A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

Positive associations fuel soil biodiversity and ecological networks worldwide.

Microbial interactions are key to maintaining soil biodiversity. However, whether negative or positive associations govern the soil microbial system at a global scale remains virtually unknown, limiting our understanding of how microbes interact to support soil biodiversity and functions. Here, we explored ecological networks among multitrophic soil organisms involving bacteria, protists, fungi, and invertebrates in a global soil survey across 20 regions of the planet and found that positive associations among both pairs and triads of soil taxa governed global soil microbial networks. We further revealed that soil networks with greater levels of positive associations supported larger soil biodiversity and resulted in lower network fragility to withstand potential perturbations of species losses. Our study provides unique evidence of the widespread positive associations between soil organisms and their crucial role in maintaining the multitrophic structure of soil biodiversity worldwide.

Risks of digestive diseases in long COVID: evidence from a population-based cohort study.

BACKGROUND: In the post-pandemic era, a wide range of COVID-19 sequelae is of growing health concern. However, the risks of digestive diseases in long COVID have not been comprehensively understood. To investigate the long-term risk of digestive diseases among COVID patients. METHODS: In this large-scale retrospective cohort study with up to 2.6 years follow-up (median follow-up: 0.7 years), the COVID-19 group (n = 112,311), the contemporary comparison group (n = 359,671) and the historical comparison group (n = 370,979) predated the COVID-19 outbreak were built using UK Biobank database. Each digestive outcome was defined as the diagnosis 30 days or more after the onset of COVID-19 infection or the index date. Hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. RESULTS: Compared with the contemporary comparison group, patients with previous COVID-19 infection had higher risks of digestive diseases, including gastrointestinal (GI) dysfunction (HR 1.38 (95% CI 1.26 to 1.51)); peptic ulcer disease (HR 1.23 (1.00 to 1.52)); gastroesophageal reflux disease (GERD) (HR 1.41 (1.30 to 1.53)); gallbladder disease (HR 1.21 (1.06 to 1.38)); severe liver disease (HR 1.35 (1.03 to 1.76)); non-alcoholic liver disease (HR 1.27 (1.09 to 1.47)); and pancreatic disease (HR 1.36 (1.11 to 1.66)). The risks of GERD were increased stepwise with the severity of the acute phase of COVID-19 infection. Even after 1-year follow-up, GERD (HR 1.64 (1.30 to 2.07)) and GI dysfunction (HR 1.35 (1.04 to 1.75)) continued to pose risks to COVID-19 patients. Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of pancreatic diseases (HR 2.57 (1.23 to 5.38)). The results were consistent when the historical cohort was used as the comparison group. CONCLUSIONS: Our study provides insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing digestive diseases. The risks exhibited a stepwise escalation with the severity of COVID-19, were noted in cases of reinfection, and persisted even after 1-year follow-up. This highlights the need to understand the varying risks of digestive outcomes in COVID-19 patients over time, particularly those who experienced reinfection, and develop appropriate follow-up strategies.

An Anti-Noise Convolutional Neural Network for Bearing Fault Diagnosis Based on Multi-Channel Data.

In real world industrial applications, the working environment of a bearing varies with time, and some unexpected vibration noises from other equipment are inevitable. In order to improve the anti-noise performance of neural networks, a new prediction model and a multi-channel sample generation method are proposed to address the above problem. First, we proposed a multi-channel sample representation method based on the envelope time-frequency spectrum of a different channel and subsequent three-dimensional filtering to extract the fault features of samples. Second, we proposed a multi-channel data fusion neural network (MCFNN) for bearing fault discrimination, where the dropout technique is used in the training process based on a dataset with a wide rotation speed and various loads. In a noise-free environment, our experimental results demonstrated that the proposed method can reach a higher fault classification of 99.00%. In a noisy environment, the experimental results show that for the signal-to-noise ratio (SNR) of 0 dB, the fault classification averaged 11.80% higher than other methods and 32.89% higher under a SNR of -4 dB.

