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Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Type 2 diabetes mellitus (T2DM) represents approximately 90 % of all DM cases and is primarily caused by an imbalance in blood glucose homeostasis due to inadequate insulin secretion or insulin resistance. This study explores the potential therapeutic effects of chitosan guanidine (CSG) on a T2DM mouse model. The findings reveal that CSG significantly enhances oral glucose tolerance (OGTT) and insulin sensitivity (ITT), reduces fasting blood glucose (FBG) levels, and suppresses the expression of proinflammatory cytokines in T2DM mice. These changes improve insulin resistance and diminish inflammation. Additionally, CSG markedly ameliorates lipid metabolism disorders, lowers total cholesterol (TC) and triglyceride (TG) levels, and inhibits hepatic fat accumulation. 16S rRNA and Spearman correlation analyses indicate that CSG promotes the relative abundance of probiotic genera such as Bacteroidota, Patescibacteria, Actinobacteria, and Cyanobacteria. These bacteria are positively correlated with short-chain fatty acids (SCFAs) and high-density lipoprotein cholesterol (HDLC) levels. Conversely, CSG reduces the relative abundance of pathogenic bacteria, including Proteobacteria and Ralstonia, leading to an improved intestinal microbial community composition in T2DM mice and alleviating T2DM symptoms. These results suggest that CSG holds significant potential as a non-insulin therapeutic agent for diabetes management.

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In recent years, microbial fermentation has become a sustainable alternative to traditional petrochemical processes for producing biomass nylon 56 (i.e., PA56). This study is centered on creating a highly efficient antibacterial nanofiber membrane using bio-nylon 56 as the main material. The membrane was fabricated via a multi-step process involving sodium alginate, chitosan, and poly(hexamethylene biguanide) (PHMB). The PA56 nanofiber was chemically modified by sequential coupling with alginate (AG) and chitosan (CS), introducing a significant number of functional groups (-COOH and -NH2). This process resulted in the formation of PA56-AG and PA56-AG-CS nanofibers. Further modification with PHMB led to obtaining the PA56-AG-PHMB and PA56-AG-CS-PHMB antibacterial nanofiber membranes. The optimal preparation conditions for these membranes were determined, including the pH and concentration of AG, the molecular weight, pH, and concentration of CS, and the pH and concentration of PHMB. The PA56-based membranes demonstrated nearly 100 % antibacterial efficiency within a short time. However, the PA56-AG-PHMB membrane exhibited faster antibacterial rates and higher efficiency in repeated use compared to the PA56-AG-CS-PHMB membrane. The two-step coupling reaction in the preparation of PA56-AG-CS-PHMB may have reduced its surface accessibility to E. coli cells, resulting in slower bacterial attachment. Furthermore, the PA56-related membranes showed excellent biocompatibility, with a 100 % cell survival rate. Despite some limitations in reusability, biomass nylon PA56 stands out as an environmentally friendly material derived from renewable resources through microbial fermentation. It offers significant sustainability advantages over traditional petroleum-based nylons, as evidenced by the favorable cytotoxicity test results.

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The abundant defects on the perovskite surface greatly impact the efficiency improvement and long-term stability of carbon-based perovskite solar cells. Molecules with electron-donating or electron-withdrawing functional groups have been cited for passivating various defects. However, few studies have investigated the potential adverse effects arising from the synergistic interactions among functional groups. Herein, we investigate the correlation between functional group configurations and passivation strength as well as the potential adverse impacts of strong electrostatic structures by methodically designing three distinct interface molecules functionalized with different ending groups, which both belong to biguanide derivatives, including 1-(3,4-dichlorophenyl) biguanide hydrochloride (DBGCl), metformin hydrochloride (MFCl), and biguanide hydrochloride (BGCl). The results indicate that DBGCl establishes comparatively mild active sites, not only passivates defects but also aids in forming a surface with a uniform potential. Conversely, MFCl exerts a more pronounced adverse effect on the perovskite surface, which is attributable to the electronic state perturbations induced by its functional groups. Due to the lack of hydrophobic groups, devices treated with BGCl demonstrate insufficient moisture resistance. Devices passivated with DBGCl demonstrate superior average efficiency, showcasing a 12% enhancement relative to the pristine. Furthermore, DBGCl-treated devices exhibit enhanced stability in three different environments, respectively, achieving the highest PCE retention rates under nitrogen conditions (25 °C), room-temperature air conditions (25 °C, RH = 40 ± 2%), and high-temperature air conditions (65 °C, RH = 40 ± 2%).

