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Abstract Basic science educators play a significant role in medical and health professions curricula, particularly in the biomedical science components. Although the shift from basic scientists to educators seems promising, no study has yet explored the transition process from the perspective of basic scientists themselves, especially in the early stages of their transition. An anonymous survey with voluntary participation was administered to all basic scientists in National University of Singapore (NUS) Yong Loo Lin School of Medicine. The survey aimed to identify the perceived challenges faced by basic scientists transitioning to basic science educators in medical and health professions education. This study consisted of Likert scale questions, followed by one multiple-choice question and two open-ended questions. Twenty-one basic scientists either postdoctoral fellows or instructors, completed the study. The study found that gaps in clinical content and experience, along with teaching pedagogy and training were among the major concerns for basic scientists aspiring to be basic science educators. These challenges and shortcomings could potentially be addressed by providing them with clinical shadowing opportunities, education mentorship and teaching training. Since most respondents lacked teaching experience, the results might differ if the majority had been involved in teaching within medical and health professions education. Nonetheless, it is important to understand and acknowledge the challenges and concerns experienced by basic scientists and examine how they can navigate them in the process of their transition to teaching medical and health professions. This also provides opportunities for personal reflection and development so that basic science educators will be more prepared for greater challenges and the ever-changing demands of contemporary medical and health professions education.

Abstract The advancement of microcomb sources, which serve as a versatile and powerful platform for various time–frequency measurements, have spurred widespread interest across disciplines. Their uses span coherent optical and microwave communications, atomic clocks, high-precision LiDARs, spectrometers, and frequency synthesizers. Recent breakthroughs in fabricating optical micro-cavities, along with the excitation and control of microcombs, have broadened their applications, bridging the gap between physical exploration and practical engineering systems. These developments pave the way for pioneering approaches in both classical and quantum information sciences. In this review article, we conduct a thorough examination of the latest strategies related to microcombs, their enhancement and functionalization schemes, and cutting-edge applications that cover signal generation, data transmission, quantum analysis, and information gathering, processing and computation. Additionally, we provide in-depth evaluations of microcomb-based methodologies tailored for a variety of applications. To conclude, we consider the current state of research and suggest a prospective roadmap that could transition microcomb technology from laboratory settings to broader real-world applications.

Abstract Solitons, the distinct balance between nonlinearity and dispersion, provide a route toward ultrafast electromagnetic pulse shaping, high-harmonic generation, real-time image processing, and RF photonic communications. Here we uniquely explore and observe the spatio-temporal breather dynamics of optical soliton crystals in frequency microcombs, examining spatial breathers, chaos transitions, and dynamical deterministic switching – in nonlinear measurements and theory. To understand the breather solitons, we describe their dynamical routes and two example transitional maps of the ensemble spatial breathers, with and without chaos initiation. We elucidate the physical mechanisms of the breather dynamics in the soliton crystal microcombs, in the interaction plane limit cycles and in the domain-wall understanding with parity symmetry breaking from third-order dispersion. We present maps of the accessible nonlinear regions, the breather frequency dependences on third-order dispersion and avoided-mode crossing strengths, and the transition between the collective breather spatio-temporal states. Our range of measurements matches well with our first-principles theory and nonlinear modeling. To image these soliton ensembles and their breathers, we further constructed panoramic temporal imaging for simultaneous fast- and slow-axis two-dimensional mapping of the breathers. In the phase-differential sampling, we present two-dimensional evolution maps of soliton crystal breathers, including with defects, in both stable breathers and breathers with drift. Our fundamental studies contribute to the understanding of nonlinear dynamics in soliton crystal complexes, their spatio-temporal dependences, and their stability-existence zones.

Abstract Dissipative Kerr soliton microcombs in microresonators have enabled fundamental advances in chip-scale precision metrology, communication, spectroscopy, and parallel signal processing. Here we demonstrate polarization-diverse soliton transitions and deterministic switching dynamics of a self-stabilized microcomb in a strongly-coupled dispersion-managed microresonator driven with a single pump laser. The switching dynamics are induced by the differential thermorefractivity between coupled transverse-magnetic and transverse-electric supermodes during the forward-backward pump detunings. The achieved large soliton existence range and deterministic transitions benefit from the switching dynamics, leading to the cross-polarized soliton microcomb formation when driven in the transverse-magnetic supermode of the single resonator. Secondly, we demonstrate two distinct polarization-diverse soliton formation routes – arising from chaotic or periodically-modulated waveforms via pump power selection. Thirdly, to observe the cross-polarized supermode transition dynamics, we develop a parametric temporal magnifier with picosecond resolution, MHz frame rate and sub-ns temporal windows. We construct picosecond temporal transition portraits in 100-ns recording length of the strongly-coupled solitons, mapping the transitions from multiple soliton molecular states to singlet solitons. This study underpins polarization-diverse soliton microcombs for chip-scale ultrashort pulse generation, supporting applications in frequency and precision metrology, communications, spectroscopy and information processing.

