Pathogens

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17 pages, 4354 KB

Open AccessArticle

Exploring the Mechanism of Tannic Acid Against Pichia kudriavzevii in the VK2/E6E7 Vaginal Epithelial Cell Line and Its Synergy with Azoles on Drug-Resistant Candida Species

by Meng Zhou, Kun Ren, Huan Mei, Hang Yang, Dongmei Li, Weida Liu, Lulu Zhang and Xiaodong She

Pathogens 2026, 15(5), 464; https://doi.org/10.3390/pathogens15050464 (registering DOI) - 24 Apr 2026

Abstract

Vulvovaginal candidiasis (VVC) is a common gynecological infection, with Pichia kudriavzevii emerging as a significant pathogen due to its intrinsic fluconazole resistance and biofilm-forming capacity. This study investigates the antifungal efficacy and mechanisms of tannic acid (TA) against P. kudriavzevii, as well [...] Read more.

Vulvovaginal candidiasis (VVC) is a common gynecological infection, with Pichia kudriavzevii emerging as a significant pathogen due to its intrinsic fluconazole resistance and biofilm-forming capacity. This study investigates the antifungal efficacy and mechanisms of tannic acid (TA) against P. kudriavzevii, as well as its potential to reverse azole resistance across multiple Candida species with distinct resistance profiles. TA significantly inhibited P. kudriavzevii growth, surface colonization, and virulence gene expression at 3 μg/mL. Mechanistically, TA protected the human vaginal epithelial cell line VK2/E6E7 by reducing ROS levels, restoring mitochondrial membrane potential, and suppressing IL-1β and IL-18 release through modulation of the NLRP3-Caspase1-ASC axis. Furthermore, TA demonstrated synergistic activity when combined with azoles against five clinically azole-resistant Candida isolates spanning three Candida species with distinct resistance mechanisms: P. kudriavzevii (intrinsic), C. albicans (acquired), and N. glabrata (FKS-mediated). This study highlights TA as a promising natural therapeutic agent for P. kudriavzevii infections and offers a novel strategy for combating multidrug-resistant Candida through combination therapy. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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22 pages, 3195 KB

Open AccessArticle

Profile of Priority Antimicrobial-Resistant Pathogens and the Behavior of Multidrug-Resistant Tuberculosis in the Santiago de Cali District, Colombia

by Alejandra Mondragón Quiguanas, Jorge Iván Montoya Salazar, Juan Camilo Mosquera-Hernandez, Margareth Zuluaga Aricapa, Carlos Eduardo Pinzón Flórez, German Escobar Morales, Johana Alejandra Moreno-Drada, Bruno Gutiérrez and Lucy Marcela Díaz Rivadeneira

Pathogens 2026, 15(3), 329; https://doi.org/10.3390/pathogens15030329 - 19 Mar 2026

Viewed by 546

Abstract

Background: Antimicrobial resistance is a threat that increases morbidity and mortality. This cross-sectional study aimed to describe the profile of priority antimicrobial-resistant pathogens and to analyze the behavior of multidrug-resistant tuberculosis (MDR-TB) in the Santiago de Cali District, Colombia. Methods: researchers compiled information [...] Read more.

Background: Antimicrobial resistance is a threat that increases morbidity and mortality. This cross-sectional study aimed to describe the profile of priority antimicrobial-resistant pathogens and to analyze the behavior of multidrug-resistant tuberculosis (MDR-TB) in the Santiago de Cali District, Colombia. Methods: researchers compiled information from data provided by healthcare institutions, the National Public Health Surveillance System, and laboratory-based surveillance using the World Health Organization’s WHONET v.5.6 software. Univariate statistical analysis described trends in pathogen resistance, and multivariate analysis analyzed the behavior of MDR-TB. Results: Among Gram-negative bacteria, high levels of carbapenem resistance were observed in A. baumannii (84% aztreonam resistance) and in K. pneumoniae (63%). P. aeruginosa exhibited elevated multidrug resistance, consistent with extensive antimicrobial selective pressure. MDR-TB exhibited a high burden of resistance, reaching 96%, with projections indicating a potential increase driven by monoresistance and resistance to rifampicin. Patients with drug-resistant tuberculosis who were HIV-positive or experiencing homelessness had a significantly higher likelihood of hospitalization (OR 5.59; 95% CI 3.09–10.11 and OR 2.94; 95% CI 1.48–5.81, respectively) and mortality (OR 3.34; 95% CI 1.72–6.49 and OR 2.59; 95% CI 1.16–5.79, respectively). Conclusions: The expansion of resistance mechanisms suggests sustained selective pressure, underscoring the need for strategies to optimize antibiotics. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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17 pages, 1142 KB

