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Zhiqiang Wang

Publications and source records attributed to Zhiqiang Wang.

At least 19 recordsLinked to original sources

Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cancer biology. While persistent, moderately elevated ROS levels can promote genomic instability, tumor progression, and immune evasion, excessive ROS accumulation can overwhelm antioxidant defenses and trigger cancer cell death. Despite promising preclinical findings, clinical translation remains a challenge because of the context-dependent effects of ROS. A deeper understanding of oxidative stress regulation may lead to the development of novel precision medicine strategies, optimizing cancer therapies while minimizing adverse effects. This review highlights the concentration-dependent effects of oxidative stress in tumorigenesis, focusing on its impact on DNA damage, metabolic reprogramming, and immune modulation. We discuss recent advancements in ROS-targeting strategies, including pro-oxidant therapies that exploit redox vulnerabilities in cancer cells and antioxidant-based approaches aimed at mitigating oxidative stress-driven resistance to treatment. Moreover, we examine the interplay between oxidative stress and the tumor microen-vironment, emphasizing its influence on immune surveillance and therapeutic responses. This re-view provides insights into ROS-targeting interventions and their potential in oncologic treatment paradigms.

malignant tumors↗

A genome-wide CRISPRi screen identifies homologous recombination pathway as potential target for broad-spectrum antibiotic adjuvants.

INTRODUCTION: The widespread misuse and overuse of antibiotics have driven the emergence of multidrug-resistant and pan drug-resistant bacteria, constituting a formidable global health threat. Antibiotic adjuvants that potentiate the efficacy of existing antibiotics represent a particularly promising avenue to address this challenge. METHODS: We performed a genome-wide CRISPR interference (CRISPRi) screening to identify potential targets for broad-spectrum antibiotic adjuvants, which highlighted the homologous recombination pathway as a promising candidate. To functionally validate this pathway, we employed three strategies to suppress the expression and function of recA, a key component of homologous recombination, including a CRISPRi system delivered via transconjugation, a RecX-derived peptide (RecX-20) fused to a cell-penetrating motif, and a small-molecule inhibitor cisplatin validated by surface plasmon resonance. RESULTS: Disruption of the homologous recombination pathway not only significantly increased bacterial susceptibility to multiple classes of antibiotics, including quinolones, β-lactams, aminoglycosides, and nitrofurantoin, but also reduced horizontal gene transfer of antibiotic resistance. In addition, recA deficiency resulted in a cascade of physiological disruptions, including membrane damage, efflux pump dysfunction, oxidative stress imbalance and metabolic disruption. All three recA-targeting strategies enhanced the antibacterial activity, with cisplatin exhibiting the most pronounced potentiating effect both in vitro and in vivo. CONCLUSIONS: This study reveals that the homologous recombination pathway, particularly RecA, is a viable target for the development of broad-spectrum antibiotic adjuvant. Our findings provide mechanistic insights and practical strategies to restore the effectiveness of existing antibiotics and address the growing threat of antimicrobial resistance.

Anti-Bacterial Agents↗

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5&#xb7;0 [IQR 3&#xb7;3-6&#xb7;0] vs 2&#xb7;0 [2&#xb7;0-3&#xb7;0]; p<0&#xb7;0001) and acquired antimicrobial resistance genes (12&#xb7;0 [7&#xb7;3-15&#xb7;8] vs 3&#xb7;0 [3&#xb7;0-5&#xb7;3]; p<0&#xb7;0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31&#xb7;3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15&#xb7;0 [IQR 11&#xb7;0-17&#xb7;0] vs 12&#xb7;0 [3&#xb7;0-16&#xb7;0]; p<0&#xb7;0001) and enhanced plasmid maintenance capacity (median replicons 5&#xb7;0 [IQR 4&#xb7;0-7&#xb7;0] vs 4&#xb7;0 [3&#xb7;0-6&#xb7;0]; p<0&#xb7;0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii↗

Suicide in the Northern Territory, 1981-2002.

