The nonvesicular sterol transporter Aster-C plays a minor role in whole body cholesterol balance.

Introduction: The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions. Method: Age-matched Gramd1c +/+ and Gramd1c -/- mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterol-derived metabolites were assessed in the feces, liver, and plasma. Results: Compared to wild type controls (Gramd1c +/+) mice, mice lackingGramd1c (Gramd1c -/-) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c +/+ controls, Gramd1c -/- mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c -/- mice. Bulk RNA sequencing in the liver showed that Gramd1c -/- mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions. Discussion: Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.

A serine-conjugated butyrate prodrug with high oral bioavailability suppresses autoimmune arthritis and neuroinflammation in mice.

Butyrate-a metabolite produced by commensal bacteria-has been extensively studied for its immunomodulatory effects on immune cells, including regulatory T cells, macrophages and dendritic cells. However, the development of butyrate as a drug has been hindered by butyrate's poor oral bioavailability, owing to its rapid metabolism in the gut, its low potency (hence, necessitating high dosing), and its foul smell and taste. Here we report that the oral bioavailability of butyrate can be increased by esterifying it to serine, an amino acid transporter that aids the escape of the resulting odourless and tasteless prodrug (O-butyryl-L-serine, which we named SerBut) from the gut, enhancing its systemic uptake. In mice with collagen-antibody-induced arthritis (a model of rheumatoid arthritis) and with experimental autoimmune encephalomyelitis (a model of multiple sclerosis), we show that SerBut substantially ameliorated disease severity, modulated key immune cell populations systemically and in disease-associated tissues, and reduced inflammatory responses without compromising the global immune response to vaccination. SerBut may become a promising therapeutic for autoimmune and inflammatory diseases.

Treatment ideas of acupuncture and moxibustion for adenomyosis based on "etiology, location, nature and development of disease". / 基于"ç— å› ã€ç— ä½ã€ç— æ€§ã€ç— åŠ¿"æµ æžå­å®«è ºè‚Œç—‡çš„é’ˆç¸æ²»ç–—æ€è·¯.

Focusing on the syndrome/pattern differentiation to determine treatment, the approaches to the diagnosis and treatment of acupuncture and moxibustion for adenomyosis are explored by identifying the etiology, location, nature and development of disease. The syndromes/patterns of adenomyosis are differentiated in view of both zangfu and meridian theories. The treatment is delivered complying with the menstrual cycle and the basic rule of treatment, "treating the symptoms in the acute stage, while the root causes in the recovery stage". During menstrual period, stopping pain and eliminating stasis are dominant; while during the other days of menstrual cycle, regulating zangfu dysfunction (excess or deficiency) is emphasized. In general, the functions of the thoroughfare vessel and the conception vessel should be specially considered and adjusted, and the principles of treatment include strengthening the spleen, regulating the kidney and soothing the liver. Acupoints are selected mainly from the spleen meridian of foot-taiyin, the kidney meridian of foot-shaoyin and the conception vessel. Ciliao (BL 32), Shiqizhui (EX-B 8), Zigong (EX-CA 1), Diji (SP 8) and four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]) are used in menstrual period; Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3) in postmenstrual phase; Guanyuan (CV 4), Luanchao (Ovary, Extra) and Qihai (CV 6) in intermenstrual phase; while, Guanyuan (CV 4), Qihai (CV 6) and Shenque (CV 8), combined with Gongsun (SP 4), Neiguan (PC 6) and Jianshi (PC 5) in premenstrual phase. According to the dynamic development of patient's conditions, the reinforcing or reducing techniques of acupuncture and moxibustion are feasibly applied in treatment of adenomyosis.

Urban heat mitigation by green and blue infrastructure: Drivers, effectiveness, and future needs.

