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Asian seabass (Lates calcarifer) is an important foodfish species. It has been cultured in Singapore since the 1980s. A selective breeding program to improve growth, meat quality and disease resistance has been ongoing in Singapore since 2004. In 2012, outbreaks of the big belly disease (BBD) occurred in two batches of offspring generated by a mass-cross among F1 brooders in a hatchery. After the outbreaks, only 437 survived in 6000 F2 juveniles. Molecular parentage analysis with 10 microsatellites revealed that four parents (F1) produced high percentage of offspring that survived the BBD outbreaks. Eighty-two BBD survivor offspring (F2) were selected based on their growth performance at 90 days post hatch (dph), family origin and allelic diversity. They were used as brooders to generate F3. In a period of five years, these F2 brooders produced six batches of offspring, where no outbreak of BBD occurred. In the same period, outbreaks of BBD occurred in 4 out of 18 batches produced by F2 brooders selected for growth, with mortality rates ranging from 85.1% to 95.4%. In F3, the average body weight (57.1 ± 1.09 g, n = 3068) of the line for BBD survival was slightly lower than that (60.6 ± 2.29 g, n = 4280) of the line for growth at 90 dph. In both lines, the body weight of F3 was much higher than that (46.90 ± 0.19 g, n = 12117) of F2. The genetic diversity in the line for BBD survival (F3) was much lower than that in F3 line for growth due to small founder population. These data indicate that the selection of BBD survival during BBD outbreaks using molecular parentage analysis is effective to reduce BBD outbreaks. Avoiding further reduction of genetic diversity is essential in the line selected for increased survival against BBD.

Background: Dental caries remains a significant global health problem. One of the fundamental mechanisms underlying the development and progression of dental caries is the dynamic process of demineralisation/remineralisation. In vitro models have played a critical role in advancing our understanding of this process and identifying potential interventions to prevent or arrest dental caries. This literature review aims to provide a structured oversight of in vitro mineralisation models which have been used to study the tooth demineralisation/remineralisation process. Methods: Publications from 2019 to 2023 were screened to identify articles reporting the use of in vitro models to study the demineralisation/remineralisation of tooth caries. The included studies were methodologically assessed for their information on (i) substrate, (ii) lesion formation, and (iii) mineralisation models. Results: The most reported substrates used in the studies were human teeth along with bovine incisors. Acetic/lactic buffers were the most common solutions to induce caries lesions. pH cycling was the most frequently used mineralisation model for simulating the daily change within the oral environment. This review discussed the advantages and limitations of various approaches. Conclusions: Standardisation of in vitro mineralisation models is crucial for enabling effective comparison between studies and advancing caries research.

Abstract Background Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. Methods We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. Results Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0–20.0] in K-mediated HDFN and 26.5% [IQR: 18.0–42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0–56.0] and 60.0% [IQR: 20.0–72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0–4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. Conclusion Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. Systematic review registration PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940 .

Kristine Heidemeyer,1,2 Marco May Lee,3 Simone Cazzaniga,1,2 Nikhil Yawalkar,1 Luigi Naldi2,4 1Department of Dermatology, Inselspital University Hospital of Bern, Bern, Switzerland; 2Centro Studi GISED, Bergamo, Italy; 3Section of Dermatology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; 4Dermatology Department, S. Bortolo Hospital, Vicenza, ItalyCorrespondence: Kristine Heidemeyer, Department of Dermatology, Inselspital University Hospital of Bern, Freiburgstrasse 34, Bern, CH-3010, Switzerland, Tel +41 31 632 20 94, Email kristine.heidemeyer@insel.chAbstract: Palmoplantar pustulosis (PPP) is a chronic, relapsing, inflammatory disease that can occur alone or in association with arthritis. There is still controversy about whether it should be separated from psoriasis or classified as pustular psoriasis. Furthermore, drug-induced paradoxical PPP is a special variant of PPP that differs from classic PPP in several ways. Treatment of PPP is still challenging, and there are a number of treatment-resistant cases. This review summarizes the risk factors for the development of PPP and the currently available treatment modalities. Female sex, smokers or ex-smokers, obesity, thyroid dysfunction, and treatment with a tumor necrosis factor (TNF)-α inhibitor have been identified as risk factors for the disease’s development, severity, and course. Topical treatments and phototherapy are effective for some patients and are used as a first-line or adjuvant treatment modality. Conventional treatments including retinoids and fumaric acid show good effects and can increase the efficacy of treatment with psoralen + ultraviolet light therapy (PUVA). Ciclosporin is fast acting, but relapse mostly occurs immediately after cessation. TNF-α inhibitors are efficient, and an even better response can be achieved with IL-17 and IL-23 blockers as well as apremilast. The effect of Janus kinase inhibitors seems to be promising according to case reports, but further investigations with larger cohorts are needed.Keywords: palmoplantar, pustulosis, psoriasis, treatment, risk factors