OBJECTIVE: To examine trends in suicide in the Northern Territory between 1981 and 2002, and demographic and other characteristics of people completing suicide in the Top End region in 2000-2002. DESIGN: Retrospective descriptive analysis of Australian Bureau of Statistics death registration data and data from the NT Coroner's Office. SETTING AND PARTICIPANTS: All residents of the NT who completed suicide between 1981 and 2002. MAIN OUTCOME MEASURES: Changes in the age-adjusted and age- and sex-specific rates of suicide in Indigenous and non-Indigenous NT residents over time; prior diagnosis of mental illness and use of alcohol or other drugs by those completing suicide. RESULTS: The age-adjusted suicide rate in the NT increased significantly between 1981 and 2002 (P < 0.001). Over this period, the rates among the Indigenous and non-Indigenous male populations increased by 800% (P < 0.05) and 30% (P > 0.05), respectively. Indigenous males aged under 45 years and non-Indigenous males aged 65 years and over were most at risk. In the Top End, a history of diagnosed mental illness was present in 49% of suicide cases, and misuse of alcohol or other drugs around the time of death was associated with 72% of suicide cases. CONCLUSION: Our study highlights the rising rate of suicide in the NT and suggests that suicide prevention initiatives need to specifically target Indigenous and non-Indigenous males in the age groups most at risk.

Adolescent↗

C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians.

OBJECTIVE: To investigate the association between C-reactive protein (CRP) and the risk of developing diabetes in Aboriginal Australians. RESEARCH DESIGN AND METHODS: High sensitivity CRP levels were measured in 620 Aboriginal participants aged 20-74 years free from diabetes at baseline in a remote community in the Northern Territory of Australia. Participants were followed for a median of 11 years to identify newly diagnosed cases of diabetes. Cox proportional hazards models were used to assess the relationship of CRP levels with the risk of developing diabetes over the follow-up period. RESULTS: A total of 109 participants were newly diagnosed with diabetes. Incident rates were 10.8, 16.6 and 28.8 per 1000 person-years for people in the lower, middle and upper tertile groups of baseline CRP levels, respectively. After adjusting for age, sex, BMI, baseline glucose regulation status, total cholesterol, urine albumin to creatinine ratio, systolic blood pressure, smoking and alcohol drinking, the association between diabetes and CRP remained significant, with a hazard ratio of 1.23 (95% confidence interval (CI) 1.05, 1.45) corresponding to a doubling in CRP values. Similarly, the adjusted hazard ratio for development of diabetes in people in the upper tertile versus the bottom two tertiles of CRP was 1.75 (95% CI 1.19, 2.56). CONCLUSIONS: CRP is independently associated with the development of diabetes in Aboriginal people. Our findings support a role of inflammation in the etiology of diabetes in the high risk population of Aboriginal Australians.

Adult↗

Specialist outreach to isolated and disadvantaged communities: a population-based study.

BACKGROUND: Visiting-specialist clinics (specialist outreach) have the potential to overcome some of the substantial access barriers faced by disadvantaged rural, remote, and Indigenous communities, but the effectiveness of outreach clinics has not been assessed outside urban and non-disadvantaged settings. We aimed to assess the effects of outreach clinics on access, referral patterns, and care outcomes in remote communities in Australia. METHODS: We undertook a population-based observational study of regular surgical, ophthalmological, gynaecological, and ear, nose, and throat outreach visits, compared with hospital clinics alone, on access, referral practices, and outcomes for the populations of three remote Indigenous communities in northern Australia for 11 years. We assessed all new non-emergency potential specialist surgical cases who presented initially between Jan 1, 1990, and Jan 1, 2001. The effects of outreach clinics on the proportion of patients referred, the time from referral to initial specialist consultation, and the rates of community-based and hospital-based procedures were analysed using logic regression and Cox proportional hazard models. FINDINGS: 2339 new surgical problems presented in 2368 people between 1990 and 2001. Outreach improved the rate of referral completion (adjusted hazard ratio 1.41, 95% CI 1.07-1.86) and the risk of timely completion according to the urgency of referral (adjusted relative risk 1.30, 1.05-1.53). Outreach had no significant effect on initiation of elective referrals, but there were 156 opportunistic presentations on outreach clinic days. Specialist investigations and procedures in community clinics removed the need for many patients to travel to hospital, and outreach consultations were associated with a reduced rate of procedures that needed hospital admission (adjusted hazard ratio 0.67, 0.43-1.03). INTERPRETATION: Specialist outreach visits to remote disadvantaged Indigenous communities in Australia improve access to specialist consultations and procedures without increasing elective referrals or demands for hospital inpatient services.