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A hydrated salt of decavanadate containing diprotonated metforminium(2+) (H2Met2+), hydronium (H3O+) and either neutral biguanide (Bg) or monoprotonated guanylurea (HGU+) exhibits a previously seen complex charge-stabilized hydrogen-bonded network [Chatkon et al. (2022). Acta Cryst. B78, 798-808]. Charge balance is achieved in two ways through substitutional disorder: a 0.6 occupied HGU+ cation is paired with a V10O286- anion, and a 0.4 occupied neutral Bg molecule is paired with a HV10O285- anion, with the remaining charge in both cases balanced by two H2Met2+ dications and one H3O+ monocation. Bg/HGU+ moieties exhibit bifurcated N-H...O hydrogen bonding to the H3O+ cation and are substitutionally/positionally disordered along with the H3O+ cation about an inversion center. The HGU+ V10O286- synthon seen in the previous study occurs again. Bg exhibits bifurcated hydrogen bonding from two amino groups to two rows of cluster O atoms running diagonally across the equatorial plane of the HV10O285- anion with a return hydrogen bond from the cluster H atom to the imino N atom of the Bg. Thus, a Bg...cluster synthon similar to the HGU+...cluster synthon previously reported is found. The disordered moieties occupy spaces with excess volume in the 3-D network structure. Interestingly, when the crystallographic unit cell of the current compound, whose X-ray data was collected at 100 K, is compared with that of a previous compound exhibiting the same supramolecular framework, unit-cell parameter c does not shorten as a and b expectantly do because of the lower data collection temperature. The lack of contraction on unit-cell parameter c is possibly due to the supramolecular structure.

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This investigation examined the potential antibacterial and antidiabetic effects of wound dressings created using electrospun nanofibers containing Ziziphus jujuba fruit extract (ZJ). These nanofibers were composed of a combination of Polycaprolactone (PCL), Polyvinyl Alcohol (PVA), and Polyhexamethylene Biguanide (PHMB). The process of creating these nanofibers involved electrospinning. The nanofiber products, which included PCL, PCL/PVA, PCL/PVA/ZJ, PCL/PVA/PHMB, and PCL/PVA/PHMB/ZJ, underwent a morphology, physicochemical, and biological assessment. Incorporating PHMB into the nanofibers enhanced the antibacterial properties, effectively preventing bacterial infections in wounds. Furthermore, including ZJ fruit extract in the nanofibers provided antidiabetic properties, making these dressings suitable for diabetic patients. The PCL/PVA/PHMB/ZJ combination exhibited exceptional healing capabilities and superior antibacterial efficiency in MRSA-infected wounds. The histological assay confirmed complete wound healing by day 14, accompanied by reduced inflammation. Based on these findings, using PCL/PVA/PHMB/ZJ as innovative wound dressings is recommended, as they can expedite wound healing while offering significant antidiabetic and antibacterial features. Ultimately, these electrospun nanofibers possess the potential to serve as advanced wound dressings with enhanced antibacterial and anti-diabetes properties.

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AUTAC-Biguanide is a hybrid compound designed to target mitochondria, inducing their degradation by mitophagy. This study unveils the potential of biguanides as cancer cell-targeting agents, emphasizing AUTAC-Biguanide's superior antiproliferative properties compared to metformin and its selectivity for cancer cells. The mechanism behind this heightened effect includes the ability of AUTAC-Biguanide to trigger mitophagy. By providing a comprehensive analysis of these findings, this study adds valuable insights to the field of mitochondrial-targeting anticancer agents.