Open AccessArticle

Prevalence, Virulence Determinants, and Antimicrobial Resistance of Staphylococcus aureus and Escherichia coli Isolated from Computer Devices Used by Staff and Students at a Northern Thailand University

by Sorawit Upakut, Achiraya Siriphap, Ornampai Japa, Pathumwan Watsing, Peerapat Bunpak, Aacharaporn Ta-In, Cholthicha Inmanee, Chutamas Thepmalee, Nittiya Suwannasom and Krissana Khoothiam

Pathogens 2026, 15(3), 274; https://doi.org/10.3390/pathogens15030274 - 3 Mar 2026

Viewed by 578

Abstract

Computer devices in university settings are frequently shared and repeatedly handled, making them potential reservoirs for pathogenic bacteria. This study aimed to investigate the prevalence, virulence determinants, and antimicrobial resistance profiles of Staphylococcus aureus and Escherichia coli isolated from computer devices used by [...] Read more.

Computer devices in university settings are frequently shared and repeatedly handled, making them potential reservoirs for pathogenic bacteria. This study aimed to investigate the prevalence, virulence determinants, and antimicrobial resistance profiles of Staphylococcus aureus and Escherichia coli isolated from computer devices used by staff and students at a university in Northern Thailand. A total of 400 computer devices were sampled, with each device defined as a single sampling unit comprising both the keyboard and computer mouse. Bacterial identification was performed using PCR, while staphylococcal enterotoxin (se) genes and diarrheagenic E. coli (DEC)-associated virulence genes were detected by PCR. Antimicrobial susceptibility was assessed using the disk diffusion method. Overall, 74 (18.5%) S. aureus isolates and 6 (1.5%) E. coli isolates were recovered. The highest prevalence of S. aureus was observed among personal-use student computer devices (29%; p < 0.001), whereas E. coli was most frequently detected on public-use staff computer devices (4%). Among S. aureus isolates, 24.3% (18/74) carried at least one se gene, with sec being the most prevalent (13.5%). Half of the E. coli isolates harbored the astA gene. Low resistance rates (<10%) were observed among S. aureus; however, four isolates (5.4%) were classified as MRSA, three of which exhibited multidrug resistance. All E. coli isolates were resistant to ampicillin, and 50% displayed multidrug-resistant phenotypes. These findings suggest that computer devices can act as occasional reservoirs of potentially pathogenic and antimicrobial-resistant bacteria in university environments. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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12 pages, 1549 KB

Open AccessArticle

Whole Genome Sequencing of Drug-Resistant Vibrio cholerae Serotype Ogawa from an Outbreak in Khyber Pakhtunkhwa

by Aftab Ali, Momin Khan, Taj Ali Khan, Sajjad Ahmad, Noor Rahman, Aiman Waheed and Taane G. Clark

Pathogens 2026, 15(1), 39; https://doi.org/10.3390/pathogens15010039 - 29 Dec 2025

Cited by 1 | Viewed by 890

Abstract

Background: Cholera, caused by Vibrio cholerae, remains endemic in many developing countries, including Pakistan. The extensive use of antibiotics has led to the emergence of antimicrobial resistance in V. cholerae, limiting available treatment options. In this study, we performed molecular characterisation [...] Read more.