The palm family (Arecaceae), consisting of ∼ 2600 species, is the third most economically important family of plants. The African oil palm (Elaeis guineensis) is one of the most important palms. However, the genome sequences of palms that are currently available are still limited and fragmented. Here, we report a high-quality chromosome-level reference genome of an oil palm, Dura, assembled by integrating long reads with ∼ 150× genome coverage. The assembled genome was 1.7 Gb in size, covering 94.5% of the estimated genome, of which 91.6% was assigned into 16 pseudochromosomes and 73.7% was repetitive sequences. Relying on the conserved synteny with oil palm, the existing draft genome sequences of both date palm and coconut were further assembled into chromosomal level. Transposon burst, particularly long terminal repeat retrotransposons, following the last whole-genome duplication, likely explains the genome size variation across palms. Sequence analysis of the VIRESCENS gene in palms suggests that DNA variations in this gene are related to fruit colors. Recent duplications of highly tandemly repeated pathogenesis-related proteins from the same tandem arrays play an important role in defense responses to Ganoderma. Whole-genome resequencing of both ancestral African and introduced oil palms in Southeast Asia reveals that genes under putative selection are notably associated with stress responses, suggesting adaptation to stresses in the new habitat. The genomic resources and insights gained in this study could be exploited for accelerating genetic improvement and understanding the evolution of palms.

Abstract Background This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system. Methods Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine. Results Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P

Heterogeneity in contact patterns, mortality rates, and transmissibility among and between different age classes can have significant effects on epidemic outcomes. Adaptive behavior in response to the spread of an infectious pathogen may give rise to complex epidemiological dynamics. Here we model an infectious disease in which adaptive behavior incentives, and mortality rates, can vary between two and three age classes. The model indicates that age-dependent variability in infection aversion can produce more complex epidemic dynamics at lower levels of pathogen transmissibility and that those at less risk of infection can still drive complexity in the dynamics of those at higher risk of infection. Policymakers should consider the interdependence of such heterogeneous groups when making decisions.

Abstract Background Folates are crucial for the biosynthesis of nucleotides and amino acids, essential for cell proliferation and development. Folate deficiency induces DNA damage, developmental defects, and tumorigenicity. The obligatory enzyme folylpolyglutamate synthetase (FPGS) mediates intracellular folate retention via cytosolic and mitochondrial folate polyglutamylation. Our previous paper demonstrated the association of the cytosolic FPGS (cFPGS) with the cytoskeleton and various cell protrusion proteins. Based on these recent findings, the aim of the current study was to investigate the potential role of cFPGS at cell protrusions. Results Here we uncovered a central role for two G-quadruplex (GQ) motifs in the 3′UTR of FPGS mediating the localization of cFPGS mRNA and protein at cell protrusions. Using the MBSV6-loop reporter system and fluorescence microscopy, we demonstrate that following folate deprivation, cFPGS mRNA is retained in the endoplasmic reticulum, whereas upon 15 min of folate repletion, this mRNA is rapidly translocated to cell protrusions in a 3′UTR- and actin-dependent manner. The actin dependency of this folate-induced mRNA translocation is shown by treatment with Latrunculin B and inhibitors of the Ras homolog family member A (RhoA) pathway. Upon folate repletion, the FPGS 3′UTR GQs induce an amoeboid/mesenchymal hybrid cell phenotype during migration and invasion through a collagen gel matrix. Targeted disruption of the 3′UTR GQ motifs by introducing point mutations or masking them by antisense oligonucleotides abrogated cell protrusion targeting of cFPGS mRNA. Conclusions Collectively, the GQ motifs within the 3′UTR of FPGS regulate its transcript and protein localization at cell protrusions in response to a folate cue, inducing cancer cell invasive phenotype. These novel findings suggest that the 3′UTR GQ motifs of FPGS constitute an attractive druggable target aimed at inhibition of cancer invasion and metastasis.

