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We report a promiscuous flavonoid 7,4′-di-O-glycosyltransferase (ZjOGT3), which shows high catalytic efficiency and regio-selectivity. And the regio-selectivity of ZjOGT3 was controlled by intrinsic reactivity and the enzyme microenvironment.

Ying Li1,2 *, Jia-Jing Lu1,2 *, Xiao-Yuan Zhong1,2 *, Ying-Yuan Yu1,2 *, Ning Yu,1,2 Yu Wang,1,2 Xue-Mei Yi,1,2 Yang-Feng Ding,1,2 Yu-Ling Shi1,2 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Ling Shi; Yang-Feng Ding, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Road, Shanghai, 200443, People’s Republic of China, Email shiyuling1973@tongji.edu.cn; dingyangfeng@hotmail.comBackground: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions.Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan–Meier curves and Log rank tests.Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence.Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.Keywords: biologics, drug survival, real-world, psoriasis, ixekizumab, secukinumab, guselkumab, adalimumab

Uterine endometrial cancer (UEC) is an estrogen-related tumor. Succinate and heme metabolism play important roles in the progression of multiple tumors. However, the relationship between estrogen, succinate, and heme metabolism and related regulatory mechanisms remain largely unknown. In this study, we observed that the expression of aminolevulinate delta synthase 1 (ALAS1) and solute carrier family member 38 (SLC25A38) in UEC tissues is significantly higher than that in normal tissues. Further analysis showed that estrogen and succinate increased the expression of ALAS1 and SLC25A38 in uterine endometrial cancer cells (UECC), and the administration of succinate upregulated the level of the estrogen receptor (ER). Silencing nuclear receptor coactivator 1 (NCOA1) reversed the effects of estrogen and succinate via downregulation of ALAS1 expression. Additionally, exposure of UECC to heme increased cell viability and invasiveness, while silencing the NCOA1 gene weakened this effect. These findings revealed that estrogen and succinate can synergistically increase the expression of ALAS1 and SLC25A38 via the ERβ/NCOA1 axis, promoting heme accumulation and increasing the proliferative and invasive potential of UECC.

Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members ofHunnivirus,PestivirusandCopiparvoviruspangolin-associated viruses. We report that thel-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus,Orthopneumovirus,RotavirusAandMammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.

In order to improve the coloration efficiency of fashion design, an automatic color matching mechanism based on adaptive color clustering of image scenes is proposed for clothing patterns. Taking images of Sung porcelain as an example, 300 porcelain images from six different kilns were collected as testing samples. The porcelain area of each sample image was detected by image segmentation and denoising. The bipartite K-means clustering algorithm was utilized to adaptively extract the main colors of each sample. Also, the secondary clustering was carried out to obtain the main color values, proportions and co-occurrence ratios of each kiln’s image. A dynamic color matching mechanism integrating the number of color clusters, co-occurrence ratio, and structure characteristics of the target pattern, was designed and automatic color parsing and matching software was developed. The experiment results show that the color matching control parameters, source images, pattern shape, and other factors affect the main color selection sequence and the final matching effect. The time consumed for single sample color extraction and pattern automatic color matching are all less than 1 s, which can quickly realize the pattern color migration based on image scenes and further provide auxiliary decision-making for clothing pattern color design.

In this paper, a N-rich B–N polymorph named as B20N24 is proposed through first-principles calculations. The stability of the B20N24 polymorph at ambient conditions is confirmed using the phonon dispersion spectra and the Born stability criteria. Electronic properties calculations show that B20N24 exhibits a semiconducting feature, with a 0.87 eV direct band gap derived from HSE06 functions, which is much lower than many other B–N polymorphs. Specifically, owing to its cage-like framework, B20N24 may be used in hydrogen storage at a capacity of ~6.8 wt.%. The B20N24 polymorph enriches the B–N system theoretically, and this polymorph is promising for use in electronic devices and hydrogen storage.

