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The Laryngeal Mask Airway (LMA) Supreme is a new supraglottic airway incorporating features of the LMA Proseal, LMA Fastrach and LMA Unique. We evaluated the LMA Supreme in 100 patients with normal airways having elective surgery. Our success rates of insertion and ventilation were 96% at the first attempt and 100% after two attempts. The median time to successful placement was 15 seconds (interquartile range 12 to 18 seconds). Forty-five patients breathed spontaneously and 55 patients had controlled ventilation. The incidence of blood staining on removal was 7% and 7% of patients had mild sore throat one hour postoperatively. One patient who had been placed in the left lateral position during surgery had left lingual nerve palsy postoperatively, which recovered completely after one month. Our findings suggest that in patients with normal airways, the LMA Supreme is easy to insert and provides a satisfactory airway with adequate seal pressures for ventilation. [ABSTRACT FROM AUTHOR]

Background: The GlideScope (Verathon Inc., Bothell, WA, USA) and Airway Scope (Hoya Corp., Tokyo, Japan) have both been used for difficult airway management, including in patients with cervical spine pathology. The Airway Scope's disposable blade has a tube channel to guide tracheal tube insertion through the glottis. Our hypothesis is that this tube guidance system improves the ease of tracheal intubation compared with the GlideScope, which does not have a tube guiding system. We tested this hypothesis in a randomized comparison of the two videolaryngoscopes in patients whose cervical spines were immobilized.Methods: Seventy consenting patients were randomized to have tracheal intubation with the GlideScope (n=35) or the Airway Scope (n=35). In all patients, we applied manual in-line stabilization of the cervical spine throughout airway management. All the airway procedures were carried out by two anaesthetists experienced in the use of both videolaryngoscopes.Results: The tracheal intubation time was 34.2 (sd 25.1) s with the Airway Scope compared with 71.9 (47.9) s with the GlideScope (P<0.001). Tracheal intubation was successful with the Airway Scope in 35 (100%) patients compared with 31 (88.6%) patients with the GlideScope (P=0.114). Tracheal intubation was successful within 60 s in 33 (94.3%) patients with the Airway Scope and 22 (62.9%) patients with the GlideScope (P=0.003).Conclusions: These results suggest that the Airway Scope's tube guide system enables more rapid tracheal intubation compared with the GlideScope in patients with cervical spine immobilization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several case reports have shown that the Pentax-AWS (Hoya Corporation, Tokyo, Japan), a new video laryngoscope, is useful in patients with difficult airways. METHODS: We assessed the effectiveness of the Pentax-AWS in two groups. Group 1 included 270 patients in whom direct laryngoscopy using a Macintosh laryngoscope had been difficult. Group 2 included 23 patients with predicted difficult intubation and difficult mask ventilation without previous use of the Macintosh laryngoscope. RESULTS: In group 1, the view of the glottis with the Macintosh laryngoscope was Cormack and Lehane grade 2 in 14 patients, grade 3 in 208 patients, and grade 4 in 48 patients. In 256 patients in whom the grade was 3 or 4 with the Macintosh laryngoscope, the view with the Pentax-AWS was either grade 1 or 2 in 255 patients (99.6%; 95% confidence intervals 97.8-100%). Tracheal intubation was successful with the Pentax-AWS in 268 of 270 patients (99.3%; 95% confidence interval 97.4-100%), and it failed (after two attempts) in two patients. In group 2, tracheal intubation was successful in 22 of 23 patients, and it failed in one patient. The reasons for failed intubation using the Pentax-AWS were failure to position the blade toward the glottic side of the epiglottis, inability to maneuver the endotracheal tube away from the arytenoids and into the trachea, and bleeding and swelling of the oropharynx. CONCLUSION: The success rate of tracheal intubation using the Pentax-AWS was high in patients with difficult laryngoscopy with a Macintosh laryngoscope and in patients with predicted difficult intubation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The LMA CTrach system (The Laryngeal Mask Company, Singapore) is a development of the LMA Fastrach system (The Laryngeal Mask Company, Singapore), with integrated fiberoptic bundles and a detachable liquid crystal display viewer. This randomized study of 271 patients compared tracheal intubation with these two systems. METHODS: In both groups, ventilation was optimized after insertion of the laryngeal mask conduit before proceeding further: intubation with the LMA Fastrach, and optimizing the conduit placement and view and then intubation with the LMA CTrach. The first-attempt and overall success rates of tracheal intubation, and the times required, were recorded. RESULTS: Tracheal intubation was successful on the first attempt in 93.3% of patients with the LMA CTrach and 67.9% of patients with the LMA Fastrach (P < 0.001). The success rates within three attempts were 100% with the LMA CTrach and 96.4% with the LMA Fastrach (P = 0.06). The median (interquartile range) time for the complete tracheal intubation process was 116 (82-156) s with the LMA CTrachand 100 (74-121) s with the LMA Fastrach (P = 0.002). There was no correlation between the grade of conventional laryngoscopy and success of intubation with either system. CONCLUSIONS: The ability to view the glottis and optimize placement of the LMA CTrach under vision enabled a higher first-attempt success rate of tracheal intubation with the LMA CTrach. However, more time is required with the LMA CTrach, there are failed views in some patients, and its cost effectiveness remains unclear. [ABSTRACT FROM AUTHOR]

