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Chemical biology investigation of a triple-action,smart-decomposition antimicrobial booster based-combination therapy against “ESKAPE” pathogens

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Science China Chemistry 2024年第9期67卷 3071-3082页

作者： Min Wang Huangsheng Pu Yangfan Xu Chenxuan Wu Yuanxin Gu Qingyun Cai Guoxing Yin Peng Yin Chunhui Zhang wing-leung wong Muyang Wan Yugang Bai Xinxin Feng State Key Laboratory of Chem-/Bio-Sensing and Chemometrics Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biologyand School of Chemistry and Chemical Engineering Hunan University College of Biology Hunan University College of Advanced Interdisciplinary Studies & Hunan Provincial Key Laboratory of Novel Nano Optoelectronic Information Materials and Devices National University of Defense Technology Nanhu Laser Laboratory National University of Defense Technology Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education) College of Chemistry and Chemical Engineering Hunan Normal University State Key Laboratory of Chemical Biology and Drug Discovery Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs The Third Hospital of Changsha (The Affiliated Changsha Hospital of Hunan University)

The global antibiotic resistance crisis necessitates urgent solutions. One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters. A major drawback of these membrane-active boosters is their limited biocompatibility, as they struggle to differentiate between prokaryotic and eukaryotic membranes. This study reports the chemical biology investigation of a dual-action oligoamidine(OA1) booster with a glutathione-triggered decomposition mechanism. OA1, when combined with other antimicrobial molecules, exhibits a triple-targeting mechanism including cell membrane disruption, DNA targeting, and intracellular enzyme inhibition. This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant “ESKAPE” pathogens, but also suppresses the development of bacterial resistance. Furthermore, OA1 maintains its activity in bacterial cells by creating an oxidative environment, while it quickly decomposes in mammalian cells due to high glutathione levels. These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.

关键词： antimicrobial booster oligoamidine membrane disruption DNA targeting triggered degradation anti-resistance

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Impact of IPMOE on nursing tasks in the medical ward: A time-motion study

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International Journal of Nursing Sciences 2018年第1期5卷 50-56页

作者： Ming leung Kenny Kin Chung Chan wing leung wong Alexander Chun Bon Law Princess Margaret Hospital Hong KongChina Tuen Mun Hospital Hong KongChina Hong Kong Baptist University Hong KongChina

Introduction:The In-patient Medication Order Entry System (IPMOE) was first implemented in the medical ward of Princess Margaret Hospital,Hong *** was a local developed close-loop system including prescription,dispensing and administration *** on its impact on nursing tasks would be important for practice improvement and subsequent system ***:The study was conducted to quantify the nursing times across medication-associated tasks for paper-based MAR and computer-based IPMOE,including change in the tasks and time patterns before and after IPMOE ***:This was a prospective observation study in medical wards before (Jan 2014-Jun 2014) and after (Mar 2015-Jun 2015) the implementation of *** conducted 8-hr observation studies of individual nurses with a customized application to time various pre-categorized nursing *** inferences and interrupted time series analysis was performed to identify the change in the intercept and trends over time after ***:The average number of medication-related tasks was significantly reduced from 61.07 to 29.81,a reduction of 31.26 episodes per duty (P < 0.001,95% CI 22.9-39.63).The time for the medication-related tasks was reduced from 32 min (SD =21.57) to 26.57 min (SD =11.35) and the medication administration time increased from 37.93 min (SD-14.78) to 44.37 min (SD 19.45),but there was no overall significant difference in the time spent on each duty (P =0.315) between the two *** improving trend in the delayed effect was observed (P =0.03),which indicated a run-in period for new application was needed in clinical ***:Our study had shown the time motion observation could be applied to measure the impact of the IPMOE in a busy clinical *** classification of activities,validation,objective measurement and longitudinal evaluation,the method could be applied in various systems as well as different clinical settings in

关键词： In-patient medication order entry system Medication systems Nursing Time and motion studies

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The electroweak monopole–antimonopole pair in the standard model

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Communications in Theoretical Physics 2024年第3期76卷 113-119页

作者： Dan Zhu Khai-Ming wong Guo-Quan wong School of Physics Universiti Sains Malaysia11800 USMPenangMalaysia

We present the first numerical solution that corresponds to a pair of Cho–Maison monopoles and antimonopoles(MAPs) in the SU(2) × U(1) Weinberg–Salam(WS) *** monopoles are finitely separated,while each pole carries a magnetic charge ±4π/*** positive pole is situated in the upper hemisphere,whereas the negative pole is in the lower *** Cho–Maison MAP is investigated for a range of Weinberg angles,0.4675≤ tan θ_(W)≤10,and Higgs self-coupling,0 ≤ β ≤ *** magnetic dipole moment(μm) and pole separation(d_(z)) of the numerical solutions are calculated and *** total energy of the system,however,is infinite due to point singularities at the locations of monopoles.

关键词： magnetic monopole Cho-Maison monopole Weinberg-Salam model

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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching Chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng leung Chun Yin Tong Kai Kap wong wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

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Synthetic brochosomes:Design,synthesis,and applications

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Nano Research 2024年第2期17卷 734-742页

作者： Lin Wang Jinsol Choi Tak-Sing wong Department of Mechanical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Materials Research Institute The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA

Brochosomes,which are nanoscopic buckyball-shaped granules produced by leafhoppers,are one of the most intricate structures discovered in *** functions of brochosomes have been proposed but only a few have been experimentally validated due to the challenge of fabricating their synthetic *** in micro-and nanofabrication have recently led to the emergence of synthetic brochosomes,opening up new possibilities for innovative *** review explores the early discovery of natural brochosomes and their geometrical features,followed by the recent progress in fabricating synthetic brochosomes and their *** on future applications and challenges in the scalable manufacturing of synthetic brochosomes are discussed.