Abstract Background Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research. Methods We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality. Results We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2–66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0–50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks. Conclusion These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Abstract Backgroud Root caries in aging population was prevalent worldwide. Due to the absence of enamel and specific structure of dentine, bacteria are able to penetrate further into dentine at an earlier stage of lesion development. The aim of this study was to investigate the effect of adding of a strontium-doped bioactive glass-ceramic (HX-BGC) to a fluoride-free toothpaste on prevention of formation of artificial dentine caries. Methods Thirty-six human tooth specimens were allocated to three groups (n = 12 per group). Group 1 treated with slurry containing a fluoride-free toothpaste and 5% HX-BGC, Group 2 was treated with fluoride-free toothpaste slurry, and Group 3 received deionized water as a negative control. The specimens were subjected to four cycles (15 h demineralization and 8 h remineralization for one cycle) of biochemical cycling. A mixed suspension of five bacteria species (Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Actinomyces naeslundii) were prepared in brain heart infusion broth with 5% sucrose and used as acidic challenge in biochemical cycling. Subsequently, surface morphology of the dentine lesion was assessed by scanning electron microscopy, while the lesion depths and mineral loss were assessed by micro-computed tomography. Results The mean lesion depths in dentine in Groups 1 to 3 were 87.79 ± 16.99 μm, 101.06 ± 10.04 μm and 113.60 ± 16.36 μm, respectively (p = 0.002). The mean amounts of mineral loss in Groups 1 to 3 were 0.82 ± 0.10 g/cm3, 0.89 ± 0.09 g/cm3 and 0.96 ± 0.11 g/cm3, respectively (p = 0.016). No obvious differences in the surface morphology were seen among the groups. Conclusion Addition of strontium-doped bioactive glass-ceramic to fluoride-free toothpaste has potential to reduce formation of dentine lesions.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is mediated by maternal alloantibodies, a consequence of immune sensitization during pregnancy with maternal-fetal incompatibility with ABO, Rhesus factor (Rh), and/or other red blood cell antigens. RhD, Kell, and other non-ABO alloantibodies are the primary cause of moderate to severe HDFN, whereas ABO HDFN is typically mild. HDFN live birth prevalence owing to Rh alloimmunization among newborns in the United States was last estimated to be 106 per 100,000 births in 1986. HDFN live birth prevalence owing to all alloantibodies was estimated to be 817 to 840 per 100,000 in Europe. There is a need for updated prevalence estimates in the United States and a better understanding of disease demographics, severity, and treatments. OBJECTIVE: This study aimed to estimate the live birth prevalence of HDFN and the proportion of severe cases of HDFN in the United States, to describe the associated risk factors, and to compare the clinical outcomes and treatments among healthy newborns, newborns with HDFN, and newborns who are sick without HDFN using a nationally representative hospital discharge database. STUDY DESIGN: In this retrospective, observational cohort study, we used data from the 1996 to 2010 National Hospital Discharge Survey to identify live births, defined by inpatient visits with the newborn flag, with and without a diagnosis of HDFN across 200 to 500 sampled hospitals (≥6 beds) per year. Patient and hospital characteristics, alloimmunization status, disease severity, treatment, and clinical outcomes were evaluated. Frequencies and weighted percentages were calculated for all variables. Logistic regression was used to compare the characteristics between newborns with HDFN and other newborns using odds ratios. RESULTS: Of 480,245 live births identified, 9810 HDFN cases were recorded. When weighted to the United States population, this corresponded to a live birth prevalence of 1695 per 100,000 live births. Compared with other newborns, newborns with HDFN were more likely to be female, Black, living in the South (vs the Midwest or West), and treated at larger (>100 beds) and government-owned hospitals. ABO and Rh alloimmunization accounted for 78.1% and 4.3% of newborns with HDFN, respectively, whereas HDFN caused by other antigens, such as Kell and Duffy, accounted for 17.6% of the cases. Among newborns with HDFN, 22% received phototherapy, 1% received simple transfusions, and 0.5% received exchange transfusions or intravenous immunoglobulin. Newborns affected by HDFN caused by Rh alloimmunization were more likely to require medical interventions, including simple or exchange transfusions, and more likely to be delivered by cesarean delivery. Overall, HDFN was associated with a longer hospital length of stay in the neonatal intensive care unit when compared with healthy and other sick newborns, a higher rate of cesarean delivery, and a higher rate of nonroutine discharge than healthy newborns. CONCLUSION: Overall, the live birth prevalence of HDFN was higher than those previously reported, whereas Rh-induced HDFN live birth prevalence was similar to those previously reported. HDFN live birth prevalence owing to Rh alloimmunization decreased over time, likely because of continued Rh immune globulin prophylaxis. Treatment patterns for newborns with HDFN and the comparative clinical outcomes when compared with healthy newborns confirm the continued clinical needs of this population.

The purpose of the study is to develop a novel peptide for caries management. Gallic-Acid-Polyphemusin-I (GAPI) was synthesised by grafting Polyphemusin I (PI) and gallic acid (GA). Biocompatibility was evaluated using a Cell Counting Kit-8 Assay. Antimicrobial properties were assessed using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). The bacterial and fungal morphology after GAPI treatment was investigated using transmission electron microscopy (TEM). The architecture of a consortium biofilm consisting of Streptococcus mutans, Lacticaseibacillus casei and Candida albicans was evaluated using scanning electron microscopy (SEM) and confocal laser scanning microscopy. The growth kinetics of the biofilm was examined using a propidium monoazide–quantitative polymerase chain reaction. The surface and calcium-to-phosphorus molar ratio of GAPI-treated enamel after pH cycling were examined with SEM and energy-dispersive X-ray spectroscopy. Enamel crystal characteristics were analysed using X-ray diffraction. Lesion depths representing the enamel’s mineral loss were assessed using micro-computed tomography. The MIC of GAPI against S. mutans, L. casei and C. albicans were 40 μM, 40 μM and 20 μM, respectively. GAPI destroyed the biofilm’s three-dimensional structure and inhibited the growth of the biofilm. SEM showed that enamel treated with GAPI had a relatively smooth surface compared to that treated with water. The calcium-to-phosphorus molar ratio of enamel treated with GAPI was higher than that of the control. The lesion depths and mineral loss of the GAPI-treated enamel were less than the control. The crystallinity of the GAPI-treated enamel was higher than the control. This study developed a biocompatible, mineralising and antimicrobial peptide GAPI, which may have potential as an anti-caries agent.