Abstract Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m2). All presented with diabetes ketosis or ketoacidosis and low C‐peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required.

Summary: Following kidney removal, the remaining kidney enlarges and increases its function. The mechanism and signals driving this compensatory kidney hypertrophy and the enlargement of its constituent kidney cells remains elusive. RNA-seq studies in mice undergoing hypertrophy 24, 48, and 72 h following nephrectomy were undertaken to understand the early transcriptional changes. This revealed substantial enhancement of cholesterol biosynthesis pathways, increases in mitochondrial gene expression and cell cycle perturbations. Single nuclei RNA-seq delineated cell specific changes at 24 h post nephrectomy and showed that sterol binding protein 2 (SREBP2) activity increases in medullary thick ascending limb cells in keeping with promotion of cholesterol synthesis. Cultured renal tubular cells were examined for insulin-like growth factor-1 (IGF-1) stimulated hypertrophy and SREBP2 was found to be required for increase in cell size. This work describes the early cell specific growth pathways mediating cellular and kidney hypertrophy with an intriguing role for cholesterol synthesis.

Abstract Amorphous photonic structures are mesoscopic optical structures described by electrical permittivity distributions with underlying spatial randomness. They offer a unique platform for studying a broad set of electromagnetic phenomena, including transverse Anderson localization, enhanced wave transport, and suppressed diffusion in random media. Despite this, at a more practical level, there is insufficient work on both understanding the nature of optical transport and the conditions conducive to vector-wave localization in these planar structures, as well as their potential applications to photonic nanodevices. In this study, we fill this gap by investigating experimentally and theoretically the characteristics of optical transport in a class of amorphous photonic structures and by demonstrating their use to some basic waveguiding nanostructures. We demonstrate that these 2-D structures have unique isotropic and asymmetric band gaps for in-plane propagation, controlled from first principles by varying the scattering strength and whose properties are elucidated by establishing an analogy between photon and carrier transport in amorphous semiconductors. We further observe Urbach band tails in these random structures and uncover their relation to frequency- and disorder-dependent Anderson-like localized modes through the modified Ioffe-Regel criterion and their mean free path - localization length character. Finally, we illustrate that our amorphous structures can serve as a versatile platform in which photonic devices such as disorder-localized waveguides can be readily implemented.

The Japanese occupation of Malaysia during the Second World War has occupied a significant space in national history textbooks in Malaysia. The period has been associated with nationalist movements and independence from colonial rule. However, narratives of the Japanese occupation in school history textbooks have changed in terms of the importance given to the experiences of the three major ethnic groups in Malaysia (the Malay, Chinese, and Indian ethnic groups). This article presents an analysis of the Japanese occupation as portrayed in Malaysian national history textbooks from 1978 to 2020. It demonstrates a link between ideology and the state curriculum in Malaysia, which shows how cultural and ideological factors (namely, the political ideology of Malay dominance, or ketuanan Melayu) explain the changes made to the narratives in history textbooks.

BackgroundThe clinical management of type 2 diabetes mellitus (T2DM) presents a significant challenge due to the constantly evolving clinical practice guidelines and growing array of drug classes available. Evidence suggests that artificial intelligence (AI)–enabled clinical decision support systems (CDSSs) have proven to be effective in assisting clinicians with informed decision-making. Despite the merits of AI-driven CDSSs, a significant research gap exists concerning the early-stage implementation and adoption of AI-enabled CDSSs in T2DM management. ObjectiveThis study aimed to explore the perspectives of clinicians on the use and impact of the AI-enabled Prescription Advisory (APA) tool, developed using a multi-institution diabetes registry and implemented in specialist endocrinology clinics, and the challenges to its adoption and application. MethodsWe conducted focus group discussions using a semistructured interview guide with purposively selected endocrinologists from a tertiary hospital. The focus group discussions were audio-recorded and transcribed verbatim. Data were thematically analyzed. ResultsA total of 13 clinicians participated in 4 focus group discussions. Our findings suggest that the APA tool offered several useful features to assist clinicians in effectively managing T2DM. Specifically, clinicians viewed the AI-generated medication alterations as a good knowledge resource in supporting the clinician’s decision-making on drug modifications at the point of care, particularly for patients with comorbidities. The complication risk prediction was seen as positively impacting patient care by facilitating early doctor-patient communication and initiating prompt clinical responses. However, the interpretability of the risk scores, concerns about overreliance and automation bias, and issues surrounding accountability and liability hindered the adoption of the APA tool in clinical practice. ConclusionsAlthough the APA tool holds great potential as a valuable resource for improving patient care, further efforts are required to address clinicians’ concerns and improve the tool’s acceptance and applicability in relevant contexts.