In culture experiments and many low temperature environments, the distribution of isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs) commonly shows a strong correlation with temperature; however, this is often not the case in hot springs. We studied 26 hot springs in Yunnan, China, in order to determine whether temperature or other factors control the distribution of GDGTs in these environments. The hot springs ranged in temperature from 39°C to 94°C, and in pH from 2.35 to 9.11. Water chemistry including nitrogen-, sulfur- and iron species was also determined. Lipids from the samples were analyzed using LC-MS (liquid chromatography-mass spectrometry). Distributions of GDGTs in these hot springs were examined using cluster analysis, which resulted in two major groups. Group 1 was characterized by the lack of dominance of any individual GDGTs, while Group 2 was defined by the dominance of GDGT-0 or thaumarchaeol. Temperature was the main control on GDGT distribution in Group 1, whereas pH played an important role in the distribution of GDGTs in Group 2. However, no correlations were found between the distribution of GDGTs and any of the nitrogen-, sulfur- or iron species. Results of this study indicate the predominance of temperature or pH control on archaeal lipid distribution, which can be better evaluated in the context of lipid classification.

Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park (YNP), Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with

Introduction: We aimed to fill the research gap between DII and herpes simplex virus infection among adults in the US by analyzing the association between dietary inflammatory index and herpes simplex virus and to provide new ideas for herpes simplex virus prevention and treatment., Method: We used data from 8636 participants in NHANES 2007-2016, which were statistically analyzed by participant baseline study, one-way analysis of variance, multiple regression equations, smoothed curve fitting, and stratified analysis., Result: In the fully adjusted model, the DII high concentration group was positively associated with the prevalence of herpes simplex (1.15 (0.89, 1.48), p = 0.0027), and the results of the stratified analyses indicated that the positive association between DII and herpes simplex virus type II was stable in the population., Conclusion: This study demonstrates a positive association between DII and herpes simplex virus II in US adults, suggesting that a proinflammatory diet may be an independent risk factor for herpes simplex virus II., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Qikui granule (QKG), a hospital preparation of traditional Chinese medicine, has been widely used for diabetic kidney disease (DKD) in clinical practice. However, its holistic therapeutic effects and the underlying therapeutic mechanisms remain unclear. In the present study, the integrated analysis of network pharmacology, 16S rRNA sequencing, and non-targeted lipidomics was performed to explore the anti-DKD effects of QKG and the underlying mechanisms in db/db mouse DKD model. The results of the network pharmacology analysis identified the PI3K-AKT, EGFR, MAPK, JAK-STAT, FoxO, and AGE-RAGE signaling pathways as the potential molecular mechanisms responsible for the efficacy of QKG. Importantly, these signaling pathways were found to be closely related to lipid metabolism and gut microbiota. The therapeutic effectiveness of QKG against DKD was manifested by reducing body weight, alleviating oxidative stress, improving kidney function indicators, promoting the recovery of renal histopathological damage, and regulating the lipid metabolic profile of serum and kidney in db/db mice. A total of 26 lipid metabolites were identified as potential pharmacological biomarkers (PPBs) of QKG for the treatment of DKD, which were mainly involved in glycerophospholipid metabolism. Meanwhile, QKG could alleviate DKD-induced gut microbiota dysbiosis primarily by enriching Candidatus&#95;Arthromitus, which showed a negative correlation with all 26 lipid PPBs as well as 5 biochemical parameters, including 2 oxidative stress factors and 3 kidney function indices. In conclusion, our findings suggest that QKG may upregulate the gut level of Candidatus&#95;Arthromitus to suppress the abnormal activation of PI3K-AKT related signaling pathway, thereby reducing the levels of PC and LPC in the glycerophospholipid metabolism, to finally ameliorate the progression of DKD in db/db mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, polysaccharides derived from natural sources have garnered significant attention due to their safety and potential anti-osteoporotic effects. This review provides a comprehensive overview of the sources, distribution, structures, and mechanisms of anti-osteoporosis polysaccharides, as well as an investigation into their structure-activity relationships. Over thirty distinct, homogenous polysaccharides with anti-osteoporosis properties have been extracted from natural sources, primarily categorized as glucans, fructans, galactomannans, glucomannans, and various other heteropolysaccharides. Natural polysaccharides can effectively enhance osteoblast differentiation and mineralization while suppressing osteoclast activation, with the mechanism regulated by the BMP/SMAD/RUNX2, Wnt/Catenin, OPG/RANKL/RANK, and TLR2/NF-κB/NFATc1 signaling pathways. Furthermore, polysaccharides contribute to the prevention of osteoporosis by mitigating oxidative stress, decreasing inflammation, and modulating the gut microbiota. This review also summarizes the relationship between the monosaccharide composition, molecular weight, and glycosidic bond type of polysaccharides and their anti-osteoporotic activity. A comprehensive summary and analysis of the existing deficiencies and challenges in the research of anti-osteoporotic polysaccharides is also concluded. This review may serve as a significant reference for the discovery and utilization of naturally derived anti-osteoporotic polysaccharides in the pharmaceutical and health industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults., Methods: The study was based on data collected from the 1999-2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors., Results: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80-0.94, P < 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women., Conclusions: An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to identify and quantify the primary components in lotus leaf and to explore the hypolipidemic components through spectral-effect relationships and chemometric methods. Utilizing a data-dependent acquisition-diagnostic fragment ion/characteristic neutral loss screening strategy (DFI-NLS), a reliable HPLC-Q-TOF-MS analysis was conducted, identifying 77 compounds, including 36 flavonoids, 21 alkaloids, 3 terpenoids, 11 organic acids, 4 phenols, 1 lignin and 1 unsaturated hydrocarbon. A straightforward HPLC-DAD method was developed for the simultaneous determination of seven major components in lotus leaf, and quercetin-3-O-glucuronide (Q3GA) was identified as the most abundant component. The HPLC fingerprints of 36 lotus leaf sample batches were assessed using chemometric approaches such as principal component analysis and hierarchical cluster analysis. The hypolipidemic effect of these samples was analyzed by measuring total cholesterol (TC) and total triglycerides (TG) levels in palmitic acid (PA) and oleic acid (OA)-induced lipid modeling in HepG-2 cells, employing partial least squares regression and grey relation analysis to investigate the spectral-effect relationship of the lotus leaf. The in vivo hypolipidemic effect of these compounds was assessed using an egg yolk powder-induced high-fat zebrafish model. The findings indicated that peak No.11 (Q3GA) in the chemical fingerprint was significantly associated with hypolipidemic activity, suggesting it as a potential hypolipidemic compound in lotus leaf. In summary, this study facilitates the exploration of the phytochemical compounds and their bioactive properties in the lotus leaf., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4 254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored., Purpose: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL., Methods: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments., Results: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1β pathway and increased proinflammatory IL1β in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1β pathway., Conclusions: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1β pathway, specifically by targeting AKK and tryptophan metabolites., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored., Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice., Methods: In vivo : 3.5% DSS-induced experimental colitis mice were treated with BTW ( Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro : Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels., Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway., Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Lin, Zhang, Hu, Liu, Liu and Liu.)