VvPL15 Is the Core Member of the Pectate Lyase Gene Family Involved in Grape Berries Ripening and Softening.

The process of ripening and softening in grape begins at veraison and is closely related to the depolymerization of pectin components. A variety of enzymes are involved in pectin metabolism and one class of enzyme, pectin lyases (PLs), have been reported to play an important role in softening in many fruits; however, little information is available on the VvPL gene family in grape. In this study, 16 VvPL genes were identified in the grape genome using bioinformatics methods. Among them, VvPL5, VvPL9, and VvPL15 had the highest expression levels during grape ripening, which suggests that these genes are involved in grape ripening and softening. Furthermore, overexpression of VvPL15 affects the contents of water-soluble pectin (WSP) and acid-soluble pectin (ASP) in the leaves of Arabidopsis and significantly changes the growth of Arabidopsis plants. The relationship between VvPL15 and pectin content was further determined by antisense expression of VvPL15. In addition, we also studied the effect of VvPL15 on fruit in transgenic tomato plants, which showed that VvPL15 accelerated fruit ripening and softening. Our results indicate that VvPL15 plays an important role in grape berry softening during ripening by depolymerizing pectin.

Anti-fatigue properties of the ethanol extract of Moringa oleifera leaves in mice.

BACKGROUND: Moringa oleifera (M. oleifera) leaves are rich in nutrients and bioactive ingredients. This study was aimed at evaluating the anti-fatigue effect of the ethanol extract of M. oleifera leaves (MLEE) on mice and its primary mechanism of action using a weight-loaded forced swimming test. In the present study, MLEE was prepared by ultrasound-assisted extraction, and its anti-fatigue effect and antioxidant capacity were evaluated in mice. Mice were administrated MLEE (320 mg kg-1 body weight) for 15 days. RESULTS: MLEE supplementation significantly increased levels of glucose and non-esterified fatty acids (NEFA), while decreasing levels of lactate and blood urea nitrogen in serum (P < 0.05); the levels of glycogen in the liver and muscle were also increased, as was the activity of glycogen synthase and the level of NEFA in muscle (P < 0.05). According to a Western blot analysis, MLEE increased the expression of AMPKα1, JNK, AKT and STAT3 in the muscle of mice. CONCLUSION: Our findings indicate that MLEE has an anti-fatigue effect via the AMPK-linked route, which enables it to control energy metabolism and enhance antioxidant enzyme activity. © 2023 Society of Chemical Industry.

Efficacy and Safety of Left Atrial Appendage Occlusion in Mild Mitral Stenosis Patients with High Bleeding Risk.

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.

Differential Responses of Arbuscular Mycorrhizal Fungal Communities to Long-Term Fertilization in the Wheat Rhizosphere and Root Endosphere.

Arbuscular mycorrhizal fungi (AMF) provide essential nutrients to crops and are critically impacted by fertilization in agricultural ecosystems. Understanding shifts in AMF communities in and around crop roots under different fertilization regimes can provide important lessons for improving agricultural production and sustainability. Here, we compared the responses of AMF communities in the rhizosphere (RS) and root endosphere (ES) of wheat (Triticum aestivum) to different fertilization treatments, nonfertilization (control), mineral fertilization only (NPK), mineral fertilization plus wheat straw (NPKS), and mineral fertilization plus cow manure (NPKM). We employed high-throughput amplicon sequencing and investigated the diversity, community composition, and network structure of AMF communities to assess their responses to fertilization. Our results elucidated that AMF communities in the RS and ES respond differently to fertilization schemes. Long-term NPK application decreased the RS AMF alpha diversity significantly, whereas additional organic amendments (straw or manure) had no effect. In contrast, NPK fertilization increased the ES AMF alpha diversity significantly, while additional organic amendments decreased it significantly. The effect of different fertilization schemes on AMF network complexity in the RS and ES were similar to their effects on alpha diversity. Changes to AMF communities in the RS and ES correlated mainly with the pH and phosphorus level of the rhizosphere soil under long-term inorganic and organic fertilization regimes. We suggest that the AMF community in the roots should be given more consideration when studying the effects of fertilization regimes on AMF in agroecosystems. IMPORTANCE Arbuscular mycorrhizal fungi are an integral component of rhizospheres, bridging the soil and plant systems and are highly sensitive to fertilization. However, surprisingly little is known about how the response differs between the roots and the surrounding soil. Decreasing arbuscular mycorrhizal fungal diversity under fertilization has been reported, implying a potential reduction in the mutualism between plants and arbuscular mycorrhizal fungi. However, we found opposing responses to long-term fertilization managements of arbuscular mycorrhizal fungi in the wheat roots and rhizosphere soil. These results suggested that changes in the arbuscular mycorrhizal fungal community in soils do not reflect those in the roots, highlighting that the root arbuscular mycorrhizal fungal community is pertinent to understand arbuscular mycorrhizal fungi and their crop hosts' responses to anthropogenic influences.

