Association between p53 Pro72Arg polymorphism and prostate cancer risk:a meta-analysis

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios （RR） with 95% confidence intervals （CIs） were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found （Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, P heterogeneity = 0.016, I 2 = 55.8%; Pro/Pro＋Pro/Arg vs Arg/ Arg, RR = 1.05, 95%CI=1.00-1.11, P heterogeneity = 0.077, I 2 = 51.1%）. In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model （RR = 0.31, 95%CI=0.10- 0.91, P heterogeneity = 0.110, I 2 =60.8%）. This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

基于直接数字波形合成技术的主动式太赫兹安检仪基带信号源设计

由于主动式太赫兹安检仪中信号源的波形质量会直接影响成像质量,文中采用直接数字波形合成(Direct Digital Waveform Synthesis,DDWS)技术,实现了主动式太赫兹人体安检仪雷达发射机基带宽频信号源的设计与研制。阐述了DDWS技术的原理,确定了DDWS作为该信号源的技术基础;根据理论,利用Matlab进行线性调频信号(LFM)的仿真,并产生所需线性调频信号;论述了基于FPGA的高速数据传输设计、系统时钟设计、高速DAC设计。通过对输出信号频谱的测试,可以得出该系统带宽为210~330 MHz、脉宽为120μs、相位噪声小于-142 dBc/Hz@1 MHz。

儿童孤独症谱系障碍的药物治疗现状与研究进展

孤独症谱系障碍(autism spectrum disorder,ASD)是以社交障碍和受限的重复刻板行为为基本特征的神经发育障碍。ASD发病机制尚不明确,目前没有公认的药物可用于改善ASD核心症状。药物治疗主要针对其情绪问题和不当行为,以利培酮、阿立哌唑为代表的非典型二代抗精神病药是处理ASD儿童情绪行为问题的常用药物。注意缺陷多动障碍、癫痫、胃肠道症状与睡眠障碍等共患病在ASD儿童中常见,哌甲酯、托莫西汀是治疗ASD共患注意缺陷多动障碍的首选药物。目前仍有一些药物尚未广泛应用于临床,需要有更多循证医学证据支持。

Host defense peptide-mimicking peptide polymer-based antibacterial hydrogel enables efficient healing of MRSA-infected wounds

Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.

Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis

Dihydrofolate reductase(DHFR),a housekeeping enzyme in primary metabolism,has been extensively studied as a model of acid-base catalysis and a clinic drug target.Herein,we investigated the enzymology of a DHFR-like protein SacH in safracin(SAC)biosynthesis,which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance.Furthermore,based on the crystal structure of SacH−NADPH−SAC-A ternary complexes and mutagenesis,we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore.These findings expand the functions of DHFR family proteins,reveal that the common reaction can be catalyzed by distinct family of enzymes,and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.

具有高效抗MRSA活性的Alpha-Beta杂化多肽聚合物分子刷（英文）

近年来,以耐甲氧西林金黄色葡萄球菌(MRSA)为代表的"超级细菌"不断被发现和扩散,已经严重威胁人类健康,因此,研制新型、高效的抗菌剂迫在眉睫.以宿主防御肽及其模拟物为代表的多肽和聚合物近年来得到广泛关注.而分子刷作为一类独特的聚合物也显示了很多特殊的性能.我们结合前期研究,首次将两种开环聚合体系即β-内酰胺开环聚合和N-羧基环内酸酐(NCA)开环聚合体系相结合,以β多肽为骨架结构进而通过其氨基功能基团进一步引发NCA开环聚合,合成了侧链具有多个聚赖氨酸的α/β杂化多肽聚合物分子刷.这种新型分子刷对多种MRSA菌株均展现出高效的抗菌活性,甚至优于万古霉素.通过扫描电子显微镜(SEM)表征,揭示了α/β杂化多肽聚合物分子刷的抗菌机理与宿主防御肽类似,是通过破坏细菌细胞膜的完整性杀菌.α/β杂化多肽聚合物分子刷高度可调的结构特点和高效的抗菌活性,显示了其在抗菌研究和应用中的潜力.