Background: Cholera, caused by Vibrio cholerae, remains endemic in many developing countries, including Pakistan. The extensive use of antibiotics has led to the emergence of antimicrobial resistance in V. cholerae, limiting available treatment options. In this study, we performed molecular characterisation of antibiotic-resistant V. cholerae serotype Ogawa isolates from a recent cholera outbreak in Khyber Pakhtunkhwa, Pakistan. Methodology: Suspected cholera stool samples were collected from hospitalised patients at various district hospitals of Khyber Pakhtunkhwa Province (KPK), Pakistan. The samples were transported to the Public Health Reference Microbiology Laboratory at Khyber Medical University, Peshawar. V. cholerae were identified based on colonial morphology, Gram staining, and biochemical tests using EPI 10E. For serotype identification, monovalent antisera were used. Antibiotic susceptibility testing (AST) was performed using CLSI M45 and EUCAST guidelines. DNA was extracted from pure colonies of multidrug-resistant (MDR) V. cholerae and subjected to whole-genome sequencing (WGS) for genomic characterisation using an Illumina MiSeq platform. Results: Of the 350 active diarrheal cases investigated, 70 were confirmed as V. cholerae. The outbreak was initially reported in Dir and was subsequently followed by a high incidence of cholera in the Peshawar district of KPK. All strains belong to the Ogawa serotype, which shows high antibiotic resistance, particularly to ampicillin (n = 62, 88.57%), Sulfamethoxazole/Trimethoprim (n = 60, 85.71%), Erythromycin (n = 59, 84.29%), and Tetracycline (n = 53, 75.71%). The lowest resistance was against Meropenem (n = 1, 1.4%), followed by amikacin (n = 7, 10.0%) and levofloxacin (n = 13, 18.57%). Furthermore, 34 (48.57%) of the isolates were MDR, while 13 (18.57%) were extensively drug-resistant. Six samples were selected for whole-genome sequencing. The selection of six V. cholerae samples for WGS was based on their drug resistance pattern and origin of isolation. At the genomic level, all sequenced V. cholerae strains harboured multiple antimicrobial resistance determinants. Quinolone resistance was associated with mutations and genes in gyrA, gyrB, parC, and parE; resistance to sulfamethoxazole–trimethoprim with folA, folP, and dfr; tetracycline resistance with tetA and tet35; chloramphenicol resistance with catB and S10p; and aminoglycoside resistance with hns, S12p, and gigB. In addition, β-lactam resistance was linked to the presence of efflux and β-lactamase genes, including blaSHV and mox-3. Mutations were identified in gyrA at positions S83I, S177A, and S202A, and in parC at positions S85L and I231V. Collectively, the presence of these resistance determinants likely enables V. cholerae to survive exposure to high concentrations of multiple antibiotics. Conclusions: Our V. cholerae isolates showed close genetic relatedness to previously sequenced strains from Pakistan (2010 and 2022), as well as to recently reported international strains from the USA, Australia, and China. These findings highlight both the long-term persistence of these lineages within Pakistan and their international dissemination, likely facilitated by globalisation. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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19 pages, 10016 KB

Open AccessArticle

A Novel Enterococcus Phage Endolysin Lys22 with a Wide Host Range Against Mixed Biofilm of Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii

by Ziqin Yang, Xue Du, Nannan Hu, Meng-Ai Feng, Jiaoyang Xu, Hailin Jiang, Na Zhang, Honglan Huang, Jinghua Li and Hongyan Shi

Pathogens 2025, 14(10), 1060; https://doi.org/10.3390/pathogens14101060 - 20 Oct 2025

Cited by 1 | Viewed by 1257

Abstract

The global surge in multidrug-resistant (MDR) bacterial pathogens has created an urgent imperative for innovative antimicrobial strategies. Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii demonstrate remarkable antibiotic resistance and dominate hospital-acquired infections. These bacteria often form biofilms, a complex community structure [...] Read more.

The global surge in multidrug-resistant (MDR) bacterial pathogens has created an urgent imperative for innovative antimicrobial strategies. Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii demonstrate remarkable antibiotic resistance and dominate hospital-acquired infections. These bacteria often form biofilms, a complex community structure that shields them from immune system phagocytosis, resists antibiotic penetration, and enhances their survival in hostile environments. In clinical cases, these bacteria often form mixed biofilms and lead to treatment failures. Phages and their derivatives have emerged as promising candidates in the fight against drug-resistant bacteria. Lys22, an endolysin derived from an enterococcus phage, has been cloned and demonstrated to possess a broad host range, effectively targeting E. faecalis, various Staphylococcus species, and A. baumannii. When applied to the biofilms formed by these bacteria, Lys22 was found to significantly inhibit both simple and complex biofilms in vitro. Virulent genes, including agrA, sarA, and icaA in S. aureus; asa1, cylA, and gelE in E. faecalis; and OmpA and lpsB in A. baumannii were also downregulated by Lys22. Notably, Lys22 also exhibited a robust protective effect against dual or triple infections involving E. faecalis, S. aureus, and A. baumannii in a zebrafish embryos model, highlighting its potential as a therapeutic agent in combatting multi-bacterial infections. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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Review