Ji Cheng Zhang, Jin Hua Wang, Jia Lin, Guo Ming Su, Yi Lin Shen, Qi Wei Guo, Jia Jing Cai, Jun Yi Liu, Ke Xin Jia, Ding Zhi Fang Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ding Zhi Fang, Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China, Email dzfang@scu.edu.cnAim: To explore anthropometric, metabolic and dietary factors associated with and their interplays with the Val66Met polymorphism at brain-derived neurotrophic factor (BDNF) gene (Bdnf) on serum BDNF levels in adolescents.Methods: Serum BDNF levels were quantified using an enzyme-linked immunosorbent assay in 644 high school students (278 males/366 females). A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for Bdnf Val66Met genotyping followed by verification using DNA sequencing. Serum levels of metabolic characteristics were assayed by routine methods. The intake of macro and micronutrients was collected by a three-day food record.Results: Serum BDNF levels were found to be significantly different in the subjects with different genotypes of Bdnf Val66Met (Val/Val homozygotes, 60.05 ± 28.07 ng/mL vs Val/Met heterozygotes, 56.37 ± 29.34 ng/mL vs Met/Met homozygotes, 51.32 ± 24.54 ng/mL, p = 0.022). Among the 36 tested variables, waist–hip ratio (WHR) (β = − 0.163, p < 0.001), iodine intake (β = 0.132, p = 0.001), heart rate (β = 0.108, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (β = 0.098, p = 0.011) and dietary fiber intake (β = 0.082, p = 0.084) were the predictor of serum BDNF levels, while SBP (β = 0.097, p = 0.013) and WHR (β = 0.091, p = 0.021) were related with Bdnf Val66Met. Moreover, WHR was observed to play a partial mediating role in the relationship between Bdnf Val66Met and serum BDNF levels (95% CI [− 1.161, − 0.087]) and contribute 13.05% of its total effect on serum BDNF levels.Conclusion: There are interplays between WHR and Bdnf Val66Met on serum BDNF levels, which may be among the explanations for the previous heterogeneous reports and provide novel insights into the regulation of serum BDNF levels.Keywords: serum, brain-derived neurotrophic factor, Val66Met, waist–hip ratio, mediator, adolescent

Background: Many clinical studies have shown that patients with major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) display evident cognitive deficits. However, little is known about the impact of these disorders on cognitive symptoms. Methods: This cross-sectional study was conducted with a convenience sampling method to distribute QR codes as an outpatient service. The Patient Health Questionnaire-9 (PHQ-9) assessed for depressive symptoms, and those with a total score ≥ 5 were selected for the analysis. A total of 218 outpatients with MDD were included. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used for OCS. MDD patients with a Y-BOCS score ≥ 6 were classified as MDD with comorbid OCS (MDDOC). The Perceived Deficits Questionnaire-Depression (PDQ-D-5) was used to evaluate subjective cognitive symptoms. A multivariate analysis of covariance and regression models was performed to estimate the effects of OCS on cognitive symptoms. Results: There was no significant difference in cognitive symptoms between MDD alone and MDDOC patients (p＞0.05). In the MDDOC subgroup, both the Y-BOCS score and the subdomain (obsession/compulsion) had significant correlations with the PDQ-5 score (r=0.510, 0.504, 0.428, all p＜0.01, respectively). Further hierarchical regression analyses showed that OCS or the OCS subdomain (compulsion/obsession) contributed to cognitive symptoms (all p﹤0.05), even when controlling for depression severity (p＜0.001; p=0.032; p=0.012, respectively). Moreover,mediation anallysis indicated the ralation between PHQ-9 and subjective cognitive sympton was mediated by OCS. Conclusions: Our findings suggest there is no significant difference in cognitive symptoms between the MDD alone and the MDDOC groups. However, OCS or OCS subdomain may contribute to subjective cognitive symptoms in MDDOC patients. Notably, when controlling for the severity of depression, comorbid OCS aggravated cognition impairment in the MDDOC group.

Renal impairment (RI) is a very common complication of multiple myeloma (MM) with a negative impact on survival. Herein we retrospectively analyzed 334 MM patients with renal impairment at diagnosis from three hospitals in China. All 334 patients were divided into three groups, including dialysis dependence (n=43), dialysis independence (n=42), and without dialysis (n=249). Compared with dialysis independence and without dialysis groups, dialysis dependence group had the lowest overall hematologic response (48.8% vs. 97.6% vs. 77.1%, P

S-phase kinase-associated protein 2 (Skp2) is a substrate-specific adaptor in Skp1-CUL1-ROC1-F-box E3 ubiquitin ligases and widely regarded as an oncogene. Therefore, Skp2 has remained as an active anticancer research topic since its discovery. Accordingly, the structure of Skp2 has been solved and numerous Skp2 inhibiting compounds have been identified. In this review, we would describe the structural features of Skp2, introduce the ubiquitination function of SCFSkp2, and summarize the diverse natural and synthetic Skp2 inhibiting compounds reported to date. The IC50 data of the Skp2 inhibitors or inhibiting compounds in various kinds of tumors at cellular levels implied that the cancer type, stage and pathological mechanisms should be taken into consideration when selecting Skp2-inhibiting compound for cancer treatment.