Adolescent↗

Block copolymer micelles as matrixes for incorporating diselenide compounds: a model system for a water-soluble glutathione peroxidase mimic fine-tuned by ionic strength.

We report on the use of block copolymer micelles of polystyrene-b-poly(acrylic acid) (PS-b-PAA) as matrixes for incorporating dibenzyl diselenide. We found that the water-insoluble diselenide, after being incorporated into the micelles, demonstrates glutathione peroxidase (GPx) activity in water. Surprisingly, the mimicking system can be adjusted to show higher GPx activity by increasing the ionic strength of the solution simply upon addition of NaCl. Moreover, dibenzyl diselenide incorporated into the micelles is quite stable and maintains its GPx activity even after exposure to the atmosphere.

Acrylates↗

Albuminuria as a marker of the risk of developing type 2 diabetes in non-diabetic Aboriginal Australians.

BACKGROUND: Aboriginal Australians experience a higher risk of diabetes than the general Australian population. In this paper, we conducted a nested case-control study to determine whether the presence of microalbuminuria and macroalbuminuria is associated with the development of diabetes among diabetes-free Aboriginal people at baseline. METHODS: Urine albumin to creatinine ratios (ACRs) were obtained from 882 Aboriginal people aged 20-74 years from one community. Among them 750 were free of either clinical known diabetes or newly diagnosed diabetes according to WHO 1999 criteria. Over an 11 year follow-up period, 117 participants developed diabetes. They were defined as cases. Each case was matched by an individual control with same sex and body mass index (BMI) category, and age within 2 years. Conditional logistic regression was used to assess the association between albuminuria and diabetes. RESULTS: The baseline level of ACR was significantly higher among cases than among controls. The odds ratios for future diabetes were 2.36 [95% confidence interval (95% CI) 1.01-5.50] and 3.27 (95% CI 1.38-7.77) for middle and upper tertiles, respectively, with adjustment for age, BMI, serum total cholesterol, serum C-reactive protein values, and fasting plasma glucose at the baseline. The adjusted odds ratios were 1.90 (95% CI 0.88-4.06) and 2.51 (95% CI 1.08-5.87) for those with microalbuminuria and macroalbuminuria, respectively. CONCLUSIONS: The presence of microalbuminuria and macroalbuminuria predicts diabetes independent of other known risk markers of development of type 2 diabetes in Aboriginal people.

Adult↗

Investigating the sustainability of outcomes in a chronic disease treatment programme.

This study examines trends in chronic disease outcomes from initiation of a specialised chronic disease treatment programme through to incorporation of programme activities into routine service delivery. We reviewed clinical records of 98 participants with confirmed renal disease or hypertension in a remote indigenous community health centre in Northern Australia. For each participant the review period spanned an initial three years while participating in a specialised cardiovascular and renal disease treatment programme and a subsequent three years following withdrawal of the treatment programme. Responsibility for care was incorporated into the comprehensive primary care service which had been recently redeveloped to implement best practice care plans. The time series analysis included at least six measures prior to handover of the specialised programme and six following handover. Main outcome measures were trends in blood pressure (BP) control, and systolic and diastolic BP. We found an improvement in BP control in the first 6-12 months of the programme, followed by a steady declining trend. There was no significant difference in this trend between the pre- compared to the post-programme withdrawal period. This finding was consistent for control at levels below 130/80 and 140/90, and for trends in mean systolic and diastolic BP. Investigation of the sustainability of programme outcomes presents major challenges for research design. Sustained success in the management of chronic disease through primary care services requires better understanding of the causal mechanisms related to clinical intervention, the basis upon which they can be 'institutionalised' in a given context, and the extent to which they require regular revitalisation to maintain their effect.