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31 pages, 1502 KB

Open AccessReview

Antimicrobial Consumption and Resistance Dynamics Across Healthcare Level: Global Evidence and Stewardship Implications

by Neha Raut, Anis A. Chaudhary, Harshad Patil, Supriya Shidhaye, Ruchi Khobragade, Milind Umekar, Mohamed A. M. Ali and Rashmi Trivedi

Pathogens 2026, 15(4), 414; https://doi.org/10.3390/pathogens15040414 - 10 Apr 2026

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Abstract

Background/Objectives: Antimicrobial resistance (AMR) is a critical global public health challenge driven by inappropriate and excessive antimicrobial use (AMU) across human, animal, and environmental sectors. Method: This narrative review synthesizes recent evidence on antimicrobial utilization and resistance patterns. A structured search of PubMed, [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is a critical global public health challenge driven by inappropriate and excessive antimicrobial use (AMU) across human, animal, and environmental sectors. Method: This narrative review synthesizes recent evidence on antimicrobial utilization and resistance patterns. A structured search of PubMed, Scopus, and Web of Science was conducted for studies published between 2015 and 2025. Eligible sources included surveillance reports, registry-based analyses, and clinical studies. Data were qualitatively analyzed to identify key trends and regional variations. Result: Marked geographical variation in AMR was observed. Carbapenem resistance in Escherichia coli remains low globally (2–3%) but is higher in Southeast Asia (17–18%) and India (~40%). Klebsiella pneumoniae shows consistently high resistance (>40% globally; ~54% in India), while Pseudomonas aeruginosa exhibits stable resistance levels (35–45%). Resistance prevalence increases from primary to tertiary care settings, reflecting greater antimicrobial exposure. Vulnerable populations—including pediatric, elderly, pregnant, and immunocompromised patients—face higher risks of antimicrobial exposure and adverse outcomes, including nephrotoxicity, hepatotoxicity, and microbiome disruption. WHO AWaRe data indicate a global shift toward increased use of Watch-category antibiotics. Stewardship interventions, such as audit and feedback, prescribing restrictions, rapid diagnostics, and decision support systems, effectively reduce inappropriate AMU. Conclusions: Integrated, data-driven antimicrobial stewardship and robust surveillance systems are essential to mitigate the global burden of AMR. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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Graphical abstract

17 pages, 275 KB

Open AccessReview

Ceftazidime/Avibactam Monotherapy Versus Other Antibiotics: Where Do We Stand?

by Georgios Vougiouklakis, Constantinos Tsioutis, Nayia Vasileiadi, Konstantinos Alexakis, Nikolaos Spernovasilis and Aris P. Agouridis

Pathogens 2025, 14(11), 1119; https://doi.org/10.3390/pathogens14111119 - 3 Nov 2025

Cited by 2 | Viewed by 3129

Abstract

The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens [...] Read more.

The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens poses a formidable challenge. The combination ceftazidime/avibactam (CAZ/AVI) has emerged as a pivotal agent in the management of multidrug-resistant Gram-negative infections. Avibactam, a novel β-lactamase inhibitor, demonstrates a wider spectrum of activity against Ambler Class A, C, and partially D β-lactamases in comparison to older inhibitors, thus enhancing the antimicrobial activity of ceftazidime against organisms producing ESBL and carbapenemases, such as oxacillinase (OXA)-type and Klebsiella pneumoniae Carbapenemase (KPC). This review synthesizes findings from randomized controlled trials and cohort studies, evaluating the efficacy of CAZ/AVI across diverse clinical settings, including complicated intra-abdominal infections, urinary tract infections, nosocomial pneumonia, skin and soft tissue infections, and bloodstream infections. The non-inferiority of CAZ-AVI with respect to carbapenems and superiority over polymyxins in terms of both clinical outcomes and safety are outlined, along with evidence supporting the use of CAZ/AVI in high-risk populations such as immunocompromised and critically ill patients. Overall, CAZ/AVI represents a compelling therapeutic option with favorable efficacy and safety, thus appearing as a reasonable frontline treatment for resistant Gram-negative infections. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

16 pages, 3105 KB

Open AccessReview

Novel Therapies for Prosthetic Joint Infections Caused by Methicillin-Resistant Staphylococcus aureus

by Xi Xiang, Xin Jin, Qi Yang, Lili Zou, Yueqing Wang, Tianxu Wang and Xun Sun

Pathogens 2025, 14(11), 1102; https://doi.org/10.3390/pathogens14111102 - 29 Oct 2025

Viewed by 1581

Abstract

Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA’s antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for [...] Read more.

