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Abstract Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.

Diabetes mellitus is a prevalent metabolic disorder worldwide. A variety of antidiabetic medications have been developed to help manage blood glucose levels in diabetic patients, but adverse reactions and efficacy loss over time have spurred research into new therapeutic agents. In view of this, investigations into the antidiabetic effect of herbal products have been encouraged due to their potential availability, inexpensiveness, and relatively minimal side effects. This review explores the antidiabetic potentials of the eight most promising medicinal plants in terms of molecular mechanisms, phytochemistry, toxicology, and efficacy. These plant extracts have gone through clinical trials and demonstrated good control of blood glucose levels by increasing serum insulin levels, enhancing tissue glucose uptake, and/or decreasing intestinal glucose uptake. Yet, medicinal plants are far from being able to replace conventional antidiabetic drugs for patient management but they have the potential for further development if rigorous clinical trials on their mechanisms, delivery, and dose regimen are performed. To date, no study has been performed to isolate and characterize active compounds in these plant extracts, suggesting that further investigations in this area would be the next step to advance this field.

The deep cement mixing (DCM) is used to improve the capacity and reduce the settlement of the soft ground by forming cemented clay columns. The investigation on the mechanical behaviour of the DCM samples is limited to either laboratory-prepared samples or in-situ samples under unconfined compression. In this study, a series of drained and undrained triaxial shearing tests was performed on the in-situ cored DCM samples with high cement content to assess their mechanical behaviours. It is found that the drainage condition affects significantly the stiffness, peak and residual strengths of the DCM samples, which is mainly due to the state of excess pore water pressure at different strain levels, i.e. being positive before the peak deviatoric stress and negative after the peak deviatoric stress, in the undrained tests. The slope of the failure envelope changes obviously with the confining pressures, being steeper at lower stress levels and flatter at higher stress levels. The strength parameters, effective cohesion and friction angle obtained from lower stress levels (c′0 and φ′0) are 400 kPa and 58°, respectively, which are deemed to be true for design in most DCM applications where the in-situ stress levels are normally at lower values of 50–200 kPa. Additionally, the computed tomography (CT) scanning system was adopted to visualize the internal structures of DCM samples. It is found that the clay pockets existing inside the DCM samples due to uneven mixing affect markedly their stress-strain behaviour, which is one of the main reasons for the high variability of the DCM samples.

IntroductionThis study explores the motivators to use learning management systems (LMS) adopted and used in eLearning by Hong Kong universities among Mainland Chinese postgraduate students amid COVID-19 pandemic.MethodsAn adapted and extended UTUAT2 model was first proposed and tested using the structural equation modeling approach. Through self-report online questionnaire, data were collected in 2022 from 352 Mainland Chinese postgraduate students of nine universities in Hong Kong. The reliability and validity of the data were tested using the confirmatory factor analysis, followed by path analysis to test the hypotheses in the proposed model.ResultsThe study revealed nine motivators which explained 50% of the variance in LMS use intention. Trust (0.204), instructor characteristics (0.202), performance expectancy (0.181), and facilitating conditions (0.181) were identified as strong motivators of behavioral intention. Other factors such as effort expectancy (0.148), learning value (0.118) and social influence (0.115) also had significant positive effects on LMS use intention. Habit (0.014) and hedonic motivation (−0.016) had no significant direct effect on it.DiscussionThese findings provide inspirations for educational stakeholders to promote the acceptance of LMS platforms among distance and online learners who adopt the cyberspace as the only means of learning. They also offer insights about instructor recruitment and evaluation methods.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

ChatGPT stands out among other AI technology tools to provide assessment support in the higher education context. This exploratory study investigates the motivators and barriers which influence the use intention of ChatGPT for assessment support among undergraduates in Hong Kong. We tested the adapted and extended UTUAT model using the structural equation modeling approach. Through self-report online questionnaire, we received usable responses from 483 undergraduates of eight Hong Kong universities.In a highly competitive Chinese context, assessment results hold immense significance in determining the value and merit of students. The findings reveal that trust acts as the strongest determinant while moral obligation and perceived risk serve as major inhibitors to students’ acceptance of ChatGPT in assessments. Perceived risk does not mediate the relationship between trust and students’ behavioral intention. Both performance expectancy and effort expectancy positively influence behavioral intention to use ChatGPT for assessment support. However, social influence is found to be statistically insignificant.The results contribute to the education literature by extending the adapted UTAUT model with additional variables for ChatGPT adoption in the assessment context. They offer practical insights to promote ethical and optimal use of ChatGPT in the higher education context.