关键词： synthetic brochosomes leafhopper antireflection superhydrophobicity surface-enhanced Raman scattering photocatalyst energy harvesting

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung leung Chun-Kwok wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Artificial intelligence analysis of videos to augment clinical assessment:an overview

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Neural Regeneration Research 2024年第4期19卷 717-718页

作者： David C.wong Stefan Williams University of Leeds Leeds Teaching Hospitals Trust LeedsUK

Observation is a fundamental part of the practice of clinical *** of movement is particularly important for the *** such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic *** some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of *** clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to ***,that practice depends upon a limited resource of experienced *** addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(Williams et al.,2023).

关键词： clinical epilepsy diagnosis

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Free-electron crystals for enhanced X-ray radiation

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Light(Science & Applications) 2024年第7期13卷 1299-1309页

作者： Lee Wei Wesley wong Xihang Shi Aviv Karnieli Jeremy Lim Suraj Kumar Sergio Carbajo Ido Kaminer Liang Jie wong School of Electrical and Electronic Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore. Solid State Institute and Faculty of Electrical and Computer Engineering Technion–Israel Institute of TechnologyHaifa 3200003Israel. School of Electrical Engineering Fleischman Faculty of EngineeringTel Aviv UniversityTel Aviv 69978Israel Department of Applied Physics Stanford UniversityStanfordCA 94305USA. Science Mathematics and TechnologySingapore University of Technology and Design8 Somapah RoadSingapore 487372Singapore. Electrical and Computer Engineering Department UCLA420 WestwoodLos AngelesCA 90095USA. Physics and Astronomy Department UCLA475 Portola PlazaLos AngelesCA 90095USA. SLAC National Accelerator Laboratory Stanford University2575 Sand Hill RoadMenlo ParkCA 94025USA

Bremsstrahlung—the spontaneous emission of broadband radiation from free electrons that are deflected by atomic nuclei—contributes to the majority of X-rays emitted from X-ray tubes and used in applications ranging from medical imaging to semiconductor chip ***,we show that the bremsstrahlung intensity can be enhanced significantly—by more than three orders of magnitude—through shaping the electron wavefunction to periodically overlap with atoms in crystalline ***,we show how to shape the bremsstrahlung X-ray emission pattern into arbitrary angular emission profiles for purposes such as unidirectionality and ***,we find that these enhancements and shaped emission profiles cannot be attributed solely to the spatial overlap between the electron probability distribution and the atomic centers,as predicted by the paraxial and nonrecoil theory for free electron light *** work highlights an unprecedented regime of free electron light emission where electron waveshaping provides multi-dimensional control over practical radiation processes like *** results pave the way towards greater versatility in table-top X-ray sources and improved fundamental understanding of quantum electron-light interactions.

关键词： overlap attributed arbitrary

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Tribological behavior of lubricant-impregnated porous polyimide

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Friction 2024年第4期12卷 711-725页

作者： Jinbang LI Ningning ZHOU Janet S.S.wong School of Mechanical Engineering and Mechanics Ningbo UniversityNingbo 315211China Beijing Key Laboratory of Long-life Technology of Precise Rotation and Transmission Mechanisms Beijing Institute of Control EngineeringBeijing 100029China Department of Mechanical Engineering Imperial College LondonLondon SW72AZUK

Porous materials impregnated with lubricants can be used in conditions where limited lubricant is *** this work,three porous polyimides(PPI)with different densities were ***(PAO)impregnated PPI(iPPI)discs were rubbed against steel and sapphire *** operando observations of the iPPI-sapphire contacts show that oil is released under an applied load,forming a meniscus around *** at the outlet is created at high sliding *** amount of released oil increases with increasing PPI *** moduli,E*,estimated based on the actual contact size show that trapped oil in iPPIs contributes to load *** higher speeds,tribological rehydration of the contact occurs in low density iPPI,with that E*rises with *** high density PPIs,high speeds give a constantly high E*which is limited by the viscoelastic properties of the PPI network and possibly the rate of oil *** of iPPI-steel contacts is governed by the mechanical properties of the PPI,the flow of the lubricant,and the roughness of the PPI *** low-and medium-density(highly porous,high roughness)PPIs,large amount of oil is released,and lubrication is mainly via lubricant restricted in the contact in the pores and possibly tribological *** high density(low porosity)PPI,with lower roughness,hydrodynamic lubrication is achieved which gives the lowest *** results show that polymeric porous materials for effective lubrication require the optimization of its surface roughness,stiffness,oil flow,and oil retentions.

关键词： polyimide porous material friction mechanism polymer limited lubrication

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Navigating reflux disease after achalasia treatments:Balancing risks and benefits

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World Journal of Gastroenterology 2024年第21期30卷 2740-2743页

作者： Ewen A Griffiths Enoch wong Department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWWest MidlandsUnited Kingdom Department of Immunology and Immunotherapy University of BirminghamBirmingham B152TTWest MidlandsUnited Kingdom

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by *** its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully *** this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after *** is a purely endoscopic procedure which is usually performed without any anti-reflux *** patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for *** article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

关键词： Achalasia Gastro-esophageal reflux disease Laparoscopic heller’s myotomy Peroral endoscopic myotomy Fundoplication

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