Risk Factor Analysis and Nomogram for Early Progression of COVID-19 Pneumonia in Older Adult Patients in the Omicron Era.

Background and Objective: Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era. Methods: A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves. Results: A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3-5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count <400/µL, the Activities of Daily Living (ADL) score ≤40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively. Conclusion: We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.

Photoinduced Cobalt Catalyzed Radical Heck-Type Reaction of Alkyl Electrophiles.

We report here a general alkylation reaction of terminal alkenes with nucleophilic cobaloxime complex catalysis under visible light irradiation. A broad range of vinyl arenes and heteroarenes, as well as a diverse set of alkyl(pseudo)halides or strained rings as alkyl electrophiles, can efficiently undergo the transformation up to the gram scale. Mechanistic study reveals the radical nature of the reaction and corroborates our design involving alkylcobaloxime as the key intermediate.

Inflammasome activation and metabolic remodelling in p16-positive aging cells aggravates high-fat diet-induced lung fibrosis by inhibiting NEDD4L-mediated K48-polyubiquitin-dependent degradation of SGK1.

BACKGROUND: Chronic changes caused by a high-fat diet (HFD) may be associated with weakened lung function in obese patients. However, few studies have focused on the role of senescent cells in HFD-induced pulmonary fibrosis. This study aimed to determine whether (i) obesity causes the accumulation of aging cells in the lungs, (ii) p16 accumulation in aging epithelial cells or fibroblasts exacerbates long-term HFD-induced senescence-associated pulmonary fibrosis (SAPF) and (iii) p16 deletion or clearance of aging cells ameliorates HFD-induced SAPF through inactivation of the inflammasome and metabolic remodelling. METHODS: Twelve-month old male mice of p16INK4a (hereafter p16) knockout (p16-- ) and wild-type (WT), ApoE knockout (ApoE-- ) and ApoE-- p16-- were fed a HFD to induce obesity, and the effects of treatment with the senolytic drug ABT263 or the SGK1 specific inhibitor EMD638683 on fibrosis, inflammaging, gene expression, integrin-inflammasome signalling and metabolism were examined. A549 and IMR-90 cells were transduced with p16-overexpressing adenovirus, and treated with palmitic and oleic acids (P&O) to induce steatosis in vitro. RESULTS: We found that long-term HFD promoted the expression of p16 and the increase of senescent cells in the lung. P16 knockout or ABT263 treatment alleviated pulmonary fibrosis, the increase of senescent cells and senescence-associated secretory phenotype (SASP) in HFD-fed mice, as well as in P&O-treated A549 and IMR-90 cells. RNA sequencing and bioinformatics analyses revealed that p16 knockout inhibited activation of the integrin-inflammasome pathway and cellular glycolysis. Mass spectrometry, co-immunoprecipitation and GST pull-down assays demonstrated that p16 bound to the N-terminal of SGK1, thereby interfering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, and subsequently inhibiting K48-polyubiquitin-dependent degradation of SGK1 mediated by the NEDD4L-Ubch5 complex. EMD638683 was found to alleviate HFD-induced pulmonary fibrosis and activation of the integrin-inflammasome pathway. CONCLUSION: P16 accumulation promoted activation of integrin- inflammasome pathway and cell glycolysis by binding to the N- terminal of SGK1, intefering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, thereby inhibiting K48- polyubiquitin- dependent degradation of SGK1 mediated by the NEDD4L-Ubch5 complex. ABT263 or EMD638683 could be used as potential drugs to treat pulmonary fibrosis in obese patients.

Bioreduction performance of Cr(VI) by microbial extracellular polymeric substances (EPS) and the overlooked role of tryptophan.

Extracellular polymeric substances (EPS) have exhibited promising advantages in mitigating heavy metal contamination, e.g., single-valent silver (Ag(I)), trivalent gold (Au(III)), and hexavalent chromium (Cr(VI)). However, knowledge of the specific substrate in EPSs that supports Cr(VI) reduction has remained elusive. Here, we isolated a novel Cr(VI)-reducing strain with self-mediating properties in an aquatic environment with various pH values to investigate the mechanisms. After analysis by a batch assay coupled with X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and scanning electron microscopy-energy dispersive spectrometry (SEM-EDS) spectroscopic techniques, it was found that Cr(VI) was reduced by the strain and soluble-EPS (S-EPS), and then, organo-trivalent chromium (organo-Cr(III)) was successfully formed. In addition, compared with other components of the strain, the strain and S-EPS completely removed Cr(VI), and the S-EPS exhibited a positive effect on Cr(VI) reduction with a strong monotonic correlation (R2 = 0.999, p = 9.03 × 10-5), indicating that the reduction is an EPS-dependent process. Specifically, the Cr(VI) reduction efficiency was enhanced to 48.85% and 99.4% after EPS and EPS plus tryptophan were added; their respective efficiencies were 3.94 and 8.02 times higher than that of the control assay in which the reductant was depleted. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis showed that the tryptophan concentration concomitantly decreased by 61.54%. These findings highlighted the importance of S-EPS and tryptophan and improved our understanding of EPS for Cr(VI) reduction, which might provide a novel strategy for decontaminating targeted heavy metals in future applications.