In high-density cities, pedestrians frequently traverse many publicly accessible indoor spaces, such as metro stations and footbridges, which seamlessly connect with outdoor sidewalks, forming indoor-outdoor combined pedestrian networks. However, the information island phenomenon hinders these connections in the digital world because outdoor sidewalks and indoor spaces are modelled using Geographical Information Systems (GIS) and Building Information Modelling (BIM) technologies, respectively, which challenges obtaining integrated information for intelligent pedestrian services. This study presents an approach for interlinking BIM and GIS data for a semantic pedestrian network using semantic web technologies. The proposed approach automatically converts BIM and GIS data into linked data and establishes interlinkages between BIM and GIS data through semantic queries and inferences. The resulting semantic pedestrian network based on integrated linked data graphs forms a knowledge base, including topological and geometrical information and abundant semantic information from BIM and GIS datasets. The application potential of the semantic pedestrian network is demonstrated through information query and semantic route planning. This research contributes to establishing indoor-outdoor combined semantic pedestrian networks ensuring seamless data integration.

Agarwood essential oil (AEO) has gained attention from healthcare industries due to its numerous pharmacological properties. However, a comprehensive understanding of the chemical composition and its cytotoxic property is lacking. The objective of this study was to investigate the chemical profile as well as the cytotoxic concentration range of AEO derived from Aquilaria sinensis agarwood. Gas chromatography-mass spectrometry (GC-MS) was employed to identify the AEO components. Results showed that sesquiterpenes and sesquiterpenoids constitute 95.85% of the AEO. Among the major compounds identified are allo-aromadendrene (13.04%), dihydro-eudesmol (8.81%), α-eudesmol (8.48%), bulnesol (7.63%), τ-cadinol (4.95%), dehydrofukinone (3.83%), valerenol (3.54%), cis-nerolidol (2.75%), agarospirol (2.72%), dehydrojinkoh-eremol (2.53%), selina-3,11-dien-9-al (2.36%), guaiol (2.12%) and caryophyllene oxide (2.0%). The presence of volatile quality marker compounds such as 10-epi-ϒ-eudesmol, aromadendrane, β-agarofuran, α-agarofuran, γ-eudesmol, agarospirol and guaiol, with no contaminants detected, indicates that the extracted AEO is of high purity. Interestingly, the AEO displayed moderate to high toxicity in brine shrimp lethality test (BLST). All studied tumor cell lines (MDA-MB-231, HepG2, B16F10) exhibited varying degrees of sensitivity to AEO, which resulted in time and dose-dependent reduction of cell proliferation. Moreover, flow cytometry analysis revealed that AEO could induce apoptosis in treated HepG2 cells. Our findings showed that AEO contains bioactive components that may be exploited in future studies for the development of anti-cancer therapeutics.

Abstract Although the use of intra-articular polynucleotide (IA PN) injection as a viscosupplement for knee osteoarthritis (OA) treatment has been proposed, its efficacy and safety compared to high molecular weight hyaluronic acid (HMWHA) injection has not yet been established. The present double-blind, multicenter, randomized controlled trial aimed to investigate the efficacy and safety of IA PN injection compared to IA HMWHA injection. A total of 60 patients (15 men, 45 women, 64.5 ± 7.5 years) with knee OA (Kellgren–Lawrence grade 1–4) were randomly allocated to each group. All patients were given three IA injections of PN (n = 30) or HMWHA (n = 30) at intervals of 1 week. The primary endpoint was the change rate in weight-bearing pain (WBP) 16 weeks from the baseline. The secondary endpoint included multiple measurements: the change rate in WBP rate at 8 weeks; the change rate in pain level at rest and during walking at 8 and 16 weeks; the Korean-Western Ontario and McMaster University Osteoarthritis index; the Euro-Quality of Life-5 Dimension; Clinical Global Impression, Patient Global Impression at 8 and16 weeks, and total consumption of rescue medicine. The mean change rate in the WBP at 16 weeks from the baseline was − 54.0 ± 38.1% in the IA PN group and − 42.8 (± 35.8%) in the IA HMWHA group, and there was no significant difference between the two groups (p = 0.296). All secondary endpoints related with pain and functional outcome also showed no significant difference between the two groups. Pain at the injection site and swelling were reported as adverse events, and the incidence was similar between the two groups. IA PN showed comparable efficacy and safety to IA HMWHA at 3 times injection with an interval of 1 week. IA PN can be useful alternative to IA HMWHA for the treatment of knee OA.