The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate change. Yet, the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure (GBGI), such as parks, wetlands, and engineered greening, which have the potential to effectively reduce summer air temperatures. Despite many reviews, the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are unclear. This systematic literature review synthesizes the evidence base for heat mitigation and related co-benefits, identifies knowledge gaps, and proposes recommendations for their implementation to maximize their benefits. After screening 27,486 papers, 202 were reviewed, based on 51 GBGI types categorized under 10 main divisions. Certain GBGI (green walls, parks, street trees) have been well researched for their urban cooling capabilities. However, several other GBGI have received negligible (zoological garden, golf course, estuary) or minimal (private garden, allotment) attention. The most efficient air cooling was observed in botanical gardens (5.0 ± 3.5°C), wetlands (4.9 ± 3.2°C), green walls (4.1 ± 4.2°C), street trees (3.8 ± 3.1°C), and vegetated balconies (3.8 ± 2.7°C). Under changing climate conditions (2070-2100) with consideration of RCP8.5, there is a shift in climate subtypes, either within the same climate zone (e.g., Dfa to Dfb and Cfb to Cfa) or across other climate zones (e.g., Dfb [continental warm-summer humid] to BSk [dry, cold semi-arid] and Cwa [temperate] to Am [tropical]). These shifts may result in lower efficiency for the current GBGI in the future. Given the importance of multiple services, it is crucial to balance their functionality, cooling performance, and other related co-benefits when planning for the future GBGI. This global GBGI heat mitigation inventory can assist policymakers and urban planners in prioritizing effective interventions to reduce the risk of urban overheating, filling research gaps, and promoting community resilience.

Harnessing and delivering microbial metabolites as therapeutics via advanced pharmaceutical approaches.

Microbial metabolites have emerged as key players in the interplay between diet, the gut microbiome, and host health. Two major classes, short-chain fatty acids (SCFAs) and tryptophan (Trp) metabolites, are recognized to regulate inflammatory, immune, and metabolic responses within the host. Given that many human diseases are associated with dysbiosis of the gut microbiome and consequent reductions in microbial metabolite production, the administration of these metabolites represents a direct, multi-targeted treatment. While a multitude of preclinical studies showcase the therapeutic potential of both SCFAs and Trp metabolites, they often rely on high doses and frequent dosing regimens to achieve systemic effects, thereby constraining their clinical applicability. To address these limitations, a variety of pharmaceutical formulations approaches that enable targeted, delayed, and/or sustained microbial metabolite delivery have been developed. These approaches, including enteric encapsulations, esterification to dietary fiber, prodrugs, and nanoformulations, pave the way for the next generation of microbial metabolite-based therapeutics. In this review, we first provide an overview of the roles of microbial metabolites in maintaining host homeostasis and outline how compromised metabolite production contributes to the pathogenesis of inflammatory, metabolic, autoimmune, allergic, infectious, and cancerous diseases. Additionally, we explore the therapeutic potential of metabolites in these disease contexts. Then, we provide a comprehensive and up-to-date review of the pharmaceutical strategies that have been employed to enhance the therapeutic efficacy of microbial metabolites, with a focus on SCFAs and Trp metabolites.

Undescribed sesquiterpenoids with NO production inhibitory activity from oleo-gum resin of Commiphora myrrha.

Six undescribed cadinane sesquiterpenoids (1-6), two undescribed guaiane sesquiterpenoids (7-8), and an undescribed germacrane sesquiterpenoid (9) were isolated from the oleo-gum resin of Commiphora myrrha. Their structures were determined by the analysis of 1D/2D NMR and HRESIMS data, as well as quantum chemical ECD and NMR calculations. All the sesquiterpenoids were evaluated for their NO production inhibitory activity in LPS-stimulated RAW 264.7 mouse monocyte-macrophages. The results revealed that commiphone A (1) and commipholide D (7) exhibited significant inhibitory effect on NO generation with IC50 values of 18.6 ± 2.0 and 37.5 ± 1.5 µM, respectively. Furthermore, 1 and 7 dose-dependently inhibited the mRNA expression of inflammatory cytokines IL-1ß, IL-6 and TNF-α induced by LPS in the RAW264.7 cells, indicating that 1 and 7 possess potent anti-inflammatory activity in vitro.

Zonal demand-controlled ventilation strategy to minimize infection probability and energy consumption: A coordinated control based on occupant detection.

