Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

Collision of herbal medicine and nanotechnology: a bibliometric analysis of herbal nanoparticles from 2004 to 2023.

BACKGROUND: Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. RESULTS: In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal "International Journal of Nanomedicine" has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. "Traditional Chinese medicine," "drug delivery," and "green synthesis" are the main research focal points. Themes such as "green synthesis," "curcumin," "wound healing," "drug delivery," and "carbon dots" may represent emerging research areas. CONCLUSIONS: Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine.

Secretory leukocyte protease inhibitor as a novel predictive biomarker in patients with diabetic kidney disease.

Background: Secretory leukocyte protease inhibitor (SLPI) is a multifunctional protein involved in the chronic inflammatory process, implicated in the pathogenesis of diabetic kidney disease (DKD). However, its potential as a diagnostic and prognostic biomarker of DKD has yet to be evaluated. This study explored the clinical utility of SLPI in the diagnosis and prognosis of renal endpoint events in patients with DKD. Methods: A multi-center cross-sectional study comprised of 266 patients with DKD and a predictive cohort study comprised of 120 patients with stage IV DKD conducted between December 2016 and January 2022. The clinical parameters were collected for statistical analysis, a multivariate Cox proportional hazards model was used to evaluate the independent risk factors for renal endpoints. Results: Serum SLPI levels gradually increased with DKD progression (p<0.01). A significant correlation was observed between serum SLPI levels and renal function in patients with DKD. The mean follow-up duration in this cohort study was 2.32 ± 1.30 years. Multivariate Cox regression analysis showed SLPI levels≥51.61ng/mL (HR=2.95, 95% CI[1.55, 5.60], p<0.01), 24h urinary protein levels≥3500 mg/24h (HR=3.02, 95% CI[1.66, 5.52], p<0.01), Alb levels<30g/l (HR=2.19, 95% CI[1.12, 4.28], p<0.05), HGB levels<13g/dl (HR=3.18, 95% CI[1.49, 6.80], p<0.01), and urea levels≥7.1 mmol/L (HR=8.27, 95% CI[1.96, 34.93], p<0.01) were the independent risk factors for renal endpoint events in DKD patients. Conclusions: Serum SLPI levels increased with DKD progression and were associated with clinical parameters of DKD. Moreover, elevated SLPI levels showed potential prognostic value for renal endpoint events in individuals with DKD. These findings validate the results of previous studies on SLPI in patients with DKD and provide new insights into the role of SLPI as a biomarker for the diagnosis and prognosis of DKD that require validation.

Global research trends and hot spots on autophagy and kidney diseases: a bibliometric analysis from 2000 to 2022.

Background: Autophagy is an essential cellular process involving the self-degradation and recycling of organelles, proteins, and cellular debris. Recent research has shown that autophagy plays a significant role in the occurrence and development of kidney diseases. However, there is a lack of bibliometric analysis regarding the relationship between autophagy and kidney diseases. Methods: A bibliometric analysis was conducted by searching for literature related to autophagy and kidney diseases in the Web of Science Core Collection (WoSCC) database from 2000 to 2022. Data processing was carried out using R package "Bibliometrix", VOSviewers, and CiteSpace. Results: A total of 4,579 articles related to autophagy and kidney diseases were collected from various countries. China and the United States were the main countries contributing to the publications. The number of publications in this field showed a year-on-year increasing trend, with open-access journals playing a major role in driving the literature output. Nanjing Medical University in China, Osaka University in Japan, and the University of Pittsburgh in the United States were the main research institutions. The journal "International journal of molecular sciences" had the highest number of publications, while "Autophagy" was the most influential journal in the field. These articles were authored by 18,583 individuals, with Dong, Zheng; Koya, Daisuke; and Kume, Shinji being the most prolific authors, and Dong, Zheng being the most frequently co-cited author. Research on autophagy mainly focused on diabetic kidney diseases, acute kidney injury, and chronic kidney disease. "Autophagy", "apoptosis", and "oxidative stress" were the primary research hotspots. Topics such as "diabetic kidney diseases", "sepsis", "ferroptosis", "nrf2", "hypertension" and "pi3k" may represent potential future development trends. Research on autophagy has gradually focused on metabolic-related kidney diseases such as diabetic nephropathy and hypertension. Additionally, PI3K, NRF2, and ferroptosis have been recent research directions in the field of autophagy mechanisms. Conclusion: This is the first comprehensive bibliometric study summarizing the relationship between autophagy and kidney diseases. The findings aid in identifying recent research frontiers and hot topics, providing valuable references for scholars investigating the role of autophagy in kidney diseases.

