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Background: Constructing knowledge through collaborative practical work is a complex process and involves the use of multiple modalities by group members. In practical work sessions, students often manipulate visual objects or textual materials but do not develop their scientific ideas. Purpose: This study illustrates (a) the challenges that science students face when they create thematic patterns in a laboratory class and (b) characterises the processes of how students make meaning of practical work activities. Sample: Drawing from a video database, we chose to investigate an 80-min chemistry lesson with eight Year 10 students who were unpacking the complex ideas behind practical work. This lesson episode was transcribed multimodally, with snapshots of the pictures of students' actions and gestures. Methods: This study adopts a case-study approach. A multimodal discourse analysis approach was taken to examine the classroom discourse of the students when they were determining the strength of acids and alkalis through electroconductivity. Results: We identified various challenges when students integrated gestures, pictures and verbal discourse during the practical work section. These challenges include those when students realise textual and visual modes and those when students associate components of apparatus into a system of functional set-up. Moreover, students cannot construct thematic patterns because they reorient their focus from the domain of ideas to the domain of objects and observables. The study recorded a number of strategies that students use to overcome these challenges that impede their meaning-making. Conclusion: The findings of this study contribute to the literature by identifying the challenges and strategies faced by students when they were connecting the scientific ideas with the practical work. When science education researchers advocate an inquiry oriented approach, they should provide ample scaffolds for these multimodal challenges.

Stratified teaching is an effective method and means to implement teaching students per their aptitude. Domestic and foreign scholars have carried out many experimental and quasiexperimental studies to observe the impact of stratified teaching on students' academic performance, but the results are quite different. So, can stratified teaching effectively help Chinese students improve their academic performance? How big is its impact? Which model is more suitable for Chinese students? To answer these questions, this article uses meta-analysis to quantitatively analyze 22 Chinese studies on the impact of Stratified teaching on student academic performance. We found that (i) stratified teaching has a positive effect on students' academic performance, and the overall combined effect size is 0.53; (ii) among the seven subjects of mathematics, English, physics, chemistry, biology, geography, and information technology, stratified teaching has had a positive effect on their learning. Stratified teaching's order of effect on different subjects was English > Physics > Geography > Information Technology > Mathematics > Biology > Chemistry; (iii) stratified teaching is suitable for students of different sizes of classrooms. However, the smaller the number of students in the classroom, the better the learning effect, and (iv) stratified teaching is more suitable for improving their learning in the mobile learning system.

This study proposed frameworks for designing inquiry approaches with multimedia in science e-textbooks through exploring the extent and features of inquiry approaches with science topics in a digital textbook. Results revealed that the experiential, evidence-based and predict-observe-explain approaches are designed in 70% of the science topics. Such design differs by subject (earth science, biology, or physics). Through analyzing concrete examples, frameworks are consolidated to demonstrate how these approaches involve resources such as dialogue cartoons, animations, or simulations to assist students' inquiry and understanding of science phenomena. This study has implications for science e-textbook design and inquiry-based teaching in primary schools.

This study applied an unconventional use of past examination papers by converting questions into hands-on experiments for students. Students in an experimental group were engaged in use of those experiments while the remainder attended conventional lectures with written practice. The results reflect that the experimental group positively improved in understanding, observational skills and learning attitude compared with the control group.

For students to be successful in school chemistry, a strong sense of self-efficacy is essential. Chemistry self-efficacy can be defined as students' beliefs about the extent to which they are capable of performing specific chemistry tasks. According to Bandura ("Psychol. Rev." 84:191-215, 1977), students acquire information about their level of self-efficacy from four sources: performance accomplishments, vicarious experiences, verbal persuasion, and physiological states. No published studies have investigated how instructional strategies in chemistry lessons can provide students with positive experiences with these four sources of self-efficacy information and how the instructional strategies promote students' chemistry self-efficacy. In this study, questionnaire items were constructed to measure student perceptions about instructional strategies, termed efficacy-enhancing teaching, which can provide positive experiences with the four sources of self-efficacy information. Structural equation modeling was then applied to test a hypothesized mediation model, positing that efficacy-enhancing teaching positively affects students' chemistry self-efficacy through their use of deep learning strategies such as metacognitive control strategies. A total of 590 chemistry students at nine secondary schools in Hong Kong participated in the survey. The mediation model provided a good fit to the student data. Efficacy-enhancing teaching had a direct effect on students' chemistry self-efficacy. Efficacy-enhancing teaching also directly affected students' use of deep learning strategies, which in turn affected students' chemistry self-efficacy. The implications of these findings for developing secondary school students' chemistry self-efficacy are discussed.

