well as some compound concentrations of the kombucha. The results showed that two types of kombucha had high antioxidant capacities. Moreover, kombucha fermented with bamboo leaf residues (infusion plus residues) significantly enhanced its antioxidant capabilities (maximum increase 83.6%), total phenolic content (maximum increase 99.2%), concentrations of some compounds (luteolin-6-C-glucoside and isovitexin), and sensory acceptability, compared to that without residues (only infusion). In addition, fermentation with leaf residues had no significant effect on mulberry leaf kombucha. Overall, the bamboo leaf was more suitable for making kombucha with residues, while the mulberry leaf kombucha was suitable for fermentation with or without residues.

Preparation, Antioxidant Activities and Bioactive Components of Kombucha Beverages from Golden-Flower Tea (Camellia petelotii) and Honeysuckle-Flower Tea (Lonicera japonica).

Kombucha is a fermented tea known for its health benefits. In this study, golden-flower tea (Camellia petelotii) and honeysuckle-flower tea (Lonicera japonica) were first used as raw materials to prepare kombucha beverages. The antioxidant activities, total phenolic contents, concentrations of bioactive components, and sensory scores of two kombucha beverages were assessed. Additionally, effects of fermentation with or without tea residues on kombucha beverages were compared. The results found that two kombucha beverages possessed strong antioxidant activities and high scores of sensory analysis. In addition, fermentation with golden-flower tea residues could remarkably enhance the antioxidant activity (maximum 2.83 times) and total phenolic contents (3.48 times), while fermentation with honeysuckle tea residues had a minor effect. Furthermore, concentrations of several bioactive compounds could be increased by fermentation with golden-flower tea residues, but fermentation with honeysuckle-flower tea residues had limited effects. Moreover, the fermentation with or without tea residues showed no significant difference on sensory scores of golden-flower tea kombucha and honeysuckle-flower tea kombucha, and golden-flower tea kombucha had higher sensory scores than honeysuckle-flower tea kombucha. Therefore, it might be a better strategy to produce golden-flower tea kombucha by fermentation with tea residues, while honeysuckle-flower tea kombucha could be prepared without tea residues.

The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components.

The number of individuals experiencing mental disorders (e.g., anxiety and depression) has significantly risen in recent years. Therefore, it is essential to seek prevention and treatment strategies for mental disorders. Several gut microbiota, especially Firmicutes and Bacteroidetes, are demonstrated to affect mental health through microbiota-gut-brain axis, and the gut microbiota dysbiosis can be related to mental disorders, such as anxiety, depression, and other mental disorders. On the other hand, dietary components, including probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., dietary fiber and alpha-lactalbumin), synbiotics, postbiotics (e.g., short-chain fatty acids), dairy products, spices (e.g., Zanthoxylum bungeanum, curcumin, and capsaicin), fruits, vegetables, medicinal herbs, and so on, could exert protective effects against mental disorders by enhancing beneficial gut microbiota while suppressing harmful ones. In this paper, the mental disorder-associated gut microbiota are summarized. In addition, the protective effects of dietary components on mental health through targeting the gut microbiota are discussed. This paper can be helpful to develop some dietary natural products into pharmaceuticals and functional foods to prevent and treat mental disorders.

Quality evaluation of citrus varieties based on phytochemical profiles and nutritional properties.