Abstract Background Genital Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease that causes severe complications including pelvic inflammatory disease, ectopic pregnancy, and infertility in females. The Pgp3 protein encoded by C. trachomatis plasmid has been speculated to be an important player in chlamydial pathogenesis. However, the precise function of this protein is unknown and thus remains to be thoroughly investigated. Methods In this study, we synthesized Pgp3 protein for in vitro stimulation in the Hela cervical carcinoma cells. Results and conclusion We showed that Pgp3 induced prominent expression of host inflammatory cytokine genes including interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and chemokine C-X-C motif ligand 1 (CXCL1), implying a possible role of Pgp3 in modulating the inflammatory reaction in the host.

Abstract Background DNA methylation in prokaryotes is involved in many different cellular processes including cell cycle regulation and defense against viruses. To date, most prokaryotic methylation systems have been studied in culturable microorganisms, resulting in a limited understanding of DNA methylation from a microbial ecology perspective. Here, we analyze the distribution patterns of several microbial epigenetics marks in the ocean microbiome through genome-centric metagenomics across all domains of life. Results We reconstructed 15,056 viral, 252 prokaryotic, 56 giant viral, and 6 eukaryotic metagenome-assembled genomes from northwest Pacific Ocean seawater samples using short- and long-read sequencing approaches. These metagenome-derived genomes mostly represented novel taxa, and recruited a majority of reads. Thanks to single-molecule real-time (SMRT) sequencing technology, base modification could also be detected for these genomes. This showed that DNA methylation can readily be detected across dominant oceanic bacterial, archaeal, and viral populations, and microbial epigenetic changes correlate with population differentiation. Furthermore, our genome-wide epigenetic analysis of Pelagibacter suggests that GANTC, a DNA methyltransferase target motif, is related to the cell cycle and is affected by environmental conditions. Yet, the presence of this motif also partitions the phylogeny of the Pelagibacter phages, possibly hinting at a competitive co-evolutionary history and multiple effects of a single methylation mark. Conclusions Overall, this study elucidates that DNA methylation patterns are associated with ecological changes and virus-host dynamics in the ocean microbiome. Video Abstract

Abstract Background Cestrum diurnum L. (Solanaceae), locally known as buno-Hasnahena, is widely used in different traditional medicinal practices to treat pain, burn, swelling and related disorders. Adequate evidence is not available to support its medicinal properties for further use and drug development. Present study was designed to evaluate its traditional use in pain and inflammation with further characterisation of its chemical constituents through liquid chromatography-mass spectroscopic (LC-MS) analysis. Methods Antinociceptive and analgesic potential of methanol extract of the aerial parts of C. diurnum was carried out using carrageenan induced paw oedema and formalin induced paw licking test in mice at the oral doses of 150 and 300 mg/kg body weight. Inhibition of the inflammatory mediator nuclear factor kappa B (NF-κB) was evaluated by tumour necrosis factor α (TNF-α) induced NF-κB activation assay in macrophage cells at the concentration of 100 μg/ml. LC-MS analysis of the extract was performed to characterise the active component responsible for bioactivities. Results The extract significantly inhibited (p