OBJECTIVE: To evaluate the effect of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia identified as liver-Qi stagnation pattern in terms of Traditional Chinese Medicine. METHODS: Sixty Wistar rats were randomly divided into blank group (n = 10), the rest of the rats were clamped tail as stimulation combined with injected intraperitoneally p-chlorophenylalanine (PCPA) to establish sleep deprivation model. After the successful replication of the model, they were randomly divided into model group, grabbing group, Western Medicine group, acupuncture group and sham acupuncture group, with 10 rats in each group. The model group was given normal saline; The grasping group was grasped in the same way as the two treatment groups; Western medicine group was given estazolam solution; The acupuncture group was treated with the acupuncture method of "soothing the liver Qi and regulating mind" needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3); The sham acupuncture group were needled with four non-acupoint sites. After 7 d of treatment of rats in each group, sodium pentobarbital sleep experiment was used to evaluate the sleep latency (SL) and sleep time (ST). The percentage of rats entering the open arm (OE%) and the percentage of time entering the open arm (OT%) in each group were monitored by elevated cross maze, and the vertical score, horizontal crossing times, central grid score and modification times were monitored by open field test, functional near infrared spectroscopy (fNIRs) was used to monitor the changes of oxygenated hemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb) in the cerebral cortex of rats in each group under light stimulation and dark stimulation, the statistically significant channel combinations were selected from 8 light sources and 12 detectors (S-D). According to the position of the light source detector covering the cerebral cortex, Preliminarily determine the key brain areas of insomnia (the preliminary experiment found that 6S-8D and 7S-9D were the key channels of insomnia under light stimulation, and the corresponding brain areas were prefrontal lobe and occipital lobe respectively; 7S-7D channel under dark stimulation, and the corresponding brain area was occipital lobe); The hemodynamic map of cerebral cortex was constructed through the absolute value of whole brain blood oxygen level. Further identify key brain regions for insomnia. RESULTS: Compared with the blank group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score, the concentration of Deoxy-Hb in prefrontal and occipital lobes were decreased significantly (P0.05); After treatment, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and Deoxy-Hb concentration in acupuncture group and Western medicine group increased significantly, while SL, modification times, Oxy-Hb and Total-Hb concentrations were decreased significantly (P0.05); Compared with the acupuncture group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and the concentration of deoxy Hb in the sham acupuncture group decreased significantly (P

An approach to autogenerate voxel-based absorbed dose for nuclear medicine is proposed using generative adversarial networks. The method is based on image-to-image transformation and promises to achieve real-time visualization of the absorbed dose and optimization of therapeutic strategies. The activity-density superimposed image is input to generator (G) as a reference image to generate a pseudoabsorbed dose image (DI), which is then mixed with ground truth (GT) DI and recognized by discriminator (D). If the pseudoimage is recognized, the information is fed back, and G regenerates a pseudodose image until D drops to obtain a lifelike DI. As a feasibility study, we used the dose distribution of segmented human anatomy from different sources and activities as training and test datasets. The activity source was assumed to be 1, 2, 3, 4, or 7 subsource blocks. The 3-subsource model was used as the test dataset, and the others were used as the training dataset. The activity distribution in the subsource was assumed to be uniform or heterogeneous (i.e., Gaussian diffusion with sigma 0.0, 0.3, or 0.6). Differences were assessed by Gamma analysis. Results showed that the same or quasi-inhomogeneity model can well predict the dose distribution of different activity-inhomogeneity. Although the 1-source model was trained with very few datasets, it showed an optimal balance between accuracy and training efficiency. There were offsets in the mean absorbed dose between the predicted and GT, but they all showed a higher Gamma-pass-rate ( 93%) and ~ 10% std.