Sanguinarine: A Double-Edged Sword of Anticancer and Carcinogenesis and Its Future Application Prospect.

BACKGROUND: Sanguinarine, a kind of benzophenanthridine alkaloid, is a natural compound with potential development value for its anticancer activity. Hundreds of studies have been carried out in vivo or in vitro, trying to make it feasible for the anticancer clinic medication of sanguinarine. However, sanguinarine was branded as a toxicant or even a carcinogen according to some toxicological experiments and cancer investigations. OBJECTIVE: Aiming at safety and effectiveness of sanguinarine, this article reviews the extant information on present studies of sanguinarine, and both anticancer carcinogenesis mechanism details are summarized. The future potential research directions of this valued compound are also discussed to provide reference for future drugs development. METHODS: PubMed, Web of Science, CNKI and WanFang databases were used to search current studies and experimental researches about anticancer effect or carcinogenic information of sanguinarine. RESULTS: Our results indicated that sanguinarine exhibited anticancer effect through anti-proliferation, anti-invasion, anti-angiogenesis and apoptosis within cancer lesion. Also, many clinical investigations indicated that sanguinarine and its related products might be associated to pre-carcinoma within oral or skin potentially. CONCLUSION: Sanguinarine is a natural compound with good development value for its potent anticancer activity; however, its carcinogenesis effect should also be taken seriously. Studies on structural modification and analogue design should be carried out to improve its safety and efficiency in the future.

Enhancing nitrate removal from wastewater by integrating heterotrophic and autotrophic denitrification coupled manganese oxidation process (IHAD-MnO): Internal carbon utilization performance.

Due to cause the deterioration of water quality and can produce toxic nitrite, the nitrate constituted of great threatens to human health and eco-systematic safety. Among most well-known biotechnology to remove nitrate, the integrated heterotrophic and autotrophic denitrification (IHAD) process is promising, especially for the organic-limited polluted water. In this work, the IHAD coupled manganese oxidation (IHAD-MnO) process was developed by using Pseudomonas sp. SZF15 (Gram negative strain, and rod-shaped morphology with 2.3 µm in length) in the glass serum bottles. It was found that limited organic content could accelerate nitrate removal rate, and manganese oxidation efficiency can reach up to 60.08%. To further explain carbon conversion characteristics of the process, pure heterotrophic condition assays were conducted, the results confirmed that inorganic carbon will be generated by organic carbon metabolism in heterotrophic condition, the maximum accumulation content of inorganic carbon was 142.21 mg/L (when the initial organic carbon level was 293 mg-C/L). Subsequently, since the consumption of organic carbon, biogenic inorganic carbon can be further utilized by microorganisms to support autotrophic denitrification (AuDN). Besides, X-ray photoelectron spectroscopy (XPS) was employed to analyze precipitation products produced from the process. The magnified Mn 2p spectra results showed that a typical characteristic peak of manganese dioxide was observed with the intense peak at 641.8 eV and a satellite peak at 653.7 eV, respectively. This showed that Mn(II) was oxidized to manganese dioxide by the process, which may be a functional material with adsorption properties. The process posed a highly efficient and cost effective solution with less carbon consumption and less greenhouse gas emission for sustainable water treatment technologies.

Impact of Red Yeast Rice on Metabolic Diseases: A Review of Possible Mechanisms of Action.

Metabolic diseases constitute a major public health burden and are linked with high morbidity and mortality. They comprise atherosclerosis dyslipidemia, diabetes, hypertension, and obesity. However, there is no single drug that can simultaneously treat multiple diseases with complex underlying mechanisms. Therefore, it is necessary to identify a class of adjuvant drugs that block the development of metabolic diseases from a preventive perspective. Red yeast rice is a food fermentation product widely used to promote blood circulation and remove blood stasis. Modern pharmacology has shown that red yeast rice exerts potential protective effects on the liver, pancreas, blood vessels, and intestines. Therefore, this study was carried out to analyze and summarize the effect of red yeast rice on several metabolic diseases and the mechanisms of action involved. It was found that red yeast rice may be beneficial in the prevention and treatment of metabolic diseases.

Modulation of Apoptosis by Plant Polysaccharides for Exerting Anti-Cancer Effects: A Review.

Cancer has become a significant public health problem with high disease burden and mortality. At present, radiotherapy and chemotherapy are the main means of treating cancer, but they have shown serious safety problems. The severity of this problem has caused further attention and research on effective and safe cancer treatment methods. Polysaccharides are natural products with anti-cancer activity that are widely present in a lot of plants, and many studies have found that inducing apoptosis of cancer cells is one of their important mechanisms. Therefore, this article reviews the various ways in which plant polysaccharides promote apoptosis of cancer cells. The major apoptotic pathways involved include the mitochondrial pathway, the death receptor pathway, and their upstream signal transduction such as MAPK pathway, PI3K/AKT pathway, and NF-κB pathway. Moreover, the paper has also been focused on the absorption and toxicity of plant polysaccharides with reference to extant literature, making the research more scientific and comprehensive. It is hoped that this review could provide some directions for the future development of plant polysaccharides as anticancer drugs in pharmacological experiments and clinical researches.