Effects of Secondary Acceptors on Excited-State Properties of Sky-Blue Thermally Activated Delayed Fluorescence Molecules: Luminescence Mechanism and Molecular Design.

The development of efficient sky-blue thermally activated delayed fluorescence (TADF) emitters is highly desired. However, the types and amounts of sky-blue TADF are far from meeting the requirements, and effective molecular design strategies are expected. Herein, the photophysical properties and excited-state dynamics of 12 molecules are theoretically studied based on the thermal vibration correlation function method. Distributions of holes and electrons are analyzed by the heat maps. The frontier molecular orbital distribution, adiabatic singlet-triplet energy gap, and reorganization energy are analyzed in detail. Furthermore, the radiative and non-radiative as well as the intersystem crossing (ISC) and reverse intersystem crossing (RISC) processes are studied, and the up-conversion process is illustrated. Our results indicate that different substitution positions and numbers play an important role in the luminescence properties of TADF molecules. The meta-position substitutions restrict the geometry variations, hinder the non-radiative energy consumption process, and promote the radiative process of TADF molecules. Meanwhile, molecules with ortho-position substitutions possess the smallest energy gaps (ΔEst) and the largest RISC rates. Moreover, molecules with the substitutions of one tBCz group and two PO groups have the smallest ΔEst and the largest spin orbital coupling. Thus, a wise molecular design strategy, namely, ortho-position substitutions as well as substitutions with one tBCz group and two PO groups, is proposed to facilitate the RISC process. Based on this rule, new efficient TADF molecules are theoretically designed and proposed. Our work reasonably elucidates the experimental measurements, and the effects of different substitution numbers and positions of secondary acceptors on TADF properties are highlighted, which could provide a theoretical perspective for designing efficient sky-blue TADF molecules.

SARS-CoV-2 infection activates a subset of intrinsic pathways to inhibit type I interferons in vitro and in vivo.

SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells and ferrets, and the results confirmed the strong inhibitory effect of SARS-CoV-2 on the induction of I-IFNs. Moreover, we identified genes that are negatively correlated with IFNB1 expression in vitro and in vivo based on Pearson correlation analysis. We found that SARS-CoV-2 activates numerous intrinsic pathways, such as the circadian rhythm, phosphatidylinositol signaling system, peroxisome, and TNF signaling pathways, to inhibit I-IFNs. These intrinsic inhibitory pathways jointly facilitate the successful immune evasion of SARS-CoV-2. Our study elucidates the underlying mechanism by which SARS-CoV-2 evades the host innate antiviral response in vitro and in vivo, providing theoretical evidence for targeting these immune evasion-associated pathways to combat SARS-CoV-2 infection.

A cascade targeting strategy based on modified bacterial vesicles for enhancing cancer immunotherapy.

BACKGROUND: As an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application. RESULTS: Herein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuated Salmonella outer membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody. CONCLUSIONS: Interesting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing "vaccine effects", conclusively highlighting its potential in preventing tumor recurrence and improving prognosis.