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INTRODUCTION: To evaluate the antimicrobial efficacy of an ophthalmic formulation containing hexamidine diisethionate (HD) 0.05%, polyhexamethylene biguanide (PHMB) 0.0001%, and edetate disodium (EDTA) 0.01% (Keratosept®, Bruschettini, Genova, Italy) on the microbial flora of a healthy ocular surface. METHODS: Patients were enrolled consecutively. Each patient applied two drops of Keratosept® in the eye scheduled for cataract surgery (study eye) three times daily in the 2 days prior to surgery and one time in the morning of surgery. The contralateral eyes were considered as control (control eye). Bilateral conjunctival swabs were collected before the first administration (T0) and the morning of surgery (T1). The swabs were processed within 3 h from sampling for the automated detection of the presence of replicating microorganisms (colony-forming units, CFU/mL) and the provision of real-time growth curves. RESULTS: Conjunctival swabs of 32 patients (n = 128) were examined. Six patients were excluded from the efficacy analysis because of microbial load < 50 CFU/mL at T0 in the study eye. No difference between study and control eyes was observed at T0 (p = 0.40). Compared with T0, 20 (76.9%) study eyes and 10 (38.5%) control eyes showed a ≥ 1 log reduction of the microbial load at T1, with a significant difference between groups (p = 0.005). Keratosept® showed good tolerability, and no adverse events or eye discomfort were recorded. CONCLUSIONS: This study showed that the low-dose combination of antiseptic agents in the Keratosept® ophthalmic solution effectively reduces the bacterial load of healthy flora on the ocular surface.

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The biguanide Cu(II) complexes [Cu(L1-4)2](ClO4)2 were synthesized and spectroscopic/analytical techniques were used to clarify their structures. Single crystals of complex [Cu(L4)2](ClO4)2 was obtained and its definite structure was determined by single crystal X-ray diffraction study. The complexes [Cu(L1-4)2](ClO4)2 were screened for their FSds-DNA interactions by using UV-Vis absorption and fluorescence spectroscopies. The complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 were shown to exhibit higher affinity for binding DNA. Examining the EB-DNA interaction, it is believed that the complexes interact with DNA through a groove binding mechanism. The interaction of complexes with BSA were observed through the quenching of the fluorescence emission. Complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 show moderate binding affinity to BSA through a static mode. Additionally, the Cu(II) complexes were screened for their antibacterial activities against various bacterial strains. Complexes showed potential antimicrobial activity against Salmonella typhimurium, Bacillus cereus, Salmonella typhimurium and S. aureus.

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Pectin (PEC)/polyvinyl alcohol (PVA), plasticizers, and polyaminopropyl biguanide (Pb) (0.125%-1%) were used to prepare the film solution. The results demonstrated significantly enhanced tensile strength and elongation at break of PEC/PVA/Pb 0.25% film than PEC/PVA film. Scanning electron microscopy was carried out to investigate the continuous and dense structure of the PEC/PVA/ Pb0.25% film. FTIR, XPS, and XRD revealed that Pb addition to the PEC/PVA film matrix changed its physicochemical properties by forming new hydrogen and CN bonds. Moreover, the composite films exhibited strong antimicrobial activity against food-borne microorganisms (E. coli and S. aureus), and post-harvest pathogens (P. italicum and F. proliferatum) in vitro. The composite film effectively inhibited P. italicum growth during citrus experiments, while maintaining nutritional components (vitamin C, total flavonoid, and total polyphenol content). Overall, the antimicrobial composite film presented promising applicability in food packaging.

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Background: In burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses the role of polyhexamethylene biguanide (PHMB) in managing pediatric superficial partial-thickness burns, focusing on the effects of various patient-specific factors on recovery. Methods: Through a retrospective analysis of 27 pediatric cases treated with PHMB, we evaluated the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the time until reepithelialization (TTRE). Results: The majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. A mean healing time of 8.78 (SD: 2.64) days was observed, with the extent of the burn showing a strong correlation (r: 0.63) to TTRE. Most treatments were managed outpatient, evidenced by a negligible average hospital stay (0.96 days), with recorded no complications. Conclusions: Our findings endorse PHMB as a promising treatment for superficial second-degree burns in young patients, due to the observed stable and rapid wound closure without the association of increased risks. Continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management is necessary. Future research should assess long-term outcomes, including functionality, scar quality, and patient satisfaction.

