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A UPLC-MS/MS method was developed to determinate curdione in the mouse blood, and the pharmacokinetics of curdione in mice after intravenous (5 mg kg−1) and oral (20 mg kg−1) administration were studied. The HSS T3 column was used for separation, and column temperature was set at 40 °C. Multiple reaction monitoring (MRM) mode were used for determination of curdione. Blood samples were taken from the caudal vein of Institute of Cancer Research (ICR) mice after administration of curdione. It showed a good linear relationship in the range of 1–500 ng mL−1 (r > 0.998); the intra-day precision was 77%, and the matrix effect was 97%–107%. The half-life was relatively short, and the bioavailability was 6.5%. The developed method was suitable for the pharmacokinetics of curdione in mice.

Modafinil has a strong and long-lasting awakening effect. Short-term use can improve cognitive and work efficiency. Therefore, it has been known to be abused by students and parents as a “smart drug.” It is in the first category of psychotropic drugs and strictly controlled. To detect modafinil in rat plasma and study the differences in the pharmacokinetics of modafinil between oral and sublingual administration in rats, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed. Rats were injected with modafinil by oral gavage and sublingual vein, respectively, blood was collected within a certain period, and the plasma was obtained by centrifugation. Midazolam was used as the internal standard, and the concentration of modafinil in the plasma was determined by UPLC-MS/MS, where a drug-time curve was created to calculate the pharmacokinetic parameters. The standard curve for modafinil ranged from 1 to 2000 ng mL−1 with good linearity. The intra-day accuracy of modafinil was between 86% and 104%, and the intra-day accuracy was between 90% and 103%. Intra-day precision (RSD%) was less than 15%, inter-day precision (RSD%) was less than 15%. The matrix effect was between 93% and 102%, and the recovery was greater than 91%. The UPLC-MS/MS method established in this work has good selectivity and high sensitivity, and the UPLC-MS/MS method was successfully applied to the pharmacokinetics of modafinil by oral gavage and sublingual injection in rats. The bioavailability of modafinil was calculated to be 55.8%.

In increasingly complex scenes, multi-scale information fusion becomes more and more critical for semantic image segmentation. Various methods are proposed to model multi-scale information, such as local to global, but this is not enough for the scene changes more and more, and the image resolution becomes larger and larger. Cross-Scale Sampling Transformer is proposed in this paper. We first propose that each scale feature is sparsely sampled at one time, and all other features are fused, which is different from all previous methods. Specifically, the Channel Information Augmentation module is first proposed to enhance query feature features, highlight part of the response to sampling points and enhance image features. Next, the Multi-Scale Feature Enhancement module performs a one-time fusion of full-scale features, and each feature can obtain information about other scale features. In addition, the Cross-Scale Fusion module is used for cross-scale fusion of query feature and full-scale feature. Finally, the above three modules constitute our Cross-Scale Sampling Transformer(CSSFormer). We evaluate our CSSFormer on four challenging semantic segmentation benchmarks, including PASCAL Context, ADE20K, COCO-Stuff 10K, and Cityscapes, achieving 59.95%, 55.48%, 50.92%, and 84.72% mIoU, respectively, outperform the state-of-the-art.

The lightweight MLP-based decoder has become increasingly promising for semantic segmentation. However, the channel-wise MLP cannot expand the receptive fields, lacking the context modeling capacity, which is critical to semantic segmentation. In this paper, we propose a parametric-free patch rotate operation to reorganize the pixels spatially. It first divides the feature map into multiple groups and then rotates the patches within each group. Based on the proposed patch rotate operation, we design a novel segmentation network, named PRSeg, which includes an off-the-shelf backbone and a lightweight Patch Rotate MLP decoder containing multiple Dynamic Patch Rotate Blocks (DPR-Blocks). In each DPR-Block, the fully connected layer is performed following a Patch Rotate Module (PRM) to exchange spatial information between pixels. Specifically, in PRM, the feature map is first split into the reserved part and rotated part along the channel dimension according to the predicted probability of the Dynamic Channel Selection Module (DCSM), and our proposed patch rotate operation is only performed on the rotated part. Extensive experiments on ADE20K, Cityscapes and COCO-Stuff 10K datasets prove the effectiveness of our approach. We expect that our PRSeg can promote the development of MLP-based decoder in semantic segmentation., Comment: Accepted by IEEE TCSVT

