HST-MRF: Heterogeneous Swin Transformer with Multi-Receptive Field for Medical Image Segmentation

The Transformer has been successfully used in medical image segmentation due to its excellent long-range modeling capabilities. However, patch segmentation is necessary when building a Transformer class model. This process may disrupt the tissue structure in medical images, resulting in the loss of relevant information. In this study, we proposed a Heterogeneous Swin Transformer with Multi-Receptive Field (HST-MRF) model based on U-shaped networks for medical image segmentation. The main purpose is to solve the problem of loss of structural information caused by patch segmentation using transformer by fusing patch information under different receptive fields. The heterogeneous Swin Transformer (HST) is the core module, which achieves the interaction of multi-receptive field patch information through heterogeneous attention and passes it to the next stage for progressive learning. We also designed a two-stage fusion module, multimodal bilinear pooling (MBP), to assist HST in further fusing multi-receptive field information and combining low-level and high-level semantic information for accurate localization of lesion regions. In addition, we developed adaptive patch embedding (APE) and soft channel attention (SCA) modules to retain more valuable information when acquiring patch embedding and filtering channel features, respectively, thereby improving model segmentation quality. We evaluated HST-MRF on multiple datasets for polyp and skin lesion segmentation tasks. Experimental results show that our proposed method outperforms state-of-the-art models and can achieve superior performance. Furthermore, we verified the effectiveness of each module and the benefits of multi-receptive field segmentation in reducing the loss of structural information through ablation experiments

Endogenous Sulfur Dioxide: A New Member of Gasotransmitter Family in the Cardiovascular System

Sulfur dioxide (SO2) was previously regarded as a toxic gas in atmospheric pollutants. But it has been found to be endogenously generated from metabolism of sulfur-containing amino acids in mammals through transamination by aspartate aminotransferase (AAT). SO2 could be produced in cardiovascular tissues catalyzed by its synthase AAT. In recent years, studies revealed that SO2 had physiological effects on the cardiovascular system, including vasorelaxation and cardiac function regulation. In addition, the pathophysiological effects of SO2 were also determined. For example, SO2 ameliorated systemic hypertension and pulmonary hypertension, prevented the development of atherosclerosis, and protected against myocardial ischemia-reperfusion (I/R) injury and isoproterenol-induced myocardial injury. These findings suggested that endogenous SO2 was a novel gasotransmitter in the cardiovascular system and provided a new therapy target for cardiovascular diseases.National Natural Science Foundation of China [81400311, 31440052, 91439110]SCI(E)[email protected]

Hydrogen Sulfide Inhibits L-Type Calcium Currents Depending upon the Protein Sulfhydryl State in Rat Cardiomyocytes

Hydrogen sulfide (H2S) is a novel gasotransmitter that inhibits L-type calcium currents (I Ca, L). However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H2S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused rat hearts. The L-type calcium currents were recorded by using a whole cell voltage clamp technique on the isolated cardiomyocytes. The L-type calcium channel containing free sulfhydryl groups in H9C2 cells were measured by using Western blot. The results showed that sodium hydrosulfide (NaHS, an H2S donor) produced a negative inotropic effect on cardiac function, which could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). H2S donor inhibited the peak amplitude of I Ca, L in a concentration-dependent manner. However, dithiothreitol (DTT), a reducing sulfhydryl modifier markedly reversed the H2S donor-induced inhibition of I Ca, L in cardiomyocytes. In contrast, in the presence of DM, H2S donor could not alter cardiac function and L type calcium currents. After the isolated rat heart or the cardiomyocytes were treated with DTT, NaHS could markedly alter cardiac function and L-type calcium currents in cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl group in the L-type Ca2+ channel, which could be reversed by thiol reductant, either DTT or reduced glutathione. Therefore, our results suggest that H2S might inhibit L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes

ESIA: An Efficient and Stable Identity Authentication for Internet of Vehicles

Decentralized, tamper-proof blockchain is regarded as a solution to a challenging authentication issue in the Internet of Vehicles (IoVs). However, the consensus time and communication overhead of blockchain increase significantly as the number of vehicles connected to the blockchain. To address this issue, vehicular fog computing has been introduced to improve efficiency. However, existing studies ignore several key factors such as the number of vehicles in the fog computing system, which can impact the consensus communication overhead. Meanwhile, there is no comprehensive study on the stability of vehicular fog composition. The vehicle movement will lead to dynamic changes in fog. If the composition of vehicular fog is unstable, the blockchain formed by this fog computing system will be unstable, which can affect the consensus efficiency. With the above considerations, we propose an efficient and stable identity authentication (ESIA) empowered by hierarchical blockchain and fog computing. By grouping vehicles efficiently, ESIA has low communication complexity and achieves high stability. Moreover, to enhance the consensus security of the hierarchical blockchain, the consensus process is from the bottom layer to the up layer (bottom-up), which we call B2UHChain. Through theoretical analysis and simulation verification, our scheme achieves the design goals of high efficiency and stability while significantly improving the IoV scalability to the power of 1.5 (^1.5) under similar security to a single-layer blockchain. In addition, ESIA has less communication and computation overhead, lower latency, and higher throughput than other baseline authentication schemes

Common genetic variants in ADCY5 and gestational glycemic traits.