Background: ChatGPT, a powerful artificial intelligence chatbot, has great potential for active learning because of its ability to generate instant responses to academic inquiries and foster spontaneous interactions. Purpose: This exploratory study investigated the roles of intrinsic motivation and factors of the technology acceptance model that influence ChatGPT acceptance for active learning among undergraduates in Hong Kong. Method: Using a structural equation modeling approach, we examined the extended technology acceptance model in the context of higher education. Using self-report questionnaires, we obtained useful responses from 473 undergraduate students in Hong Kong in July 2023. The reliability and validity of the data were measured using confirmatory factor analysis, followed by path analysis to investigate the hypotheses in the proposed model. Results: We identified intrinsic motivation as the strongest motivator for ChatGPT use intention. Consistent with the prior literature on technology acceptance, perceived usefulness was found to be a strong predictor of behavioral intention. In contrast to extant research, the findings indicate no significant relationship between perceived ease of use and behavioral intention. Neither perceived usefulness nor perceived ease of use were significant mediators in the relationship between intrinsic motivation and behavioral intention. Conclusion: These findings highlight the significant effect of intrinsic motivation on ChatGPT acceptance in supporting students’ active learning. They also provide inspiration for ChatGPT developers and educationalists regarding the importance of intrinsic and extrinsic motivation (perceived usefulness) in promoting the broader acceptance of chatbots in the educational context. Efforts should be made to improve students’ positive subjective experiences and the response quality of ChatGPT.

Cold-active bacteriophages are bacterial viruses that infect and replicate at low temperatures (≤4 °C). Understanding remains limited of how cold-active phage–host systems sustain high viral abundance despite the persistently low temperatures in pelagic sediments in polar seas. In this study, two Pseudoalteromonas phages, ACA1 and ACA2, were isolated from sediment core samples of the continental shelf in the western Arctic Ocean. These phages exhibited successful propagation at a low temperature of 1 °C and displayed typical myovirus morphology with isometric icosahedral heads and contractile tails. The complete genome sequences of phages ACA1 and ACA2 were 36,825 bp and 36,826 bp in size, respectively, sharing almost the same gene content. These are temperate phages encoding lysogeny-related proteins such as anti-repressor, immunity repressor and integrase. The absence of cross-infection between the host strains, which were genomically distinct Pseudoalteromonas species, can likely be attributed to heavy divergence in the anti-receptor apparently mediated by an associated diversity-generating retroelement. HHpred searching identified genes for all of the structural components of a P2-like phage (family Peduoviridae), although the whole of the Peduoviridae family appeared to be divided between two anciently diverged tail modules. In contrast, Blast matching and whole genome tree analysis are dominated by a nonstructural gene module sharing high similarity with Pseudoalteromonas phage C5a (founder of genus Catalunyavirus). This study expands the knowledge of diversity of P2-like phages known to inhabit Peudoalteromonas and demonstrates their presence in the Arctic niche.

Bias Blind Spot (BBS) is the phenomenon that people tend to perceive themselves as less susceptible to biases than others. In three pre-registered experiments (overall N = 969), we replicated two experiments of the first demonstration of the phenomenon by Pronin et al. (2002). We found support of the BBS hypotheses, with effects in line with findings in the original study: Participants rated themselves as less susceptible to biases than others (d = -1.00 [-1.33, -0.67]). Deviating from the original, we found an unexpected effect that participants rated themselves as having fewer shortcomings (d = -0.34 [-0.46, -0.23]), though there was support for the target's main premise that BBS was stronger for biases than for shortcomings (d = -0.43 [-0.56, -0.29]). Extending the replications, we found that beliefs in own free will were positively associated with BBS (r ~ 0.17–0.22) and that beliefs in both own and general free will were positively associated with self-other asymmetry related to personal shortcomings (r ~ 0.16–0.24). Materials, datasets, and code are available on https://osf.io/3df5s/.