Large language models (LLMs) underlie remarkable recent advanced in natural language processing, and they are beginning to be applied in clinical contexts. We aimed to evaluate the clinical potential of state-of-the-art LLMs in ophthalmology using a more robust benchmark than raw examination scores. We trialled GPT-3.5 and GPT-4 on 347 ophthalmology questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions. The performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p

Abstract High-dimensional quantum entanglement is a cornerstone for advanced technology enabling large-scale noise-tolerant quantum systems, fault-tolerant quantum computing, and distributed quantum networks. The recently developed biphoton frequency comb (BFC) provides a powerful platform for high-dimensional quantum information processing in its spectral and temporal quantum modes. Here we propose and generate a singly-filtered high-dimensional BFC via spontaneous parametric down-conversion by spectrally shaping only the signal photons with a Fabry-Pérot cavity. High-dimensional energy-time entanglement is verified through Franson-interference recurrences and temporal correlation with low-jitter detectors. Frequency- and temporal- entanglement of our singly-filtered BFC is then quantified by Schmidt mode decomposition. Subsequently, we distribute the high-dimensional singly-filtered BFC state over a 10 km fiber link with a post-distribution time-bin dimension lower bounded to be at least 168. Our demonstrations of high-dimensional entanglement and entanglement distribution show the singly-filtered quantum frequency comb’s capability for high-efficiency quantum information processing and high-capacity quantum networks.

Time-reversibility, which is inherent in many physical systems, is crucial in tailoring temporal waveforms for optimum light–matter interactions. Among the time-reversible atomic systems, narrowband biphoton sources are essential for efficient quantum storage. In this work, we demonstrate time-reversed and fully time-resolved ultra-narrowband single-sided biphoton frequency combs with an average free-spectral range (FSR) of 42.66 MHz and an average linewidth of 4.60 MHz in the telecommunication band. We experimentally observe the fully time-resolved and reversible temporal oscillations by second-order cross correlation and joint temporal intensity measurements. The potential benefits of the time-reversed and fully time-resolved temporal oscillations from our source include enhancing the efficiency of quantum storage in atomic memories and maximizing the utilization of temporal information in multimode biphoton frequency combs. We further verify the heralded single-photon state generation from the multimode biphoton frequency combs by using Hanbury Brown and Twiss interference measurements. To the best of our knowledge, this 42.66 MHz FSR of our photon-pair source represents the narrowest among all of the different configurated biphoton sources reported to date. This ultra-narrow FSR and its 4.60 MHz linewidth provide the highest frequency mode number of 5786 and the longest coherence time among all the singly configurated biphoton sources so far. Our time-reversed and fully time-resolved massive-mode biphoton source could be useful for high-dimensional quantum information processing and efficient time–frequency multiplexed quantum storage toward long-distance and large-scale quantum networks.

Background: The main objective of public health law is to pursue the highest possible level of physical and mental health in the population, consistent with the values of social justice. Aims: To elaborate on Malaysia’s public health laws that share unique commonalities with those of the United States of America, due to both countries’ colonial past as part of the British Empire. Methods: Historical review and analysis of current public health law issues in both nations. Results: The United States of America gained full independence from the British Empire on 3 September 1783, while almost three years later, on 11 August 1786, the Union Jack was raised on the island of Pulau Pinang in Malaysia. When the colonies first formed the United States, there was no national public health law; the American colonies adopted the English laws on the control of diseases. This is similar to Pulau Pinang, after the implementation of the Charter of Justice in 1807. Conclusion: Current applications of the law, which include quarantine, sanitation, disease reporting, and vaccination,exhibit interesting similarities as well as differences between the United States and Malaysia.

Summary: Many viruses produce microRNAs (miRNAs), termed viral miRNAs (v-miRNAs), with the capacity to target host gene expression. Bioinformatic and cell culture studies suggest that SARS-CoV-2 can also generate v-miRNAs. This patient-based study defines the SARS-CoV-2 encoded small RNAs present in nasopharyngeal swabs of patients with COVID-19 infection using small RNA-seq. A specific conserved sequence (CoV2-miR-O8) is defined that is not expressed in other coronaviruses but is preserved in all SARS-CoV-2 variants. CoV2-miR-O8 is highly represented in nasopharyngeal samples from patients with COVID-19 infection, is detected by RT-PCR assays in patients, has features consistent with Dicer and Drosha generation as well as interaction with Argonaute and targets specific human microRNAs.