Tunable lifetimes and efficiencies of room temperature phosphorescent liquids by modulating the length and number of alkyl chains.

Organic room temperature phosphorescence (RTP) liquid composites exhibit the potential to make innovative changes in large area flexible lighting applications, and it is extremely challenging to achieve high-efficiency RTP in pure organic solvent-free liquid systems. The excited state properties and inner lighting mechanisms of these composites are unclear; therefore, a theoretical perspective to design high efficiency RTP liquids with tunable lifetime is highly desired. Herein, we systematically investigate the photophysical properties of a series of long swallow-tailed bromonaphthalimide (BT unit) molecules by the newly proposed optimally tuned range-separated (RS) functional method, and a state-of-the-art RTP molecule with an absolute quantum yield (ΦRTP) of 57.1% and a lifetime (τ) of 160 ms in solvent-free liquid is obtained. Moreover, theoretical results show that the energy gap between the lowest singlet excited state (S1) and triplet excited state (T1) can be reduced and the non-radiative energy consumption process can be restricted by modulating the length and number of alkyl chains in organic RTP molecules. Thus, a wise molecular design strategy is proposed and five additional efficient RTP molecules with tunable lifetimes (43, 19, 136, 0.11 and 0.005 ms) and efficiencies (11.3%, 6.8%, 5.9%, 0.2% and 0.05%) are theoretically proposed. This study sheds light on the relationship among molecular structure, lifetime and efficiency, and can provide an important prototype to explore high-efficiency RTP by pure organic solvent-free liquid systems.

Solid-State Effect Induced Thermally Activated Delayed Fluorescence with Tunable Emission: A Multiscale Study.

Thermally activated delayed fluorescence (TADF) molecules with tunable solid-state luminescence have shown great application potential in organic light-emitting diodes. However, theoretical studies on luminescence properties of organic emitters with consideration of solid-state effect are limited. In this work, the photophysical properties of a difluoroboron ß-diketonate-based molecule (M1) in liquid, crystal, and amorphous states are studied using multiscale methods combined with the thermal vibration correlation function theory. Our results indicate that the geometric structures of M1 in liquid with toluene and crystal state are all in straight-chain form. However, M1 in amorphous state is subjected to form bending deformation at the triphenylamine unit under collaboration between intramolecular π-hydrogen bond and disordered intermolecular interactions. Moreover, in the amorphous state, the energy gap between the first singlet excited state (S1) and the first triplet excited state (T1) (ΔEST) of M1 is significantly reduced, and the spin-orbit coupling constant is remarkably increased in comparison with those of M1 in liquid with toluene and crystal state. As a result, the up-conversion of T1 → S1 in the amorphous state is favored, and remarkable TADF is thus observed. Besides, M1 in the solid state gives fluorescence in red shift emission compared to that in liquid with toluene. On the basis of the results above, we further theoretically design a new molecule noted as M2 which emits fluorescence in the near-infrared region in the solid state. Our theoretical results help in understanding the light-emitting mechanism induced by the solid-state effect and provide information for designing new-type TADF emitters with tunable solid-state emission.

The exploration of disease-specific gene regulatory networks in esophageal carcinoma and stomach adenocarcinoma.

BACKGROUND: Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial. RESULTS: In this paper, we presented a computational framework to explore common and distinct FFLs, and molecular biomarkers for ESCA and STAD. We identified FFLs by combining regulation pairs and RNA-seq data. Then we constructed disease-specific co-expression networks based on the FFLs identified. We also used random walk with restart (RWR) on disease-specific co-expression networks to prioritize candidate molecules. We identified 148 and 242 FFLs for these two types of cancer, respectively. And we found that one TF, E2F3 was related to ESCA, two genes, DTNA and KCNMA1 were related to STAD, while one TF ESR1 and one gene KIT were associated with both of the two types of cancer. CONCLUSIONS: This proposed computational framework predicted disease-related biomolecules effectively and discovered the correlation between two types of cancers, which helped develop the diagnostic and therapeutic strategies of Esophageal Carcinoma and Stomach Adenocarcinoma.