This study aimed to investigate the antibiofilm and remineralising effects of peptide GAPI on artificial dentin caries. After creating artificial carious lesions, eighty dentine blocks were randomly assigned for treatment twice daily with GAPI (GAPI group) or deionised water (control group). Both groups underwent a 7-day biochemical cycle. Scanning electron microscopy (SEM) showed S. mutans with damaged structures that partially covered the dentine in the GAPI group. The dead–live ratios for the GAPI and control groups were 0.77 ± 0.13 and 0.37 ± 0.09 (p < 0.001). The log colony-forming units for the GAPI and control groups were 7.45 ± 0.32 and 8.74 ± 0.50 (p < 0.001), respectively. The lesion depths for the GAPI and control groups were 151 ± 18 µm and 214 ± 15 µm (p < 0.001), respectively. The mineral losses for the GAPI and control groups were 0.91 ± 0.07 gHAcm−3 and 1.01 ± 0.07 gHAcm−3 (p = 0.01), respectively. The hydrogen-to-amide I ratios for the GAPI and control groups were 2.92 ± 0.82 and 1.83 ± 0.73 (p = 0.014), respectively. SEM micrographs revealed fewer exposed dentine collagen fibres in the GAPI group compared to those in the control group. Furthermore, X-ray diffraction (XRD) patterns indicated that the hydroxyapatite in the GAPI group was more crystallised than that in the control group. This study demonstrated GAPI’s antibiofilm and remineralising effects on artificial dentin caries.

Abstract Background Fishes are the one of the most diverse groups of animals with respect to their modes of sex determination, providing unique models for uncovering the evolutionary and molecular mechanisms underlying sex determination and reversal. Here, we have investigated how sex is determined in a species of both commercial and ecological importance, the Siamese fighting fish Betta splendens. Results We conducted association mapping on four commercial and two wild populations of B. splendens. In three of the four commercial populations, the master sex determining (MSD) locus was found to be located in a region of ~ 80 kb on LG2 which harbours five protein coding genes, including dmrt1, a gene involved in male sex determination in different animal taxa. In these fish, dmrt1 shows a male-biased gonadal expression from undifferentiated stages to adult organs and the knockout of this gene resulted in ovarian development in XY genotypes. Genome sequencing of XX and YY genotypes identified a transposon, drbx1, inserted into the fourth intron of the X-linked dmrt1 allele. Methylation assays revealed that epigenetic changes induced by drbx1 spread out to the promoter region of dmrt1. In addition, drbx1 being inserted between two closely linked cis-regulatory elements reduced their enhancer activities. Thus, epigenetic changes, induced by drbx1, contribute to the reduced expression of the X-linked dmrt1 allele, leading to female development. This represents a previously undescribed solution in animals relying on dmrt1 function for sex determination. Differentiation between the X and Y chromosomes is limited to a small region of ~ 200 kb surrounding the MSD gene. Recombination suppression spread slightly out of the SD locus. However, this mechanism was not found in the fourth commercial stock we studied, or in the two wild populations analysed, suggesting that it originated recently during domestication. Conclusions Taken together, our data provide novel insights into the role of epigenetic regulation of dmrt1 in sex determination and turnover of SD systems and suggest that fighting fish are a suitable model to study the initial stages of sex chromosome evolution.

Drought stress is a major environmental hazard. Stomatal development is highly responsive to abiotic stress and has been used as a cellular marker for drought-tolerant crop selection. C3 and C4 crops have evolved into different photosynthetic systems and physiological responses to water deficits. The genome sequences of maize, sorghum, and sugarcane make it possible to explore the association of the stomatal response to drought stress with the evolution of the key stomatal regulators. In this study, phylogenic analysis, gene expression analysis and stomatal assay under drought stress were used to investigate the drought tolerance of C3 and C4 plants. Our data shows that C3 and C4 plants exhibit different drought responses at the cellular level. Drought represses the growth and stomatal development of C3 crops but has little effect on that of C4 plants. In addition, stomatal development is unresponsive to drought in drought-tolerant C3 crops but is repressed in drought-tolerant C4 plants. The different developmental responses to drought in C3 and C4 plants might be associated with the divergent expression of their SPEECHLESS genes. In particular, C4 crops have evolved to generate multiple SPEECHLESS homologs with different genetic structure and expression levels. Our research provides not only molecular evidence that supports the evolutionary history of C4 from C3 plants but also a possible molecular model that controls the cellular response to abiotic stress in C3 and C4 crops.

Abstract Background Methicillin-resistance S. aureus (MRSA) possesses the ability to resist multiple antibiotics and form biofilm. Currently, vancomycin remains the last drug of choice for treatment of MRSA infection. The emergence of vancomycin-resistant S. aureus (VRSA) has necessitated the development of new therapeutic agents against MRSA. In this study, the antimicrobial and antibiofilm activities of two copper-complexes derived from Schiff base (SBDs) were tested individually, and in combination with oxacillin (OXA) and vancomycin (VAN) against reference strains methicillin-susceptible and methicillin-resistant Staphylococcus aureus. The toxicity of the SBDs was also evaluated on a non-cancerous mammalian cell line. Methods The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay. Results The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells. Conclusion Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.