Introduction: Bacterial vaginitis (BV) is a common vaginal disease. Vitamin E has been shown to reduce BV by enhancing immune function, but no studies have analyzed the relationship between vitamin E and BV at different BMIs and ages., Method: This study used 2242 participants from four cycles of NHANES 1999-2006 in American. Participants' vitamin E levels were divided into four groups, and analyses such as study population description, stratified analysis, multiple logistic regression analysis, and curve fitting were performed. To perform data processing, the researchers used the statistical package R (The R Foundation; http://www.r-project.org ; version 3.6.3) and Empower Stats software ( www.empowerstats.net , X&Y solutions, Inc. Boston, Massachusetts)., Result: The concentrations of serum vitamin E were negatively correlated with the risk of BV, especially when vitamin E were at 1198-5459ug/dL with (OR = -0.443, 95%CI = 0.447-0.923, P = 0.032) or without (OR = -0.521, 95%CI = 0.421-0.837, P = 0.006) adjustment for variables. At the same time, at lower levels, there was no significant association. Vitamin E supplementation may significantly reduce the risk of BV (p < 0.001). In addition, the risk of having BV decreased and then increased with increasing vitamin E concentrations at high BMI levels (p < 0.01)., Conclusion: Vitamin E at moderate to high concentrations may significantly reduce BV risk, says the study, providing clinical evidence for the prevention and the treatment of BV., (© 2024. The Author(s).)

Citrus reticulata cv. Chachiensis (CRC) is an important medicinal plant, its dried mature peels named "Guangchenpi", has been used as a traditional Chinese medicine to treat cough, indigestion, and lung diseases for several hundred years. However, the biosynthesis of the crucial natural products polymethoxylated flavonoids (PMFs) in CRC remains unclear. Here, we report a chromosome-scale genome assembly of CRC with the size of 314.96 Mb and a contig N50 of 16.22 Mb. Using multi-omics resources, we discover a putative caffeic acid O-methyltransferase (CcOMT1) that can transfer a methyl group to the 3-hydroxyl of natsudaidain to form 3,5,6,7,8,3',4'-heptamethoxyflavone (HPMF). Based on transient overexpression and virus-induced gene silencing experiments, we propose that CcOMT1 is a candidate enzyme in HPMF biosynthesis. In addition, a potential gene regulatory network associated with PMF biosynthesis is identified. This study provides insights into PMF biosynthesis and may assist future research on mining genes for the biosynthesis of plant-based medicines., (© 2024. The Author(s).)