In this laboratory experiment, lower- and upper-division students dissolved bismuth subsalicylate tablets in acid and precipitated the resultant Bi[superscript 3+] in solution with sodium phosphate for a gravimetric determination of bismuth subsalicylate in the tablets. With a labeled concentration of 262 mg/tablet, the combined data from three different courses (general chemistry I and II and quantitative analysis) determined an average tablet concentration of 272.0 mg/tablet, with a standard deviation of ±48.46 mg. When analyzed by upper-division students, an average of 268.8 mg/tablet with a standard deviation of 16.02 mg was obtained, which confirmed the labeled concentration. In addition, students were given an opportunity to react the remaining solution with aluminum to reduce the ionic bismuth and produce a solid metal product, which reinforced the concepts of precipitation, stoichiometry, and reduction-oxidation in a single laboratory experiment.

Gas adsorption on porous solids is a topic that is often discussed in an undergraduate chemistry or chemical engineering course. The idea of porosity and gas adsorption on a porous solid is usually discussed with adsorption isotherms recorded using commercially available equipment. This discussion can be rather abstract and can be difficult for students to visualize. Here, four demonstrations highlight the adsorption of CO2 gas on adsorbents. These simple demonstrations show gas adsorption in a dynamic way that can help students understand the properties of porous solids.

One of the characteristics of teaching chemistry through inquiry is that teachers need to encourage students to design their experimental procedures. Although the benefits of inquiry teaching are well documented in the literature, few teachers implement it in schools. The purpose of this study was to develop a guided-inquiry scale (GIS) to measure teachers' beliefs about implementing guided-inquiry labs in secondary schools. Construction of this guided-inquiry scale was based on a model with three dimensions: the value of guided-inquiry labs, limitations of cookbook-style labs, and implementation issues with guided-inquiry labs. Data were collected from 200 Hong Kong chemistry teachers. They responded to the GIS items using a seven-point Likert scale. The GIS data were of adequate reliability. Confirmatory factor analysis indicated that a good fit exists between the hypothesized model and data. Both users and nonusers of guided-inquiry labs valued this kind of lab work and recognized the limitations of cookbook-style labs; however, nonusers tended to believe that students dislike guided inquiry and it is not feasible for students to design experiments. The length of chemistry teaching experience and the level of student ability did not influence teachers' beliefs about implementing guided-inquiry labs. (Contains 5 tables.)

Nineteen pre-service and in-service teachers taking a chemistry teaching methods course at a university in Hong Kong were asked to take a diagnostic assessment. It consisted of seven multiple-choice questions about the chemistry of the lead-acid battery. Analysis of the teachers' responses to the questions indicated that they had difficulty in solving problems regarding the recharging reaction at the anode, the direction of electron flow when recharging the battery, and the role of sulfuric acid. A class discussion was conducted to identify the teachers' misconceptions about the chemistry of lead-acid battery. A laboratory experiment was also carried out to help teachers dispel their misconceptions. (Contains 3 tables and 2 figures.)

The importance of research on misconceptions about chemical equilibrium is well recognized by educators, but in the past, researchers' interest has centered on student misconceptions and has neglected teacher misconceptions. Focusing on the effects of adding more reactants or products on chemical equilibrium, this article discusses the various misconceptions held by high school teachers. A misconception test was administered to two samples of chemistry teachers in Nanjing, China. Of the 109 teachers who participated in the test, only one understood that adding more CS[subscript 2] gas to the equilibrium system CS[subscript 2](g) + 4H[subscript 2](g) [rightwards harpoon over leftwards harpoon] CH[subscript 4](g) + 2H[subscript 2]S(g) at constant pressure and temperature can shift the equilibrium to the reactant or product side, depending upon the amount of CS[subscript 2] in the initial equilibrium system. Most of the teachers relied on Le Chatelier's principle and thus made erroneous predictions. The misconception test also revealed that those teachers who managed to compute equilibrium constants had a limited conceptual understanding of chemical equilibrium. Implications of these findings for teacher education and chemistry curriculum development are discussed.

Students' attitudes toward chemistry lessons in school are important dependent variables in curriculum evaluation. Although a variety of instruments have been developed by researchers to evaluate student attitudes, they are plagued with problems such as the lack of theoretical rationale and of empirical evidence to support the construct validity of data. This paper describes a study of students' attitudes toward chemistry lessons in Hong Kong secondary schools. One of the scales in the Test of Science-Related Attitudes developed by Fraser was modified to form an Attitude Toward Chemistry Lessons Scale (ATCLS). The construction of the ATCLS was based on a theoretical model with four dimensions: liking for chemistry theory lessons, liking for chemistry laboratory work, evaluative beliefs about school chemistry, and behavioural tendencies to learn chemistry. The arguments for inclusion of these four dimensions are presented. The final version of ATCLS was administered to 954 students. The results of confirmatory factor analysis indicated that there was a good fit between the hypothesised model and the observed data. (Contains 1 figure and 5 tables.)