A novel antimicrobial peptide, GAPI, has been developed recently by grafting gallic acid (GA) to polyphemusin I (PI). The objective of this study was to investigate the antibacterial effects of GAPI on common oral pathogens. This laboratory study used minimum inhibitory concentrations and minimum bactericidal concentrations to assess the antimicrobial properties of GAPI against common oral pathogens. Transmission electron microscopy was used to examine the bacterial morphology both before and after GAPI treatment. The results showed that the minimum inhibitory concentration ranged from 20 μM (Lactobacillus rhamnosus) to 320 μM (Porphyromonas gingivalis), whereas the minimum bactericidal concentration ranged from 80 μM (Lactobacillus acidophilus) to 640 μM (Actinomyces naeslundii, Enterococcus faecalis, and Porphyromonas gingivalis). Transmission electron microscopy showed abnormal curvature of cell membranes, irregular cell shapes, leakage of cytoplasmic content, and disruption of cytoplasmic membranes and cell walls. In conclusion, the GAPI antimicrobial peptide is antibacterial to common oral pathogens, with the potential to be used to manage oral infections.

Salvia hispanica (chia) is a highly nutritious food source and has gained popularity due to its high omega-3 fatty acid content. Red spider mites are a serious problem in the production of S. hispanica. However, no study has been conducted to analyze the defensive response to the infestation of red spider mites in S. hispanica. To elucidate the molecular mechanisms of the defensive response of S. hispanica to red spider mites, we performed a transcriptomic analysis of S. hispanica when infested by red spider mites. In the comparative assessment of leaf transcriptomes, a total of 1743 differentially expressed genes (DEGs) were identified between control and mite-infested S. hispanica. From these, 1208 (69%) transcripts were upregulated and 535 (31%) were downregulated. The DEGs included transcription factors, defense hormones, and secondary metabolites that were either suppressed or activated in response to spider mite herbivory. Gene Ontology (GO) enrichment analysis revealed that plant secondary metabolites, such as glucosinolates, and signaling pathways, including the jasmonic acid signaling pathway, may play an important role in the defense against red spider mites. This study provides novel insights into the defense response of S. hispanica to insect herbivory and could be a resource for the improvement of pest resistance in the chia.

With less than 10% of 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal types of cancer. Current literature supports that gemcitabine is the first-line treatment of PDAC. However, poor cellular penetration of gemcitabine along with the acquired and intrinsic chemoresistance of tumor against it often reduced its efficacy and hence necessitates the administration of high gemcitabine dose during chemotherapy. Photodynamic therapy (PDT), a more selective and minimally invasive treatment, may be used synergistically with gemcitabine to reduce the doses utilized and dose-related side effects. This study reports the synergistic use of Re(I) bisquinolinyl complex, a transition metal complex photosensitizer with gemcitabine against PDAC. Re(I) bisquinolinyl complex was found to act synergistically with gemcitabine against PDAC in vitro at various ratios. With the aim to enhance cellular uptake and therapeutic efficiency, the Re(I) bisquinolinyl complex and gemcitabine were encapsulated into liquid crystalline nanoparticles (LCNPs) system. The formulations were found to produce homogeneous drug-loaded LCNPs (average size: 159–173 nm, zeta potential +1.06 to −10 mV). Around 70% of gemcitabine and 90% of the Re(I) bisquinolinyl complex were found to be entrapped efficiently in the formulated LCNPs. The release rate of gemcitabine or/and the Re(I) bisquinolinyl complex loaded into LCNPs was evaluated in vitro, and the hydrophilic gemcitabine was released at a faster rate than the lipophilic Re(I) complex. LCNPs loaded with gemcitabine and Re(I) bisquinolinyl complex in a 1:1 ratio illustrated the best anti-cancer activity among the LCNP formulations (IC50 of BxPC3: 0.15 μM; IC50 of SW 1990: 0.76 μM) through apoptosis. The current findings suggest the potential use of transition metal-based photosensitizer as an adjunctive agent for gemcitabine-based chemotherapy against PDAC and the importance of nano-formulation in such application.

To help prepare students to address future challenges in Science, Technology, Engineering, and Mathematics (STEM), they need to develop 21st-century skills. These skills are mediated by their beliefs about the nature of scientific knowledge and practices, or epistemological beliefs. One approach shown to support students’ development of these beliefs and skills is problem-based instruction (PBI), which encourages collaborative self-directed learning while working on open-ended problems. We used a mixed-method qualitative approach to examine how implementing PBI in a physics course taught at a Dutch university affected students’ beliefs about physics and learning physics. Analysis of the responses to the course surveys (41–74% response rates) from the first implementation indicated students appreciated opportunities for social interactions with peers and use of scientific equipment with PBI but found difficulties connecting to the Internet given the COVID-19 restrictions. The Colorado Learning Attitudes towards Science Survey (CLASS), a validated survey on epistemological beliefs about physics and learning physics, was completed by a second cohort of students in a subsequent implementation of PBI for the same course; analysis of the students’ pre- and post-responses (28% response rate) showed a slight shift towards more expert-like perspectives despite challenges (e.g., access to lab). Findings from this study may inform teachers with an interest in supporting the development of students’ epistemological beliefs about STEM and the implementation of PBI in undergraduate STEM courses.