This article examines how lesbians and gay men imagine and build their 'intimate networks of care' and negotiate moral expectations towards intergenerational family care as they age. To date, little is known about the strength and complexities of different intimate ties or the role of intergenerational dynamics in shaping ageing sexual minority people's care needs and choices. Based on narrative interviews with ageing Chinese lesbians and gay men, the findings reveal their experiences of constantly juggling their ties with families of origin, moral values around intergenerational care and the urge to receive support from and offer support to chosen networks of people. Participants exercised agency in expanding their networks of care by building friendship and (online and offline) community networks for mutual care and support in later life. Nevertheless, as evidenced by the centrality of ageing with(out) children, and the moral obligation of caring for parents in participants' narratives, participants experienced tensions between enacting what was considered morally right/wrong and developing networks of care that were perceived as emotionally intimate. Linking relational sociology with the sociology of morality, we discuss the conceptual utility of 'intimate networks of care' for sociological theorising of the linkages between sexuality, care and relational lives., (© 2023 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

Ulcerative colitis is closely associated with the dysregulation of gut microbiota. There is growing evidence that natural products may improve ulcerative colitis by regulating the gut microbiota. In this research, we demonstrated that bergenin, a naturally occurring isocoumarin, significantly ameliorates colitis symptoms in dextran sulfate sodium (DSS)-induced mice. Transcriptomic analysis and Caco-2 cell assays revealed that bergenin could ameliorate ulcerative colitis by inhibiting TLR4 and regulating NF-κB and mTOR phosphorylation. 16S rRNA sequencing and metabolomics analyses revealed that bergenin could improve gut microbiota dysbiosis by decreasing branched-chain amino acid (BCAA) levels. BCAA intervention mediated the mTOR/p70S6K signaling pathway to exacerbate the symptoms of ulcerative colitis in mice. Notably, bergenin greatly decreased the symbiotic bacteria Bacteroides vulgatus ( B. vulgatus ), and the gavage of B. vulgatus increased BCAA concentrations and aggravated the symptoms of ulcerative colitis in mice. Our findings suggest that gut microbiota-mediated BCAA metabolism plays a vital role in the protective effect of bergenin on ulcerative colitis, providing novel insights for ulcerative colitis prevention through manipulation of the gut microbiota.

Two new natural products named 5,7-dihydroxy-3,3',6,8-tetramethoxy-4',5'-methylenedioxyflavone ( 1 ) and 3,3',5,7-tetramethoxy-4',5'-methylenedioxyflavone ( 2 ), along with thirteen known compounds, β-sitosterol ( 3 ), desmethoxyyangonin ( 4 ), hexadecane ( 5 ), 3,9-bis(2,4-di-tert-butylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro [5.5] undecane 3,9-dioxide ( 6 ), 2'6'-dihydroxy-4'-methoxydihydrochalcone ( 7 ), cardamonin ( 8 ), 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone ( 9 ), isofraxidin ( 10 ), aniba dimer A ( 11 ), 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone ( 12 ), quercetin ( 13 ), quercitrin ( 14 ) and isoquercitrin ( 15 ) were isolated from Sarcandra glabra (Thunb.) Nakai by various chromatographic methods. Compounds 1 , 2 , 4 , 6 , 11 , and 12 were isolated from S. glabra for the first time. Their chemical structures were identified through the analysis of NMR and HR-MS spectra. The anti-inflammatory and cytotoxic activities of compounds 1-15 were evaluated in cell assays. The results indicated that compounds 1 , 7 , 8 , 10 , 14 , and 15 significantly inhibited the NO production in LPS-induced RAW 264.7 murine macrophage cells. Moreover, compounds 1 , 3 , 4 , 7 , 8 , 9 , 10 and 12 exhibited a cytotoxic effect on the human HepG2 cell line.

This study examines how Chinese lesbians and gay men make sense of the prospect of growing old and plan for later life in Hong Kong, where same-sex relationships are yet to be legally recognized. Drawing on in-depth narrative interviews, the results show that lesbians and gay men in midlife reported a range of previous, current, and anticipated challenges associated with the stigma attached to homosexuality. These, in turn, shaped their ways of perceiving and planning for later life. Three forms of reflexivity in response to minority stress and the prospect of aging were identified: coping with fears of aging alone, striving for self-mastery, and planning ahead with feelings of wariness. Participants' concerns and plans around aging demonstrated differing degrees of reflexivity, through which they attempted to navigate family norms and structural constraints and find ways to accumulate resources for later life. Meanwhile, their heightened sense of uncertainty and insecurity showed that their perceptions and experiences of aging were influenced by minority stress and material, familial, and socio-political circumstances. This article builds a constructive dialogue between sexuality and aging studies by unraveling both the aging insecurity and capacities for reflexive planning among an oft-neglected group of sexual minority people in midlife.