Two meta-analysis of genome wide association studies identified two variants at adenylate cyclase 5 (ADCY5) associated with type 2 diabetes mellitus, fasting and 2-hour glucose in non-pregnant individuals of European descent. The objective of our study was to explore the role of common variants in ADCY5 on gestational glycemic traits, including plasma glucose, insulin values, β cell function and insulin resistance in the fasted state as well as plasma glucose 1 hour after a 50-gram glucose challenge test among Chinese Han women. Homoeostasis model assessment (HOMA) was used to quantify β cell function (HOMA1-β and HOMA2-β) and insulin resistance (HOMA1-IR and HOMA2-IR). Thirty-five single nucleotide polymorphisms (SNPs) in ADCY5 were genotyped in 929 unrelated Chinese Han women with singleton pregnancies. Three SNPs (rs6797915, rs9856662 and rs9875803) displayed evidence for association with plasma glucose 1 hour after a 50-gram glucose challenge test (P = 0.042, 0.018 and 0.018, respectively), one (rs6777397) displayed evidence for association with HOMA1-β (P = 0.014), and one (rs6762009) displayed evidence for association with HOMA1-IR (P = 0.033). These results provide additional insight into the effects of genetic variation within ADCY5 in glucose metabolism, especially during pregnancy and in non-European descent populations

Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74

ObjectivesMast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation.MethodsHMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC β-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation.ResultsDegranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions.ConclusionThese findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases

Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases

Plasma Homocysteine Level in Children With Postural Tachycardia Syndrome

The study was designed to evaluate the changes of plasma homocysteine (Hcy) level in children with postural tachycardia syndrome (POTS) and explore its significance. A total of 65 subjects were recruited in our study, of whom 35 children were in the POTS group and 30 healthy children were in the control group. Plasma Hcy levels were determined in all subjects. The relationship between the plasma Hcy level and the symptom score was analyzed in the 35 POTS patients. The relationship between the plasma Hcy level and the change in heart rate from the supine to upright position (ΔHR) and between the plasma Hcy level and the rate of increase in heart rate from the supine to upright position (ΔHR/sHR × 100%) were analyzed in all subjects. The plasma Hcy levels were significantly higher in the children with POTS than those in the control group (9.78 [7.68, 15.31] μmol/L vs. 7.79 [7.46, 9.63] μmol/L, P < 0.05). The plasma Hcy levels were positively correlated with symptom scores in the POTS patients (n = 35, r = 0.522, P < 0.01). The plasma Hcy levels were also positively correlated with ΔHR (n = 65, r = 0.332, P < 0.01) and ΔHR/sHR × 100% (n = 65, r = 0.341, P < 0.01) in all the subjects. In conclusion, the plasma Hcy levels were elevated in the children with POTS positively correlated with the severity of POTS, suggesting that Hcy might be involved in the pathogenesis of POTS

Ион-парная ВЭЖХ производных пиримидина и пурина

ПИРИМИДИНЫГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ ОДНОКОЛЬЦЕВЫЕПУРИНЫГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ ДВУХКОЛЬЦЕВЫЕХРОМАТОГРАФИЯ ЖИДКОСТНАЯ ВЫСОКОГО ДАВЛЕНИЯХРОМАТОГРАФИЯ ИОНООБМЕННАЯДНКРНКПРОТИВООПУХОЛЕВЫЕ СРЕДСТВАПРОТИВОВИРУСНЫЕ СРЕДСТВ

Sulfur Dioxide Activates Cl-/HCO3- Exchanger via Sulphenylating AE2 to Reduce Intracellular pH in Vascular Smooth Muscle Cells

Sulfur dioxide (SO2) is a colorless and irritating gas. Recent studies indicate that SO2 acts as the gas signal molecule and inhibits vascular smooth muscle cell (VSMC) proliferation. Cell proliferation depends on intracellular pH (pHi). Transmembrane cystein mutation of Na+- independent Cl-/HCO3- exchanger (anion exchanger, AE) affects pHi. However, whether SO2 inhibits VSMC proliferation by reducing pHi is still unknown. Here, we investigated whether SO2 reduced pHi to inhibit the proliferation of VSMCs and explore its molecular mechanisms. Within a range of 50–200 μM, SO2 was found to lower the pHi in VSMCs. Concurrently, NH4Cl pre-perfusion showed that SO2 significantly activated AE, whereas the AE inhibitor 4,4′-diisothiocyanatostilbene- 2,20-disulfonic acid (DIDS) significantly attenuated the effect of SO2 on pHi in VSMCs. While 200 μM SO2 sulphenylated AE2, while dithiothreitol (DTT) blocked the sulphenylation of AE2 and subsequent AE activation by SO2, thereby restoring the pHi in VSMCs. Furthermore, DIDS pretreatment eliminated SO2-induced inhibition of PDGF-BB-stimulated VSMC proliferation. We report for the first time that SO2 inhibits VSMC proliferation in part by direct activation of the AE via posttranslational sulphenylation and induction of intracellular acidification