Effective and biocompatible antibacterial surfaces via facile synthesis and surface modification of peptide polymers

It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices.Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes.Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers.Here we reported a facile and cost-effective thermoplastic polyurethane(TPU)surface modification of peptide polymer(DLL:BLG=90:10)using plasma surface activation and substitution reaction between thiol and bromide groups.The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro.Furthermore,the peptide polymer-modified TPU surfaces showed excellent biocompatibility,displaying no hemolysis and cytotoxicity.In vivo study using methicillin-resistant Staphylococcus aureus(MRSA)for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility,compared to bare TPU surfaces.We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces,which revealed a surface contact-killing mechanism by disrupting the bacterial membrane.These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices.

Identification of seven long noncoding RNAs signature for prediction of biochemical recurrence in prostate cancer

Accumulating evidenee suggested that long noncoding RNAs(IncRNAs)possess a potential role in prostate cancer(PCa)diagnosis and prognosis.Rapid biochemical recurrence(BCR)is considered as a sign for clinical recurrence metastasis and PCa-specific mortality.Hence,the aim of the present study was to identify a IncRNA signature that can predict BCR of PCa accurately.Bioinformatics analysis,Kaplan-Meier analyses,Cox regression analyses,and Gene Set Enrichment Analysis(GSEA)were performed in a publicly available database with 499 PCa tissues and 52 matched normal tissues.A signature was identified.All these IncRNAs were differentially expressed between tumor and normal tissues and differentially expressed between high Gleason score and low Gleason score tissues.Furthermore,we developed a seven IncRNAs signature that can predict PCa BCR.Patients classified into low-risk group showed better BCR survival significantly than the patients in the high-risk group(hazard ratio=0.32,95%Cl:0.20-0.52,concordance index=0.63).The area under the curve was 0.68 for BCR.The signature also had good discrimination for BCR in men with Gleason 7 PCa.In conclusion,our results suggest that the seven IncRNAs signature is a new biomarker of BCR and high risk in PCa.In addition,the in dividual In cRNA warrants further study to un cover the associated mechanisms of PCa progression and the signature could be used to design direct clinical trials for adjuvant therapy.

Synergistic Combination of Biodegradable Peptide Polymer and Curcumin as Promising Antibiotic Substitution in Aquaculture to Alleviate the Global Challenge of Antimicrobial Resistance

The massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergistic combination of biodegradable peptide polymers and curcumin, a natural compound from plant. The synergistic combination shows strong antibacterial activity against V. fluvialis and some other common bacteria in aquaculture. The membrane-damaging antibacterial mechanism echoes our finding that the synergistic combination will not induce bacteria to develop resistance after continuous use. The synergistic combination also displays effective cure on V. fluvialis-infected zebrafish. The biodegradability of the peptide polymer enables the combination to lose antibacterial activity and will not cause selective pressure on bacterial in the environment. Our study indicates potential application of synergistic composition, biodegradable peptide polymer and curcumin, as promising antibiotic substitution in aquaculture, which represents a promising strategy to address the global challenge of antimicrobial resistance.

An unprecedented one-arrow-two-hawks strategy achieves high yield with early flowering in rice

By 2021,nearly 9%of the global population was still suffering from hunger.It has estimated that the world population will reach 9.7 billion in 2050(United Nations,2019;Tian et al.,2021),which requires a 2.4%increase per year for the yields of major crops.However,current growth rates are only half of this,imposing serious challenges in increasing grain yield by crop breeding.Plant growth and development mainly require energy and nutrients,and thus it is generally considered that the crop yield could be increased by elevating photosynthetic efficiency and higher nitrogen-use efficiency.Moreover,the uptake and transport of nitrogen must be coordinated with carbon fixation and production of carbohydrates by photosynthesis.However,effective strategies for optimizing the carbon/nitrogen status in crops are still relatively limited and therefore require new promising targets.