MORN motifs in plant PIPKs are involved in the regulation of subcellular localization and phospholipid binding

Multiple repeats of membrane occupation and recognition nexus (MORN) motifs were detected in plant phosphatidylinositl monophosphate kinase (PIPK), a key enzyme in PI-signaling pathway. Structural analysis indicates that all the MORN motifs (with varied numbers at ranges of 7-9), which shared high homologies to those of animal ones, were located at N-terminus and sequentially arranged, except those of OsPIPK1 and AtPIPK7, in which the last MORN motif was separated others by an -100 amino-acid "island" region, revealing the presence of two kinds of MORN arrangements in plant PIPKs. Through employing a yeast-based SMET (sequence of membrane-targeting) system, the MORN motifs were shown being able to target the fusion proteins to cell plasma membrane, which were further confirmed by expression of fused MORN-GFP proteins. Further detailed analysis via deletion studies indicated the MORN motifs in OsPIPK 1, together with the 104 amino-acid "island" region are involved in the regulation of differential subcellular localization, i.e. plasma membrane or nucleus, of the fused proteins. Fat Western blot analysis of the recombinant MORN polypeptide, expressed in Escherichia coli, showed that MORN motifs could strongly bind to PA and relatively slightly to PI4P and PI(4,5)P2. These results provide informative hints on mechanisms of subcellular localization, as well as regulation of substrate binding, of plant PIPKs.

Etiology spectrum and clinical characteristics of renal artery stenosis in a Chinese cohort

OBJECTIVE To analyze the causes of renal artery stenosis(RAS)and compare the clinical characteristics in accordance with the primary disease among patients aged from 30 to 50.METHODS Patients were grouped by etiologies of RAS.Groups were retrospectively examined and compared regarding demographic data,clinical manifestations,laboratory findings,and imaging findings.RESULTS A total of 152 patients(74 females,78 males;mean age:40.70±6.01 years)were enrolled,including 84 patients(55.3%)with atherosclerosis(AS),46 patients(30.3%)with Takayasu arteritis(TA),18 patients(11.8%)with fibromuscular dysplasia(FMD),and four patients(2.6%)with other etiologies.Patients in AS group had greater body mass index,higher prevalence of comorbidities and higher rate of smoking and drinking history.TA patients showed more constitutional symptoms and vascular findings,and higher erythrocyte sedimentation rate.RAS in both AS group and TA group mainly located on ostia and proximal segments,but RAS in FMD group mainly involved middle to distal segment of renal artery.The AS group had significantly lesser stenosis than the other groups.Although renal function evaluated by the estimated glomerular filtration rate did not significantly differ among the groups,the incidence of kidney shrinkage was significantly higher in the TA and FMD groups(39.1%and 50%,respectively)than in the AS group(8.3%).The FMD group had milder cardiac damage than other groups.CONCLUSIONS AS was the most common cause of RAS in patients aged from 30 to 50,followed by TA and FMD.The etiology of RAS should be carefully distinguished based on clinical manifestations,laboratory findings,and imaging to ensure that proper treatment is provided.

A Protocol for Developing Chinese Clinical Practice Guidelines of Hypertension

To improve the standard screening, diagnosis, and treatment of hypertension in patients in China;realize the standardization of clinical practice of hypertension;and improve the prevention and control level of hypertension in China, it is both important and necessary to develop a clinical practice guideline for hypertension according to a recognized methodology. Jointly sponsored by the National Center for Cardiovascular Diseases, Chinese Medical Doctor Association, Hypertension Committee of the Chinese Medical Doctor Association, Chinese Society of Cardiology, and Hypertension Committee of Cross-Straits Medicine Exchange Association, the “Chinese Clinical Practice Guidelines of Hypertension” was proposed. Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences, Guideline and Standards Research Centre of Chinese Medical Association Publishing House, Lanzhou University Institute of Health Data Science, and Lanzhou University GRADE Center will provide methodological support for the guidelines.

Methodological and reporting quality of comprehensive hypertension guidelines published between 2017 and 2022

Hypertension,also known as high blood pressure,is a serious medical condition that may cause severe health problems,such as heart attack and stroke.According to the World Health Organization(WHO),^([1])an estimated 1.28 billion adults worldwide aged 30–79 years had hypertension in 2021,two-third of whom were living in low-and middle-income countries.Many national and international clinical practice guidelines(CPGs)on the diagnosis,evaluation,and treatment of hypertension have been published to promote its control.Among these,comprehensive hypertension guidelines provide broader direction to more target users,especially primary healthcare practitioners,than“narrow”types of guidelines.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction： interim results of a multicenter, randomized, open-label trial

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction （n = 635）. The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event （serious or nonserious）. The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function （IIEF-EF） domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg （least squares [LS] mean change： 6.3; 95% confidence interval [CI]： 5.4-7.1; P 〈 0.001） and 5.0-mg （LS mean change： 7.4; 95% CI： 6.8-7.9; P 〈 0.001） tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function （IIEF-EF 〉26） following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

下一代互联网互联设备关键技术专利导航研究综述

下一代互联网是全球各国推动科技产业革命和重塑国家长期竞争力的基础设施和先导领域,同样也是高科技密布、专利密集的战略性新兴产业领域,技术研发与创新竞争异常激烈.本文运用专利导航方法对全球下一代互联网互联设备相关技术进行了分析,通过对本导航领域多位技术专家的访谈,澄清和界定了下一代互联网互联设备关键技术的基本定义与范畴,从总体趋势、地域、核心申请人、核心发明人、专利强度、我国向国外申请专利,以及技术分支等方面分析了全球及我国下一代互联网互联设备关键技术的专利布局现状、竞争前沿和未来趋势,结合本导航领域国内外典型案例的总结,对研发创新和专利运用提出了相应的导航建议.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with insulin glargine/degludec in adults with type 2 diabetes:a prospective,randomized,double-blind,phase 3 trial

Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.

Welcome to Cell Regeneration

Cell Regeneration,an open-access academic journal,was relaunched by the Chinese Society for Cell Biology in 2019(Chen and Lou 2019).This journal,founded in 2012,has published many outstanding papers in the past few years.As an official journal of the Society,Cell Regeneration has undergone major actions such as reorganization of the editorial board and reorientation of journals with new scopes.In 2020,the Society and Springer began copublishing Cell Regeneration,aiming to serve the authors and the readers better.

Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer

Right-sided colon cancer(RCC)and left-sided colon cancer(LCC)differ in their clinical and molecular features.An investigation of differentially expressed genes(DEGs)between RCC and LCC could contribute to targeted therapy for colon cancer,especially RCC,which has a poor prognosis.Here,we identified HOXB13,which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC,by using 5 datasets from the Gene Expression Omnibus(GEO).Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues.HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo.Furthermore,we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects viaβ-catenin/TCF4 signals in RCC.In conclusion,the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC.High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC.The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.