Introduction: China is one of the major producers and exporters of various kinds of citrus fruits. As one of China's major citrus planting bases, Sichuan has a citrus planting area that exceeds 400,000 hectares. Meanwhile, citrus cultivation has become one of the important agricultural pillar industries in the region. Citrus fruits are reported to show various health-promoting effects, especially antioxidant activity. However, reports on the functional, nutritional and qualitative characteristics of different citrus varieties in Sichuan are still scarce. Methods: The quality attributes (color parameters, shape, and size), juice properties (titratable acids and total soluble sugar), mineral elements, and health-promoting nutritional and functional components (protein, carbohydrates, fat, dietary fiber, ascorbic acid, phenolic acids, and flavonoids), as well as antioxidant properties of 10 typical citrus varieties cultivated in Sichuan, were systematically investigated and analyzed. Results and Discussion: Significant differences among different citrus varieties were found. In particular, the total soluble sugar content of Mingrijian was higher than that of other citrus, suggesting its potential for fresh consumption and food processing. Moreover, a total of five flavonoids and nine phenolic acids were identified and quantified. Yuanhong, with higher contents of ascorbic acid and phenolic acids, was considered to be a valuable variety with excellent antioxidant capacity and can be used for value-added processing in the food industry. Principal component analysis and hierarchical cluster heatmap analysis suggested that there were significant differences among the 10 citrus varieties. Correlation analysis confirmed the significant contribution of ascorbic acid and phenolic acids to antioxidant capacity in citrus. The results can provide some references for the cultivation and selection of nutritious citrus fruits.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

A general supramolecular adjuvant for pesticides based on host-guest recognition.

BACKGROUND: Pesticides are indispensable in agriculture and can effectively improve the yields and quality of crops. Due to their weak water solubility, most pesticides need to be dissolved by adding solubilizing adjuvants. In this work, based on molecular recognition of the macrocyclic host, we developed a novel supramolecular adjuvant, called sulfonated azocalix[4]arene (SAC4A), which significantly improves the water solubility of pesticides. RESULTS: SAC4A presents multiple advantages, including high water solubility, strong binding affinity, universality, and simple preparation. SAC4A showed an average binding constant value of 1.66 × 105 M-1 for 25 pesticides. Phase solubility results indicated that SAC4A increased the water solubility of pesticides by 80-1310 times. The herbicidal, fungicidal, and insecticidal activities of supramolecular formulations were found to be superior to those of technical pesticides, and the herbicidal effects were even better than those of commercial formulations. CONCLUSION: Overall results revealed the potential of SAC4A to improve the solubility and effectiveness of pesticides, providing a new development idea for the application of adjuvants in agriculture. © 2023 Society of Chemical Industry.

Triple targeting host-guest drug delivery system based on lactose-modified azocalix[4]arene for tumor ablation.

Host-guest drug delivery systems (HGDDSs) have been studied in an effort to modify the characteristics of therapeutic agents through noncovalent interactions, reduce toxic side effects and improve therapeutic effects. However, it is still an important task to continuously improve the targeting ability of HGDDSs, which is conducive to the development of precision medicine. Herein, we utilize the lactose-modified azocalix[4]arene (LacAC4A) as a triple targeting drug carrier customized for antitumor purposes. LacAC4A integrates three targeting features, passive targeting through the enhancing permeability and retention effect, active targeting by the interactions of lactose and the asialoglycoprotein receptors on the surface of tumor cells, and stimuli-responsive targeting via the reduction of the azo group under a hypoxia microenvironment. After loading doxorubicin (DOX) in LacAC4A, the supramolecular nanoformulation DOX@LacAC4A clearly showed the effective suppression of tumor growth through in vivo experiments. LacAC4A can achieve effective targeting, rapid release, and improve drug bioavailability. This design principle will provide a new material for drug delivery systems.

Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea. OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored. METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota. RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota. CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.

Effects and mechanisms of natural products on Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in elderly people with a high incidence rate and complicated pathogenesis, and causes progressive cognitive deficit and memory impairment. Some natural products and bioactive compounds from natural sources show great potential in the prevention and treatment of AD, such as apple, blueberries, grapes, chili pepper, Monsonia angustifolia, cruciferous vegetables, Herba epimedii, Angelica tenuissima, Embelia ribes, sea cucumber, Cucumaria frondosa, green tea, Puer tea, Amanita caesarea and Inonotus obliquus, via reducing amyloid beta (Aß) deposition, decreasing Tau hyperphosphorylation, regulating cholinergic system, reducing oxidative stress, inhibiting apoptosis and ameliorating inflammation. This review mainly summarizes the effects of some natural products and their bioactive compounds on AD with the potential molecular mechanisms.