Climate change represents a significant global health crisis, characterized by a complex interplay of environmental shifts and interconnected phenomena. These alterations have given rise to a multitude of health implications, notably impacting ocular health. Our comprehensive review delineates a spectrum of eye conditions associated with climate change-related variables. Extremes in temperature and weather events have been observed to affect the ocular surface, resulting in an increased incidence of conjunctivitis, keratitis, dry eye disease, and pterygium. Furthermore, climate change is linked to a rising occurrence of cataracts, glaucoma, periocular tumors, and infections. Prolonged food insecurity, stemming from droughts, has been associated with nutritional optic neuropathies and consequent vision loss. Elevated temperatures have also been correlated with a heightened risk of retinal detachments necessitating urgent surgical intervention to enhance prognostic outcomes.This review also outlines the influence of climate-warming pollutants on a diverse array of eye conditions, manifesting as ocular surface infections, degenerative changes like pterygium, cataracts, refractive errors (myopia), blepharitis, meibomian gland infections, glaucoma, and vascular retinal occlusions.Mitigating the effects of climate change is an urgent global imperative necessitating collaborative efforts, encompassing research and education, to devise sustainable solutions that safeguard human health and well-being. This review seeks to delineate the current extent of available research, identify gaps in the existing literature, and chart the course for future studies in this intriguing association.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 6 million deaths worldwide, and the spread of new variants over time increased the ability of this virus to cause infection. The Omicron variant was detected for the first time in Umbria, a region of central Italy, in November 2021 and it induced an unprecedented increase in the number of infection cases. Here, we analysed 3300 SARS-CoV-2 positive samples collected in Umbria between April 2022 and December 2023. We traced the molecular evolution of SARS-CoV-2 variants over time through the Next-Generation Sequencing (NGS) approach. We assessed correlation between SARS-CoV-2 infection and patients’ health status. In total, 17.3% of our samples came from patients hospitalised as a consequence of COVID-19 infection even though 81.4% of them received at least three vaccine doses. We identified only Omicron variants, and the BA.5 lineage was detected in the majority of our samples (49.2%). Omicron variants outcompeted each other through the acquisition of mutations especially in Spike glycoprotein that are fingerprints of each variant. Viral antigenic evolution confers higher immunological escape and makes a continuous improvement of vaccine formulation necessary. The continuous update of international genomic databases with sequencing results obtained by emergent pathogens is essential to manage a possible future pandemic.

Abstract Background Predictive biomarkers for oesophageal squamous cell carcinoma (ESCC) immunotherapy are lacking, and immunotherapy resistance remains to be addressed. The role of long noncoding RNA (lncRNA) in ESCC immune escape and immunotherapy resistance remains to be elucidated. Methods The tumour‐associated macrophage‐upregulated lncRNAs and the exosomal lncRNAs highly expressed in ESCC immunotherapy nonresponders were identified by lncRNA sequencing and polymerase chain reaction assays. CRISPR‐Cas9 was used to explore the functional roles of the lncRNA. RNA pull‐down, MS2‐tagged RNA affinity purification (MS2‐TRAP) and RNA‐binding protein immunoprecipitation (RIP) were performed to identify lncRNA‐associated proteins and related mechanisms. In vivo, the humanized PBMC (hu‐PBMC) mouse model was established to assess the therapeutic responses of specific lncRNA inhibitors and their combination with programmed cell death protein 1 (PD‐1) monoclonal antibody (mAb). Single‐cell sequencing, flow cytometry, and multiplex fluorescent immunohistochemistry were used to analyze immune cells infiltrating the tumour microenvironment. Results We identified a lncRNA that is involved in tumour immune evasion and immunotherapy resistance. High LINC02096 (RIME) expression in plasma exosomes correlates with a reduced response to PD‐1 mAb treatment and poor prognosis. Mechanistically, RIME binds to mixed lineage leukaemia protein‐1 (MLL1) and prevents ankyrin repeat and SOCS box containing 2 (ASB2)‐mediated MLL1 ubiquitination, improving the stability of MLL1. RIME‐MLL1 increases H3K4me3 levels in the promoter regions of programmed death‐ligand 1 (PD‐L1) and indoleamine 2,3‐dioxygenase 1 (IDO‐1), constitutively increasing the expression of PD‐L1/IDO‐1 in tumour cells and inhibiting CD8+ T cells infiltration and activation. RIME depletion in huPBMC‐NOG mice significantly represses tumour development and improves the effectiveness of PD‐1 mAb treatment by activating T‐cell‐mediated antitumour immunity. Conclusions This study reveals that the RIME‐MLL1‐H3K4me3 axis plays a critical role in tumour immunosuppression. Moreover, RIME appears to be a potential prognostic biomarker for immunotherapy and developing drugs that target RIME may be a new therapeutic strategy that overcomes immunotherapy resistance and benefits patients with ESCC.

Abstract Retinal pigment epithelial (RPE) cell dysfunction and death are characteristics of age-related macular degeneration. A promising therapeutic option is RPE cell transplantation. Development of clinical grade stem-cell derived RPE requires efficient in vitro differentiation and purification methods. Enzymatic purification of RPE relies on the relative adherence of RPE and non-RPE cells to the culture plate. However, morphology and adherence of non-RPE cells differ for different stem cell sources. In cases whereby the non-RPE adhered as strongly as RPE cells to the culture plate, enzymatic method of purification is unsuitable. Thus, we hypothesized the need to customize purification strategies for RPE derived from different stem cell sources. We systematically compared five different RPE purification methods, including manual, enzymatic, flow cytometry-based sorting or combinations thereof for parameters including cell throughput, yield, purity and functionality. Flow cytometry-based approach was suitable for RPE isolation from heterogeneous cultures with highly adherent non-RPE cells, albeit with lower yield. Although all five purification methods generated pure and functional RPE, there were significant differences in yield and processing times. Based on the high purity of the resulting RPE and relatively short processing time, we conclude that a combination of enzymatic and manual purification is ideal for clinical applications.

The mechanism of urea's action in protein denaturation remains largely unknown. To provide an experimental basis for molecular dynamics (MD) simulations on urea-protein interactions, we investigated the effect of urea on human intestinal fatty acid binding protein (hIFABP) by nuclear magnetic resonance (NMR). Hydrogen-deuterium exchange (HDX) rates at ≤ 2 M urea indicate that urea affects hIFABP in a residue-specific manner via direct urea-protein interactions and preferentially weakens hydrogen bonds between highly protected amides. Residue-specific effects of urea on NMR peak intensities and chemical shifts further support the presence of direct urea-protein interactions. Two-dimensional (2D) water-rotating frame Overhauser enhancement (ROE) data shows one protein-bound water molecule in contact with Val66 and Trp82, one putative bound water molecule in interaction with Thr76 and E-F loop, and that urea at low concentrations cannot displace these protein-bound water molecules. Our urea-nuclear Overhauser effect (NOE) experiments using 15N-urea further show no tightly protein-bound urea molecules. Our results thus suggest specific, but weak or transient, urea-protein interactions, supporting the direct interaction model of urea denaturation.

High-spectral-purity frequency-agile room-temperature THz sources are foundational elements for imaging, sensing, metrology, and communications. Here a parametric oscillator-photomixer chip with coherent 2.8-octave tunable THz radiation is achieved.

Abstract Augmented reality (AR) devices, as smart glasses, enable users to see both the real world and virtual images simultaneously, contributing to an immersive experience in interactions and visualization. Recently, to reduce the size and weight of smart glasses, waveguides incorporating holographic optical elements in the form of advanced grating structures have been utilized to provide light-weight solutions instead of bulky helmet-type headsets. However current waveguide displays often have limited display resolution, efficiency and field-of-view, with complex multi-step fabrication processes of lower yield. In addition, current AR displays often have vergence-accommodation conflict in the augmented and virtual images, resulting in focusing-visual fatigue and eye strain. Here we report metasurface optical elements designed and experimentally implemented as a platform solution to overcome these limitations. Through careful dispersion control in the excited propagation and diffraction modes, we design and implement our high-resolution full-color prototype, via the combination of analytical–numerical simulations, nanofabrication and device measurements. With the metasurface control of the light propagation, our prototype device achieves a 1080-pixel resolution, a field-of-view more than 40°, an overall input–output efficiency more than 1%, and addresses the vergence-accommodation conflict through our focal-free implementation. Furthermore, our AR waveguide is achieved in a single metasurface-waveguide layer, aiding the scalability and process yield control.

Chronic kidney disease (CKD), a common clinical problem in primary care, can be defined as any abnormality of the kidney structure and/or function that has been present for at least 3 months. Over the past 20 years, the incidence and prevalence of CKD have been increasing in Malaysia in line with the rising number of non-communicable diseases. At present, CKD has no cure. The treatment of CKD is very much dependent on early diagnosis and prevention of CKD progression. In this article, we aim to illustrate a practical approach to CKD in primary care, including diagnosis, evaluation, and management of CKD.

The present study investigated the antioxidant enzyme activities (AEA) of ascorbate peroxidase (APX), catalase (CAT), guaiacol peroxidase (GPX), and superoxide dismutase (SOD) as biomarkers of Cu and Pb stress by using Centella asiatica grown in an experimental hydroponic condition. The results showed (i) higher accumulations of Cu and Pb in the roots of C. asiatica than those in the leaves, (ii) synergistic effects of Cu and Pb stress at higher metal-level exposures, and (iii) Cu and Pb stress triggered the increment of APX, CAT, GPX, and SOD levels in both the leaves and roots of C. asiatica. The increment of four AEA indicated that C. asiatica underwent oxidative stress caused by the production of reactive oxygen species when the plant was exposed to Cu and Pb. In order to prevent damages caused by Cu and Pb stress, the AEA system was heightened in C. asiatica, in which APX, CAT, GPX, and SOD can be used as biomarkers of Pb and Cu stress in the plant.

A biosensor was designed for sensitive detection of microRNA (miR)-144-3p, a potential miR biomarker for nasopharyngeal cancer, by integrating magnetic beads (MBs) into a hybridization chain reaction-silver nanoclusters (HCR-AgNCs) system. Through careful design, each component in the MBs-HCR-AgNCs biosensor was able to perform well without affecting subsequent steps. The target miR-144-3p was first magnetically separated with MBs coated with capture probes and short assistant probes. The collected miR was then amplified via HCR and detected using fluorogenic AgNCs that were prepared in situ. The DNA hairpins used in HCR were designed to host a AgNCs nucleation sequence that is capable of dual-emissive fluorescence response, thus enabling a ratiometric analysis. The novel MBs-HCR-AgNCs biosensor exhibits a good fluorescence response towards the target miR-144-3p with a wide linear detection range of 10 fM–1 μM and a detection limit of 4.88 fM. Moreover, it shows remarkable selectivity towards the target miR and good reproducibility even in raw human serum samples. Our findings suggest that the MBs-HCR-AgNCs can be a promising tool for sensitive miR detection in clinical diagnostics, without the need for complex sample preparation.

Metabolic inhibition via PFKFB3 inhibition has demonstrated considerable tumor inhibitory effects in various studies; however, PFKFB3 inhibition did not show satisfactory tumor inhibition when used in clinical trials. PFKFB3 is a crucial metabolic enzyme that is highly upregulated in cancer cells and directly affects tumor glycolysis. Here, we showed that PFKFB3 inhibition suppresses tumors in vitro and in vivo in immune-deficient xenografts. However, this inhibition induces the upregulation of PD-L1 levels, which inactivated cocultured T-cells in vitro, compromises anti-tumor immunity in vivo, and reduced anti-tumor efficacy in an immune-competent mouse model. Functionally, PD-1 mAb treatment enhances the efficacy of PFKFB3 inhibition in immunocompetent and hu-PBMC NOG mouse models. Mechanistically, PFKFB3 inhibition increases phosphorylation of PFKFB3 at residue Ser461, which increases interaction with HIF-1α, and their colocalization into the nucleus, where HIF-1α transcriptionally upregulate PD-L1 expression and causes subsequent tumor immune evasion. Higher phos-PFKFB3 correlated with higher PD-L1 expression, lower CD8 and GRZMB levels, and shorter survival time in ESCC patients.

Growing evidence indicates a connection between cancer-associated fibroblasts (CAFs) and tumor microenvironment (TME) remodeling and tumor progression. Nevertheless, how patterns of CAFs impact TME and immunotherapy responsiveness in triple-negative breast cancer (TNBC) remains unclear. Here, we systematically investigate the relationship between TNBC progression and patterns of CAFs. By using unsupervised clustering methods in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset, we identified two distinct CAF-associated clusters that were related to clinical features, characteristics of TME, and prognosis of patients. Then, we established a CAF-related prognosis index (CPI) by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. CPI showed prognostic accuracy in both training and validation cohorts (METABRIC, GSE96058, and GSE21653). Consequently, we constructed a nomogram with great predictive performance. Moreover, the CPI was verified to be correlated with the responsiveness of immunotherapy in three independent cohorts (GSE91061, GSE165252, and GSE173839). Taken together, the CPI might help us improve our recognition of the TME of TNBC, predict the prognosis of TNBC patients, and offer more immunotherapy strategies in the future.

It is expected that secondary exposure to e-cigarette aerosol (passive vaping) will soon become an issue of public health. Passive vaping inhales e-cigarette aerosol containing similar harmful substances as active vaping. However, parallel studies on passive vaping are minimal. Therefore, there is a need for passive vaping-related health risk studies to assess the impact of vaping on public health. This research conducted a series of experiments in a room using a puffing machine and the Mobile Aerosol Lung Deposition Apparatus (MALDA) to study e-cigarette aerosol respiratory deposition through passive vaping. The experimental data acquired were applied to estimate the deposited mass and health risks caused by toxic metals contained in e-cigarette aerosol. Five popular e-cigarette products were used in this study to generate e-cigarette aerosol for deposition experiments. In addition, size-segregated e-cigarette aerosol samples were collected, and metal compositions in the e-cigarette aerosol were analyzed. Results obtained showed that estimated non-cancer risks were all acceptable, with hazard quotient and hazard index all less than 1.0. The calculated cancer risks were also found acceptable, with lifetime excess cancer risk generally less than 1E-6. Therefore, the e-cigarettes tested and the passive vaping exposure scenarios studied do not seem to induce any potential for metal-related respiratory health effects.

In light of a global organ shortage, living donor transplantation has become increasingly relevant as an alternative to deceased donor transplantation. While current research has revolved around the medical aspects of transplantation, there remains a paucity of literature regarding the quality of life (QOL) of living donors. Hence, this review aims to provide a comprehensive outline of the current landscape of living liver and kidney transplantation, with a focus on the mental health and wellbeing of donors. As highlighted in previous studies, organ donation has a significant impact on both physical and mental aspects of donor wellbeing, with marked deteriorations occurring in the short term. Furthermore, other qualitative aspects such as financial burden contribute greatly to donor distress, reflecting a need for improved donor care. To address these pertinent issues, recommendations for a successful transplant program are detailed in this review, which encompasses psychological and social aspects of donor care throughout the donation process. Further research can be done on the impact of recipient deaths on donor QOL and appropriate interventions. Overall, given the selfless sacrifices of living donors, the care of their mental wellbeing is essential. Therefore, greater emphasis should be placed on the provision of adequate psychosocial support for them.

Chaos has revolutionized the field of nonlinear science and stimulated foundational studies from neural networks, extreme event statistics, to physics of electron transport. Recent studies in cavity optomechanics provide a new platform to uncover quintessential architectures of chaos generation and the underlying physics. Here, we report the generation of dynamical chaos in silicon-based monolithic optomechanical oscillators, enabled by the strong and coupled nonlinearities of two-photon absorption induced Drude electron-hole plasma. Deterministic chaotic oscillation is achieved, and statistical and entropic characterization quantifies the chaos complexity at 60 fJ intracavity energies. The correlation dimension D2 is determined at 1.67 for the chaotic attractor, along with a maximal Lyapunov exponent rate of about 2.94 times the fundamental optomechanical oscillation for fast adjacent trajectory divergence. Nonlinear dynamical maps demonstrate the subharmonics, bifurcations and stable regimes, along with distinct transitional routes into chaos. This provides a CMOS-compatible and scalable architecture for understanding complex dynamics on the mesoscopic scale.

Free-space communication in the mid-IR domain has many potential applications, but security is still challenging. Here, the authors use chaos synchronization in a QCL-based free-space link as a way to increase privacy of such transmissions.

Abstract Strongly correlated polaritons in Jaynes–Cummings (JC) lattices can exhibit quantum phase transitions between the Mott-insulating and superfluid phases at integer fillings. The prerequisite to observe such phase transitions is to pump polariton excitations into a JC lattice and prepare them into appropriate ground states. Despite previous efforts, it is still challenging to generate many-body states with high accuracy. Here, we present an approach for the robust preparation of many-body ground states of polaritons in finite-sized JC lattices by optimized nonlinear ramping. We apply a Landau–Zener type of estimation to this finite-sized system and derive the optimal ramping index for selected ramping trajectories, which can greatly improve the fidelity of the prepared states. With numerical simulation, we show that by choosing an appropriate ramping trajectory, the fidelity in this approach can remain close to unity in almost the entire parameter space. This approach can shed light on high-fidelity state preparation in quantum simulators and advance the implementation of quantum simulation with practical devices.

Optical frequency combs can provide phase-coherent links between optical frequencies and microwaves, allowing for precise optical frequency generation; however current technologies require external optical references or multiple power-intensive peripherals that make them less suitable for on-chip applications. Here, the authors present phase stabilization of a frequency microcomb without nonlinear processes nor external optical reference signals.