Objective: Older adults are prone to the negative effects of exposure to violence on their mental health. This study aimed to examine the impact of exposure to violence during social unrest and the role of resilience in the mental health of older people., Design: A total of 1,203 people aged 65 years or older were randomly selected for a telephone survey using the random digit dialing numbering method in Hong Kong., Measurements: A 13-item scale was developed to measure exposure to violence. The Chinese versions of the Connor-Davidson Resilience Scale and the Startle, Physiological Arousal, Anger, and Numbness scales for measuring mental health status were adopted in the survey., Results: The results showed that the more frequently older people were exposed to information, the more negative mental health status they had. However, exposure to witnessing and experiencing violence was not significantly associated with mental health status. Older adults' level of resilience had a moderating effect between exposure to information and mental health, whereas the effect of exposure to information on mental health was stronger for respondents with lower resilience., Conclusion: This study showed that emotional problems caused by exposure to related information among older people should be properly addressed during massive social unrest and conflict. Their resilience capacity is an important moderating factor. Future interventions and support services should focus on enhancing the resilience of older people to better equip them with overcoming problems related to macro-social issues., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images., Materials and Methods: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape., Results: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively., Conclusions: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Platycladus orientalis leaves (POL), as the source of the traditional Chinese medicine (TCM) Platycladi Cacumen, has frequently been found to be misused with five adulterants including Chamaecyparis obtusa leaves (COL), Cupressus funebris leaves (CFL), Juniperus virginiana leaves (JVL), Sabina chinensis leaves (SCL), and Juniperus formosana leaves (JFL)., Objective: The purpose of this study was to distinguish POL (fresh leaves) from its five adulterants (fresh leaves)., Methods: The micromorphological features in terms of transection and microscopic characteristics of POL and adulterants were captured and compared using the an microscope. Both HPLC and TLC methods for the simultaneous determination of six bioactive flavonoids (myricitrin, isoquercitrin, quercitrin, amentoflavone, afzelin, and hinokiflavone) have been developed., Results: There were significant differences in microscopic features of transverse section and powders. The TLC results suggested that the spots of myricitrin in POL were more obvious than those in the five adulterants. The contents of myricitrin and quercitrin, or the total content of flavonoids in POL, determined by HPLC, were significantly higher than those in the adulterants., Conclusion: POL was successfully distinguished from its five adulterants by the comparison of morphology, microscopic characteristics, and chemical profiles., Highlights: This research provides a comprehensive morphology, microscopic identification, TLC, and HPLC analysis for authenticating POL and its five adulterants., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Growing evidence suggests gut microbiota status affects human health, and microbiota imbalance will induce multiple disorders. Natural products are gaining increasing attention for their therapeutical effects and less side effects. The emerging studies support that the activities of many natural products are dependent on gut microbiota, meanwhile gut microbiota is modulated by natural products. In this review, we summarized the interplay between the gut microbiota and host disease, and the emerging molecular mechanisms of the interaction between natural products and gut microbiota. Focusing on gut microbiota metabolite of various natural products, and the effects of natural products on gut microbiota, we summarized the biotransformation pathways of natural products, and discussed the effect of natural products on the composition modulation of gut microbiota, protection of gut mucosal barrier and modulation of the gut microbiota metabolites. Dissecting the interplay between gut microbiota and natural products will help elucidate the therapeutic mechanisms of natural products., Competing Interests: Declaration of competing interest The authors declared that they have no conflict of interest. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the classical natural product extraction and separation process, it is tedious and requires large amounts of reagents and time. In this study, an efficient coaxial liquid centrifugal oil-water-oil triple-liquid-phase system with a simple structure and convenient operation was successfully constructed and used to extract flavonoids from Platycladi Cacumen. The results showed that the coaxial liquid centrifugal platform constructed in this study had good stability and 6 ml was the minimum volume of the middle phase for 1000 rpm to stabilize the system. Besides, it was easy to repeat the operation: the relative standard deviations of the extraction yields of flavonoids and sugar in six parallel operations were all less than 10%. Moreover, it was only one-tenth of the time required for this method as traditional liquid-liquid extraction while reducing the use of volatile organic reagents. Finally, the new method was more selective than the traditional method for the extraction of flavonoids. Therefore, this study provides a possibility for the coaxial liquid centrifugal platform to be used in multi-liquid phase systems to achieve the simultaneous extraction of different parts of natural products by different liquid phases. It is expected to provide a reliable reference for further expansion of small-scale experimental operations to industrial production., (© 2023 Wiley-VCH GmbH.)

Disturbance of the gut microbiota plays a critical role in the development of nonalcoholic fatty liver disease (NAFLD). Increasing evidence supports that natural products may serve as prebiotics to regulate the gut microbiota in the treatment of NAFLD. In the present study, the effect of nobiletin, a naturally occurring polymethoxyflavone, on NAFLD was evaluated, and metabolomics, 16S rRNA gene sequencing, and transcriptomics analysis were performed to determine the underlying mechanism of nobiletin, and the key bacteria and metabolites screened were confirmed by in vivo experiment. Nobiletin treatment could significantly reduce lipid accumulation in high-fat/high-sucrose diet-fed mice. 16S rRNA analysis demonstrated that nobiletin could reverse the dysbiosis of gut microbiota in NAFLD mice and nobiletin could regulate myristoleic acid metabolism, as revealed by untargeted metabolomics analysis. Treatment with the bacteria Allobaculum stercoricanis , Lactobacillus casei , or the metabolite myristoleic acid displayed a protective effect on liver lipid accumulation under metabolic stress. These results indicated that nobiletin might target gut microbiota and myristoleic acid metabolism to ameliorate NAFLD.