Abstract Background Breast cancer is the leading cancer affecting women in Singapore. Its survivors commonly experience decline in physical function and quality of life post-mastectomy, due to their upper limb morbidity and wound issues. Rehabilitation can address the aforementioned issues. When rehabilitation is accessible and easy to adhere, it can optimize recovery. Home-based tele-rehabilitation guided by healthcare professionals and self-managed by patients can potentially optimize the patients’ adherence to rehabilitation and recovery. With that in mind, a team of breast cancer specialists (oncologists, nurses, and therapists) in Singapore has developed one of the first tele-rehabilitation systems for local women undergoing a unilateral mastectomy. To our knowledge, no such systems have been evaluated or proven effective as a treatment option among local breast cancer patients with acute disabilities. Methods This is a pilot quasi-experimental trial that aims to evaluate the feasibility of tele-rehabilitation and tele-drain care compared to usual care. Up to 40 patients (20 per group) will be recruited for this trial. They will be assigned to an intervention group that receives rehabilitation via a tele-rehabilitation system or a control group that receives rehabilitation in person at their clinic. The primary outcome of this trial is rehabilitation participation (i.e., the time spent on rehabilitation). The secondary outcomes are upper extremity functioning, perceived health, and quality of life. Discussion As part of this pilot trial, patients who opt in for the tele-rehabilitation will be asked to share their experience with and thoughts on the tele-rehabilitation system. With the evidence obtained from the tele-rehabilitation patients of this trial, we will be able to improve the current system for our future trial. Further, our additional data on rehabilitation participation, physical function, and quality of life will help us design a sufficiently powered future main trial. Trial registration The trial was approved by the National Healthcare Group’s Domain Specific Review Board (#2019/00283) and registered with www.ClinicalTrials.gov (# NCT04269967 ) in February 2020.

As soon as saliva contacts the teeth surface, salivary proteins adhere to the tooth surface to form acquired salivary pellicle. The formation of this acquired salivary pellicle is a dynamic and selective process of macromolecular adsorption and desorption. Although acquired salivary pellicle contains proteins and peptides, it also contains lipids, and other macro-molecules, all of which contribute to its protective properties. Acquired salivary pellicle is related to the development of common oral diseases, such as erosion, dental caries, and periodontal disease. Acquired salivary pellicle acts as a natural barrier to prevent a tooth's surface from making direct contact with acids and to protect it from erosive demineralization. It contributes to the control of dental erosion by modulating calcium and phosphate concentrations on the tooth surface. It also influences the initial colonizer of oral biofilm and affects the transportation pathway of the acidic products of cariogenic bacteria, which affects the development of dental caries. In addition, it influences periodontal disease by acting on the colonization of periodontal pathogens. This paper's aim is to provide an overview of the acquired salivary pellicle, highlighting its composition, structure, function, role in common oral diseases, and modification for the prevention of oral diseases.

Abstract Background Acute myeloid leukemia (AML) remains a devastating disease with a 5-year survival rate of less than 30%. AML treatment has undergone significant changes in recent years, incorporating novel targeted therapies along with improvements in allogeneic bone marrow transplantation techniques. However, the standard of care remains cytarabine and anthracyclines, and the primary hindrance towards curative treatment is the frequent emergence of intrinsic and acquired anticancer drug resistance. In this respect, patients presenting with chemoresistant AML face dismal prognosis even with most advanced therapies. Herein, we aimed to explore the potential implementation of the characterization of chemoresistance mechanisms in individual AML patients towards efficacious personalized medicine. Methods Towards the identification of tailored treatments for individual patients, we herein present the cases of relapsed AML patients, and compare them to patients displaying durable remissions following the same chemotherapeutic induction treatment. We quantified the expression levels of specific genes mediating drug transport and metabolism, nucleotide biosynthesis, and apoptosis, in order to decipher the molecular mechanisms underlying intrinsic and/or acquired chemoresistance modalities in relapsed patients. This was achieved by real-time PCR using patient cDNA, and could be readily implemented in the clinical setting. Results This analysis revealed pre-existing differences in gene expression levels between the relapsed patients and patients with lasting remissions, as well as drug-induced alterations at different relapse stages compared to diagnosis. Each of the relapsed patients displayed unique chemoresistance mechanisms following similar treatment protocols, which could have been missed in a large study aimed at identifying common drug resistance determinants. Conclusions Our findings emphasize the need for standardized evaluation of key drug transport and metabolism genes as an integral component of routine AML management, thereby allowing for the selection of treatments of choice for individual patients. This approach could facilitate the design of efficacious personalized treatment regimens, thereby reducing relapse rates of therapy refractory disease.

Abstract Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.