The external auditor cooperates and communicates with the audit committee of a company to ensure effective external audit, including detection of material misstatements in financial statements. Trust is an important element to facilitate information exchange and cooperation. This exploratory research examines the impacts of external auditors’ trust in audit committee members’ competence, integrity and goodwill on perceived quality of their interactions. Through questionnaire survey, the data were collected from audit managers, senior managers, directors and partners in Hong Kong with a response rate of 27.2 percent. Partial least square structural equation modeling and principal component analysis were employed to test the proposed model. The results reveal that the external auditor’s competence trust and integrity trust in the audit committee members are two strong motivators, which improve their interactions with the audit committee. The findings also confirm that perceived quality of interactions during pre-engagement investigation mediates the impacts of competence trust and integrity trust on perceived quality during audit performance stage. The implication of the study is that audit committee members should display high levels of competence and integrity for better interactions with external auditors. These findings provide inspirations for board of directors, executives and policymakers to implement policies that enhance trust among actors to improve audit quality.

A Gram-negative, strictly aerobic, non-motile, slightly curved rod-shaped bacterial strain, designated as HL-RS19T, was isolated from a sea surface microlayer (SML) sample of the brackish Lake Shihwa. Here, we characterized the new strain HL-RS19T using a polyphasic approach to determine its taxonomic position. A phylogenetic analysis of its 16S rRNA gene sequence revealed that strain HL-RS19T belonged to the genus Lacinutrix and was closely related to L. mariniflava AKS432T (97.9%), L. algicola AKS293T (97.8%), and other Lacinutrix species (T comprised a circular chromosome of 3.9 Mbp with a DNA G+C content of 35.2%. Genomic comparisons based on the average nucleotide identity and digital DNA-DNA hybridization showed that strain HL-RS19T was consistently discriminated from its closely related taxa in the genus Lacinutrix. Strain HL-RS19T showed optimal growth at 20–25 °C, pH 6.5–7.0, and 3.0–3.5% (w/v) sea salts. The major fatty acids (>5%) of strain HL-RS19T were identified as iso-C15:1 G (16.5%), iso-C16:0 3-OH (12.9%), anteiso-C15:1 A (9.9%), anteiso-C15:0 (9.7%), iso-C15:0 (9.0%), and iso-C15:0 3-OH (8.3%). The polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids, an unidentified phospholipid, and two unidentified lipids. The major respiratory quinone was MK-6. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic data, strain HL-RS19T represents a novel species belonging to the genus Lacinutrix, for which the name Lacinutrix neustonica sp. nov. is proposed. The type strain is HL-RS19T (=KCCM 90497T = JCM 35710T). The genome sequence analysis of strain HL-RS19T suggests that it may be well adapted to a harsh SML environment and is likely involved in arsenic cycling, potentially contributing to the bioremediation of anthropogenic arsenic pollution.

ΦGT1 is a lytic podovirus of an alphaproteobacterial Sulfitobacter species, with few closely matching sequences among characterized phages, thus defying a useful description by simple sequence clustering methods. The history of the ΦGT1 core structure module was reconstructed using timetrees, including numerous related prospective prophages, to flesh out the evolutionary lineages spanning from the origin of the ejectosomal podovirus >3.2 Gya to the present genes of ΦGT1 and its closest relatives. A peculiarity of the ΦGT1 structural proteome is that it contains two paralogous tubular tail A (tubeA) proteins. The origin of the dual tubeA arrangement was traced to a recombination between two more ancient podoviral lineages occurring ~0.7 Gya in the alphaproteobacterial order Rhizobiales. Descendants of the ancestral dual A recombinant were tracked forward forming both temperate and lytic phage clusters and exhibiting both vertical transmission with patchy persistence and horizontal transfer with respect to host taxonomy. The two ancestral lineages were traced backward, making junctions with a major metagenomic podoviral family, the LUZ24-like gammaproteobacterial phages, and Myxococcal phage Mx8, and finally joining near the origin of podoviruses with P22. With these most conservative among phage genes, deviations from uncomplicated vertical and nonrecombinant descent are numerous but countable. The use of timetrees allowed conceptualization of the phage’s evolution in the context of a sequence of ancestors spanning the time of life on Earth.