A High-Nuclearity Copper Sulfide Nanocluster [S-Cu50] Featuring a Double-Shell Structure Configuration with Cu(II)/Cu(I) Valences.

This work represents an important step in the quest for creating atomically precise binary semiconductor nanoclusters (BS-NCs). Compared with coinage metal NCs, the preparation of BS-NCs requires strict control of the reaction kinetics to guarantee the formation of an atomically precise single phase under mild conditions, which otherwise could lead to the generation of multiple phases. Herein, we developed an acid-assisted thiolate dissociation approach that employs suitable acid to induce cleavage of the S-C bonds in the Cu-S-R (R = alkyl) precursor, spontaneously fostering the formation of the [Cu-S-Cu] skeleton upon the addition of extra Cu sources. Through this method, a high-nuclearity copper sulfide nanocluster, Cu50S12(SC(CH3)3)20(CF3COO)12 (abbreviated as [S-Cu50] hereafter), has been successfully prepared in high yield, and its atomic structure was accurately modeled through single-crystal X-ray diffraction. It was revealed that [S-Cu50] exhibits a unique double-shell structural configuration of [Cu14S12]@[Cu36S20], and the innermost [Cu14] moiety displays a rhombic dodecahedron geometry, which has never been observed in previously synthesized Cu metal, hydride, or chalcogenide NCs. Importantly, [S-Cu50] represents the first example incorporating mixed Cu(II)/Cu(I) valences in reported atomically precise copper sulfide NCs, which was unambiguously confirmed by XPS, EPR, and XANES. In addition, the electronic structure of [S-Cu50] was established by a variety of optical investigations, including absorption, photoluminescence, and ultrafast transient absorption spectroscopies, as well as theoretical calculations. Moreover, [S-Cu50] is air-stable and demonstrates electrocatalytic activity in ORR with a four-electron pathway.

Clinical evaluation of radiation-induced sinusitis by MRI-based scoring system in nasopharyngeal carcinoma patients.

OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. RESULTS: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040). CONCLUSION: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

Bibliometric visualization analysis of gut-kidney axis from 2003 to 2022.

Background: The gut-kidney axis refers to the interaction between the gastrointestinal tract and the kidneys, and its disorders have become increasingly important in the development of kidney diseases. The aim of this study is to identify current research hotspots in the field of the gut-kidney axis from 2003 to 2022 and provide guidance for future research in this field. Methods: We collected relevant literature on the gut-kidney axis from the Web of Science Core Collection (WoSCC) database and conducted bibliometric and visualization analyses using biblioshiny in R-Studio and VOSviewer (version 1.6.16). Results: A total of 3,900 documents were retrieved from the WoSCC database. The publications have shown rapid expansion since 2011, with the greatest research hotspot emerging due to the concept of the "intestinal-renal syndrome," first proposed by Meijers. The most relevant journals were in the field of diet and metabolism, such as Nutrients. The United States and China were the most influential countries, and the most active institute was the University of California San Diego. Author analysis revealed that Denise Mafra, Nosratola D. Vaziri, Fouque, and Denis made great contributions in different aspects of the field. Clustering analysis of the keywords found that important research priorities were "immunity," "inflammation," "metabolism," and "urinary toxin," reflecting the basis of research in the field. Current research frontiers in the field include "hyperuricemia," "gut microbiota," "diabetes," "trimethylamine n-oxide," "iga nephropathy," "acute kidney injury," "chronic kidney disease," "inflammation," all of which necessitate further investigation. Conclusion: This study presents a comprehensive bibliometric analysis and offers an up-to-date outlook on the research related to the gut-kidney axis, with a specific emphasis on the present state of intercommunication between gut microbiota and kidney diseases in this field. This perspective may assist researchers in selecting appropriate journals and partners, and help to gain a deeper understanding of the field's hotspots and frontiers, thereby promoting future research.

Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.

BACKGROUND: Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation. METHOD: PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity. RESULTS: The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, p = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, p = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, p = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, p = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, p = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (r= -0.49; 95% CI= -0.75, -0.24; p < 0.001) and inflammatory markers (r = 0.43; 95% CI= 0.03, 0.84; p = 0.036) in non-dialysis patients. CONCLUSIONS: Increased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.

Cardiovascular and renal outcomes with sodium glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus: A system review and network meta-analysis.

Cardiovascular and renal impairment are the most common complications of type 2 diabetes mellitus (T2DM). As an emerging class of glucose-lowing agents sodium glucose co-transporter 2 (SGLT2), possesses beneficial effects on cardiovascular and renal outcomes in patients with T2DM. The aim of this study is to assess the efficacy of different SGLT2 inhibitors for cardiovascular and renal outcomes for patients with T2DM when compared with placebo. We performed a systematic search of PubMed, Embase, and the Cochrane library from inception through November 2021. Randomized clinical trials enrolling participants with T2DM were included, in which SGLT2 inhibitors were compared with each other or placebo. The primary outcomes including all-caused mortality, Cardiovascular outcomes (cardiovascular mortality, hospitalization for heart failure), and the renal composite outcomes (worsening persistent microalbuminuria or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death). The data for the outcomes were pooled and recorded as Hazard rations (HRs) with 95% confidence intervals (CLs). Two researcher independently screened the trials and drawn the data. Ten trials enrolling 68,723 patients were included. Compared with placebo groups, Canagliflozin [HR, 0.85 (95%CI, 0.75-0.98)], ertugliflozin [HR, 0.93 (95%CI, 0.78-1.11)], and sotagliflozin [HR, 0.94 (95%CI, 0.79-1.12)] were associated with a reduction in all-cause mortality. Canagliflozin [HR, 0.84 (95%CI, 0.72-0.97)], dapagliflozin [HR, 0.88 (95%CI, 0.79-0.99)], empagliflozin [HR, 0.62 (95%CI, 0.49-0.78)], ertugliflozin [HR, 0.92 (95%CI, 0.77-1.10)], and sotagliflozin [HR, 0.88 (95%CI, 0.73-1.06)] were associated with a reduction in cardiovascular mortality; Canagliflozin [HR, 0.64 (95%CI, 0.53-0.77)], dapagliflozin [HR, 0.71 (95%CI, 0.63-0.81)], empagliflozin [HR, 0.65 (95%CI, 0.50-0.85)], ertugliflozin [HR, 0.70 (95%CI, 0.54-0.90)], and sotagliflozin [HR, 0.66 (95%CI, 0.56-0.77)] were associated with a reduction in hospitalization for heart failure. Dapagliflozin [HR, 0.55 (95%CI, 0.47-0.63)], Empagliflozin [HR, 0.54 (95%CI, 0.39-0.74)], canagliflozin [HR, 0.64 (95%CI, 0.54-0.75)], sotagliflozin [HR, 0.71 (95%CI, 0.46-1.09)], and ertugliflozin [HR, 0.81 (95%CI, 0.63-1.04)] were associated with a reduction in the renal composite outcome. All SGLT2 inhibitors showed a reduction in cardiovascular mortality, hospitalization for heart failure, renal composite outcomes and all-cause mortality. Canagliflozin and empagliflozin seemed to have the same efficacy in reducing hospitalization for heart failure, but empagliflozin had advantage in reducing cardiovascular mortality, whereas dapagliflozin most likely showed the best renal composite outcomes.