Background Depression is a common psychiatric disorder associated with the defects in GABAergic neurotransmission. α-Dystroglycan (α-DG), a cell adhesion molecule known to be essential for skeletal muscle integrity, is also present at inhibitory synapses in the central nervous system and forms a structural element in certain synapses. However, the role of α-DG in the regulation of depressive-like behaviors remains largely unknown. Methods Depressive-like behaviors were induced by chronic social defeat stress (CSDS). Surface protein was extracted by a biotin kit and the expression of protein was detected by western blotting. Intra-hippocampal microinjection of the lentivirus or adeno-associated virus or agrin intervention were carried out using a stereotaxic instrument and followed by behavioral tests. The miniature inhibitory postsynaptic currents (mIPSCs) were recorded by whole-cell patch-clamp techniques. Results The expression of α-DG and glycosylated-α-DG (GLY-α-DG) in the ventral hippocampus (vHip) was significantly lower in CSDS susceptible male mice than that in controls, accompanied with a decreased surface expression of GABAAR γ2 and reduced GABAergic neurotransmission. RNAi-mediated knockdown of dystroglycan encoding gene dystroglycan 1 (DAG1) increased the susceptibility of mice to sub-threshold stress. Both in vivo administration of agrin and overexpression of like-acetylglucosaminyltransferase (LARGE) ameliorated depressive-like behaviors and restored the decrease in surface expression of GABAAR γ2 and the amplitude of mIPSCs in CSDS-treated mice. Conclusions Our findings demonstrate that GLY-α-DG plays a role in the pathophysiological process of depressive-like behaviors by regulating the surface expression of GABAAR γ2 and the GABAergic neurotransmission in the vHip.

Atherosclerosis is a chronic inflammatory disease implicated in oxidative stress and endothelial dysfunction. Protein disulfide-isomerase A3 (PDIA3) has been reported to regulate oxidative stress and suppress inflammation. This study aimed to explore the function of PDIA3 in atherosclerosis and the underlying mechanisms. PDIA3 expression in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was detected using RT-qPCR and Western blotting. Following PDIA3 knockdown through transfection with small interfering RNA targeting PDIA3, cell viability, oxidative stress and inflammation in ox-LDL-induced HUVECs was examined using a Cell Counting Kit-8, corresponding kits and ELISA, respectively. The levels of CD31, α-smooth muscle, iNOS, p-eNOS, eNOS and NO were assessed using RT-qPCR, Western blotting and an NO kit to reflect endothelial dysfunction in ox-LDL-induced HUVECs. The relationship between PDIA3 and the activating transcription factor 2 (ATF2) was confirmed using co-immunoprecipitation. In addition, ATF2 expression was examined following PDIA3 silencing. The results indicated that PDIA3 was highly expressed in ox-LDL-induced HUVECs. PDIA3 silencing increased cell viability, and reduced oxidative stress and inflammation, as evidenced by the decreased levels of reactive oxygen species, malondialdehyde, TNF-α, IL-1β and IL-6, and increased superoxide dismutase and glutathione peroxidase activity. In addition, PDIA3 deletion improved endothelial dysfunction. PDIA3 interacted with ATF2, and PDIA3 deletion downregulated ATF2 expression. Furthermore, ATF2 overexpression reversed the effects of PDIA3 knockdown on ox-LDL-induced damage of HUVECs. Collectively, PDIA3 knockdown was found to attenuate ox-LDL-induced oxidative stress, inflammation and endothelial dysfunction in HUVECs by downregulating ATF2 expression, showing promise for the future treatment of atherosclerosis.

A “green” novel polar perovskite-derivative, [C6H5CH2N(CH2CH3)3]3Bi2Cl9, with phase-matchable SHG effects was obtained by utilizing asymmetric quaternary ammonium cation substitution.

GuRhaGT is the first saponin 2′′-O-rhamnosyltransferase with broad substrate promiscuity, high sugar donor- and regio-specificity. It could be an efficient biocatalyst for the synthesis of bioactive saponins.

Regioisomeric 24-nuclear exohedral cuprofullerenes were realized using a heteroleptic ligand strategy. They show regular C60@CuI24 rhombicuboctahedron, irregular C60@CuI24 in triplet C60@CuI24CuI8 core–shells and even a 3D coordination polymer.