A series of novel 9-N-substituted-13-alkylberberine derivatives from Chinese medicine were designed and synthesized with improved anti-hepatocellular carcinoma (HCC) activities. The optimal compound 4d showed strong activities against HepG2, Sk-Hep-1, Huh-7 and Hep3B cells with IC 50 values of 0.58-1.15 μM, which were superior to positive reference cisplatin. Interestingly, 4d exhibited over 40-fold more potent activity against cisplatin-resistant HepG2/DPP cells while showing lower cytotoxicity in normal LX-2 cells. The mechanism studies revealed 4d greatly stabilized G-quadruplex DNA leading to intracellular c-MYC expression downregulation, blocked G2/M-phase cell cycle by affecting related p-cdc25c, cdc2 and cyclin B1 expressions, and induced apoptosis by a ROS-promoted PI3K/Akt-mitochondrial pathway. Furthermore, 4d possessed good pharmacokinetic properties and significantly inhibited the tumor growth in the H22 liver cancer xenograft mouse model without obvious toxicity. Altogether, the remarkably biological profiles of 4d both in vitro and in vivo would make it a promising candidate for HCC therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Low-molecular-weight chitosan (LMWCS) damaged cell membranes in zebrafish showed its possibility to release reporter proteins for detection. In this study, we developed a simple fluorometric-based assay for the evaluation of clinical antiangiogenic drugs using LMWCS and Tg(fli1:EGFP) transgenic zebrafish, which expressed green-fluorescence protein (GFP) in the endothelial cells of blood vessel. In vitro stable and transiently transfected cell lines was released luciferase and green fluorescent protein (GFP) for intensity evaluation upon LMWCS fluorometric-based assay. In vivo Tg(fli1:EGFP) transgenic zebrafish was also released GFP from endothelial cells of blood vessels and show an increase of fluorescent intensity upon LMWCS fluorometric-based assay. Treatment with the clinical antiangiogenic drug sorafenib and analyzed by LMWCS fluorometric-based assay showed significantly reduction of angiogenesis. Furthermore, treatment with 2 μM sorafenib showed a significant reduction in angiogenesis of the intersegmental vein (ISV) and dorsal longitudinal anastomotic vessels (DLAV) in Tg(fli1:EGFP) transgenic zebrafish. Fluorescence intensity reduction from 2 μM sorafenib was used as a factor in the LMWCS fluorescence-based assay for relative antiangiogenic evaluation. Relative angiogenesis evaluation of the clinical drugs axitinib, cabozantinib, and regorafenib showed a significant reduction. Collectively, this study provided a simple, convenient, and rapid LMWCS fluorometric-based assay for evaluating angiogenic drugs using transgenic zebrafish., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Cassiae Semen (CS) is consumed as fried tea or medicinal food in Asian areas. Its two commercial forms, namely raw and fried CS, exert different clinical applications, in which fried CS is commonly applied as a functional tea for losing weight. To prevent confusion in the use of the two forms of CS, a comprehensive strategy by combining plant metabolomics and spectrum-effect relationship analyses was developed for the fast and efficient discrimination of raw and fried CS, and further for the discovery of the potential hypoglycemic metabolites of CS to control its quality. First, the plant metabolic profiling of raw and processed samples was performed by UHPLC-QTOF-MS/MS. A total of 1111 differential metabolites were found to well distinguish the raw and fried CS after analyzing by MPP software. Subsequently, α-glucosidase inhibition of raw and fried CS was investigated. As a result, fried CS demonstrated much stronger α-glucosidase inhibition activity than the raw sample. By analyzing the spectrum-effect relationship with GRA, BCA, and PLSR, 14 potential hypoglycemic-related compounds were discovered. As anticipated, they were also found as the differential metabolites of the raw and fried samples with a potential hypoglycemic effect, which might be beneficial for the quality control of CS tea. Additionally, molecular docking analysis was conducted to reveal the underlying inhibition mechanisms of the four most critical constituents, including physcion, chrysoobtusin, aurantio-obtusin, and obtusifolin. This study provides a powerful tool for the discrimination of processed samples and fast screening of the active constituents in complex natural products on a high-throughput basis.