Australia↗

Surface gradient material: from superhydrophobicity to superhydrophilicity.

We have developed a simple method to fabricate a gradient from superhydrophobicity to superhydrophilicity. It is based on the controlled self-assembled monolayer consisting of a thiol molecule on a gold surface and the amplifying effect of the wetting property on a rough surface. Using a relatively dilute HS(CH2)11CH3 solution (0.05 mmol/L), we found that the density of molecules on the surface can be controlled by varying the immersion time. Slowly adding the dilute solution to the container holding the rough gold substrate will lead to a density gradient along the surface. After the complementary adsorption of HS(CH2)10CH2OH, the surface exhibits a gradient from superhydrophobicity to superhydrophilicity. The slope of the gradient can be conveniently tuned by varying the speed of addition. Cassie-Baxter and Wenzel equations are employed to explain this special property based on the rough structure and the molecular composition gradient that have been determined by XPS. This kind of material would provide a larger oriented driving force for many important biological and physical processes and might have potential applications in water droplet movement, oriented axonal specification of neurons, protein adhesion, and so on.

Gold↗

Investigation into pH-responsive self-assembled monolayers of acylated anthranilate-terminated alkanethiol on a gold surface.

This article describes the preparation of pH-responsive self-assembled monolayers (SAMs) of acylated anthranilate-terminated alkanethiol. These monolayers are formed by chemisorption of the alkanethiol molecules onto a gold surface, resulting in different wetting properties of the surfaces depending upon the pH. By using various characterization techniques (e.g., infrared spectroscopy, cyclic voltammetry, contact angle measurements, and surface energy analysis), we have found that the changes in the wetting properties originate from the different surface structures of the monolayers in different pH environments. From surface energy analysis, we found that the disperse components of the surface energy on such SAMs predominate after treatment with pH 1 water, whereas the polar components of the surface energy on such SAMs predominate after treatment with pH 13 water. It is greatly anticipated that this line of research will provide new insight into the mechanism behind pH-responsive properties, facilitating the design and synthesis of new surface-active molecules for the fabrication of pH-responsive functional surfaces.

Journal Article↗

Polymer micelles as building blocks for the incorporation of azobenzene: enhancing the photochromic properties in layer-by-layer films.

We described the use of block copolymer micelles as building blocks for the incorporation of water-insoluble photochromic species of azobenzene and the fabrication of multilayer films by alternating the deposition of the block copolymer micelles of poly(styrene-b-acrylic acid), incorporating azobenzene and poly(diallyl-dimethylammonium chloride). The azobenzene incorporated into the block copolymer micelles can undergo a reversible photoisomerization under the irradiation of UV and visible light sources. An interesting finding is that the photoisomerization of the azobenzene in the multilayer film is faster than it is in its normal solid film, but very similar to that in its diluted solution. Furthermore, the amount of azobenzene incorporated into the micelles can influence the photoisomerization rates in the films. Therefore, we expect that the block copolymer micelles may provide a proper microenvironment for the photoisomerization of azobenzene and the as-prepared polyelectrolyte/block copolymer micelle thin films will be useful for photoswitching materials.

Journal Article↗

Prevalence of type 2 diabetes mellitus of Chinese populations in Mainland China, Hong Kong, and Taiwan.