Supplementary Tables S1-S2 from Global and Regional CpG Methylation in Pheochromocytomas and Abdominal Paragangliomas: Association to Malignant Behavior

Purpose: This study aims to quantitatively assess promoter and global methylation changes in pheochromocytomas and abdominal paragangliomas and its relation to tumor phenotypes.Experimental Design: A panel of 53 primary tumors (42 benign, 11 malignant) was analyzed by quantitative bisulfite pyrosequencing. Based on methylation levels in the tumor suppressor genes, p16INK4A, CDH1, DCR2, RARB, RASSF1A, NORE1A, TP73, APC, DAPK1, p14ARF, and PTEN, a CpG island methylator phenotype (CIMP) was defined as concerted hypermethylation in three or more genes. Mean Z scores for the hypermethylated promoters were calculated to characterize overall promoter methylation. Global DNA methylation was quantified for LINE-1 promoter sequences and by using luminescent methylation analysis.Results: Five primary tumors (9.4%) exhibited a CIMP phenotype, four of which were malignant paragangliomas. CIMP was significantly associated with malignant behavior (P = 0.005) and younger age at presentation (P < 0.007) but did not result from BRAF V600E mutation. Global hypomethylation of LINE-1 elements was observed in tumors compared with normal adrenal samples (P < 0.02).Conclusion: We here describe the identification of CIMP in abdominal paragangliomas and a strong association of this phenotype with malignant behavior, as well as young age at presentation. The findings raise a prospective for potential benefits of epigenetically acting drugs for a subgroup of young abdominal paraganglioma patients with adverse prognosis.

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity., Brown adipocytes contribute to energy balance, and adipocyte development and brown adipocyte thermogenesis are in part regulated by epigenetic modifications. Here the authors report that the histone demethylase Utx maintains brown adipocyte identity via demethylation of PRDM16, which in turn represses myogenic remodelling via DNMT1-mediated Myod1 promoter hypermethylation in mice.

Background N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity. Results In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro. Conclusions Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.

Women with newly diagnosed ovarian cancer who receive chemotherapy experience distressing symptoms and reduced quality of life (QOL). Previous study results identifying changes in symptom distress and QOL over time are limited.This study examined the trajectory of symptom distress and QOL among women with newly diagnosed ovarian cancer from before their first chemotherapy appointment to two weeks after completing six cycles of chemotherapy.A longitudinal design was used to examine symptom distress and QOL in 36 participants across eight time points. Generalized estimating equation analyses identified how participants' symptom distress and QOL changed over time.Psychological symptom distress was highest at baseline and then decreased. Physical symptom distress increased at the second chemotherapy cycle. Similar results were found for QOL, with the lowest QOL reported after the fifth cycle.

The COVID‐19 pandemic has significantly impacted everyone's lives, challenging us in ways that can be frustrating, daunting, and intensely emotive. This qualitative study explored the isolation experiences of patients with COVID‐19 in a hospital in northern Taiwan. We collected data from nine patients in June–July 2020, conducting semi‐structured, virtual face‐to‐face, in‐depth interviews to gather input on two topics: (1) the psychological effect of hospital isolation on patients, including the psychological burden, stress response, support, disease stigma, and fear of returning to society; and (2) the patients' cognition and behaviors, which included tracking epidemic information, monitoring disease progression, soliciting suggestions about hospital isolation, and gauging comprehension after recovery. The results confirmed that hospital isolation significantly impacts patients physically, psychologically, spiritually, and socially. Thus, the isolated patients faced the dual challenges of fighting, adapting to, and recovering from the disease itself and struggling in isolation to maintain positive beliefs, independently assess their condition, and gain strength from the knowledge of continuing social support.

Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NT-3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NT-3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NT-3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NT-3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC +/−). Increasing NT-3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC + /− or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NT-3 is a fat-derived neurotrophic factor that regulates SNS innervation, energy metabolism and obesity. Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