Background: Cuscutae Semen (CS) is a commonly used hepatoprotective traditional Chinese medicine, but the chemical components responsible for its hepatoprotective activity are unclear., Objective: The purpose of this study was to evaluate the spectrum-effect relationships between HPLC fingerprints and hepatoprotective effects of CS, and to identify its bioactive components., Methods: Phytochemical isolation of CS extracts was first carried out and 14 potential bioactive compounds were obtained. Chemical fingerprinting was performed on 27 batches of CS from different sources by HPLC, and further analyzed by similarity analysis (SA) and hierarchical clustering analysis (HCA). Pharmacodynamic testing was performed in a CCl4-induced, acute liver injury cell model to assess the hepatoprotective activity of CS by measuring the cell viability and levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Bivariate correlations analysis (BCA) and orthogonal projections to latent structures (OPLS) were used to analyze the spectrum-effect relationships of CS., Results: The results showed that the chemical fingerprints of CS were closely correlated with its hepatoprotective activity. Peaks 1, 10, 18, 19, 21, 22, and 24 might be potential hepatoprotective compounds in CS, and the validation experiments of isolated compounds indicated that chlorogenic acid (P10), hyperoside (P21), isoquercitrin (P22), and astragalin (P24) were the main hepatoprotective components., Conclusion: By combining chemical fingerprints with hepatoprotective evaluation, the present study provides important guidance for QC and clinical use of CS., Highlights: (1) Ten potential bioactive compounds were isolated from CS; (2) The spectrum-effect relationship of CS was molded by HPLC and analysed by OPLS and BCA. (3) Four compounds including chlorogenic acid were the main hepatoprotective components., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dynamic-exponential intravoxel incoherent motion (IVIM) imaging is a potential technique for prediction, monitoring, and differential diagnosis of hepatic diseases, especially liver tumors. However, the use of such technique at voxel level is still limited., Purpose: To develop an unsupervised deep learning approach for voxel-wise dynamic-exponential IVIM modeling and parameter estimation in the liver., Study Type: Prospective., Population: Ten healthy subjects (4 males; age 28 ± 6 years)., Field Strength/sequence: Single-shot spin-echo echo planar imaging (SE-EPI) sequence with monopolar diffusion-encoding gradients (12 b-values, 0-800 seconds/mm 2 ) at 3.0 T., Assessment: The proposed deep neural network (DNN) was separately trained on simulated and in vivo hepatic IVIM datasets. The trained networks were compared to the approach combining least squares with Akaike information criterion (LSQ-AIC) in terms of dynamic-exponential modeling accuracy, inter-subject coefficients of variation (CVs), and fitting residuals on the simulated subsets and regions of interest (ROIs) in the left and right liver lobes. The ROIs were delineated by a radiologist (H.-X.Z.) with 7 years of experience in MRI reading., Statistical Tests: Comparisons between approaches were performed with a paired t-test (normality) or a Wilcoxon rank-sum test (nonnormality). P < 0.05 was considered statistically significant., Results: In simulations, DNN gave significantly higher accuracy (91.6%-95.5%) for identification of bi-exponential decays with respect to LSQ-AIC (79.7%-86.8%). For tri-exponential identification, DNN was also superior to LSQ-AIC despite not reaching a significant level (P = 0.08). Additionally, DNN always yielded comparatively low root-mean-square error for estimated parameters. For the in vivo IVIM measurements, inter-subject CVs (0.011-0.150) of DNN were significantly smaller than those (0.049-0.573) of LSQ-AIC. Concerning fitting residuals, there was no significant difference between the two approaches (P = 0.56 and 0.76) in both the simulated and in vivo studies., Data Conclusion: The proposed DNN is recommended for accurate and robust dynamic-exponential modeling and parameter estimation in hepatic IVIM imaging., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2022 International Society for Magnetic Resonance in Medicine.)

In this work, the hypoglycemic components in Platycladi Cacumen, an essential traditional Chinese medicine, were evaluated by combining phytochemical investigation, spectrum-effect relationship analysis, and chemometric methods. The phytochemical studies on Platycladi Cacumen extract lead to the isolation of 21 potential bioactive compounds. The chromatographic fingerprints of Platycladi Cacumen samples were established by high-performance liquid chromatography. The hypoglycemic effects of Platycladi Cacumen samples were further evaluated by inhibition of α-glucosidase and detected by the high-performance liquid chromatography method. The spectrum-effect relationship study by bivariate correlations analysis and orthogonal partial least squares regression revealed that myricitrin (P9), quercitrin (P13), afzelin (P18), and amentoflavone (P24) were more relevant to the α-glucosidase inhibitory activity. The results of α-glucosidase inhibitory activity of 21 isolated compounds and molecular docking studies also indicated these flavonoids had potent α-glucosidase inhibitory activity. Collectively, the present study established the spectrum-effect relationship mode of Platycladi Cacumen and discovered the major hypoglycemic components, which provides a feasible method for screening bioactive components., (© 2022 Wiley-VCH GmbH.)

Objectives: Uncariae Rammulus Cum Uncis (URCU) is a commonly used herbal medicine to treat diabetes. This work is aimed to discover and identify the antidiabetic components from URCU extract., Methods: Column chromatography and recrystallisation were used to separate individual compounds from URCU extract, and the obtained individual compounds were used for determination of α-glucosidase inhibitory activity. Molecular docking was applied to predict the molecular interactions. High-performance liquid chromatography (HPLC) was used for fingerprint analysis of 12 batches of URCU. HPLC fingerprints were assessed by the similarity analysis (SA) and hierarchical clustering analysis (HCA). The spectrum-effect relationship analysis of URCU was assessed by orthogonal partial least squares (OPLS) and bivariate correlation analysis (BCA)., Results: A total of 10 potential bioactive compounds were isolated and six of them showed potent α-glucosidase inhibitory activity (IC 50  = 4.21-166.10 μM). The molecular docking results revealed that the binding energy was consistent with the results of α-glucosidase inhibition activity analysis (-8.55 to -4.84 kcal/mol). The ethanol extracts of the 12 batches of URCU showed inhibitory effect on α-glucosidase in a dose-dependent manner, and the IC 50 values ranged from 0.94 μg/mL to 12.57 μg/mL. The spectrum-effect relationship analysis results indicated that 13 peaks might be potential antidiabetic compounds in URCU, including 18 (hyperoside) and 19 (rutin)., Conclusion: A comprehensive connection between URCU chemical components and α-glucosidase inhibitory activity was established for the first time by using a spectrum-effect relationship model, which might be applicable to the quality control of URCU., (© 2022 John Wiley & Sons, Ltd.)