Flavonoids are the most abundant components in Salvia plebeia, with significant pharmacological antioxidant and hepatoprotective properties. Hispidulin and homoplantaginin are the main flavonoid components in S. Plebeia. In this study, we established an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine hispidulin and homoplantaginin in rat plasma samples, which were precipitated using acetonitrile-methanol (9:1, v/v). We used a UPLC HSS T3 (100 mm × 2.1 mm, 1.7 μm diameter) chromatographic column, an acetonitrile-water (containing 0.1% formic acid) mobile phase, and a gradient elution flow rate of 0.4 mL min−1 in an elution time of 4 min. We used electrospray ionization (ESI) detection in positive ion mode, and multiple reaction monitoring mode (MRM) for quantitative analysis: m/z 301 → 286 for hispidulin, m/z 463 → 301 for homoplantaginin, and m/z 465 → 303 for internal standard (IS). In pharmacokinetic studies, 24 rats were orally administered hispidulin and homoplantaginin (5 mg kg−1) and received sublingual intravenous injections (1 mg kg−1) at two different doses, four groups with six rats/group. Differences in hispidulin and homoplantaginin pharmacokinetics in rat plasma were evaluated. The calibration curve showed good linearity in the 0.5–1,000 ng mL−1 range, with r > 0.99. Precision, accuracy, recovery, matrix effects, and stability results all met standard biological sample detection requirements. Our pharmacokinetic studies showed hispidulin bioavailability was much higher than homoplantaginin at 17.8% and 0.1%, respectively.

This study developed a UPLC-MS/MS method to detect isoscoparin in mouse blood, determined the pharmacokinetics of isoscoparin in mice after intravenous (5 mg/kg) and intragastric (20 mg/kg) administration, and calculated the absolute bioavailability. A HSS T3 column was used for separation, and the column temperature was set at 40°C. The mobile phases were acetonitrile and 0.1% formic acid, and the gradient elution procedure was used. The blood sample was treated with protein precipitant with acetonitrile-methanol (9:1, v/v). Multiple reaction monitoring mode was used for quantitative analysis in electrospray positive-ion mode. It showed a good linear relationship in the range of 1-4000 ng/mL (r 0.998); the intra-day and inter-day precision was12%, and the accuracy was 86-112%. The recovery was68%, and the matrix effect was 86-90%. The half-life of isoscoparin was relatively short in mice, and the bioavailability was 2.6%. The developed UPLC-MS/MS method was rapid, sensitive, and suitable for the pharmacokinetics of isoscoparin in mice.

Background: ship emissions have an adverse effect on air quality in coastal regions, and this effect can be exacerbated by onshore winds. Objectives and methods: to investigate the impact of ship emissions on air pollutant concentrations during the onshore wind period in a low-latitude region in China, this study applied the WRF/Chem model to simulate the contribution of ship emissions to PM2.5 and O3 by “zero-out” in 2018, in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). Results/findings: results show that the onshore winds facilitated the transport of ship-emitted pollutants to inland areas, causing the contribution of ship emissions to PM2.5 exceeding 4 μg/m3 to areas north of Guangzhou in April and west of the GBA in October. The impact of onshore winds on the ship contribution to the O3 concentration shows a bidirectional trend both spatially and monthly. The onshore winds raised the ship contribution to O3 concentrations in April by 1.54 μg/m3, while exacerbated the decreasing contribution in other months. In VOC-sensitive cities such as Foshan, onshore winds exacerbated the negative contribution of ship emissions to O3 concentrations; while in NOx-sensitive cities such as Huizhou, they enhanced the contribution of ship-induced O3. Novelty/Improvement: this paper fills a gap in the study of pollutants transportation characteristics from ship emissions under the influence of onshore winds in the GBA. Our results demonstrate the importance of considering meteorological conditions and atmospheric chemical mechanisms regarding the coastal air pollution prevention caused by ship emissions.

Objective BMI is a well-established factor affecting the transcriptome profile of adipose tissue, but there are few reports on the relationship between the metabolic health status of people with obesity and the transcriptional changes, particularly in visceral adipose tissue. Methods Visceral adipose tissue was collected from three subgroups of patients, lean (n = 11), metabolically healthy obesity (MHO; n = 22), and metabolically unhealthy obesity (MUO; n = 26), and RNA sequencing was conducted to profile the transcriptome changes between these groups in a pairwise manner. Results Comparing MUO with lean and comparing MHO with lean revealed similar patterns in gene expression and pathway changes: obesity, regardless of metabolic health, was associated with upregulated inflammatory pathways. However, the inflammatory signature in MUO was stronger than in MHO. Pairwise comparisons among MUO, MHO, and lean samples identified 34 common differentially expressed genes; 12 out of 34 genes were associated with inflammatory pathways and exhibited a gradually increased expression pattern in the order of lean, MHO, and MUO. Conclusions This study reveals not only that BMI plays an important role in determining the gene expression profile in visceral adipose tissue but also that a metabolically healthy condition is associated with a less inflammatory transcriptional change during obesity.