Abstract Background Silver diamine fluoride (SDF) solution gains increasing popularity in arresting dentine caries in clinical practice. The aim of this systematic review was to summarize the findings from laboratory studies on the influence of SDF application on the bond strength of dentine to various adhesives and to glass ionomer cements (GICs). Methods Two independent reviewers conducted a literature search in the databases Medline, Ovid, PubMed and Web of Science until 15th August 2019 using the search keywords [‘bond strength’] AND [‘silver diamine fluoride’ OR ‘silver diammine fluoride’ OR ‘SDF’ OR ‘silver fluoride’ OR ‘diamine silver fluoride’]. Articles investigating the effect of SDF application on the bond strength of dentine to various adhesives and to GICs were included in this review. Information on how SDF application influenced the bond strength was extracted from the included articles. Besides, related information, e.g. test method of bond strength, concentration and brand of SDF, type of adhesive system and GIC, testing dental substrate, protocol of specimen preparation, and failure mode was also reviewed. Results A total of 13 articles were included in this review, with 8 and 6 studies investigating the effect of SDF application on the bond strength of dentine to various adhesives and to GICs, respectively. Sound dentine as well as demineralized dentine created by chemical methods, e.g. immersing in a demineralizing solution, was commonly adopted as the testing dental substrate. The microtensile bond strength (mTBS) test was the predominant method employed. However, the bond strength values had large variations among studies, ranging from

Abstract Background This study investigated the remineralisation effect of bioactive glass on artificial dentine caries. Methods Dentine disks with artificial caries were treated with bioactive glass (group BAG), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) (group CPP-ACP), sodium fluoride glycerol (group F) or deionized water (group W). All disks were subjected to pH cycling for 28 days subsequently. The topography, microhardness and remineralisation depth of the dentine carious lesion were assessed by atomic force microscopy (AFM), microhardness testing and confocal laser scanning microscope (CLSM), respectively. Results AFM images indicated mineral depositions on the surface of the carious lesion in group BAG. The changes of Vickers hardness number (ΔVHN, mean ± SD) after pH cycling were 9.67 ± 3.60, 6.06 ± 3.83, 5.00 ± 2.19 and − 1.90 ± 2.09 (p

Researchers have developed novel bioactive materials for caries management. Many clinicians also favour these materials, which fit their contemporary practice philosophy of using the medical model of caries management and minimally invasive dentistry. Although there is no consensus on the definition of bioactive materials, bioactive materials in cariology are generally considered to be those that can form hydroxyapatite crystals on the tooth surface. Common bioactive materials include fluoride-based materials, calcium- and phosphate-based materials, graphene-based materials, metal and metal-oxide nanomaterials and peptide-based materials. Silver diamine fluoride (SDF) is a fluoride-based material containing silver; silver is antibacterial and fluoride promotes remineralisation. Casein phosphopeptide-amorphous calcium phosphate is a calcium- and phosphate-based material that can be added to toothpaste and chewing gum for caries prevention. Researchers use graphene-based materials and metal or metal-oxide nanomaterials as anticaries agents. Graphene-based materials, such as graphene oxide-silver, have antibacterial and mineralising properties. Metal and metal-oxide nanomaterials, such as silver and copper oxide, are antimicrobial. Incorporating mineralising materials could introduce remineralising properties to metallic nanoparticles. Researchers have also developed antimicrobial peptides with mineralising properties for caries prevention. The purpose of this literature review is to provide an overview of current bioactive materials for caries management.

Dental caries is one of the most common human diseases which can occur in both primary and permanent dentitions throughout the life of an individual. Hydroxyapatite is the major inorganic component of human teeth, consequently, nanosized hydroxyapatite (nHAP) has recently attracted researchers’ attention due to its unique properties and potential for caries management. This article provides a contemporary review of the potential beneficial effects of nHAP on caries lesions demonstrated in in vitro studies. Data showed that nHAP has potential to promote mineralization in initial caries, by being incorporated into the porous tooth structure, which resulted from the caries process, and subsequently increased mineral content and hardness. Notably, it is the particle size of nHAP which plays an important role in the mineralization process. Antimicrobial effects of nHAP can also be achieved by metal substitution in nHAP. Dual action property (mineralizing and antimicrobial) and enhanced chemical stability and bioactivity of nHAP can potentially be obtained using metal-substituted fluorhydroxyapatite nanoparticles. This provides a promising synergistic strategy which should be explored in further clinical research to enable the development of dental therapeutics for use in the treatment and management of caries.

The objective of this study was to review the design methods that have been used to create peptides for use in caries management. Two independent researchers systematically reviewed many in vitro studies in which peptides were designed for use in caries management. They assessed the risk of bias in the included studies. This review identified 3592 publications, of which 62 were selected. Forty-seven studies reported 57 antimicrobial peptides. Among them, 31 studies (66%, 31/47) used the template-based design method; 9 studies (19%, 9/47) used the conjugation method; and 7 studies (15%, 7/47) used other methods, such as the synthetic combinatorial technology method, the de novo design method and cyclisation. Ten studies reported mineralising peptides. Seven of these (70%, 7/10) used the template-based design method, two (20%, 2/10) used the de novo design method, and one study (10%, 1/10) used the conjugation method. In addition, five studies developed their own peptides with antimicrobial and mineralising properties. These studies used the conjugation method. Our assessment for the risk of bias in the 62 reviewed studies showed that 44 publications (71%, 44/62) had a medium risk and that 3 publications had a low risk (5%, 3/62). The two most common methods for developing peptides for use in caries management that were used in these studies were the template-based design method and the conjugation method.