Probiotics for the improvement of metabolic profiles in patients with metabolic-associated fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

Objective: This meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy of probiotics in the treatment of metabolic-associated fatty liver disease (MAFLD) mainly in terms of liver function, glucose and lipid metabolism, and inflammation. Methods: RCTs were searched on PubMed, Web of Science, Embase, and the Cochrane Library until June 2022. A meta-analysis was performed on the therapeutic efficacy of probiotics on liver function, glucose and lipid metabolism, and inflammatory biomarkers by using RevMan 5.4 software. Results: A total of 772 patients from 15 studies were included in the analysis. The methodological quality varied across studies. We found that adding probiotic therapies could reduce the levels of alanine aminotransferase [mean difference (MD): -11.76 (-16.06, -7.46), p < 0.00001], aspartate aminotransferase (MD: -9.08 (-13.60, -4.56), p < 0.0001], γ-glutamyltransferase [MD: -5.67 (-6.80, -4.54), p < 0.00001] and homeostasis model assessment-insulin resistance [MD: -0.62 (-1.08, -0.15), p = 0.01], in patients with MAFLD compared with those in control individuals. However, there was no statistically significant improvement in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, C-reactive protein and tumor necrosis factor α among patients with MAFLD. Subgroup analyses showed that other key factors, such as age, participants' baseline body mass index, and the duration of intervention, may influence probiotic therapy outcomes. Conclusion: There is promising evidence that probiotic supplementation can reduce liver enzyme levels and regulate glycometabolism in patients with MAFLD. Further rigorous and long-term trials exploring these novel therapeutic perspectives are warranted to confirm these results.

Case report: Joint deformity associated with systemic lupus erythematosus.

OBJECTIVE: Typically, Jaccoud arthropathy (JA) is characterized by joint deformation without bone erosion. However, some recent studies have shown that bone erosion also occurs in JA; however, this remains controversial. To date, there have been no unified diagnostic standards for JA. Herein, we report a case of systemic lupus erythematosus complicated with JA without bone erosion. METHODS: A 27-year-old woman was admitted to our department with a 2-year history of pain, swelling, and progressive deformities of her hands and feet. She was diagnosed with systemic lupus erythematosus and class V lupus nephritis 5 years prior. Upon examination, her erythrocyte sedimentation rate and C-reactive protein levels were found to be increased. She was positive for antinuclear antibodies, antidouble stranded DNA antibodies, and antiextractable nuclear antigen antibodies, with a decreased complement C3 and C4. Radiography and magnetic resonance imaging revealed no bone erosion. The patient was diagnosed with JA. She was treated with oral prednisone (10 mg daily), tofacitinib (5 mg twice daily), methotrexate (10 mg weekly), and celecoxib (0.2 g twice daily). RESULTS: The patient's joint symptoms improved after treatment. No further progress was observed during the 4-month follow-up period. CONCLUSION: We believe that bone erosion is the key to distinguish rhupus syndrome from JA. However, this needs to be confirmed with further long-term follow-up studies. We found that the use tofacitinib, MTX, and celecoxib in combination with prednisone may be an effective regimen for the treatment of JA.

Identification of molecular mechanism and key biomarkers in membranous nephropathy by bioinformatics analysis.

OBJECTIVES: Membranous nephropathy (MN) is an autoimmune nephropathy. The incidence of MN is increasing gradually in recent years. Previous studies focused on antibody production, complement activation and podocyte injury in MN. However, the etiology and underlying mechanism of MN remain to be further studied. METHODS: GSE104948 and GSE108109 of glomerular expression profile were downloaded from Gene Expression Omnibus (GEO) database, GSE47184, GSE99325, GSE104954, GSE108112, GSE133288 of renal tubule expression profile, and GSE73953 of peripheral blood mononuclear cells (PBMCs) expression profile. After data integration by Networkanalyst, differentially expressed genes (DEGs) between MN and healthy samples were obtained. DEGs were enriched in gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks of these genes were constructed through Metascape, etc. We further understood the function of hub genes through gene set enrichment analysis (GSEA). The diagnostic value of DEGs in MN was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: A total of 3 genes (TP53, HDAC5, and SLC2A3) were screened out. Among them, the up-regulated TP53 expression may be closely related to MN renal pathological changes. However, the expression of MN podocyte target antigen was not significantly different from that of healthy controls. In addition, the changes of Wnt signaling pathway in PBMCs and the effects of SLC2A3 on the differentiation of M2 monocyte need further study. CONCLUSION: It is difficult to unify a specific mechanism for the changes of glomerulus, renal tubules and PBMCs in MN patients. This may be related to the pathogenesis, pathology and immune characteristics of MN. MN podocyte target antigen may not be the root cause of the disease, but a stage result in the pathogenesis process.