Current extraction, purification, and identification techniques of tea polyphenols: An updated review.

Tea, as a beverage, has been reputed for its health benefits and gained worldwide popularity. Tea polyphenols, especially catechins, as the main bioactive compounds in tea, exhibit diverse health benefits and have wide applications in the food industry. The development of tea polyphenol-incorporated products is dependent on the extraction, purification, and identification of tea polyphenols. Recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of tea polyphenols. This review, therefore, introduces the classification of tea and summarizes the main conventional and novel techniques for the extraction of polyphenols from various tea products. The advantages and disadvantages of these techniques are also intensively discussed and compared. In addition, the purification and identification techniques are summarized. It is hoped that this updated review can provide a research basis for the green and efficient extraction, purification, and identification of tea polyphenols, which can facilitate their utilization in the production of various functional food products and nutraceuticals.

Effects and mechanisms of tea on obesity.

Obesity has become a global health concern. It increases the risk of several diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain cancers, which threatens human health and increases social economic burden. As one of the most consumed beverages, tea contains various phytochemicals with potent bioactive properties and health-promoting effects, such as antioxidant, immune-regulation, cardiovascular protection and anticancer. Tea and its components are also considered as potential candidates for anti-obesity. Epidemiological studies indicate that regular consumption of tea is beneficial for reducing body fat. In addition, the experimental studies demonstrate that the potential anti-obesity mechanisms of tea are mainly involved in increasing energy expenditure and lipid catabolism, decreasing nutrient digestion and absorption as well as lipid synthesis, and regulating adipocytes, neuroendocrine system and gut microbiota. Moreover, most of clinical studies illustrate that the intake of green tea could reduce body weight and alleviate the obesity. In this review, we focus on the effect of tea and its components on obesity from epidemiological, experimental, and clinical studies, and discuss their potential mechanisms.

Dietary sources, health benefits, and risks of caffeine.

Dietary intake of caffeine has significantly increased in recent years, and beneficial and harmful effects of caffeine have been extensively studied. This paper reviews antioxidant and anti-inflammatory activities of caffeine as well as its protective effects on cardiovascular diseases, obesity, diabetes mellitus, cancers, and neurodegenerative and liver diseases. In addition, we summarize the side effects of long-term or excessive caffeine consumption on sleep, migraine, intraocular pressure, pregnant women, children, and adolescents. The health benefits of caffeine depend on the amount of caffeine intake and the physical condition of consumers. Moderate intake of caffeine helps to prevent and modulate several diseases. However, the long-term or over-consumption of caffeine can lead to addiction, insomnia, migraine, and other side effects. In addition, children, adolescents, pregnant women, and people who are sensitive to caffeine should be recommended to restrict/reduce their intake to avoid potential adverse effects.

An Antitumor Dual-Responsive Host-Guest Supramolecular Polymer Based on Hypoxia-Cleavable Azocalix[4]arene.

The exploitation of specific guests which can respond to external stimuli is the main approach for the construction of stimuli-responsive supramolecular polymers (SPs) based on host-guest interactions. Most functional guests, however, fail to manifest stimuli-responses. Herein, a hypoxia-responsive dimeric azocalixarene (D-SAC4A) with outstanding hosting properties was used as the macrocyclic building block for the preparation of host stimuli-responsive SPs. Since azocalixarenes can also be compatible with stimuli-responsive guests, an antitumor drug, camptothecin (CPT), was chosen and linked via a disulfide-containing linker to afford a glutathione (GSH)-responsive ditropic guest (D-CPT). A unique dual-responsive SP was obtained by 1 : 1 mixing of D-SAC4A and D-CPT in water, which further assembled into SP nanoparticles (DSPNs). DSPNs displayed outstanding stability against dilution and biological interferants, as well as precise CPT-release under GSH and hypoxia conditions. In vitro and in vivo experiments demonstrated the good biosafety and tumor-suppressive effects of DSPNs.