As a typical land element, buildings play a dominant role in land use, urban planning, and disaster risk assessment, which is an important goal of remote-sensing-based surveying and mapping. Presently, with the rapid development of island economies, it is particularly important to extract island buildings accurately to avoid disorderly expansion. Machine learning is a common method for extracting terrain objects from high-resolution remote sensing images. However, the remote sensing features of buildings are complex: traditional machine learning methods suffer from poor robustness and have difficulty in fully mining deep-seated features. The overall accuracy and Mean Intersection over Union (mIoU) score of the deep learning architecture DeepLabv3plus is higher than those of other semantic segmentation models, making it suitable for remote sensing building extraction. In this study, the DeepLabv3plus segmentation architecture is adapted, based on the Xception network and hole convolution, to reduce the large number of pictures (batch size) and video memory required to train a deep learning model. Group Normalization (GN) is used to replace the original Batch Normalization (BN), to improve the feature extraction accuracy for a small batch size. Compared with the original DeepLabv3plus architecture, the DeepLabv3plus-G method can train models with a smaller batch size under limited Video Graphics Array (VGA) memory, and the segmentation accuracy is improved. DeepLabv3plus-G can effectively extract island buildings, which provides a new method for Chinese island construction supervision. As a result of limited island building data, this study designs an intelligent collection of pre-training sets and an annotation method based on multi-source data of domestic urban building datasets. Transfer learning strategy is also adopted to train the network model on the automatically annotated domestic urban building datasets. The final pre-training model was saved in the form of a network architecture and weights. The model size was 158 MB, the number of parameters was 22910480, and the depth was 65 layers. Remote sensing images of buildings from 29 temperate islands (including Chrysanthemum Island, etc.), 48 subtropical islands (including Chongming Island, etc.), and six tropical islands (including Haidian Island) in China from Google Earth, with a spatial resolution of 0.6 m, were employed. After automatic clipping, 891 images of island buildings with dimensions of 512 × 512 pixels were obtained. The open source labeling software Labelme was used for manual labeling before the algorithm experiments. Results showed that both the mIoU and mean Average Precision (mAP) of DeepLav3plus-Gare improved under the same batch size, compared to traditional methods. When the batch size was two, the mIoU and mAP improved by 8.95% and 10.45%, respectively, compared to the scores for the DeepLabv3plus architecture. Under the same network, the accuracy of DeepLabv3plus pixel segmentation improved with increasing patch size. The mIoU and mAP scores for a model with a batch size of eight were 10.51% and 10.26% higher than those of models with a batch size of two, respectively. However, the mAP of DeepLabv3plus-G pixel segmentation hardly changed with an increase in the batch size. In conclusion, when the batch size is small, the mAP and mIoU of the DeepLabv3plus building classification algorithm based on GN increase, and more accurate pixel-level island building extraction results are obtained.

For the research of wireless power transfer, loosely coupled inductive power transfer (LCIPT) is one of the widely adopted technologies. There are already various researches focusing on development of high-efficiency LCIPT. However, when the transmission and receiver coils are misaligned, the power transfer efficiency will be significantly dropped. This article considers the change of mutual inductance when two induction coils are misaligned. A fuzzy control approach to solve for this problem by adaptively adjusting operational frequency is introduced. Experiments show that it can reduce the power transferring efficiency drop by 11% when two conduction coils are misaligned up to 50 mm. This research also supports adaptive maximum power transfer using tracking mechanism. Before conducting power transmission, the system can choose G2V or V2G according to the vehicle battery capacity via handshaking communication without the need of radio frequency links. In addition, the phase shift pulsewidth modulation technique is proposed for simultaneous data transmission enabling binary quadrature amplitude modulation for digital signal transmission. Fast over current protection is incorporated for power transfer safety when current overload happens. The transmission frequency of this article is controlled to meet the frequency specified by SAE TIR J2954 .