Chlamydia infection represents an important cause for concern for public health worldwide. Chlamydial infection of the genital tract in females is mostly asymptomatic at the early stage, often manifesting as mucopurulent cervicitis, urethritis, and salpingitis at the later stage; it has been associated with female infertility, spontaneous abortion, ectopic pregnancy, and cervical cancer. As an obligate intracellular bacterium, Chlamydia depends heavily on host cells for nutrient acquisition, energy production, and cell propagation. The current review discusses various strategies utilized by Chlamydia in manipulating the cell metabolism to benefit bacterial propagation and survival through close interaction with the host cell mitochondrial and apoptotic pathway molecules.

Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an alternative to oral administration, offers patient convenience, avoids first-pass hepatic metabolism, provides local targeting, and reduces effective drug toxicities. Nanomaterials provide alternatives to conventional transdermal drug delivery including patches, gels, sprays, and lotions, but it is crucial to understand the transport mechanisms involved. This article reviews the recent research trends in transdermal drug delivery and emphasizes the mechanisms and nano-formulations currently in vogue.

Transdermal patches are a non-invasive method of drug administration. It is an adhesive patch designed to deliver a specific dose of medication through the skin and into the bloodstream throughout the body. Transdermal drug delivery has several advantages over other routes of administration, for instance, it is less invasive, patient-friendly, and has the ability to bypass first-pass metabolism and the destructive acidic environment of the stomach that occurs upon the oral ingestion of drugs. For decades, transdermal patches have attracted attention and were used to deliver drugs such as nicotine, fentanyl, nitroglycerin, and clonidine to treat various diseases or conditions. Recently, this method is also being explored as a means of delivering biologics in various applications. Here, we review the existing literatures on the design and usage of medical patches in transdermal drug delivery, with a focus on the recent advances in innovation and technology that led to the emergence of smart, dissolvable/biodegradable, and high-loading/release, as well as 3D-printed patches.

Helicobacter pylori colonization and persistence could precede gastric adenocarcinoma. Elucidating immune recognition strategies of H. pylori is therefore imperative to curb chronic persistence in the human host. Toll-like receptor 7 (TLR7) and TLR8 are widely known as viral single-stranded RNA (ssRNA) sensors yet less studied in the bacteria context. Here, we investigated the involvement of these receptors in the immunity to H. pylori. Human THP-1 monocytic cells were infected with H. pylori, and the expression levels of human Toll-like receptors (TLRs) were examined. The roles of TLR7 and TLR8 in response to H. pylori infection were further investigated using receptor antagonists. Among all TLR transcripts examined, TLR8 exhibited the most prominent upregulation, followed by TLR7 in the THP-1 cells infected with H. pylori J99 or SS1 strains. H. pylori infection-mediated IFN-α and IFN-β transactivation was significantly abrogated by the TLR7/8 (but not TLR7) antagonist. Additionally, TLR7/8 antagonist treatment reduced H. pylori infection-mediated phosphorylation of interferon regulatory factor 7 (IRF7). Our study suggests a novel role of TLR8 signaling in host immunity against H. pylori through sensing live bacteria to elicit the production of type I interferon.

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host–viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection.

The use of the transdermal delivery system has recently gained ample recognition due to the ability to deliver drug molecules across the skin membrane, serving as an alternative to conventional oral or injectable routes. Subcutaneous insulin injection is the mainstay treatment for diabetes mellitus which often leads to non-compliance among patients, especially in younger patients. Apart from its invasiveness, the long-term consequences of insulin injection cause the development of physical trauma, which includes lipohypertrophy at the site of administration, scarring, infection, and sometimes nerve damage. Hence, there is a quest for a better alternative to drug delivery that is non-invasive and easily adaptable. One of the potential solutions is the transdermal delivery method. However, the stratum corneum (the top layer of skin) is the greatest barrier in transporting large molecules like insulin. Therefore, various chemical enhancers have been proposed to promote stratum corneum permeability, or they are designed to increase the permeability of the full epidermis, such as the use of ionic liquid, peptides, chemical pre-treatment as well as packaging insulin with carriers or nanoparticles. In this review, the recent progress in the development of chemical enhancers for transdermal insulin delivery is discussed along with the possible mechanistic of action and the potential outlook on the proposed permeation approaches in comparison to other therapeutical drugs