Due to the outbreak of COVID-19, an increased risk of airborne transmission has been experienced in buildings, particularly in confined public places. The need for ventilation as a means of infection prevention has become more pronounced given that some basic precautions (like wearing masks) are no longer mandatory. However, ventilating the space as a whole (e.g., using a unified ventilation rate) may lead to situations where there is either insufficient or excessive ventilation in localized areas, potentially resulting in localized virus accumulation or large energy consumption. It is of urgent need to investigate real-time control of ventilation systems based on local demands of the occupants to strike a balance between infection risk and energy saving. In this work, a zonal demand-controlled ventilation (ZDCV) strategy was proposed to optimize the ventilation rates in sub-zones. A camera-based occupant detection method was developed to detect occupants (with eight possible locations in sub-zones denoted as 'A' to 'H'). Linear ventilation model (LVM), dimension reduction, and artificial neural network (ANN) were integrated for rapid prediction of pollutant concentrations in sub-zones with the identified occupants and ventilation rates as inputs. Coordinated ventilation effects between sub-zones were optimized to improve infection prevention and energy savings. Results showed that rapid prediction models achieved an average prediction error of 6 ppm for CO2 concentration fields compared with the simulation under different occupant scenarios (i.e., occupant locations at ABH, ABCFH, and ABCDEFH). ZDCV largely reduced the infection risk to 2.8% while improved energy-saving efficiency by 34% compared with the system using constant ventilation rate. This work can contribute to the development of building environmental control systems in terms of pollutant removal, infection prevention, and energy sustainability.

Withanolides: Promising candidates for cancer therapy.

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.

Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics.

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients that reduces efficacy and increases adverse reactions. Our laboratory has shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer, p(Man). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We find that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by T regulatory cells. We identify increased T cell receptor signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.

Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy.

The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We develop a tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously (s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified ß-lactoglobulin (BLG) is effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows superior safety and potential in treating existing allergies in combination with anti-CD20 co-therapy. This platform provides an antigen-specific immunomodulatory strategy to prevent and treat food allergies.

Development of dual-mode ELISA based on ALP-catalyzed APP hydrolysis for IL-6 detection.

Sensitive and accurate detection of interleukin 6 (IL-6) is crucial for the early diagnosis of cerebral infarction to improve patient survival rates. However, the low-abundance of IL-6 in cerebral infarction presents a significant challenge in developing effective diagnosis method. Herein, we studied and analyzed the strong fluorescence property of 4-aminophenol phosphate (APP) and developed an enzyme-linked immunosorbent assay (ELISA) for IL-6 detection. The detection was based on the integration of optical signal change induced by alkaline phosphatase (ALP)-catalyzed APP hydrolysis and ALP-mediated ELISA. The generated colorimetric signal of 4-aminophenol, APP hydrolysis product, was used for ELISA of IL-6 with a detection limit of 0.1 ng/mL, and the visual detection of IL-6 was achieved. The changes in APP fluorescence have a good linear relationship with the logarithm of IL-6 concentration in the range of 0.005 ng/mL to 5.0 ng/mL, with a detection limit of 0.001 ng/mL, which was 100 times lower than that of conventional pNPP-based ELISA. Furthermore, the constructed ELISA effectively distinguished between samples from patients with cerebral infarction and volunteers with non-cerebral infarction, and the severity of symptoms was well distinguished based on IL-6 measurement. The dual-mode ELISA demonstrated high feasibility of low-abundance biomarker detection and displayed good potential for accurate in vitro diagnosis.

Metaorganismal choline metabolism shapes olfactory perception.

Microbes living in the intestine can regulate key signaling processes in the central nervous system that directly impact brain health. This gut-brain signaling axis is partially mediated by microbe-host-dependent immune regulation, gut-innervating neuronal communication, and endocrine-like small molecule metabolites that originate from bacteria to ultimately cross the blood-brain barrier. Given the mounting evidence of gut-brain crosstalk, a new therapeutic approach of "psychobiotics" has emerged, whereby strategies designed to primarily modify the gut microbiome have been shown to improve mental health or slow neurodegenerative diseases. Diet is one of the most powerful determinants of gut microbiome community structure, and dietary habits are associated with brain health and disease. Recently, the metaorganismal (i.e., diet-microbe-host) trimethylamine N-oxide (TMAO) pathway has been linked to the development of several brain diseases including Alzheimer's, Parkinson's, and ischemic stroke. However, it is poorly understood how metaorganismal TMAO production influences brain function under normal physiological conditions. To address this, here we have reduced TMAO levels by inhibiting gut microbe-driven choline conversion to trimethylamine (TMA), and then performed comprehensive behavioral phenotyping in mice. Unexpectedly, we find that TMAO is particularly enriched in the murine olfactory bulb, and when TMAO production is blunted at the level of bacterial choline TMA lyase (CutC/D), olfactory perception is altered. Taken together, our studies demonstrate a previously underappreciated role for the TMAO pathway in olfactory-related behaviors.