Anti-Freezing Nanocomposite Organohydrogels with High Strength and Toughness.

Hydrogels based on nanocomposites (NC) structure have acquired a great deal of interest, but they are still limited by relatively low mechanical strength, inevitably losing elasticity when applied below subzero temperatures, due to the formation of ice crystallization. In this study, an anti-freezing and mechanically strong Laponite NC organohydrogel was prepared by a direct solvent replacement strategy of immersing Laponite NC pre-hydrogel into ethylene glycol (EG)/water mixture solution. In the organohydrogel, a part of water molecules was replaced by EG, which inhibited the formation of ice crystallization even at extremely low temperatures. In addition, the formation of hydrogen bonds between Laponite and the monomers of N-isopropylacrylamide (NIPAM) and hydroxyethyl acrylate (HEA) endowed the organohydrogels with high mechanical strength and toughness. The NC organohydrogel can maintain its mechanical flexibility even at -25 °C. The compressive stress, tensile stress, and elongation at the break of N5H5L reached 3871.71 kPa, 137.05 kPa, and 173.39%, respectively, which may be potentially applied as ocean probes in low temperature environment.

Genomics divergence of Lactococcus lactis subsp. lactis isolated from naturally fermented dairy products.

Lactococcus lactis subsp. lactis (L. lactis subsp. lactis) is commonly found in naturally fermented dairy products (NFDPs). This subspecies is of high economic value due to its wide application in dairy industry. However, the genetic background and evolutionary history of L. lactis subsp. lactis are still poorly understood, analysis of its genetic background and functional genome will lay a genetic foundation for its application. This study analyzed the whole genomes of 227 novel L. lactis subsp. lactis isolated from NFDPs and investigated the genetic history of this subspecies from a population genetic perspective. These strains were classified into four phylogenetically distinct groups, which were likely derived from only a few wild ancestors through three divergence events, resulting in genetic and phenotypic divergence. Functional genomic analysis found that the divergence events caused strong lineage-specific selection for carbohydrate utilization and lactic acid production genes. Moreover, the time of the divergence coincided with mass migration of nomads due to climate change and decrease in average annual temperature, suggesting that these drastic environmental changes might be evolutionary drivers of the divergence. Genome-wide association analysis results showed that the single nucleic acid polymorphic loci we associated with pepF and CoiA genes were significantly correlated with fermentation capability, and based on this, a rapid screening model for potential starter strains was constructed. Our findings shed light on the evolutionary history and genomic diversity of NFDP-originated L. lactis subsp. lactis, and provide a new insight for screening strains with excellent characteristics.

Nutraceutical potential of industrial hemp (Cannabis sativa L.) extracts: physicochemical stability and bioaccessibility of cannabidiol (CBD) nanoemulsions.

Cannabidiol (CBD) is one of the most promising functional food ingredients, which displays a number of health benefits. However, its low solubility and bioavailability impede its applications in functional foods. Herein, we developed a food-grade CBD nanoemulsion system using medium chain triacylglycerides (MCT), canola oil (CO), or hemp seed oil (HSO) as the carrier oil to compare the physicochemical stability and bioaccessibility of CBD. Encouragingly, all formulations were well maintained for 90 days under the tested temperatures (4, 25 and 37 °C) and pH values (3.5 and 7.0). Quantitative analysis of CBD during storage using high performance liquid chromatography revealed that the light exposure and acidity of the solution are two important factors affecting the chemical stability of CBD. Moreover, improved bioaccessibility of CBD in all three nanoemulsion formulations compared to that of bulk oil forms was confirmed, and the long chain triacylglyceride (LCT)-based nanoemulsion was superior to the MCT-based counterpart.

[Randomized controlled trial outcome indicators of traditional Chinese medicine for gastrointestinal dysfunction in sepsis in recent two years].