Periprosthetic joint infection (PJI) is a serious complication following total joint replacement, with methicillin-resistant Staphylococcus aureus (MRSA) being the primary pathogen. The treatment challenges posed by MRSA’s antibiotic resistance further highlight the critical importance of research in this field. Current antibiotic therapies for periprosthetic joint infection caused by methicillin-resistant Staphylococcus aureus (MRSA-PJI) are limited by considerable side effects, such as high costs and the development of resistance. Therefore, there is an urgent need to explore novel alternative or adjunctive therapies. This review provides a comprehensive overview of several innovative therapeutic strategies. These include monoclonal antibody therapies that target specific bacterial components; phage therapy, which can either independently or synergistically degrade biofilms and enhance antimicrobial efficacy, characterized by its high specificity; antimicrobial peptides, capable of disrupting bacterial membrane integrity and exhibiting dual antibiofilm activity, with a reduced tendency to induce resistance; and nanoparticles and hydrogels, which function as drug delivery systems for sustained release, thereby improving both preventive and therapeutic outcomes. However, these novel therapies also face challenges such as high production costs and limited stability, underscoring the need for further research and optimization. Future efforts should focus on additional studies, clinical trials, and the development of robust regulatory frameworks to fully realize the potential of these treatments for MRSA-PJI. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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33 pages, 1065 KB

Open AccessReview

Disarming Staphylococcus aureus: Review of Strategies Combating This Resilient Pathogen by Targeting Its Virulence

by Abdelaziz Touati, Nasir Adam Ibrahim and Takfarinas Idres

Pathogens 2025, 14(4), 386; https://doi.org/10.3390/pathogens14040386 - 15 Apr 2025

Cited by 23 | Viewed by 8630

Abstract

Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key [...] Read more.

Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key approaches include inhibiting adhesion and biofilm formation, neutralizing toxins, disrupting quorum sensing (e.g., Agr system inhibitors), and blocking iron acquisition pathways. Additionally, interventions targeting two-component regulatory systems are highlighted. While promising, challenges such as strain variability, biofilm resilience, pharmacokinetic limitations, and resistance evolution underscore the need for combination therapies and advanced formulations. Integrating anti-virulence strategies with traditional antibiotics and host-directed therapies offers a sustainable solution to combat multidrug-resistant S. aureus, particularly methicillin-resistant strains (MRSA), and mitigate the global public health crisis. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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Other

Jump to: Research, Review

10 pages, 1195 KB

Open AccessBrief Report

Elevated Antibacterial Activity of a Polygalacturonic + Caprylic Acids Wound Ointment Compared with Hypochlorous Acid in a Three-Dimensional Wound Biofilm Model

by Bahgat Gerges, Joel Rosenblatt, Y-Lan Truong, Ying Jiang and Issam Raad

Pathogens 2026, 15(2), 188; https://doi.org/10.3390/pathogens15020188 - 8 Feb 2026

Viewed by 460

Abstract

Bacterial biofilms play a major role in delayed wound-healing and in the development of chronic, non-healing wounds. Natural, plant-based agents, which can eradicate bacterial biofilms, are alternatives to antibiotics and antiseptics in the treatment of bacterially contaminated wounds. Bacterial wound biofilms are three-dimensional [...] Read more.

Bacterial biofilms play a major role in delayed wound-healing and in the development of chronic, non-healing wounds. Natural, plant-based agents, which can eradicate bacterial biofilms, are alternatives to antibiotics and antiseptics in the treatment of bacterially contaminated wounds. Bacterial wound biofilms are three-dimensional and complex microbial communities. Therefore, in this study, we used a three-dimensional fibrin-gel wound biofilm (FGWB) model to compare a commonly used natural agent in wound care, hypochlorous acid (HOCl), to a combination of two natural plant-based agents, polygalacturonic acid (PG) and caprylic acid (CAP) (PG + CAP), for their abilities to eradicate resistant bacterial biofilms of common wound pathogens methicillin resistant Staphylococcus aureus (MRSA), multi-drug resistant (MDR) Pseudomonas aeruginosa, metallo β-Lactamase Escherichia coli, and Streptococcus pyogenes. PG + CAP produced a significantly greater reduction in viable organisms when compared to HOCL (p ≤ 0.05) against all tested bacterial isolates. PG + CAP was highly effective against biofilms of all resistant bacterial isolates and is a promising option that merits further study for treating chronic wounds contaminated with bacterial biofilms. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

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