Background. Serum bilirubin is an endogenous antioxidant that has protective effects against obesity-related metabolic diseases. Objectives. This study aimed to evaluate the characteristics of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) and their relationships with insulin sensitivity in obese patients with impaired glucose regulation and type 2 diabetes mellitus (IGR/T2DM) in China. Patients and Methods. Cohort 1 comprised obese patients (n = 71) was divided into the IGR/T2DM group (n = 38, obesity with IGR/T2DM) and control group (n = 33, obesity without IGR/T2DM). Insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique (HEC) with glucose disposal rate (GDR, M value). Cohort 2 comprised obese patients with IGR/T2DM who underwent metabolic surgery (n = 109) as complementary to cohort 1. Insulin sensitivity was evaluated with the Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS). Results. In cohort 1, TBIL, DBIL, and IBIL were higher within the physiological range in the IGR/T2DM group compared with the control group; IBIL was positively correlated with M value (r = 0.342, p=0.044) in the IGR/T2DM group, and multivariate logistic regression showed that IBIL might be independent protective factors against insulin resistance (odds ratio (OR) = 0.602; 95% confidence interval (CI): 0.413–0.878; p=0.008). In cohort 2, at 1 month after metabolic surgery, serum bilirubin levels (TBIL, DBIL, and IBIL) increased, and the percentage change in IBIL was positively correlated with the change of the Matsuda Index (r = 0.195, p=0.045). Conclusions. The relationships between different types of bilirubin and insulin sensitivity varied. Serum indirect bilirubin might be a protective factor that enhances insulin sensitivity.

Knowing plant water content (PWC) is of great significance for precision irrigation of field crop. The aim of this study is to monitor the PWC of cotton non-destructively in situ. A six-ban...

Air pollutants from ship exhaust have a negative impact on air quality in coastal areas, which can be greatly exacerbated by sea breeze circulation. However, our understanding of this issue is still limited, especially in coastal areas with a complex topography and winding coastlines, such as the Bohai Rim region in China. In order to fill this knowledge gap, the Weather Research and Forecast model coupled with the chemistry (WRF/Chem) modeling system was employed to investigate the influence of sea breeze circulation on the transport of PM2.5 emitted by ships from April to September in 2014. The major findings are as follows: (1) The concentration of PM2.5 due to ship emissions was 2.94 μg/m3 on days with a sea breeze and 2.4 times higher than on days without a sea breeze in coastal cities in the region. (2) The difference in the contribution of ship emissions during days with a sea breeze and days without a sea breeze decreases with increasing distance from the coastline but remains non-negligible up to 50 km inland. (3) The shape of the coastline, the topographic height of the land area, and the latitude have a significant impact on sea breeze circulation and thus on the transport of ship emissions. (4) The differences in the contribution of ship emissions under days with a sea breeze versus days without a sea breeze were more evident than those under onshore versus alongshore and offshore winds, indicating that sea breeze circulation can cause cyclic accumulation of pollutants and thus reinforce the impact of ship emissions on coastal air quality more than by onshore winds. It should be emphasized that during the switching from sea breeze to a non-sea breeze, the pollutants that have been transported to the land area by sea breeze have not yet been carried back to sea, resulting in the ship contribution value still not significantly reduced even if the wind is a non-sea breeze at that moment. In addition, other factors e.g., emissions, precipitation, and chemistry can also play an important role in the observed trends in this study.

BackgroundThis study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity.ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria.ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.

In this study, a new class of thermal insulation composites was prepared by blending a modified hollow glass microsphere (HGM) with furan resin. The particle dispersion between the microparticles and resin matrix was improved using 3-methacryloxypropyltrimethoxy silane (KH-570). Furthermore, the structure and morphology of the modified HGM were characterised by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). In addition, the effects of the modified HGM on the thermal insulation, flame retardancy, and thermal properties of the composites were investigated. The thermal conductivity of the composites was lower than that of the native furan resin. The minimum thermal conductivity of the composites was 0.0274 W/m&middot, K, the flame retardancy of the composites improved, and the limiting oxygen index become a maximum of 31.6%, reaching the refractory material level. Furthermore, the thermal analysis of the composites demonstrated enhanced thermal stability. This study demonstrates that the composite material exhibited good thermal insulation performance and flame retardancy and that it can be applied in the field of thermal insulation.