Contrasting effects of host species and phylogenetic diversity on the occurrence of HPAI H5N1 in European wild birds.

Studies on the highly pathogenic avian influenza (HPAI) H5N1 suggest that wild bird migration may facilitate its long-distance spread, yet the role of wild bird community composition in its transmission risk remains poorly understood. Furthermore, most studies on the diversity-disease relationship focused on host species diversity without considering hosts' phylogenetic relationships, which may lead to rejecting a species diversity effect when the community has host species that are only distantly related. Here, we explored the influence of waterbird community composition for determining HPAI H5N1 occurrence in wild birds in a continental-scale study across Europe. In particular, we tested the diversity-disease relationship using both host species diversity and host phylogenetic diversity. Our results provide the first demonstration that host community composition-compared with previously identified environmental risk factors-can also effectively explain the spatial pattern of H5N1 occurrence in wild birds. We further show that communities with more higher risk host species and more closely related species have a higher risk of H5N1 outbreaks. Thus, both host species diversity and community phylogenetic structure, in addition to environmental factors, jointly influence H5N1 occurrence. Our work not only extends the current theory on the diversity-disease relationship, but also has important implications for future monitoring of H5N1 and other HPAI subtypes.

Uric acid transporters BCRP and MRP4 involved in chickens uric acid excretion.

BACKGROUND: Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that renal proximal tubular epithelial cells participate in uric acid excretion in chickens, the roles of BCRP and MRP4 therein remain unclear. This study evaluated the relationship between BCRP and MRP4 expression and renal function in chickens. RESULTS: Sixty laying hens were randomly divided into four treatment groups: a control group (NC) fed a basal diet; a sulfonamide-treated group (SD) fed the basal diet and supplemented with sulfamonomethoxine sodium via drinking water (8 mg/L); a fish meal group (FM) fed the basal diet supplemented with 16% fishmeal; and a uric acid injection group (IU) fed the basal diet and intraperitoneally injected with uric acid (250 mg/kg body weight). The results showed that serum uric acid, creatinine, and blood urea nitrogen levels were significantly higher in the SD and IU, but not FM, than in the NC groups. Renal tubular epithelial cells in the SD and IU groups were damaged. Liver BCRP and MRP4 mRNA and protein levels were significantly decreased in the SD and IU groups, but slightly increased in the FM group. In the SD group, BCRP and MRP4 were significantly increased in the ileum and slightly increased in the kidney. In the FM group, BCRP and MRP4 were significantly increased in the kidney and slightly increased in the ileum. In the IU group, BCRP and MRP4 were significantly increased in the kidney and ileum. BCRP and MRP4 expression in the jejunum was not affected by the treatments. CONCLUSION: Together, these results demonstrate that BCRP and MRP4 are involved in renal and intestinal uric acid excretion in chickens and that BCRP is positively related to MRP4 expression. Further, impairment of renal function results in an increase in serum uric acid as well as a compensatory increase in BCRP and MRP4 in the ileum; however, under normal renal function, renal BCRP and MRP4 are the main regulators of uric acid excretion.

[Varieties textual research on "Bangjian": traditional Tibetan medicine including blue, black and variegated flowers].

"Bangjian" were traditional Tibetan medicine-flowers from Gentianaceae, which were widely used and had a long medicinal history for the function of detoxifying, curing heat symptoms and treating the laryngitis. The Tibetan compound preparation endowed SFDA approval number always used Bangjian aas the main raw materials for relieving cough, asthma and treating respiratory diseases such as acute and chronic bronchitis. Its commodity medicinal materials were also sold in Qinghai, Sichuan, Tibet and other local medicinal materials market and local specialty marke. However, when recorded by literatures of Tibetan medicine, Bangjian were often classified into white, blue and black or white, blue and variegated according to color of flowers, leading to disordered varieties. In this paper, different Bangjian including their original plants and the main application varieties were studied and authenticated by textual research, wild specimen collection, investigation and collection of samples from Tibetan hospitals，Tibetan pharmaceutical factories and medical material markets. Results showed that Bangjian-including blue, black and variegated flowers were originated from 14 species and 3 varietas according to literatures, and the main application varieties mainly come from Ser. Ornatae of Sect. Monopodiae, such as Gentiana veitchiorum for the most, G. sino-ornata as well as G. lawrencei var. farreri. Suggestion about establishing the quality standard of Bangjian was gived, which provided reference in reasonable use and scientific research for Bangjian, and also had practical value for its clinical use and development.