The objectives of the present study are: 1), to determine the concentrations of Zn in Ipomoea aquatica collected from ten distinct sampling sites located in Peninsular Malaysia; and 2) to assess the potential human health risks associated with Zn exposure from the collected Ipomoea aquatica in Peninsular Malaysia, across different age groups of the Malaysian population. It was found that the root of I. aquatica accumulated a significantly higher amount of this element compared to the stem and the leaf. It was also observed that all physiological parts (Leaf, Stem, and Root) of I. aquatica sampled from Market KLIA accumulated a greater amount of Zn compared to the other sites. The THQ (Target Hazard Quotient) values for element Zn in the I. aquatica species collected from 10 different sites in the Negeri Sembilan and Selangor states of Malaysia were consistently below 1.00. This observation suggests that there is no significant risk of non-carcinogenic effects associated with the consumption of water spinach by Malaysian consumers. The consistent Zn accumulation over time suggests that despite economic development in the region, Zn levels remained within safe concentrations, minimizing the risk associated with Zn accumulation in the plant biomass. [ABSTRACT FROM AUTHOR]

Abstract Qudit entanglement is an indispensable resource for quantum information processing since increasing dimensionality provides a pathway to higher capacity and increased noise resilience in quantum communications, and cluster-state quantum computations. In continuous-variable time–frequency entanglement, encoding multiple qubits per photon is only limited by the frequency correlation bandwidth and detection timing jitter. Here, we focus on the discrete-variable time–frequency entanglement in a biphoton frequency comb (BFC), generating by filtering the signal and idler outputs with a fiber Fabry–Pérot cavity with 45.32 GHz free-spectral range (FSR) and 1.56 GHz full-width-at-half-maximum (FWHM) from a continuous-wave (cw)-pumped type-II spontaneous parametric downconverter (SPDC). We generate a BFC whose time-binned/frequency-binned Hilbert space dimensionality is at least 324, based on the assumption of a pure state. Such BFC’s dimensionality doubles up to 648, after combining with its post-selected polarization entanglement, indicating a potential 6.28 bits/photon classical-information capacity. The BFC exhibits recurring Hong–Ou–Mandel (HOM) dips over 61 time bins with a maximum visibility of 98.4% without correction for accidental coincidences. In a post-selected measurement, it violates the Clauser–Horne–Shimony–Holt (CHSH) inequality for polarization entanglement by up to 18.5 standard deviations with an S-parameter of up to 2.771. It has Franson interference recurrences in 16 time bins with a maximum visibility of 96.1% without correction for accidental coincidences. From the zeroth- to the third-order Franson interference, we infer an entanglement of formation (E of) up to 1.89 ± 0.03 ebits—where 2 ebits is the maximal entanglement for a 4 × 4 dimensional biphoton—as a lower bound on the 61 time-bin BFC’s high-dimensional entanglement. To further characterize time-binned/frequency-binned BFCs we obtain Schmidt mode decompositions of BFCs generated using cavities with 45.32, 15.15, and 5.03 GHz FSRs. These decompositions confirm the time–frequency scaling from Fourier-transform duality. Moreover, we present the theory of conjugate Franson interferometry—because it is characterized by the state’s joint-temporal intensity (JTI)—which can further help to distinguish between pure-state BFC and mixed state entangled frequency pairs, although the experimental implementation is challenging and not yet available. In summary, our BFC serves as a platform for high-dimensional quantum information processing and high-dimensional quantum key distribution (QKD).

Background: Colonoscopy requires the intubation of the cecum for screening of colorectal diseases. The conventional position used for colonoscopy is the left lateral position (LLP). However, alternative positions have also been utilized to enhance the success of intubation. Thus, the aim of this study was to perform a meta-analysis of the different positions to determine the effectiveness of the individual positions for successful colonoscopy. Methods: Medline, Embase and Cochrane trials electronic databases were searched for studies on colonoscopy positions. The primary outcome was defined as the cecal intubation rate. Pooled risk ratios (RR) and 95% confidence intervals (CI) for the rates of cecal intubation were estimated. Secondary outcomes such as the cecal intubation time and adenoma detection rate were further analyzed qualitatively. Results: After reviewing 644 identified records, 7 randomized control trials (RCT) studies were included. No significant difference was observed in either comparisons, between the LLP vs. supine position (SP) (RR = 1.01, 95% CI, 0.98 to 1.04, P = 0.55) or the LLP vs. prone position (PP) (RR = 1.02, 95% CI, 0.98 to 1.06, P = 0.27). Conclusions: Amidst available literature, the use of other positions can be considered when performing colonoscopy. These further highlights that the existential practice is based predominantly on familiarity instead of evidence-based-research.