Mannose-Decorated Co-Polymer Facilitates Controlled Release of Butyrate to Accelerate Chronic Wound Healing.

Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non-healing diabetic wounds is explored. This butyrate-containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non-healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non-healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non-healing wounds.

Refined design of ventilation systems to mitigate infection risk in hospital wards: Perspective from ventilation openings setting.

To prevent respiratory infections between patients and medical workers, the transmission risk of airborne pollutants in hospital wards must be mitigated. The ventilation modes, which are regarded as an important strategy to minimize the infection risk, are challenging to be systematically designed. Studies have considered the effect of ventilation openings (inlets/outlets) or infected source locations on the airflow distribution, pollutant removal, and infection risk mitigation. However, the relationship (such as relative distance) between ventilation openings and infected sources is critical because it affects the direct exhaust of exhaled pollutants, which has not been thoroughly studied. To explore pollutant removal and infection prevention in wards, different ventilation modes (with varying ventilation openings) and infected patient locations must be jointly considered. This study investigated displacement ventilation (DV), downward ventilation (DWV), and stratum ventilation (SV) with 4, 6, and 10 scenarios of ventilation openings, respectively. The optimal ventilation mode and relative distance between outlets and infected patients were analyzed based on the simulated pollutant concentration fields and the evaluated infection risk. The pollutant removal effect and infection risk mitigation of SV in the ward were largely improved by 75% and 59% compared with DV and DWV, respectively. The average infection risk was reduced below 7% when a non-dimensional relative distance (a ratio of the actual distance to the cubic root of the ward volume) was less than 0.25 between outlets and infected patient. This study can serve as a guide for the systematic ventilation system design in hospitals during the epidemic.

Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics.

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer (p(Man)). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We found that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by Tregs. We identify increased TCR signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.

Can retro-reflective materials replace diffuse highly reflective materials for urban buildings' wall to improve outdoor thermal comfort?

In recent years, there have been numerous studies on the application of retroreflective (RR) materials to exterior building walls to relieve the urban heat island (UHI) phenomenon and save building energy consumption instead of diffuse highly reflective (DHR) materials. Experimental measurements were undertaken to investigate the impact of applying DHR and RR materials to building exterior walls on the outdoor thermal environment. DHR and RR walls were tested with three canyon aspect ratios ( H / D ) of 0.5, 1.0, and 1.5, respectively, with seven environmental indexes recorded and compared, including air temperature ( T a ), relative humidity ( R H ), sol-air temperature ( S A T ), operative temperature ( O T ), standard effective temperature ( S E T * ), change in operative temperature ( C O T ), and real-time solar reflectance ( ρ ). The results show that the RR wall is more effective in improving the outdoor thermal environment, where S A T decreased by 4.5 °C, S E T * decreased by 0.5 °C, and COT decreased by 1.2 °C, on average, while it can also improve the real-time solar reflectance ( ρ ) by 12% on average compared to the DHR wall. Moreover, it gets more effective in scenarios with a higher canyon aspect ratio.

Intelligent operation, maintenance, and control system for public building: Towards infection risk mitigation and energy efficiency.