Although the scientific inadequacy of Le Chatelier's principle has long been documented in the literature, the principle is still treated as a central concept of chemical equilibrium by textbook writers and teachers in many countries. In the past, researchers' interest has focused on student misconceptions about chemical equilibrium and has neglected teacher misconceptions. This study aimed to determine how Le Chatelier's principle adversely affects teachers' ability to solve chemical equilibrium problems. This area of research is critically important because teachers cannot help their students understand what they themselves do not understand. In this study, a misconception test was developed and administered to a sample of 33 secondary chemistry teachers in Hong Kong. The test consisted of three open-ended chemical equilibrium questions. Analysis of teacher responses revealed that most of the 33 teachers failed the test as they relied on Le Chatelier's principle rather than the equilibrium law to tackle the three chemical equilibrium problems. Teachers' misconceptions about chemical equilibrium were categorized. Implications of these findings for chemistry teacher education and selection of curriculum content for school chemistry are discussed. (Contains 3 tables.)

The purpose of this quantitative study was to examine the interaction effect between grade level and gender with respect to students' attitudes toward chemistry lessons taught in secondary schools. The sample consisted of 954 chemistry students in grades Secondary 4-7 (approximately 16-19 years of age) in Hong Kong. Students' attitudes were surveyed using an attitude toward chemistry lessons scale (ATCLS), and subscale scores were produced on four dimensions: liking for chemistry theory lessons; liking for chemistry laboratory work; evaluative beliefs about school chemistry; and behavioral tendencies to learn chemistry. When the ATCLS data were subjected to two-way MANOVA, the interaction effect between grade level and gender on students' attitudes toward chemistry lessons was statistically significant. The interaction effect was attributable to scores on the theory lessons subscale and laboratory work subscale. Male students in Secondary 4 and 5 liked chemistry theory lessons more than their female counterparts. However, male students' liking for chemistry laboratory work declined when they progressed from Secondary 4 to Secondary 7; no such a significant decline in attitude toward chemistry laboratory work was found in females. Overall, both males and females were just marginally positive about chemistry lessons during the years of secondary schooling. Implications of these findings for curriculum design are discussed.

Secondary school chemistry teachers' understanding of chemical equilibrium was investigated through interviews using the think-aloud technique. The interviews were conducted with twelve volunteer chemistry teachers in Hong Kong. Their teaching experience ranged from 3 to 18 years. They were asked to predict what would happen to the equilibrium system N[subscript 2](g) + 3H[subscript 2](g) [double-harpoon] 2NH[subscript 3](g) if a small amount of nitrogen gas is added to the system at constant pressure and temperature. Analyses of the transcribed protocols indicated that regardless of the teachers' years of teaching experience, none of the twelve teachers were able to solve the chemical equilibrium problem. An over-emphasis of Le Chatelier's principle was found to be a major contributing factor to teachers' problem-solving failures. They held the misconception that one can always cause an equilibrium system to shift to the right by increasing the concentration of a reactant. The interviewed teachers were classified into two problem-solving categories based on their cognitive sources of failures. Excerpts from the transcripts discuss the differences between the two categories as well as the hints given to teachers to help them solve the chemical equilibrium problem. (Contains 5 tables.)

Science teachers generally find inquiry-based laboratory work very difficult to manage. This research project aimed at facilitating chemistry teachers to implement inquiry-based laboratory work in Hong Kong secondary schools. The major concerns of seven chemistry teachers were identified. They were most concerned about the lack of class time, shortage of effective instructional materials, and the need to teach large classes. To allay teacher concerns, teaching strategies were developed to aid teachers. The strategies include the use of guided inquiry rather than open inquiry, development of ten examples of authentic inquiry, and inclusion of student oral presentations as a key component of the inquiry process. Trials done in schools indicated that these strategies are useful.

This authentic inquiry-based chemistry experiment provides high school students with an opportunity to investigate the effect of toothpastes on the rate of tooth decay. Students need to design and carry out a fair test to compare the effects of different brands of toothpaste. The author has developed rubrics for assessing students' planning skills and written laboratory reports.

School-based assessment of science students' practical skills has two important roles--as a complement to written papers in public examinations and as a catalyst for enriching the science curriculum in schools. This article describes a quantitative study of the concerns chemistry and biology teachers experience as they engage in the process of implementation of a school-based assessment scheme for practical work. A 23-item questionnaire was developed to measure five categories of teacher concern: evaluation, information, management, consequence and refocusing. The nature of each category of teacher concern is discussed in relation to innovation adoption and implementation. Data were collected from 400 chemistry and 412 biology teachers in Hong Kong. Teachers' information and management concerns lessened in intensity when they became experienced users of a school-based assessment scheme. However, teaching experience alone could not motivate teachers to think more about the impact of school-based assessment on student learning, their professional development in student assessment and the possible refinements in their school-based assessment scheme. Concerns-based interventions are suggested to help teachers grow professionally.

During the past decades, the source apportionment of organic aerosol (OA) in ambient air has been improving substantially. The database of source retrieval model-resolved mass spectral profiles for different sources has been built with the aerosol mass spectrometer (AMS). However, distinguishing similar sources (such as wildfires and residential wood burning) remains challenging, as the hard ionization of the AMS mostly fragments compounds and therefore cannot capture detailed molecular information. Recent mass spectrometer technologies of soft ionization and high mass resolution have allowed for aerosol characterization at the molecular formula level. In this study, we systematically estimated the emission factors and characterized the primary OA (POA) chemical composition with the AMS and the extractive electrospray ionization time-of-flight mass spectrometer (EESI-TOF) for the first time from a variety of solid fuels, including beech logs, spruce and pine logs, spruce and pine branches and needles, straw, cow dung, and plastic bags. The emission factors of organic matter estimated by the AMS and hydrocarbon gases estimated by the total hydrocarbon analyzer are 16.2 ± 10.8 g kg−1 and 30.3 ± 8.5 g kg−1 for cow dung burning, which is generally higher than that of wood (beech, spruce, and pine), straw, and plastic bag burning (in the range from 1.1 to 6.2 g kg−1 and 14.1 to 19.3 g kg−1). The POA measured by the AMS shows that the f60 (mass fraction of m/z 60) varies from 0.003 to 0.04 based on fuel types and combustion efficiency for wood (beech, spruce, and pine) and cow dung burning. On a molecular level, the dominant compound of POA from wood, straw, and cow dung is C6H10O5 (mainly levoglucosan), contributing ∼ 7 % to ∼ 30 % of the total intensity, followed by C8H12O6 with fractions of ∼ 2 % to ∼ 9 %. However, as they are prevalent in all burning of biomass material, they cannot act as tracers for the specific sources. By using the Mann–Whitney U test among the studied fuels, we find specific potential new markers for these fuels from the measurement of the AMS and EESI-TOF. Markers from spruce and pine burning are likely related to resin acids (e.g., compounds with 20–21 carbon atoms). The product from the pyrolysis of hardwood lignins is found especially in beech log burning. Nitrogen-containing species are selected markers primarily for cow dung open burning. These markers in the future will provide support for the source apportionment.

The deregulation of monounsaturated, polyunsaturated, and saturated fatty acids (MUFAs, PUFAs, SFAs) from de novo synthesis and hypoxia are central metabolic features of breast tumour. Early response markers for neoadjuvant chemotherapy (NACT) are critical for stratified treatment for patients with breast cancer, and restoration of lipid metabolism and normoxia might precede observable structural change. In this study, we hypothesised that peri-tumoural lipid composition and hypoxia might be predictive and early response markers in patients with breast cancer undergoing NACT. Female patients with breast cancer were scanned on a 3T clinical MRI scanner at baseline and Cycle1, with acquisition of lipid composition maps of MUFAs, PUFAs, and SFAs, and hypoxia maps of effective transverse relaxation rate R2*. The percentage change in lipid composition and hypoxia at Cycle1 was calculated with reference to baseline. Tumour-associated macrophages were analysed based on immunostaining of CD163 from biopsy and resection, with the percentage change in the resected tumour calculated across the entire NACT. We found no significant difference in lipid composition and R2* between good and poor responders at baseline and Cycle1; however, the correlation between the percentage change in MUFAs and PUFAs against CD163 suggested the modulation in lipids with altered immune response might support the development of targeted therapies.

RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability of targeting sequences. Nevertheless, RNA shows instability and has a short half-life in physiological environments such as the bloodstream in the presence of RNAase. Therefore, developing reliable delivery strategies is important for targeting disease sites and maximizing the therapeutic effect of RNA drugs, particularly in the field of immunotherapy. In this mini-review, we highlight two major approaches: (1) delivery vehicles and (2) chemical modifications. Recent advances in delivery vehicles employ nanotechnologies such as lipid-based nanoparticles, viral vectors, and inorganic nanocarriers to precisely target specific cell types to facilitate RNA cellular entry. On the other hand, chemical modification utilizes the alteration of RNA structures via the addition of covalent bonds such as N-acetylgalactosamine or antibodies (antibody–oligonucleotide conjugates) to target specific receptors of cells. The pros and cons of these technologies are enlisted in this review. We aim to review nucleic acid drugs, their delivery systems, targeting strategies, and related chemical modifications. Finally, we express our perspective on the potential combination of RNA-based click chemistry with adoptive cell therapy (e.g., B cells or T cells) to address the issues of short duration and short half-life associated with antibody–oligonucleotide conjugate drugs.

Kawasaki disease (KD) is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels, which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as the disease progresses, with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated with KD, but also evaluates the possibility of using circulating endothelial injury biomarkers, such as circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tools for KD: a “liquid biopsy” approach. The challenges of translating liquid biopsies to use in KD and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostic tools is promising, and we hope this will be translated to clinical applications in the near future.

Background: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Methods: Transmission electron microscopy was used to analyze mitochondria within 0–3.5 μm and 3.5–7 μm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. Results: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. Conclusion: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.

A short, semi-microscale synthesis of two 1,4-dihydropyridine drug analogues via a Hantzsch reaction is described, which is appropriate for a second-year undergraduate organic laboratory. Products are specifically chosen to highlight the biological relevance of this compound type while introducing the notion of a privileged structure. 1,4-Dihydropyridines are bioactive as calcium channel blockers and antioxidants and are lead candidates in the treatment of various medical conditions. Students generate one substituted 1,4-dihydropyridine by an operationally simple process and characterize it by melting point measurements, IR spectroscopy, and [superscript 1]H and [superscript 13]C NMR spectroscopy. This provides a springboard to discuss concepts of green chemistry, structure-activity relationships, conformational analysis, and related synthetic approaches. (Contains 1 figure, 1 scheme and 5 notes.)

A primary sink of air pollutants and their precursors is dry deposition. Dry deposition estimates differ across chemical transport models, yet an understanding of the model spread is incomplete. Here, we introduce Activity 2 of the Air Quality Model Evaluation International Initiative Phase 4 (AQMEII4). We examine 18 dry deposition schemes from regional and global chemical transport models as well as standalone models used for impact assessments or process understanding. We configure the schemes as single-point models at eight Northern Hemisphere locations with observed ozone fluxes. Single-point models are driven by a common set of site-specific meteorological and environmental conditions. Five of eight sites have at least 3 years and up to 12 years of ozone fluxes. The interquartile range across models in multiyear mean ozone deposition velocities ranges from a factor of 1.2 to 1.9 annually across sites and tends to be highest during winter compared with summer. No model is within 50 % of observed multiyear averages across all sites and seasons, but some models perform well for some sites and seasons. For the first time, we demonstrate how contributions from depositional pathways vary across models. Models can disagree with respect to relative contributions from the pathways, even when they predict similar deposition velocities, or agree with respect to the relative contributions but predict different deposition velocities. Both stomatal and nonstomatal uptake contribute to the large model spread across sites. Our findings are the beginning of results from AQMEII4 Activity 2, which brings scientists who model air quality and dry deposition together with scientists who measure ozone fluxes to evaluate and improve dry deposition schemes in the chemical transport models used for research, planning, and regulatory purposes.

Diabetes is associated with numerous comorbidities, one of which is increased vulnerability to infections. This review will focus on how diabetes mellitus (DM) affects the immune system and its various components, leading to the impaired proliferation of immune cells and the induction of senescence. We will explore how the pathology of diabetes-induced immune dysfunction may have similarities to the pathways of “inflammaging”, a persistent low-grade inflammation common in the elderly. Inflammaging may increase the likelihood of conditions such as rheumatoid arthritis (RA) and periodontitis at a younger age. Diabetes affects bone marrow composition and cellular senescence, and in combination with advanced age also affects lymphopoiesis by increasing myeloid differentiation and reducing lymphoid differentiation. Consequently, this leads to a reduced immune system response in both the innate and adaptive phases, resulting in higher infection rates, reduced vaccine response, and increased immune cells’ senescence in diabetics. We will also explore how some diabetes drugs induce immune senescence despite their benefits on glycemic control.

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions. In cancer, CNAs have been associated with almost all steps of the disease: predisposition, initiation, development, maintenance, response to treatment, resistance, and relapse. Therefore, understanding how specific CNAs contribute to tumourigenesis may provide prognostic insight and ultimately lead to the development of new therapeutic approaches to improve patient outcomes. In this review, we provide a snapshot of what is currently known about CNAs and cancer, incorporating topics regarding their detection, clinical impact, origin, and nature, and discuss the integration of innovative genetic engineering strategies, to highlight the potential for targeting CNAs using novel, dosage-sensitive and less toxic therapies for CNA-driven cancer.

Melatonin is a neuroendocrine hormone that regulates the circadian rhythm and many other physiological processes. Its functions are primarily exerted through two subtypes of human melatonin receptors, termed melatonin type-1 (MT1) and type-2 (MT2) receptors. Both MT1 and MT2 receptors are generally classified as Gi-coupled receptors owing to their well-recognized ability to inhibit cAMP accumulation in cells. However, it remains an enigma as to why melatonin stimulates cAMP production in a number of cell types that express the MT1 receptor. To address if MT1 can dually couple to Gs and Gi proteins, we employed a highly sensitive luminescent biosensor (GloSensorTM) to monitor the real-time changes in the intracellular cAMP level in intact live HEK293 cells that express MT1 and/or MT2. Our results demonstrate that the activation of MT1, but not MT2, leads to a robust enhancement on the forskolin-stimulated cAMP formation. In contrast, the activation of either MT1 or MT2 inhibited cAMP synthesis driven by the activation of the Gs-coupled β2-adrenergic receptor, which is consistent with a typical Gi-mediated response. The co-expression of MT1 with Gs enabled melatonin itself to stimulate cAMP production, indicating a productive coupling between MT1 and Gs. The possible existence of a MT1-Gs complex was supported through molecular modeling as the predicted complex exhibited structural and thermodynamic characteristics that are comparable to that of MT1-Gi. Taken together, our data reveal that MT1, but not MT2, can dually couple to Gs and Gi proteins, thereby enabling the bi-directional regulation of adenylyl cyclase to differentially modulate cAMP levels in cells that express different complements of MT1, MT2, and G proteins.

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8–61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32–29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73–14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels’ conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo.

MYCN amplification occurs in approximately 20–30% of neuroblastoma patients and correlates with poor prognosis. The TH-MYCN transgenic mouse model mimics the development of human high-risk neuroblastoma and provides strong evidence for the oncogenic function of MYCN. In this study, we identified mitotic dysregulation as a hallmark of tumor initiation in the pre-cancerous ganglia from TH-MYCN mice that persists through tumor progression. Single-cell quantitative-PCR of coeliac ganglia from 10-day-old TH-MYCN mice revealed overexpression of mitotic genes in a subpopulation of premalignant neuroblasts at a level similar to single cells derived from established tumors. Prophylactic treatment using antimitotic agents barasertib and vincristine significantly delayed the onset of tumor formation, reduced pre-malignant neuroblast hyperplasia, and prolonged survival in TH-MYCN mice. Analysis of human neuroblastoma tumor cohorts showed a strong correlation between dysregulated mitosis and features of MYCN amplification, such as MYC(N) transcriptional activity, poor overall survival, and other clinical predictors of aggressive disease. To explore the therapeutic potential of targeting mitotic dysregulation, we showed that genetic and chemical inhibition of mitosis led to selective cell death in neuroblastoma cell lines with MYCN over-expression. Moreover, combination therapy with antimitotic compounds and BCL2 inhibitors exploited mitotic stress induced by antimitotics and was synergistically toxic to neuroblastoma cell lines. These results collectively suggest that mitotic dysregulation is a key component of tumorigenesis in early neuroblasts, which can be inhibited by the combination of antimitotic compounds and pro-apoptotic compounds in MYCN-driven neuroblastoma.

Abstract Specific bioconjugation for native primary amines is highly valuable for both chemistry and biomedical research. Despite all the efforts, scientists lack a proper strategy to achieve high selectivity for primary amines, not to mention the requirement of fast response in real applications. Herein, we report a chromone‐based aggregation‐induced emission (AIE) fluorogen called CMVMN as a self‐reporting bioconjugation reagent for selective primary amine identification, and its applications for monitoring bioprocesses of amination and protein labeling. CMVMN is AIE‐active and capable of solid‐state sensing. Thus, its electrospun films are manufactured for visualization of amine diffusion and leakage process. CMVMN also shows good biocompatibility and potential mitochondria‐staining ability, which provides new insight for organelle‐staining probe design. Combined with its facile synthesis and good reversibility, CMVMN would not only show wide potential applications in biology, but also offer new possibilities for molecular engineering.

Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually. Furthermore, pet animals can be temporary carriers of strains infectious to humans. Moreover, antimicrobial resistance is a great concern in livestock infections, as there is considerable antibiotic overuse, and resistant strains can be transferred to humans. With the number of working antibiotics continuously becoming smaller due to the concomitant spread of resistant strains, alternative approaches, such as anti-virulence, are increasingly being investigated to treat staphylococcal infections. For this, understanding the virulence mechanisms of animal staphylococcal pathogens is crucial. While many virulence factors have similar functions in humans as animals, there are increasingly frequent reports of host-specific virulence factors and mechanisms. Furthermore, we are only beginning to understand virulence mechanisms in animal-specific staphylococcal pathogens. This review gives an overview of animal infections caused by staphylococci and our knowledge about the virulence mechanisms involved.

The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. However, osteosarcoma is an inherently heterogeneous tumor, both at the intra- and inter-tumor level, with no identical driver mutations. It has a pro-tumoral microenvironment, where bone cells, stromal cells, neovasculature, suppressive immune cells, and a mineralized extracellular matrix (ECM) combine to derail T cell infiltration and its anti-tumor function. To realize the potential of T cell immunotherapy in osteosarcoma, an integrated approach targeting this complex ecosystem needs smart planning and execution. Herein, we review the current status of T cell immunotherapies for osteosarcoma, summarize the challenges encountered, and explore combination strategies to overcome these hurdles, with the ultimate goal of curing osteosarcoma with less acute and long-term side effects.

Neuroinflammation is the precursor for several neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Targeting neuroinflammation has emerged as a promising strategy to address a wide range of CNS pathologies. These NDDs still present significant challenges in terms of limited and ineffective diagnosis and treatment options, driving the need to explore innovative and novel therapeutic alternatives. Aptamers are single-stranded nucleic acids that offer the potential for addressing these challenges through diagnostic and therapeutic applications. In this review, we summarize diagnostic and therapeutic aptamers for inflammatory biomolecules, as well as the inflammatory cells in NDDs. We also discussed the potential of short nucleotides for Aptamer-Based Targeted Brain Delivery through their unique features and modifications, as well as their ability to penetrate the blood-brain barrier. Moreover, the unprecedented opportunities and substantial challenges of using aptamers as therapeutic agents, such as drug efficacy, safety considerations, and pharmacokinetics, are also discussed. Taken together, this review assesses the potential of aptamers as a pioneering approach for target delivery to the CNS and the treatment of neuroinflammation and NDDs.

Despite the declining trend of Helicobacter pylori (H. pylori) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori. In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori, so that it can be managed in a sustainable and efficient manner.

Objectives: Verifying new reagent or calibrator lots is crucial for maintaining consistent test performance. The Institute for Quality Management in Healthcare (IQMH) conducted a patterns-of-practice survey and follow-up case study to collect information on lot verification practices in Ontario. Methods: The survey had 17 multiple-choice questions and was distributed to 183 licensed laboratories. Participants provided information on materials used and approval/rejection criteria for their lot verification procedures for eight classes of testing systems. The case study provided a set of lot comparison data and was distributed to 132 laboratories. Responses were reviewed by IQMH scientific committees. Results: Of the 175 laboratories that responded regarding reagent lot verifications, 74% verified all tests, 11% some, and 15% none. Of the 171 laboratories that responded regarding calibrator lot verifications, 39% verified all calibrators, 4% some, and 57% none. Reasons for not performing verifications ranged from difficulty performing parallel testing to high reagent cost. For automated chemistry assays and immunoassays, 23% of laboratories did not include patient-derived materials in reagent lot verifications and 42% included five to six patient materials; 58% of laboratories did not include patient-derived materials in calibrator lot verifications and 23% included five to six patient materials. Different combinations of test-specific rules were used for acceptance criteria. For a failed lot, 98% of laboratories would investigate further and take corrective actions. Forty-three percent of laboratories would accept the new reagent lot in the case study. Conclusion: Responses to the survey and case study demonstrated variability in lot verification practices among laboratories.