The polymorphic CAG repeat in exon 1 of androgen receptor is associated with level of HDL cholesterol and hypertension in Chinese middle-aged and elderly men.

OBJECTIVE: The length of the CAG repeats in exon 1 of the androgen receptor (AR) gene has been shown to be inversely correlated with AR transcriptional activity. This study aimed to investigate the correlations between the length of CAG repeat in AR and serum lipids and hypertension in Chinese men. DESIGN AND PATIENTS: The relationship between length of the CAG repeat in exon 1 of AR with prevalence of hypertension and the levels of serum lipids among Chinese men (aged ≥40 years). MEASUREMENTS: The physical condition of the subjects was examined and recorded. The concentrations of blood lipids and sex hormones were measured, and the CAG repeat lengths of the AR gene were determined. RESULTS: The length of the AR CAG repeats was associated with HDL cholesterol (HDL-C) concentration, and the stepwise multiple regression model showed that this association was independent of body mass index (BMI), triglycerides (TG) and total cholesterol (TC), although these factors influence HDL-C concentration. Furthermore, men with <22 vs men with ≥22 CAG repeats showed higher blood pressure and higher prevalence of hypertension. Shorter CAG repeat numbers were associated with the increased risk of hypertension in a multivariate logistic regression analysis (odds ratio = 0·715; 95% confidence interval, 0·517-0·989; P = 0·043). No significant correlation of AR CAG repeat polymorphism with sex hormone levels, TG, LDL cholesterol (LDL-C) or TC was found. CONCLUSIONS: This study provides evidence that men carrying shorter (<22) AR CAG repeats have lower HDL-C level and increased risk of hypertension. The androgenic activity may differ due to the polymorphic length of CAG repeats of the AR gene.

[Exploration on an overview of history (from Chunqiu to Ming and Qing Dynasties) and species of Chinese exotic traditional medicine].

This paper collected and analyzed literatures about starting of traditional medicine and trading of different medicine from Chunqiu Zhanguo to Ming and Qing Dynasties, in order to preliminarily explore on an overview of specie of chinese exotic traditional medicine and trade of different country in different dynasty（from Chunqiu to Ming and Qing Dynasties）, as well as the amount of exotic medicine over two thousand years. (remove repeating and doubtful species), find peculiarity of exotic medicine, sreen species that used to develop the Silk Route and establish quality standards.Finally, We get conclusions are as follows. First, primary,.prosperous and declining stages of development of exotic traditional medicine are Qin and Han, Song-Jin-Yuan, Ming and Qing Dynasties, respectively. Second, according to literature, the stage that has the most species of exotic medicine is song dynasty,approximately have 300. Removing repeating and doubtful species, the believable species are approximate 230 to 250. Meanwhile, the unknown species are approximate 30, which may be different name of one medicine or processed goods, now these medicines are named as "doubtful species". Third, the medicinal parts of exotic medicine are different from Chinese medicine of Han nation. The number of Resin, fruits and seeds kind are more than root and rhizomes kind,mineral medicines are more than animal. Fourth, the major producing area of exotic medicine is some countries and territories related to the Silk Route in the history. Ultimately, this paper preliminarily figure out basic information of exotic medicine of different dynasty in China,that provide reference for learning study and decision of industrial development.

Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors.

α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26µM, 1.88±0.35µM and 1.52±0.31µM, respectively) and favorable CC50 values (CC50>100µM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor.