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Asma M Al-Jobair,1,2 Laila F Baidas,1,2 Anfal A Al-Hamid,2 Sara G Al-Qahtani,2 Amani T Al-Najjar,2 Huda M Al-Kawari1,2 1Department of Pediatric Dentistry and Orthodontics, 2College of Dentistry, King Saud University, Riyadh, Saudi Arabia Objective: To assess and compare the severity of malocclusion and orthodontic treatment need among young Saudis receiving free treatment at public dental practices versus those paying for treatment at private practices. Materials and methods: This retrospective study evaluated the records of 300 patients (179 females, 121 males; age 13–21 years) treated at orthodontic clinics from 2013 through 2015. The public sample was selected from orthodontic clinics at the College of Dentistry, King Saud University (KSU); the private sample was selected from five private orthodontic clinics in Riyadh, Saudi Arabia. The records were examined for the severity of malocclusion and for orthodontic treatment need using the Dental Health Component of the Index of Orthodontic Treatment Need. The prevalence of each occlusal discrepancy and the Dental Health Component grade were recorded. The severity of malocclusion and orthodontic treatment need were compared between practice types, age groups, and sexes with the chi-square test. Results: Displacement, increased overjet, and Class II and III malocclusion were the most common orthodontic problems in this study. Patients attending public clinics at KSU generally had more severe malocclusion than the patients attending private clinics. Seventy-seven percent of orthodontically treated patients at KSU clinics were in great need of treatment, compared with 58.5% of patients treated at private clinics (P=0.003). Among the patients with great treatment need, approximately 62% of male patients and 70% of patients ≤16 years of age were treated at KSU clinics, compared with 38% and 48%, respectively, treated at private clinics (P

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation (> 5% of liver tissue) in the absence of alcohol abuse or other chronic liver diseases. NAFLD can progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This study aimed to assess the efficacy of probiotic (lactobacillus) supplementation on NAFLD fibrosis score., Methodology: A double-arm randomized controlled trial was conducted in the family medicine clinic of a tertiary hospital, enrolling patients with sonographic evidence of NAFLD. Fifty patients were divided into two groups: the Probiotic group received lifestyle modification instructions along with daily probiotic supplementation for twelve weeks, with regular monthly follow-up visits. The Standard Treatment group received low-fat diet and lifestyle modification instructions only., Results: The mean age of participants was 46.10 years (SD 10.11), with 70% females and 30% males. The study found a statistically significant difference in liver enzymes (ALT and AST) and BMI in the probiotic group before and after intervention. However, there was no significant difference in NAFLD fibrosis score between the two groups., Conclusion: Short-term probiotic treatment resulted in improvements in ALT, AST, and BMI in the probiotic group, but did not significantly affect NAFLD fibrosis score. Further research with larger sample sizes and longer follow-up periods is warranted., Trial Registration: The clinical trial was registered at Protocol Registration and Results System with number NCT06074094 (12/09/2021)., (© 2024. The Author(s).)

Background/Objectives: This review aims to provide a detailed understanding of the current evidence on Alpinia officinarum Hance ( A. officinarum ) and its potential therapeutic role in central nervous system (CNS) disorders. CNS disorders encompass a wide range of disorders affecting the brain and spinal cord, leading to various neurological, cognitive and psychiatric impairments. In recent years, natural products have emerged as potential neuroprotective agents for the treatment of CNS disorders due to their outstanding bioactivity and favourable safety profile. One such plant is A. officinarum , also known as lesser galangal, a perennial herb from the Zingiberaceae family. Its phytochemical compounds such as flavonoids and phenols have been documented to have a powerful antioxidants effect, capable of scavenging free radicals and preventing oxidative damage. Methods: In this review, we critically evaluate the in vitro and in vivo studies and examine the mechanisms by which A. officinarum exerts its neuroprotective effect. Results: Several studies have confirmed that A. officinarum exerts its neuroprotective effects by reducing oxidative stress and cell apoptosis, promoting neurite outgrowth, and modulating neurotransmitter levels and signalling pathways. Conclusions: Although previous studies have shown promising results in various models of neurological disorders, the underlying mechanisms of A. officinarum in Alzheimer's (AD) and Parkinson's disease (PD) are still poorly understood. Further studies on brain tissue and cognitive and motor functions in animal models of AD and PD are needed to validate the results observed in in vitro studies. In addition, further clinical studies are needed to confirm the safety and efficacy of A. officinarum in CNS disorders.

This study aims to investigate the effect of a supraphysiological dose of testosterone on the levels of sex steroid hormones and the expression and distribution of sex steroid receptors in the uterus during the endometrial receptivity development period. In this study, adult female Sprague-Dawley rats ( n = 24) were subcutaneously administered 1 mg/kg/day of testosterone alone or in combination with the inhibitors (finasteride or anastrozole or both) from day 1 to day 3 post-coitus, while a group of six untreated rats served as a control group. The rats were sacrificed on the evening of post-coital day 4 of to measure sex steroid hormone levels by ELISA. Meanwhile, gene expression and protein distribution of sex steroid receptors were analysed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. In this study, treatment with a supraphysiological dose of testosterone led to a significant reduction in oestrogen and progesterone levels compared to the control. The mRNA expression of the androgen receptor increased significantly in all treatment groups, while the mRNA expression of both the progesterone receptor and the oestrogen receptor-α decreased significantly in all treatment groups. The IHC findings of all sex steroid receptors were coherent with all mRNAs involved. This study shows that a supraphysiological dose of testosterone was able to interrupt the short period of the implantation window. This finding could serve as a basis for understanding the role of testosterone in endometrial receptivity in order to develop further therapeutic approaches targeting androgen-mediated disorders of endometrial receptivity.

Advanced atherosclerosis is linked to plaque instability, which can result in rupture and the onset of a heart attack. Evidence gathered from human atheroma plaques indicates that intraplaque neovascularization poses a risk to plaque stability and may lead to plaque hemorrhage. Hence, targeting the neovascularization within the atheroma plaque has the potential to mitigate the plaque's vulnerability. While neovascularization has been extensively explored in the context of cancer, research on pharmacological inhibition of this phenomenon in atherosclerosis remains limited. This systematic review aimed to comprehensively assess current and emerging pharmacological interventions for inhibiting intraplaque neovascularization in preclinical settings. Electronic databases (Web of Science, PubMed, Scopus, and Ovid) were searched from January 2013 until February 1, 2024. Preclinical studies reporting the effect of any pharmacological interventions targeting intraplaque neovascularization were included. A total of 10 articles involving in vivo animal studies were eligible for inclusion, with five of them incorporating in vitro experiments to complement their in vivo findings. The pharmacological interventions studied were axitinib, ghrelin, K5, rosuvastatin, atorvastatin, 3PO, everolimus, melatonin, Si-Miao-Yong-A, and protocatechuic aldehyde. All the interventions showed a positive impact in inhibiting intraplaque neovascularization in various atherosclerotic animal models through various signaling pathways. This review provides valuable insights into pharmacological approaches to attenuate intraplaque neovascularization that could serve as a promising therapeutic avenue to enhance plaque stability., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) is the leading cause of death globally and is a heart condition involving insufficient blood supply to the heart muscle due to atherosclerotic plaque formation. Atherosclerosis is a chronic disease in which plaques, made up of fat, cholesterol, calcium, and other substances, build up on the inner walls of arteries. Recently, there has been growing interest in finding reliable biomarkers to understand the pathogenesis and progression of atherosclerosis. Tissue Inhibitors of Metalloproteinases (TIMPs) have emerged as potential candidates for monitoring atherosclerotic development. TIMPs are a family of endogenous proteins that regulate matrix metalloproteinases (MMPs), enzymes involved in remodeling the extracellular matrix. A systematic search using Prisma guidelines was conducted and eleven studies were selected from four different databases: Web of Science (WOS), Scopus, Ovid, and PubMed. The Newcastle-Ottawa Scale (NOS) score was used to assess the risk of bias for each study. A meta-analysis was performed, and the hazard ratio (HR) and its 95% confidence interval (CI) were determined. Among the eleven studies, six reported a positive association between higher levels of TIMPs and an increased risk of atherosclerosis. Conversely, four studies support low TIMPs with high CAD risk and one study showed no significant association between TIMP-2 G-418C polymorphism and CAD. This divergence in findings underscores the complexity of the relationship between TIMPs, atherosclerosis, and CAD. In addition, a meta-analysis from two studies yielded a HR (95% CI) of 1.42 (1.16-1.74; p < 0.001; I 2 = 0%) for TIMP-2 in predicting major adverse cardiovascular events (MACEs). In conclusion, the existing evidence supports the notion that TIMPs can serve as biomarkers for predicting the severity of atherosclerosis, myocardial damage, and future MACEs among CAD patients. However, further exploration is warranted through larger-scale human studies, coupled with in vitro and in vivo investigations.

Throughout the educational system, students experiencing active learning pedagogy perform better and fail less than those taught through direct instruction. Can this be ascribed to differences in learning from a neuroscientific perspective? This review examines mechanistic, neuroscientific evidence that might explain differences in cognitive engagement contributing to learning outcomes between these instructional approaches. In classrooms, direct instruction comprehensively describes academic content, while active learning provides structured opportunities for learners to explore, apply, and manipulate content. Synaptic plasticity and its modulation by arousal or novelty are central to all learning and both approaches. As a form of social learning, direct instruction relies upon working memory. The reinforcement learning circuit, associated agency, curiosity, and peer-to-peer social interactions combine to enhance motivation, improve retention, and build higher-order-thinking skills in active learning environments. When working memory becomes overwhelmed, additionally engaging the reinforcement learning circuit improves retention, providing an explanation for the benefits of active learning. This analysis provides a mechanistic examination of how emerging neuroscience principles might inform pedagogical choices at all educational levels., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Southern Asian flowers offer honeybees a diversity of nectar. Based on its geographical origin, honey quality varies. Traditional methods are less authentic than DNA-based identification. The origin of honey is determined by pollen, polyphenolic, and macro-microorganisms. In this study, amplicon sequencing targets macro-microorganisms in eDNA using the ITS1 region to explore honey's geographical location and authentication. The variety of honey samples was investigated using ITS1 with Illumina sequencing. For all four honey samples, raw sequence reads showed 979,380 raw ITS1 amplicon reads and 375 ASVs up to the phylum level. The highest total number of 202 ASVs up to phylum level identified Bali honey with 211,189 reads, followed by Banggi honey with 309,207 a total number of 111 ASVs, and Lombok represents only 63 ASVs up to phylum level with several read 458,984. Based on Shannon and Chao1, honey samples from Bali (B2) and (B3) exhibited higher diversity than honey from Lombok (B1) and green honey from Sabah (B4), while the Simpson index showed that Banggi honey (B4) had higher diversity. Honey samples had significant variance in mycobiome taxonomic composition and abundance. Zygosaccharomyces and Aspergillus were the main genera found in Lombok honey, with percentages of 68.81% and 29.76% respectively. Bali honey samples (B2 and B3) were identified as having a significant amount of the genus Aureobasidium, accounting for 40.81% and 25% of the readings, respectively. The microbiome composition of Banggi honey (B4) showed a high presence of Zygosaccharomyces 45.17% and Aureobasidium 35.24%. The ITS1 analysis effectively distinguishes between honey samples of different origins and its potential as a discriminatory tool for honey origin and authentication purposes., (© 2024. The Author(s).)

Greater personalization of cancer medicine continues to shape therapy development and patient selection accordingly. The treatment of prostate cancer has evolved considerably since the discovery of androgen deprivation therapy. The comprehensive profiling of the prostate cancer genome has mapped the targetable molecular landscape of the disease and identified opportunities for the implementation of novel and combination therapies. In this review, we provide an overview of the molecular biology of prostate cancer and tools developed to aid prognostication and prediction of therapy benefit. Modern treatment of advanced prostate cancer is reviewed as a paradigm of increasing precision-informed approach to patient care, and must be considered on a global scale with respect to the state of science and care delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Angiotensin-converting enzyme (ACE) plays a crucial role in the pathogenesis of hypertension. Piper sarmentosum Roxb., an herb known for its antihypertensive effect, lacks a comprehensive understanding of the mechanism underlying its antihypertensive action. This study aimed to elucidate the antihypertensive mechanism of aqueous extract of P. sarmentosum leaves (AEPS) via its modulation of the ACE pathway in phorbol 12-myristate-13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs). HUVECs were divided into five groups: control, treatment with 200 µg/mL AEPS, induction 200 nM PMA, concomitant treatment with 200 nM PMA and 200 µg/mL AEPS, and treatment with 200 nM PMA and 0.06 μM captopril. Subsequently, ACE mRNA expression, protein level and activity, angiotensin II (Ang II) levels, and angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) mRNA expression in HUVECs were determined. AEPS successfully inhibited ACE mRNA expression, protein and activity, and angiotensin II levels in PMA-induced HUVECs. Additionally, AT1R expression was downregulated, whereas AT2R expression was upregulated. In conclusion, AEPS reduces the levels of ACE mRNA, protein and activity, Ang II, and AT1R expression in PMA-induced HUVECs. Thus, AEPS has the potential to be developed as an ACE inhibitor in the future.

Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy., Methods: Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood., Results: The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53 , and BRCA2 locus., Conclusions: The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA., (© 2024 The Authors.)

This study presents the initial structural model of L-haloacid dehalogenase (DehLBHS1) from Bacillus megaterium BHS1, an alkalotolerant bacterium known for its ability to degrade halogenated environmental pollutants. The model provides insights into the structural features of DehLBHS1 and expands our understanding of the enzymatic mechanisms involved in the degradation of these hazardous pollutants. Key amino acid residues (Arg40, Phe59, Asn118, Asn176, and Trp178) in DehLBHS1 were identified to play critical roles in catalysis and molecular recognition of haloalkanoic acid, essential for efficient binding and transformation of haloalkanoic acid molecules. DehLBHS1 was modeled using I-TASSER, yielding a best TM-score of 0.986 and an RMSD of 0.53 Å. Validation of the model using PROCHECK revealed that 89.2% of the residues were located in the most favored region, providing confidence in its structural accuracy. Molecular docking simulations showed that the non-simulated DehLBHS1 preferred 2,2DCP over other substrates, forming one hydrogen bond with Arg40 and exhibiting a minimum energy of -2.5 kJ/mol. The simulated DehLBHS1 exhibited a minimum energy of -4.3 kJ/mol and formed four hydrogen bonds with Arg40, Asn176, Asp9, and Tyr11, further confirming the preference for 2,2DCP. Molecular dynamics simulations supported this preference, based on various metrics, including RMSD, RMSF, gyration, hydrogen bonding, and molecular distance. MM-PBSA calculations showed that the DehLBHS1-2,2-DCP complex had a markedly lower binding energy (-21.363 ± 1.26 kcal/mol) than the DehLBHS1-3CP complex (-14.327 ± 1.738 kcal/mol). This finding has important implications for the substrate specificity and catalytic function of DehLBHS1, particularly in the bioremediation of 2,2-DCP in contaminated alkaline environments. These results provide a detailed view of the molecular interactions between the enzyme and its substrate and may aid in the development of more efficient biocatalytic strategies for the degradation of halogenated compounds.Communicated by Ramaswamy H. Sarma.

The human angiotensin-converting enzyme 2 (ACE-2) receptor is a metalloenzyme that plays an important role in regulating blood pressure by modulating angiotensin II. This receptor facilitates SARS-CoV-2 entry into human cells via receptor-mediated endocytosis, causing the global COVID-19 pandemic and a major health crisis. Kelulut honey (KH), one of Malaysian honey recently gained attention for its distinct flavour and taste while having many nutritional and medicinal properties. Recent study demonstrates the antiviral potential of KH against SARS-CoV-2 by inhibiting ACE-2 in vitro , but the bioactive compound pertaining to the ACE-2 inhibition is yet unknown. An ensemble docking-based virtual screening was employed to screen the phytochemical compounds from KH with high binding affinity against the 10 best representative structures of ACE-2 that mostly formed from MD simulation. From 110 phytochemicals previously identified in KH, 27 compounds passed the ADMET analysis and proceeded to docking. Among the docked compound, SDC and FMN consistently exhibited strong binding to ACE-2's active site (-9.719 and -9.473 kcal/mol) and allosteric site (-7.305 and -7.464 kcal/mol) as compared to potent ACE-2 inhibitor, MLN 4760. Detailed trajectory analysis of MD simulation showed stable binding interaction towards active and allosteric sites of ACE-2. KH's compounds show promise in inhibiting SARS-CoV-2 binding to ACE-2 receptors, indicating potential for preventive use or as a supplement to other COVID-19 treatments. Additional research is needed to confirm KH's antiviral effects and its role in SARS-CoV-2 therapy, including prophylaxis and adjuvant treatment with vaccination.Communicated by Ramaswamy H. Sarma.

This study introduces a promising and practical method for the removal of paracetamol from aqueous environments, employing graphene oxide-polymer nanocomposite beads. The approach involves the utilization of a straightforward and facile phase inversion method, offering a convenient and efficient one-step process for the creation of adsorbent beads by integrating polymers and graphene oxide (GO). The synthesized nanocomposite beads are tailored for the removal of paracetamol from simulated wastewater in batch systems. Extensive characterization techniques including XPS, FTIR, SEM, TGA, and zeta potential analysis are employed to scrutinize the chemical properties and structural attributes of the prepared beads. The investigation explores the impact of critical parameters such as adsorbent dosage, adsorption duration, initial paracetamol concentration, and solution pH on the adsorption process. These nanocomposite beads exhibit an exceptional paracetamol removal efficiency, achieving up to 99% removal. This research not only contributes to the advancement of efficient and sustainable adsorbent materials for pollutant removal but also underscores their potential for environmentally friendly and cost-effective solutions in the domain of wastewater treatment.

Introduction: The occurrence of antibiotic resistance (AR) has become a critical issue during the Novel coronavirus disease 2019 (COVID-19) pandemic. This study explores the experiences of healthcare commissioners with AR during the COVID-19 pandemic, identifies challenges, and provides recommendations for combating AR during pandemics., Methods: This qualitative study was multi-centered and used a phenomenological approach. Semi-structured interviews were conducted between December 2022 and January 2023 among 11 health commissioners using video calls., Results: Seven themes emerged from the data, including knowledge of AR and its consequences, the antibiotic prescription system, the future of AR and potential contributory factors, the impact of COVID-19 on AR and their relationship, the experience of AR during the COVID-19 pandemic in healthcare facilities, barriers that prevent the misuse of antibiotics during pandemics, and recommendations regarding antibiotic resistance during pandemics., Conclusion: The findings of this study could be used to inform policy and practice for government healthcare workers (HCWs) and the public. Furthermore, this study identified the main challenges of AR during the pandemic, and the recommendations of health commissioners were provided accordingly. Such recommendations could be beneficial on a national and international scale to reduce the impact of future pandemics on AR., Abbreviations: COVID-19: Novel coronavirus disease 2019; AR: Antibiotic Resistance; IPC: Infection prevention and control; MDRO: multi-drug resistant organism; ASP: Antimicrobial Stewardship Program; HCW: Healthcare worker; KSA: Kingdom of Saudi Arabia; WHO: World Health Organization; MOH: Ministry of Health; MOEWA: Ministry of Environment, Water, and Agriculture; AMR: Antimicrobial Resistance; PHCC: Primary Healthcare Center., Competing Interests: The authors declare no conflict of interest.No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.

Support ector achine (SVM) is a newer machine learning algorithm for classification, while logistic regression (LR) is an older statistical classification method. Despite the numerous studies contrasting SVM and LR, new improvements such as bagging and ensemble have been applied to them since these comparisons were made. This study proposes a new hybrid model based on SVM and LR for predicting small events per variable (EPV). The performance of the hybrid, SVM, and LR models with different EPV values was evaluated using COVID-19 data from December 2019 to May 2020 provided by the WHO. The study found that the hybrid model had better classification performance than SVM and LR in terms of accuracy, mean squared error (MSE), and root mean squared error (RMSE) for different EPV values. This hybrid model is particularly important for medical authorities and practitioners working in the face of future pandemics.

Plukenetia volubilis Linneo or Sacha Inchi (SI), a traditional natural remedy indigenous to Peru and Brazil, has garnered global attention due to its exceptional nutritional composition. Its protective effects against various non-communicable diseases, notably cardiovascular disease (CVD), have become a subject of interest in recent research. This comprehensive review summarizes the existing evidence from 15 relevant articles concerning the impact of SI on common CVD risk factors, including dyslipidemia, obesity, diabetes, and hypertension. The relevant articles were derived from comprehensive searches on PubMed, Scopus, Google Scholar, and Web of Science using predefined criteria and keywords related to the topic. Overall, SI demonstrated positive effects in attenuating dyslipidemia, obesity, diabetes, and hypertension. The multifaceted mechanisms responsible for the protective effects of SI against these CVD risk factors are primarily attributed to its antioxidative and anti-inflammatory properties. While preclinical studies dominate the current scientific literature on SI, there are limited clinical trials to corroborate these findings. Therefore, future well-designed, large-scale randomized clinical trials are highly recommended to establish the efficacy of SI and determine its optimal dosage, potential drug and food interactions, and practical integration into preventive strategies and dietary interventions for the high-risk populations.

Aurantiochytrium sp., a marine thraustochytrid possesses a remarkable ability to produce lipid rich in polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA). Although gene regulation underlying lipid biosynthesis has been previously reported, proteomic analysis is still limited. In this study, high DHA accumulating strain Aurantiochytrium sp. SW1 has been used as a study model to elucidate the alteration in proteome profile under different cultivation phases i.e. growth, nitrogen-limitation and lipid accumulation. Of the total of 5146 identified proteins, 852 proteins were differentially expressed proteins (DEPs). The largest number of DEPs (488 proteins) was found to be uniquely expressed between lipid accumulating phase and growth phase. Interestingly, there were up-regulated proteins involved in glycolysis, glycerolipid, carotenoid and glutathione metabolism which were preferable metabolic routes towards lipid accumulation and DHA production as well as cellular oxidative defence. Integrated proteomic and transcriptomic data were also conducted to comprehend the gene and protein regulation underlying the lipid and DHA biosynthesis. A significant up-regulation of acetyl-CoA synthetase was observed which suggests alternative route of acetate metabolism for acetyl-CoA producer. This study presents the holistic routes underlying lipid accumulation and DHA production in Aurantiochytrium sp. SW1 and other relevant thraustochytrid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A biopolymer-based adsorbent comprising chitosan (CS) and κ-carrageenan (κ-Carr) was synthesised and evaluated to treat phenolic-contaminated water. The developed CS/κ-Carr hydrogel demonstrated excellent performance with a phenol adsorption uptake of 80 %. The morphologies of CS/κ-Carr hydrogels with different ratios of CS to κ-Carr ranging from 1:2 to 7:3 were characterised using scanning electron microscopy and atomic force microscopy; their chemical structures were investigated by spectral analyses using Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry; their adsorption characteristics were determined using tests for swelling, chemical stability, hygroscopic moisture content, and hydrophilicity. Finally, a batch-type evaluation method demonstrated adsorption performance at 25 °C and pH 6.9. Adsorption isotherms and kinetic data were successfully obtained using the Freundlich and pseudo-second-order models, respectively. The results indicate that one-pot synthesis of an insoluble CS/κ-Carr hydrogel adsorbent exhibits considerable potential for the removal of phenol from aqueous solutions, providing an environmentally friendly technology enhancing the phenol adsorption performance of CS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.

microRNAs (miRNAs) play a multifaceted role in the pathogenesis of Alzheimer's disease (AD). miRNAs regulate several aspects of the disease, such as Aβ metabolism, tau phosphorylation, neuroinflammation, and synaptic function. The dynamic interaction between miRNAs and their target genes depends upon various factors, including the subcellular localization of miRNAs, the relative abundance of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. The miRNAs are released into extracellular fluids and subsequently conveyed to specific target cells through various modes of transportation, such as exosomes. In comparison, circular RNAs (circRNAs) are non-coding RNA (ncRNA) characterized by their covalently closed continuous loops. In contrast to linear RNA, RNA molecules are circularized by forming covalent bonds between the 3'and 5'ends. CircRNA regulates gene expression through interaction with miRNAs at either the transcriptional or post-transcriptional level, even though their precise functions and mechanisms of gene regulation remain to be elucidated. The current stage of research on miRNA expression profiles for diagnostic purposes in complex disorders such as Alzheimer's disease is still in its early phase, primarily due to the intricate nature of the underlying pathological causes, which encompass a diverse range of pathways and targets. Hence, this review comprehensively addressed the alteration of miRNA expression across diverse sources such as peripheral blood, exosome, cerebrospinal fluid, and brain in AD patients. This review also addresses the nascent involvement of circRNAs in the pathogenesis of AD and their prospective utility as biomarkers and therapeutic targets for these conditions in future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abidin, Mat Pauzi, Mansor, Mohd Isa and Hamid.)

Background and Objective: Several incidental cardiovascular findings are present in a routine chest computed tomography (CT) scan, many of which do not make it to the final radiology report. However, these findings have important clinical implications, particularly providing prognosis and risk-stratification for future cardiovascular events. The purpose of this article is to review the literature on these incidental cardiovascular findings in a routine chest CT and inform the radiologist on their clinical relevance., Methods: A time unlimited review of PubMed and Web of Science was performed by using relevant keywords. Articles in English that involved adults were included., Key Content and Findings: Coronary artery calcification (CAC) is the most common incidental cardiac finding detected in a routine chest CT and is a significant predictor of cardiovascular events. Noncoronary vascular calcifications in chest CT include aortic valve, mitral annulus, and thoracic aortic calcifications (TAC). Among these, aortic valve calcification (AVC) has the strongest association with coronary artery disease and cardiovascular events. Additional cardiac findings such as myocardial scar and left ventricular size and noncardiac findings such as thoracic fat, bone density, hepatic steatosis, and breast artery calcifications can also help in risk stratification and patient management., Conclusions: The radiologist interpreting a routine chest CT should be cognizant of the incidental cardiovascular findings, which helps in the diagnosis and risk-stratification of cardiovascular disease. This will guide appropriate referral and management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-79/coif). AC and PSR report that they received royalties from Elsevier, unrelated to the content of this manuscript. PSR serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from September 2021 to August 2023. The other authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgen-secreting neoplasms, Cushing's syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVβ3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertility.

Background: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought., Methods: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts., Results: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51)., Conclusions: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features., Plain Language Summary: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Honey is a sustainable nutritious substance which has been incorporated into the human diet since ancient times for its health and remedial benefits. Stingless bee honey or kelulut honey (KH) is well-known in Malaysia and has received high demand in the market due to its distinctive unique flavour. Its composition, colour, and flavour are majorly affected by the geographical location, floral source, climate, as well as the bee species. This data article presents the nontargeted metabolite profiling of the extracts of KH of Heterotrigona itama and Tetrigona binghami bee species. The KH was collected from three nests in Kuantan, Pahang, which is situated in the east coast of Peninsular Malaysia. The extracts were prepared using sugaring-out assisted liquid-liquid extraction (SULLE) method and the Liquid Chromatography-Tandem Mass Spectrometry with Quadrupole Time-of-Flight, operated in the negative ion mode, was used to identify compounds in the extracts. The data processing revealed the presence of 35 known compounds in the KH1 extract by Heterotrigona itama collected from Bukit Kuin, 38 compounds in the KH2 extract by H. itama collected from Indera Mahkota, whilst 50 known compounds were present in KH3 extract by Tetrigona binghami species from Indera Mahkota. This data article contains the m/z values, retention times, and the METLIN database search hit identities of the compounds and their respective classes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2023 The Authors. Published by Elsevier Inc.)

This paper presents a compact analog system-on-chip (SoC) implementation of a spiking neural network (SNN) for low-power Internet of Things (IoT) applications. The low-power implementation of an SNN SoC requires the optimization of not only the SNN model but also the architecture and circuit designs. In this work, the SNN has been constituted from the analog neuron and synaptic circuits, which are designed to optimize both the chip area and power consumption. The proposed synapse circuit is based on a current multiplier charge injector (CMCI) circuit, which can significantly reduce power consumption and chip area compared with the previous work while allowing for design scalability for higher resolutions. The proposed neuron circuit employs an asynchronous structure, which makes it highly sensitive to input synaptic currents and enables it to achieve higher energy efficiency. To compare the performance of the proposed SoC in its area and power consumption, we implemented a digital SoC for the same SNN model in FPGA. The proposed SNN chip, when trained using the MNIST dataset, achieves a classification accuracy of 96.56%. The presented SNN chip has been implemented using a 65 nm CMOS process for fabrication. The entire chip occupies 0.96 mm 2 and consumes an average power of 530 μW, which is 200 times lower than its digital counterpart.

Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Nazirah Samah et al.)

Background: During the novel Coronavirus 2019 (COVID-19) outbreak, there was an overuse of antibiotics in hospitals. The improper use of antibiotics during COVID-19 has increased antibiotic resistance (AR), which has been reported in multiple studies., Objectives: To assess the healthcare workers' (HCWs) knowledge, attitude and practice (KAP) in relation to AR during the era of COVID-19, and identify the associated factors with good knowledge, positive attitude and good practice., Methods: A cross-sectional design was used to assess the KAP of HCWs in Najran, Kingdom of Saudi Arabia (KSA). A validated questionnaire was used to collect participants' data, which consisted of the following information; socio-demographics, knowledge, attitude and items for practice. Data were presented as percentages and median (IQR). Mann-Whitney and Kruskal Wallis tests were used to compare them. Logistic regression was used to identify the associated factors linked to KAP., Results: The study included 406 HCWs. Their median (IQR) knowledge score was 72.73% (27.27%-81.82%), attitude score was 71.43% (28.57%-71.43%) and practice score was 50% (0%-66.67%). About 58.1% of the HCWs stated that antibiotics could be used to treat COVID-19 infection; 19.2% of the participants strongly agreed and 20.7% agreed that during the COVID-19 pandemic, antibiotics were overused at their healthcare institutions. Only 18.5% strongly agreed and 15.5% agreed when asked whether antibiotics used properly for the right indication and duration can still result in AR. The significantly associated factors with good knowledge were nationality, cadre and qualification. A positive attitude was significantly associated with age, nationality and qualification. Good practice was significantly associated with age, cadre, qualification and working place., Conclusion: Although the HCWs had a positive attitude regarding AR during COVID-19, their knowledge and practice need significant improvement. Implementation of effective educational and training programmes are urgently needed. In addition, further prospective and clinical trial studies are needed to better inform these programmes., Competing Interests: The authors have no conflict of interest in the current study., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)