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To expand the utilization of gelatin and pectin derived from agricultural by-products, the composite films composed of gelatin, citrus pectin, cellulose nanofibers (CNF), and polyhexamethylene biguanide hydrochloride (PHMB) were prepared through the solvent casting method. Fourier infrared spectroscopy analysis verified the successful integration of CNF and PHMB into the gelatin-pectin matrix. The incorporation of CNF as a reinforcing agent substantially enhanced the barrier capabilities of the composite film. Moreover, the addition of PHMB, functioning as an antimicrobial agent, not only granted the film with antibacterial properties but also improved its physical characteristics and biodegradability. A water contact angle experiment revealed the film presented a certain degree of hydrophobicity. The optimal performances were attained with a composition in which CNF and PHMB constituted 8 % and 3 %, respectively, of the total weight of gelatin and pectin. As a packaging film, the composite film demonstrated its effectiveness by reducing the decay index and weight loss rate of sweet cherries during a 12-day storage period. In the soil degradation test, the composite film exhibited notable structural degradation by the 16th day. Consequently, the composite film will be used as an innovative and biodegradable packaging material to provide a sustainable solution for food packaging industries.

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BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.

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OBJECTIVE: There is currently a wide range of cleansing and irrigation solutions available for wounds, many of which contain antimicrobial agents. The aim of this study was to assess the safety of HydroClean Solution (HARTMANN, Germany), a polyhexamethylene biguanide (PHMB)-containing irrigation solution, in a standard cytotoxicity assay, and to assess its effect in a three-dimensional (3D) full-thickness model of human skin. METHOD: A number of commercially available wound cleansing and irrigation solutions, including the PHMB-containing irrigation solution, were tested in a cytotoxicity assay using L929 mouse fibroblasts (ISO 10993-5:2009). The PHMB-containing irrigation solution was then assessed in an in vitro human keratinocyte-fibroblast 3D full-thickness wounded skin model to determine its effect on wound healing over six days. The effect of the PHMB-containing irrigation solution on tissue viability was measured using a lactate dehydrogenase (LDH) assay, and proinflammatory effects were measured using an interleukin-6 (IL-6) production assay. RESULTS: The PHMB-containing irrigation solution was shown to be equivalent to other commercially available cleansing and irrigation solutions when tested in the L929 fibroblast cytotoxicity assay. When assessed in the in vitro 3D human full-thickness wound healing model, the PHMB-containing irrigation solution treatment resulted in no difference in levels of LDH or IL-6 when compared with levels produced in control Dulbecco's phosphate-buffered saline cultures. There was, however, a pronounced tissue thickening of the skin model in the periwound region. CONCLUSION: The experimental data presented in this study support the conclusion that the PHMB-containing irrigation solution has a safety profile similar to other commercially available cleansing and irrigation solutions. Evidence also suggests that the PHMB-containing irrigation solution does not affect tissue viability or proinflammatory cytokine production, as evidenced by LDH levels or the production of IL-6 in a 3D human full-thickness wound healing model. The PHMB-containing irrigation solution stimulated new tissue growth in the periwound region of the skin model.

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The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open?

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Antimicrobial resistance is becoming a problem of concern in the veterinary field, necessitating the use of effective topical treatments to aid the healing of wounds. Honey has been used for thousands of years for its medicinal properties, but in recent years medical-grade Manuka honey has been used to treat infected wounds. The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The pathogens studied include ATCC lab-acclimated Pseudomonas aeruginosa, Escherichia coli, and methicillin-resistant Staphylococcus aureus and one from an equine sample submitted to the Colorado State Veterinary Diagnostic Laboratory (Streptococcus equi ssp. zooepidemicus (Streptococcus zooepidemicus)). An additional goal of the study was to describe the comparison of bactericidal activity of medical-grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings (20% hypertonic saline, silver sulfadiazine cream, PHMB gauze, and PHMB foam). The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting the growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka honey and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab-acclimated. Additional research for in vivo applications needs to be done to see whether differences exist in effective wound management.

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The aim was to investigate the long-term effects of metformin ingestion on high-intensity interval training on performance, glycogen concentration (GC), GLUT-4 content, and metabolomics outcomes in rats. Fifty male Wistar rats were randomly divided into baseline, metformin (500 mg daily), and control groups. Training consisted of 4 sets of 10 jumps with 30 s of passive recovery per day, 5 days/week for 8 weeks. The intensity equivalent was 50% of body mass (BM) in the first four weeks and 70% of BM in the last four weeks. The animals were submitted to a weekly jump test until exhaustion at 50% of BM. Serum and tissues were collected at baseline and after 4 and 8 weeks for biochemical and metabolomics analysis. The number of jumps increased in the Control group without a significant difference between groups at 4 and 8 weeks. GLUT4 was lower in the gastrocnemius muscle in the Metformin at the fourth week compared to Control (P=0.03) and compared to Metformin (P=0.02) and Control (P=0.01) at eight weeks. Hepatic and soleus GC were not altered by metformin. Gastrocnemius GC was lower after 8 weeks in the Metformin group compared to Control (P=0.01). Significantly lower levels of pyruvate and phenylalanine and higher levels of ethanol, formate, betaine, very low-density lipoprotein, low-density lipoprotein, and creatine were found in the Metformin compared to the Control. Although chronic administration of metformin decreased food intake and negatively influenced the synthesis of muscle glycogen, it did not significantly change physical performance compared to the Control.

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Purpose: This study was conducted to evaluate and compare the in vitro disinfection efficacies of six commercial lens cleaning and disinfecting products for planned replacement soft contact lenses. Methods: Disinfection efficacies of five multi-purpose solutions (MPSs) and one hydrogen peroxide solution (HPS) as control were evaluated in the presence of organic soil according to the International Organization for Standardization (ISO, Geneva, Switzerland) ISO 14729 stand-alone test protocol. The five specified compendial organisms, three bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens) and two fungi (Candida albicans and Fusarium solani) were incubated with each solution under standard conditions, after which microbes were recovered and quantified. Results: Each of the solutions evaluated met or exceeded the standard's primary criteria (3-log reduction of bacteria and 1-log reduction of fungi) after incubation for the manufacturer-recommended soaking time, except for COMPLETE MPS, which achieved only 0.4 ± 0.1 average log reduction for C. albicans. However, differences in efficacy between the solutions were noted. Average log reduction across all microbes for Biotrue Hydration Plus (4.6 ± 0.1) was comparable to that for CLEAR CARE PLUS HPS (4.3 ± 0.1) and greater than those for OPTI-FREE puremoist (3.6 ± 0.1), OPTI-FREE Replenish (4.0 ± 0.2), ACUVUE RevitaLens (3.9 ± 0.03), and COMPLETE MPS (3.6 ± 0.1). Biotrue Hydration Plus was especially effective at reducing the population of C. albicans (4.2 ± 0.7-log reduction). Conclusion: Products marketed for planned replacement soft CL disinfection generally meet the ISO 14729 standard's primary criteria for reducing populations of compendial organisms, with larger differences between solutions noted with C. albicans.

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Infection prevention and public health are a vital concern worldwide, especially during pandemics such as COVID-19 and seasonal influenza. Frequent manual disinfection and use of chemical spray coatings at public facilities are the typical measures taken to protect people from coronaviruses and other pathogens. However, limitations of human resources and coating durability, as well as the safety of disinfectants used are the major concerns in society during a pandemic. Non-leachable antimicrobial agent poly(hexamethylene biguanide) (PHMB) was mixed into photocurable liquid resins to produce novel and tailor-made covers for public facilities via digital light processing, which is a popular 3D printing technique for satisfactory printing resolution. Potent efficacies of the 3D-printed plastics were achieved in standard antibacterial assessments against S. aureus, E. coli and K. pneumoniae. A total of 99.9% of Human coronavirus 229E was killed after being in contact with the 3D-printed samples (containing the promising PHMB formulation) for two hours. In an eight-week field test in Hong Kong Wetland Park, antibacterial performances of the specially designed 3D-printed covers analysed by environmental swabbing were also found to be satisfactory. With these remarkable outcomes, antimicrobial products prepared by digital light processing 3D printing can be regarded as a reliable solution to long-term infection prevention and control.