In this work, we examined whether baicalin (BC), a bioactive flavonoid in Scutellaria baicalensis Georgi, can reduce high-fat diet (HFD)-induced metabolic syndrome (MetS) in mice. The UPLC-QTOF/MS was used for metabolome profiles analysis, and an analysis of bacterial 16S rDNA in feces was used to examine the effects of BC on gut microbiota composition. Our results showed that BC (400 mg/kg) could reduce the body weight gain, decrease hepatic fat accumulation and abnormal blood lipids, and increase insulin sensitivity after 8 weeks of treatment. BC could reverse the alteration of 7 metabolites induced by HFD and the metabolic pathways responsive to BC intervention including citrate cycle, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, and aminoacyl-tRNA biosynthesis. 16S rDNA analysis demonstrated that BC altered the composition and function of gut microbiota in MetS mice. Notably, we found that the change in succinic acid was negatively associated with the changes in Bacteroides and Sutterella, and positively associated with the change in Mucispirillum. Moreover, we confirmed that succinic acid displayed a metabolic protective effect on MetS mice. The antibiotic treatment verified that BC exerts metabolic protection through gut microbiota. Our findings suggested BC may be a potential therapeutic drug to ameliorate diet induced MetS and gut microbiome may be a novel mechanistic target of BC for treatment of MetS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objective: Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. Better prediction and management of this nephrotoxicity can increase patient survival. Our study aimed to build up and compare the best machine learning models with clinical and genomic features to predict platinum-induced nephrotoxicity in non-small cell lung cancer patients., Methods: Clinical and genomic data of patients undergoing platinum chemotherapy at Wan Fang Hospital were collected after they were recruited. Twelve models were established by artificial neural network, logistic regression, random forest, and support vector machine with integrated, clinical, and genomic modes. Grid search and genetic algorithm were applied to construct the fine-tuned model with the best combination of predictive hyperparameters and features. Accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were calculated to compare the performance of the 12 models., Results: In total, 118 patients were recruited for this study, among which 28 (23.73%) were experiencing nephrotoxicity. Machine learning models with clinical and genomic features achieved better prediction performances than clinical or genomic features alone. Artificial neural network with clinical and genomic features demonstrated the best predictive outcomes among all 12 models. The average accuracy, precision, recall, F1 score and area under the receiver operating characteristic curve of the artificial neural network with integrated mode were 0.923, 0.950, 0.713, 0.808 and 0.900, respectively., Conclusions: Machine learning models with clinical and genomic features can be a preliminary tool for oncologists to predict platinum-induced nephrotoxicity and provide preventive strategies in advance., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

This article examines the ways in which lesbians explore opportunities and navigate constraints in their family and work lives in urban China. It not only reveals Chinese lesbians' difficulties in gaining equal access to the labour market and developing their desired family lives, but also discusses possible ways of enhancing the applicability of the adult worker model for sexual minority women. Previous research has indicated a shift from the male breadwinner model to the adult worker model, suggesting that both men and women are expected to join the labour market, and that women should not carry all the care responsibilities within the family. However, the model largely overlooks the interplay of gender and sexuality factors in shaping work and family lives. This article adopts a qualitative mixed-methods approach, including interviews with 20 Chinese lesbians and social media analysis, to examine lesbians' experiences of taking part in the family as adults and in the wider economy as workers. It shows how gender norms, heteronormativity, and policy intersect in generating obstacles for Chinese lesbians to thrive as respectable adult workers. This has important implications for attempts to improve the adult worker model to fit better with people's diverse work/family needs.

Since the combinatorial components responsible for the antihyperlipidemic activity of Citrus reticulata 'Chachi' (CRC) peels remains unclear, we herein developed a bioactive equivalence oriented feedback screening method to discover the bioactive equivalent combinatorial components (BECCs) from CRC peels. Using palmitic acid (PA)-stimulated hepatocyte model, a combination of 5 polymethoxyflavones (PMFs) including tangeretin, sinensetin, nobiletin, 5,7,8,4'-tetramethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone was identified to be responsible for the antihyperlipidemic effect of CRC peels. Via evaluation of combination effect by combination index (CI), these 5 PMFs were found to take effect via a synergistic mode. Our data indicated that the antihyperlipidemic mechanism of PMF combination was associated with the inhibition of fatty acid and cholesterol synthesis, and inflammation. Also, the PMF combination exhibited robust antihyperlipidemic effects in HFD-fed rats in vivo. Our study offers evidence-based data to uncover the pharmacological effect of CRC peels.