Background Ruai-sanyin formula (RASYF) is composed of a variety of anticancer herbs. It is widely used in the treatment of triple negative breast cancer (TNBC) and has proved to inhibit tumor growth and lung metastasis in animal models, but there is no evidence for clinical application in the real world. Methods We conducted this prospective cohort study at 5 research centers in China from November 2016 to December 2018. RASYF was set as an exposure factor. TNBC patients within 3 months after completion of standard adjuvant treatment were included. The exposed group received RASYF treatment, while the non-exposed group received observation. The primary end point was disease-free survival (DFS). Secondary end points included, overall survival (OS), distant disease-free survival (DDFS), relapse-free survival (RFS), QLQ-BR23 assesses quality of life in patients and adverse events. Results A total of 613 eligible patients with operable TNBC were enrolled, of which 588 were included in the Full Protocol Set. At a median follow-up of 48 months, DFS time was longer in those assigned to RASYF compared with observation (3-year DFS, 89.6% vs. 83.5%, [HR = 0.61, 95%CI (0.39-0.95)]; P = 0.03). Similar outcomes were observed for RFS (3-year RFS, 92.1% vs. 85.9%, HR = 0.55, [95% CI, 0.34-0.91]; P = 0.02). However, there was no statistically significant difference in OS and DDFS between the groups. In exploratory subgroup analysis, RASYF benefits were greater in patients with age under the 40 (3-year DFS, 88.4% vs. 76.1%, [HR = 0.45, 95%CI (0.21-0.95)]; P = 0.03). And RASYF is helpful to the improvement of postoperative quality of life. Comparing to the observation group, RASYF increased the mean CFB of BR23 scores in body image (12.34 vs. 8.76, P = 0.03)，sexual function (11.79 vs. 9.23, P P= 0.04), and decreased the scores of systemic therapy side effects (-12.41 vs. -9.24, P = 0.01). Safety analysis showed that RASYF caused major adverse reactions including impaired liver function (4.0%) and stomach pain (6.1%), but the overall security is controllable. Conclusion RASYF supplementation for 2 years after standard adjuvant chemoradiotherapy has certain clinical significance in preventing recurrence and metastasis and improving the quality of life of patients with early TNBC. Trial registration ClinicalTrials.gov: NCT03332368 Registered 6 November, 2017 (retrospectively registered)

Epigenetic modulations lead to changes in gene expression, including DNA methylation, histone modifications, and noncoding RNAs. In recent years, epigenetic modifications have been related to the pathogenesis of different types of cancer, cardiovascular disease, and other diseases. Emerging evidence indicates that DNA methylation could be associated with ischemic stroke (IS) and plays a role in pathological progression, but the underlying mechanism has not yet been fully understood. In this study, we used human methylation 850K BeadChip to analyze the differences in gene methylation status in the peripheral blood samples from two groups (3 IS patients vs. 3 healthy controls). According to their bioinformatics profiling, we found 278 genes with significantly different methylation levels. Seven genes with the most significant methylation modifications were validated in two expanded groups (100 IS patients vs. 100 healthy controls). The CAMTA1 gene had significantly different methylation changes in patients compared to the controls. To understand the CAMTA1 function in stroke, we generated CAMTA1 knockout in SH-SY5Y cells. RNA seq results in CAMTA1 knockout cells revealed the pathways and gene set enrichments involved in cellular proliferation and cell cycle. Furthermore, a series of experiments demonstrated that in the oxygen-glucose deprivation/re-oxygenation (OGD/R) model system, the expression of cyclin D1, an essential regulator of cell cycle progression, was increased in SH-SY5Y CAMTA1 KO cells. Increasing evidence demonstrated that ischemic stress could inappropriately raise cyclin D1 levels in mature neurons. However, the molecular signals leading to an increased cyclin D1 level are unclear. Our findings demonstrate for the first time that the CAMTA1 gene could regulate cyclin D1 expression and implicate their role in strokes.

As a class of widely used biocatalysts, enzymes possess advantages including high catalytic efficiency, strong specificity and mild reaction condition. However, most free enzymes have high requirements on the reaction environment and are easy to deactivate. Immobilization of enzymes on nanomaterial-based substrates is a good way to solve this problem. Metal-organic framework (MOFs), with ultra-high specific surface area and adjustable porosity, can provide a large space to carry enzymes. And the tightly surrounded protective layer of MOFs can stabilize the enzyme structure to a great extent. In addition, the unique porous network structure enables selective mass transfer of substrates and facilitates catalytic processes. Therefore, these enzyme-immobilized MOFs have been widely used in various research fields, such as molecule/biomolecule sensing and imaging, disease treatment, energy and environment protection. In this review, the preparation strategies and applications of enzyme-immobilized MOFs are illustrated and the prospects and current challenges are discussed.

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.

Glucose is of great importance in cancer cellular metabolism. Working together with several glucose transporters (GLUTs), it provides enough energy for biological growth. The main glucose transporters in endometrial cancer (EC) are Class 1 (GLUTs 1–4) and Class 3 (GLUTs 6 and 8), and the overexpression of these GLUTs has been observed. Apart from providing abundant glucose uptake, these highly expressed GLUTs also participate in the activation of many crucial signaling pathways concerning the proliferation, angiogenesis, and metastasis of EC. In addition, overexpressed GLUTs may also cause endometrial cancer cells (ECCs) to be insensitive to hormone therapy or even resistant to radiotherapy and chemoradiotherapy. Therefore, GLUT inhibitors may hopefully become a sensitizer for EC precision-targeted therapies. This review aims to summarize the expression regulation, function, and therapy sensitivity of GLUTs in ECCs, aiming to provide a new clue for better diagnosis and treatment of EC.