The role of diosgenin in diabetes and diabetic complications.

Diabetes mellitus is a chronic and common metabolic disease that seriously endangers human health. Hyperglycemia and long-term metabolic disorders in diabetes will cause damage to the whole body tissues and organs, resulting in serious complications. Nowadays, drugs for treating diabetes on the market has strong side effects, new treatments thus are urgently needed. Natural therapy of natural ingredients is a promising avenue, this is because natural ingredients are safer and they also show strong activity in the treatment of diabetes. Diosgenin is such a very biologically active natural steroidal sapogenin. The research of diosgenin in the treatment of diabetes and its complications has been widely reported. This article reviews the effects of diosgenin through multiple targets and multiple pathways in diabetes and its complications which including diabetic nephropathy, diabetic liver disease, diabetic neuropathy, diabetic vascular disease, diabetic cardiomyopathy, diabetic reproductive dysfunction, and diabetic eye disease.

P16INK4a played a critical role in exacerbating acute tubular necrosis in acute kidney injury.

Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality, which is mostly caused by acute tubular necrosis (ATN). AKI is associated with many factors, including cell senescence, inflammatory infiltration, apoptosis and excessive accumulation of reactive oxygen species (ROS). P16INK4a (hereafter termed p16) inhibits cell cycle, and the absence of p16 can significantly slow the progression of cell senescence. We found that the expression of p16 was significantly increased after ATN. To determine whether p16 could exacerbate ATN degree and whether p16 deletion had protective effects against the ATN and renal dysfunction in AKI progression, glycerol-rhabdomyolysis-induced ATN was performed in eight-week-old p16 knockout and wild-type (WT) littermates. Their ATN phenotypes were analyzed; the levels of serum creatinine and serum urea nitrogen were detected; inflammation, cell apoptosis, ROS level and ROS signaling pathway molecules were examined using histopathological and molecular techniques. We found that compared to WT mice, p16 deletion has protective effects against the ATN phenotype and renal dysfunction in AKI progression through ameliorating inflammatory infiltration and proinflammatory factor expression by inhibiting NF-κB proinflammatory pathway, decreasing cell apoptosis by balancing the expressions between pro-apoptotic and anti-apoptotic molecules, and reducing ROS levels and downregulating ROS signaling pathway molecules including AIF, PGAM5 and KEAP1. Thus, p16 deletion or inhibition and p16 positive cell clearance would be a novel strategy for preventing ATN in AKI progression.

Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review.

Xanthium strumarium L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the X. strumarium. Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. X. strumarium, as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from X. strumarium, including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from X. strumarium possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for X. strumarium should also be established.

Hesperidin: A Therapeutic Agent For Obesity.

Obesity is a chronic metabolic disease caused by multiple factors and is considered to be a risk factor for type 2 diabetes, cardiovascular disease, hypertension, stroke and various cancers. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against obesity diseases. Our review discusses mechanisms of hesperidin in the treatment of obesity. Hesperidin regulates lipid metabolism and glucose metabolism by mediating AMPK and PPAR signaling pathways, directly regulates antioxidant index and anti-apoptosis, and indirectly mediates NF-κB signaling pathway to regulate inflammation to play a role in the treatment of obesity. In addition, hesperidin-enriched dietary supplements can significantly improve symptoms such as postprandial hyperglycemia and hyperlipidemia. Further clinical trials are also required for confirming lipid-lowering efficacy of this natural flavonoid and evaluating its safety profile.

Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-κB and NLRP3 inflammasome.

Muscone is the main active monomer of traditional Chinese medicine musk. Previous studies have reported a variety of beneficial effects of muscone. However, the effects of muscone on chronic inflammation after myocardial infarction (MI) are rarely reported. This study evaluated the anti-inflammatory effects of muscone on myocardial infarction by establishing a MI model in mice. We found that muscone remarkably decreased the levels of inflammatory cytokines (IL-1ß, TNF-α and IL-6), and ultimately improved cardiac function and survival rate. Furthermore, the main anti-inflammatory effect of muscone was alleviating cardiac macrophage-mediated inflammatory response in heart tissues after MI. Bone marrow-derived macrophages (BMDMs) induced with lipopolysaccharide (LPS) were used as an in vitro inflammation model to further clarify anti-inflammatory mechanisms of muscone. Muscone significantly downregulated the levels of LPS-induced inflammatory cytokines and inhibited NF-κB and NLRP3 inflammasome activation in BMDMs. Moreover, ROS and antioxidant indices in LPS-induced BMDMs were also ameliorated after muscone treatment. To sum up, our study found that muscone alleviated cardiac macrophage-mediated chronic inflammation by inhibiting NF-κB and NLRP3 inflammasome activation, thereby improving cardiac function in MI mice. Besides, the inhibitory effect of muscone on inflammation may be related to the scavenging of ROS. It is suggested that muscone may serve as a promising and effective drug for post-MI treatment.