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of gastrointestinal dysfunction in sepsis in recent two years. We systematically searched four Chinese databases, three English databases, and two clinical trial registries to analyze the reports of outcome indicators of clinical trials, and evaluated the risk of bias by using the ROB tool of Cochrane Collaboration. After screening, 55 clinical RCTs were included. The results showed that the current clinical studies of gastrointestinal dysfunction in sepsis reported the efficacy and safety indicators. The efficacy indicators included APACHE Ⅱ scores, gastrointestinal dysfunction scores, bowel sound scores, and inflammatory indicator such as C-reactive protein and procalcitonin. The safety indicators mainly include gastrointestinal reactions, skin reactions, and other adverse events and adverse reactions. However, there was no distinction between primary and secondary outcomes. The relevant indicators of health economics were not reported, and the quality of research methodology was poor. Therefore, we suggest that future researchers should be well prepared in the top-level design stage and actively construct the core outcome set, so as to improve the quality of clinical trials.

Genomics landscape of 185 Streptococcus thermophilus and identification of fermentation biomarkers.

Streptococcus (S.) thermophilus, an indispensable dairy starter, has been used in autochthonous as well as industrial milk fermentation. However, the genetic architecture underlying S. thermophilus traits and phenotypes is largely unknown. Here, we sequenced 185 S. thermophilus strains, isolated from natural fermented dairy products of China and Mongolia and used comparative genomic and genome wide association study to provide novel point for genetic architecture underlying its traits and phenotypes. Genome analysis of S. thermophilus showed association of phylogeny with environmental and phenotypic features and revealed clades with high acid production potential or with substantial genome decay. A few S. thermophilus isolated from areas with high chloramphenicol emissions had a chloramphenicol-resistant gene CatB8. Most importantly, we defined a growth score and identified a missense mutation G1118698T located at the gene AcnA that were both predictive of acidification capability of S. thermophilus. Our findings provide novel insight in S. thermophilus genetic traits, antibiotic resistant and predictive of acidification capability which both may had huge help in culture starter screening.

Carboxymethyl chitosan coated medium-chain fatty acid nanoliposomes: structure, composition, stability and in vitro release investigation.

Medium-chain fatty acids (MCFAs) have been proven as an easy energy source and active ingredient to prevent obesity and other metabolic disorders. However, the inherent hydrophobic nature of MCFAs causes poor aqueous solubility and dissolution in the gastrointestinal (GI) tract, thus limiting their applications in aqueous foods. To address these issues, a nutraceutical carrier system was developed by coating nanoliposomes with carboxymethyl chitosan (CMCS) through a series of well-designed processes, including thin-film hydration, dynamic high pressure microfluidization (DHPM) and surface modification. Electron microscopy investigation reveals an obvious morphology evolution from the uncoated nanoliposomes (UC-LPs) to the final CMCS coated nanoliposomes (CMCS-LPs). Together with the FTIR results, it confirms the successful coating of CMCS. More importantly, the resultant CMCS-LPs have a more negatively charged surface with a ζ-potential value of around -18.5 mV, which helps to increase the stability by avoiding severe particle aggregation. Owing to the above benefits, the encapsulated MCFAs can be safely retained in a long storage period of 90 days at 4 °C and the new carrier system also exhibits a more sustained release of MCFAs in the GI fluid.

Generation of a COL4A5 heterozygous mutation human embryonic stem cell line (WAe009-A-58) using an episomal vector-based CRISPR/Cas9 system.

X-linked Alport syndrome (XLAS) is the second most common inherited kidney disease which pathogenic variants related to a mutation in the COL4A5 gene encoding the type IV collagen α5 chain. Here, we have generated a COL4A5 heterozygous mutant human embryonic stem cell (hESC) line (H9-COL4A5+/-) by an episomal vector-based CRISPR/Cas9 system. The generated H9-COL4A5+/- maintained a normal stem cell morphology, stably expressed pluripotent markers, and could differentiate into all three germ layers in vivo. This cell line offers an in vitro efficient platform to explore pathogenic mechanisms in XLAS and provides a cell-based disease model for drug testing.