Objective: Researchers are studying the use of antimicrobial peptides as functional biomaterials to prevent and treat dental caries. This study aims to investigate the global research interest in antimicrobial peptides for caries management. Methods: Two independent investigators systematically searched with keywords (‘Caries’ OR ‘Dental caries’) AND (‘Antimicrobial peptide’ OR ‘AMP’ OR ‘Statherin’ OR ‘Histatin’ OR ‘Defensin’ OR ‘Cathelicidin’) on Web of Science, PubMed and Scopus. They removed duplicate publications and screened the titles and abstracts to identify relevant publications. The included publications were summarized and classified as laboratory studies, clinical trials or reviews. The citation count and citation density of the three publication types were compared using a one-way analysis of variance. The publications’ bibliometric data were analyzed using the Bibliometrix program. Results: This study included 163 publications with 115 laboratory studies (71%), 29 clinical trials (18%) and 19 reviews (11%). The number of publications per year have increased steadily since 2002. The citation densities (mean ± SD) of laboratory study publications (3.67 ± 2.73) and clinical trial publications (2.63 ± 1.85) were less than that of review articles (5.79 ± 1.27) (p = 0.002). The three publication types had no significant difference in citation count (p = 0.54). Most publications (79%, 129/163) reported the development of a novel antimicrobial peptide. China (52/163, 32%) and the US (29/163, 18%) contributed to 50% (81/163) of the publications. Conclusion: This bibliometric analysis identified an increasing trend in global interest in antimicrobial peptides for caries management since 2002. The main research topic was the development of novel antimicrobial peptides. Most publications were laboratory studies, as were the three publications with the highest citation counts. Laboratory studies had high citation counts, whereas reviews had high citation density.

Graphene is a single-layer two-dimensional carbon-based nanomaterial. It presents as a thin and strong material that has attracted many researchers’ attention. This study provides a concise review of the potential application of graphene materials in caries and periodontal disease management. Pristine or functionalized graphene and its derivatives exhibit favorable physicochemical, mechanical, and morphological properties applicable to biomedical applications. They can be activated and functionalized with metal and metal nanoparticles, polymers, and other small molecules to exhibit multi-differentiation activities, antimicrobial activities, and biocompatibility. They were investigated in preventive dentistry and regenerative dentistry. Graphene materials such as graphene oxide inhibit cariogenic microbes such as Streptococcus mutans. They also inhibit periodontal pathogens that are responsible for periodontitis and root canal infection. Graphene-fluorine promotes enamel and dentin mineralization. These materials were also broadly studied in regenerative dental research, such as dental hard and soft tissue regeneration, as well as periodontal tissue and bone regeneration. Graphene oxide-based materials, such as graphene oxide-fibroin, were reported as promising in tissue engineering for their biocompatibility, bioactivity, and ability to enhance cell proliferation properties in periodontal ligament stem cells. Laboratory research showed that graphene can be used exclusively or by incorporating it into existing dental materials. The success of laboratory studies can translate the application of graphene into clinical use.

The aim of this study was to describe the changes in oral health policies and guidelines in response to the Coronavirus disease 2019 (COVID-19) pandemic in different countries and regions around the world. Information on oral health policies and guidelines from 9 countries (Canada, China including Hong Kong, Egypt, India, Japan, New Zealand, Nigeria, Switzerland, and Thailand) were summarized, and sources of the information were mostly the national or regional health authorities and/or dental council/associations. The changes made to the oral health guidelines depended on the severity of the COVID-19 pandemic. This included suspension of non-emergency dental care services at the peak of the COVID-19 outbreak, and easing the restrictions on non-essential and elective dental care when the pandemic became under control. The COVID-19 risk mitigation strategies include strict adherence to infection control practices (use of hand sanitizers, facemask and maintaining social distancing), reducing the amount of aerosol production in the dental setting, and managing the quality of air in the dental treatment rooms by reducing the use of air conditioners and improving air exchange. The COVID-19 pandemic has shown a major impact on dental practice. Dental professionals are trying to adapt to the new norms, while the medium to long-term impact of COVID-19 on dentistry needs further investigation.

Oil palm is the most productive oil producing plant. Salt stress leads to growth damage and a decrease in yield of oil palm. However, the physiological responses of oil palm to salt stress and their underlying mechanisms are not clear. RNA-Seq was conducted on control and leaf samples from young palms challenged under three levels of salts (100, 250, and 500 mM NaCl) for 14 days. All three levels of salt stress activated EgSPCH expression and increased stomatal density of oil palm. Around 41% of differential expressed genes (DEGs) were putative EgSPCH binding target and were involved in multiple bioprocesses related to salt response. Overexpression of EgSPCH in Arabidopsis increased the stomatal production and lowered the salt tolerance. These data indicate that, in oil palm, salt activates EgSPCH to generate more stomata in response to salt stress, which differs from herbaceous plants. Our results might mirror the difference of salt-induced stomatal development between ligneous and herbaceous crops.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.