This article reviews and describes trends and differences in prevalence of type 2 diabetes mellitus of Chinese populations in Mainland China, Hong Kong and Taiwan based on literatures published in the MEDLINE Advanced database (January 1966-October 2005) in both Chinese and English languages. Chinese populations in Hong Kong and Taiwan have significant higher prevalence rates of diabetes than their Mainland counterparts, with odds ratios 1.5 (95% confidence intervals: 1.4, 1.7) and 2.0 (95% confidence intervals: 1.8, 2.2), respectively in 1995-2003 adjusted for age and diagnostic criteria. Using stratified diagnostic criteria; the odds ratios in Hong Kong and Taiwan were consistently higher than Mainland China for the periods of 1985-1994 and 1995-2003. A large proportion, i.e. 68.6% (95% confidence intervals: 67.4%, 69.7%) of diabetic patients remains undiagnosed in Mainland China as compared to 52.6% (95% confidence intervals: 49.8%, 55.5%) undiagnosed in Hong Kong and Taiwan. The prevalence rates of diabetes and impaired glucose tolerance of the Chinese populations rise in older age groups. In tandem with economic development and change toward lifestyle that is lack of physical activity and rich in high-fat diet, prevalence of diabetes of the Chinese populations are on the rise. If the undiagnosed individuals left uncontrolled, they are subject to higher risks of developing diabetes and its complications. These will increase the burdens of diabetes medically and financially.

Asian People↗

Population distribution of high sensitivity C-reactive protein values in Aboriginal Australians: a comparison with other populations.

OBJECTIVES: To examine the distribution of C-reactive protein (CRP) values in Aboriginal Australians and its relation to age and gender. METHODS: High sensitivity CRP levels were measured in 954 Aboriginal participants aged 5-74 years. Fractional polynomial regressions were used to explore the relationship between CRP and age. RESULTS: CRP values changed with age and reached its lowest level around 10 years and then increased with age. Geometric means of CRP were 7.3 (95% confidence interval (CI): 6.6, 8.1) and 4.1 (95% CI: 3.7, 4.6) for female and male adults, respectively. Adjusting for age, the ratio of female to male CRP concentrations was 1.67 (95% CI: 1.45, 1.99) for adults, and 1.09 (95% CI: 0.84, 1.42) for children 5 to 19 years. CONCLUSIONS: CRP changes with age. Females have higher CRP values than males. CRP values in Aboriginal people are substantially higher than other populations.

Adolescent↗

[Study on the application of allogeneic bone transplantation].

OBJECTIVE: To explore the clinical application of allogeneic bone transplantation. METHODS: Related literatures on clinical application of various allograft bone materials of the past 5 years were extensively reviewed. RESULTS: The allografts could be processed into various kinds of transplanting materials, such as small blocks, large segments, morselized or granular material, and bone ring, so that they could be applied to bone defect filling, prosthesis revision, limb preservation after tumor resection, and joint fusion. All these applications ended up with good clinical results. However, complications resulted in the structural transplantation of large block bones could be overlooked. CONCLUSION: The main advantage of bone allograft is that it can be integrated with host bone and be remodelled, so as to reconstruct bone structure and function. How to accelerate functions is the problem that requires solution. their integration and remodelling while exerting normal functions is the problem that requires solution.

Bone Transplantation↗

[Study on the research progress of artificial osteoconductive materials].

OBJECTIVE: To review the recent research and clinical progress of artificial osteoconductive materials. METHODS: Recent and related literatures were extensively and comprehensively reviewed. RESULTS: Many achievements about the clinical application of the artificial osteoconductive materials were made. It had become one of the hotspots of bone tissue engineering research. Some were clinically applied and good clinical results were achieved. CONCLUSION: As it provides new clinic method for treating bone defect, artificial osteoconductive material is of great potential in its application. To improve its microstructure, macro-shape, mechanism of osteoinductive ability, and to accelerate new bone formation will be the hotspots of the research on artificial osteoconductive material.

Bone Substitutes↗