Introduction Red blood cell distribution width (RDW) and mean platelet volume (MPV) are both new biomarkers for the prognosis of many diseases. This study aimed to observe the predictive values of RDW and MPV for weight loss after different metabolic surgeries in patients with obesity and abnormal glucose metabolism [diabetes mellitus or impaired glucose regulation (DM/IGR)]. Methods We retrospectively analyzed the body weight (BW), body mass index (BMI) and blood routine index of 98 patients with obesity and DM/IGR who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Results Levels of RDW and MPV in both groups were significantly higher than before 1 month after surgery and then gradually decreased. Twelve months after surgery, the RDW level in the RYGB group was significantly lower than that before surgery. In the RYGB group, the RDW level of patients in the high-level percentage weight loss (%BW) (≥ 31.90) at 6 and 12 months after surgery decreased significantly compared to those in the corresponding low level. %BW and change in BW and BMI (ΔBW and ΔBMI) at 6 and 12 months after surgery in the high-level RDW (≥ 12.90) before surgery were significantly higher than those in the low level in the RYGB group. No significant difference in weight index was found in the high and low levels of the MPV before surgery in either group at other follow-up time points. Conclusions Preoperative baseline RDW and postoperative RDW levels can preliminarily predict the effect of different metabolic surgeries in patients with obesity and DM/IGR.

Thyroid stimulating hormone (TSH) has received increasing attention as being closely associated with increased low-density lipoprotein cholesterol (LDL-c) level and higher atherosclerotic risks. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known for increasing circulating LDL-c level by inducing LDL receptor degradation. However, whether TSH influences hepatic PCSK9 expression and LDL-c metabolism remains unclear.First, the correlation between TSH and lipid profiles were investigated in euthyroid population and in subclinical hypothyroidism patients. Then, an in vitro study was conducted to validate the effects of TSH on hepatic PCSK9 expression in HepG2 cells.Serum TSH concentrations positively correlated with LDL-c levels in euthyroid subjects. Subclinical hypothyroidism patients with higher serum TSH levels showed significantly increased serum PCSK9 levels than the matched euthyroid participants (151.29 (89.51-293.03) vs. 84.70 (34.98-141.72) ng/ml, P0.001), along with increased LDL-c concentrations. In HepG2 cells, LDLR expression on the plasma membrane was decreased, and PCSK9 mRNA and protein levels were synchronously upregulated after recombinant human TSH (rhTSH) treatment, while the effects could be blocked by TSH receptor blocking antibody K1-70. Sterol regulatory element binding protein (SREBP) 1c and SREBP2 mRNA expressions were enhanced after rhTSH treatment, and specific siRNAs significantly inhibited the effects of rhTSH. Furthermore, there was a noticeable induction of PCSK9 expression by rhTSH even though HMGCR gene expression was silenced.We conclude a regulating role of TSH on hepatic PCSK9 expression, which further contributing to a higher LDL-c level.

BackgroundSPs are a group of ubiquitously produced lipids that are structurally involved in cell membranes and include SMs, ceramides, GM3s, etc. Sphingolipids and their substrates and constituents, FAs, are implicated in the pathogenesis of various metabolic diseases associated with obesity, diabetes, and atherosclerosis. Decreased insulin sensitivity or insulin secretion is a multifactorial condition related to obesity and diabetes. Therefore, it is likely that perturbations in serum SPs are associated with diseases. Identifying these associations may reveal useful predictors or give perceptive insight into disease processes. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp, and FPIR was measured to evaluate insulin secretion by the IVGTT. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity based on GIR30 derived from the glucose clamp, which is the standard method, and the cutoff point of GIR30 was set as 5.1 mg/(kg *min).ResultsDifferential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. We also found that higher concentrations of serum free FAs (FFA 22:6, FFA 22:5, FFA 18:2, FFA 18:1) were associated with a higher risk of decreased insulin secretion. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria. ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. This suggests that the balance of SMs metabolism, rather than ceramide is correlated with the pathology of insulin resistance, obesity and T2DM. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.

Background Homozygous familial hypercholesterolemia is characterized by extremely elevated serum low-density lipoprotein cholesterol (LDL-C) levels and increased risk of cardiovascular complications due to biallelic mutations in LDL receptor ( LDLR ). Objective We present a 10-year-old Chinese homozygous familial hypercholesterolemia boy with biallelic LDLR mutations including an extremely rare de novo mutation. Methods Detailed family history and clinical and biochemical data were gathered from the pedigree. Genomic DNA was isolated and the reported LDL-related genes ( LDLR , APOB , PCSK9 , ABCG5 , ABCG8 , ANGPTL3 , APOC3 , and LDLRAP1 ) were sequenced. Results The proband displayed extensive cutaneous and tendon xanthomas together with elevated serum LDL-C level of 14.87 mmol/L (575 mg/dL). A combination of simvastatin 40 mg daily and ezetimibe 10 mg daily resulted in 57% lowering of LDL-C. The proband had compound heterozygous LDLR disease-causing mutations, including p.(His583Tyr) variant transmitted from the mother and a de novo p.(Gln242*) variant on the paternal allele. Conclusions Our report supports the role of genetic testing in the proband and the parents for accurate genetic counseling. Our patient had marked lowering of LDL-C with a combination of statin and ezetimibe but may require additional therapy.