Polymeric {Cu

Purpose: To explore the therapeutic role of amber powder in endometriosis by investigating its effect on endometrial ultrastructure, ERK1/2, p38MAPK, and NF-κB mRNA pathways and CSRC/EFR/ERK1/2 proteins. Methods: Sprague Dawley (SD) rats were randomly divided into blank group, disease model group (untreated), amber powder high-dose group, amber powder medium-dose group, amber powder lowdose group and danazol group. Morphological changes in endometrial cells were studied using transmission electron microscopy. The expression of ERK1/2, p38MAPK, and NF-κB mRNA in endometrial tissues of each group was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was utilized for the measurement of C-SRC/EFR/ERK1/2 pathway protein expression. Results: The endometriosis rats treated with a high-, medium- and low-dose amber powder showed a decrease in the volume of ectopic lesions, compared with the untreated disease model group. The expressions of ERK1/2, p38MAPK, NF-κB mRNA, and C-SRC/EFR/ERK1/2 protein were higher in the eutopic and ectopic endometrial tissues in untreated disease group than those in normal control group. Moreover, treatment of endometriosis rats with amber powder revealed a reduction in the expressions of ERK1/2, p38MAPK, NF-κB mRNA and C-SRC/EFR/ERK1/2 proteins in eutopic and ectopic endometrium tissues. Conclusion: Amber powder reduces ectopic lesions and slows down the development of endometriosis, probably via inhibition of MAPK pathway genes in eutopic and ectopic endometrial tissues.

Green and environment-friendly high-efficiency flame retardants (FRs) are crucial to polymer FR modification. Here, a green FR 2-((bis(2-hydroxyethyl)amino)methyl)-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxide (HAMPP) was synthesized. The HAMPP was incorporated with a cyclic phosphorus structure, which will readily carbonize to inhibit or prevent further combustion. Moreover, the HAMPP contains dihydroxy reactive groups that can be used as a monomer in the polymerization reaction to obtain the main chain containing phosphorus polymer. Research studies on FRs were based on flexible polyurethane foam (PU-HAMPPs). The limiting oxygen index value of PU foam with 10% HAMPP could reach 23.7%, passing a UL-94 V-0 rating together. With the addition of HAMPP, the peak heat release rate of PU foam decreased significantly, the decomposition temperature increased, the heat release capacity reduced by 31%, and the char yield increased by 42%. The chemical composition and morphology of the char residual have been studied and analyzed thoroughly. We find that HAMPP forms a molten viscous protective layer uniformly on the material surface and releases some incombustible gases. These indicated that the FR exploited both condensed-phase and gas-phase flame retardancy mechanisms. Besides, the addition of FRs improved the mechanical properties.

AIM: To investigate the clinical effect of canaliculotomy joint novel R-S lacrimal tube implantation under lacrimal endoscope for canaliculitis.METHODS: Thirty-one patients(thirty-two eyes)diagnosed as canaliculitis were investigated from July 2016 to September 2019 in our department. All patients have treated with canaliculotomy joint lacrimal tube implantation under lacrimal endoscope. The patients were randomly divided into two groups. Group A was treated with novel R-S lacrimal tube for 15 cases 15 eyes, and group B was treated with annular silicone tube. They were removed the lacrimal tube after 2-3mo, and followed postoperatively for at least 1a. The treatment results were comparatively analyzed.RESULTS: The effective rate was 93% in group A and 94% in group B(P>0.05). The mean time of lacrimal tube implantation of group A was 2.27±1.335min, and group B was 5.29±1.404min. The total rate of complications was 7% in group A and 47% in group B. The rate of foreign body sensation in nasal cavity was 7% in group A and 41% in group B. The rate of increased nasal secretions was 0 in group A and 29% in group B. The difference of the mean time of lacrimal tube implantation, the rate of complications, the rate of foreign body sensation in nasal cavity and the rate of increased nasal secretions between two groups was statistically significant(P