During the post-COVID-19 era, it is important but challenging to synchronously mitigate the infection risk and optimize the energy savings in public buildings. While, ineffective control of ventilation and purification systems can result in increased energy consumption and cross-contamination. This paper is to develop intelligent operation, maintenance, and control systems by coupling intelligent ventilation and air purification systems (negative ion generators). Optimal deployment of sensors is determined by Fuzzy C-mean (FCM), based on which CO2 concentration fields are rapidly predicted by combing the artificial neural network (ANN) and self-adaptive low-dimensional linear model (LLM). Negative oxygen ion and particle concentrations are simulated with different numbers of negative ion generators. Optimal ventilation rates and number of negative ion generators are decided. A visualization platform is established to display the effects of ventilation control, epidemic prevention, and pollutant removal. The rapid prediction error of LLM-based ANN for CO2 concentration was below 10% compared with the simulation. Fast decision reduced CO2 concentration below 1000 ppm, infection risk below 1.5%, and energy consumption by 27.4%. The largest removal efficiency was 81% when number of negative ion generators was 10. This work can promote intelligent operation, maintenance, and control systems considering infection prevention and energy sustainability.

New verticillane-diterpenoid as potent NF-κB inhibitor isolated from the gum resin of Boswellia sacra.

Two new verticillane-diterpenoids (1 and 2) were isolated from the gum resin Boswellia sacra. Their structures were elucidated by physiochemical and spectroscopic analysis, as well as ECD calculation. In addition, the in vitro anti-inflammatory activities of the isolated compounds were evaluated by determining the inhibitory effects on lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse monocyte-macrophages. The results showed that compound 1 exhibited significant inhibitory effect on NO generation with an IC50 value of 23.3 ± 1.7 µM suggesting that it might be a candidate for an anti-inflammatory agent. Furthermore, 1 potently inhibited the release of inflammatory cytokines IL-6 and TNF-α induced by LPS in a dose-dependent manner. Using Western blot and Immunofluorescence methods, compound 1 was found to inhibit inflammation mainly by restraining the activation of NF-κB pathway. And in the MAPK signaling pathway, it was found to have inhibitory effects on the phosphorylation of JNK and ERK proteins and have no effect on the phosphorylation of p38 protein.

A bibliometric analysis and visualization of nonalcoholic fatty liver disease from 2012 to 2021.

As a common chronic liver disease, nonalcoholic fatty liver disease (NAFLD) has attracted increasing attention in the past decade. Nevertheless, there are few bibliometric analyses that systematically study this field as a whole. This paper explores the latest research progress and future research trends of NAFLD through the method of bibliometric analysis. The articles related to NAFLD, published from 2012 to 2021 in the Web of Science Core Collections, were searched on February 21, 2022, using relevant keywords. Two different scientometrics software tools were used to conduct the knowledge maps of NAFLD research field. A total of 7975 articles on NAFLD research were included. From 2012 to 2021, the publications related to NAFLD increased by year. China ranked on the top of the list with 2043 publications, and the University of California System emerged as the premier institution in this field. PLOs One, Journal of Hepatology and Scientific Reports became the prolific journals in this research field. Co-cited reference analysis revealed the landmark literature in this research field. In terms of potential hotspots, the burst keywords analysis revealed that liver fibrosis stage, sarcopenia, and autophagy will become the focus of future NAFLD research. The annual output of the global publications in the field of NAFLD research showed a strong upward trend. Research in the field of NAFLD in China and America is more mature than in other countries. Classic literature lays the foundation for research, and multi-field studies provide the new development directions. And besides, fibrosis stage, sarcopenia and autophagy research are the hot spots and frontiers of this field.

Puerol and pueroside derivatives from Pueraria lobata and their anti-inflammatory activity.

Five undescribed puerols and puerosides and three known analogues were obtained from the roots of Pueraria lobata. Their structures were determined by comprehensive analysis of spectroscopic data and chemical methods. Since puerol D and puerol C were racemic compounds, resolved into their enantiomers, and their absolute configurations were determined by experimental and calculated ECD spectra. Six of the isolates were evaluated for their inhibitory activities on NO generation and the expression of inflammatory factors in the LPS-stimulated RAW 264.7 macrophage cells. The results showed that (S)-puerol C, (R)-puerol C, isokuzubutenolide A and kuzubutenolide A significantly decreased the NO production (IC50 values in the range of 16.87-39.95 µM). Meanwhile, (S)-puerol C, isokuzubutenolide A and kuzubutenolide A also reduced the mRNA expression of inflammatory factors (TNF-α, IL-1ß and IL-6).