An accurate emission inventory is a crucial part of air pollution management and is essential for air quality modelling. One source in an emission inventory, an industrial source, has been known with high uncertainty in both location and magnitude in China. In this study, a new reallocation method based on blue-roof industrial buildings was developed to replace the conventional method of using population density for the Chinese emission development. The new method utilized the zoom level 14 satellite imagery (i.e. Google®) and processed it based on hue, saturation, and value (HSV) colour classification to derive new spatial surrogates for province-level reallocation, providing more realistic spatial patterns of industrial PM2.5 and NO2 emissions in China. The WRF-CMAQ-based PATH-2016 model system was then applied with the new processed industrial emission input in the MIX inventory to simulate air quality in the Greater Bay Area (GBA) area (formerly called Pearl River Delta, PRD). In the study, significant root mean square error (RMSE) improvement was observed in both summer and winter scenarios in 2015 when compared with the population-based approach. The average RMSE reductions (i.e. 75 stations) of PM2.5 and NO2 were found to be 11 µg m−3 and 3 ppb, respectively. Although the new method for allocating industrial sources did not perform as well as the point- and area-based industrial emissions obtained from the local bottom-up dataset, it still showed a large improvement over the existing population-based method. In conclusion, this research demonstrates that the blue-roof industrial allocation method can effectively identify scattered industrial sources in China and is capable of downscaling the industrial emissions from regional to local levels (i.e. 27 to 3 km resolution), overcoming the technical hurdle of ∼ 10 km resolution from the top-down or bottom-up emission approach under the unified framework of emission calculation.

Theoretical models of the Earth's atmosphere adhere to an underlying concept of flow driven by radiative transfer and the nature of the surface over which the flow is taking place: heat from the sun and/or anthropogenic sources are the sole sources of energy driving atmospheric constituent transport. However, another source of energy is prevalent in the human environment at the very local scale – the transfer of kinetic energy from moving vehicles to the atmosphere. We show that this source of energy, due to being co-located with combustion emissions, can influence their vertical distribution to the extent of having a significant influence on lower-troposphere pollutant concentrations throughout North America. The effect of vehicle-induced turbulence on freshly emitted chemicals remains notable even when taking into account more complex urban radiative transfer-driven turbulence theories at high resolution. We have designed a parameterization to account for the at-source vertical transport of freshly emitted pollutants from mobile emissions resulting from vehicle-induced turbulence, in analogy to sub-grid-scale parameterizations for plume rise emissions from large stacks. This parameterization allows vehicle-induced turbulence to be represented at the scales inherent in 3D chemical transport models, allowing this process to be represented over larger regions than is currently feasible with large eddy simulation models. Including this sub-grid-scale parameterization for the vertical transport of emitted pollutants due to vehicle-induced turbulence in a 3D chemical transport model of the atmosphere reduces pre-existing North American nitrogen dioxide biases by a factor of 8 and improves most model performance scores for nitrogen dioxide, particulate matter, and ozone (for example, reductions in root mean square errors of 20 %, 9 %, and 0.5 %, respectively).

The influence of both anthropogenic and forest-fire emissions, and their subsequent chemical and physical processing, on the accuracy of weather and air-quality forecasts, was studied using a high-resolution, online coupled air-quality model. Simulations were carried out for the period 4 July through 5 August 2019, at 2.5 km horizontal grid cell size, over a 2250×3425 km2 domain covering western Canada and USA, prior to the use of the forecast system as part of the FIREX-AQ ensemble forecast. Several large forest fires took place in the Canadian portion of the domain during the study period. A feature of the implementation was the incorporation of a new online version of the Canadian Forest Fire Emissions Prediction System (CFFEPSv4.0). This inclusion of thermodynamic forest-fire plume-rise calculations directly into the online air-quality model allowed us to simulate the interactions between forest-fire plume development and weather. Incorporating feedbacks resulted in weather forecast performance that exceeded or matched the no-feedback forecast, at greater than 90 % confidence, at most times and heights in the atmosphere. The feedback forecast outperformed the feedback forecast at 35 out of 48 statistical evaluation scores, for PM2.5, NO2, and O3. Relative to the climatological cloud condensation nuclei (CCN) and aerosol optical properties used in the no-feedback simulations, the online coupled model's aerosol indirect and direct effects were shown to result in feedback loops characterized by decreased surface temperatures in regions affected by forest-fire plumes, decreases in stability within the smoke plume, increases in stability further aloft, and increased lower troposphere cloud droplet and raindrop number densities. The aerosol direct and indirect effect reduced oceanic cloud droplet number densities and increased oceanic raindrop number densities, relative to the no-feedback climatological simulation. The aerosol direct and indirect effects were responsible for changes to the near-surface PM2.5 and NO2 concentrations at greater than the 90 % confidence level near the forest fires, with O3 changes remaining below the 90 % confidence level. The simulations show that incorporating aerosol direct and indirect effect feedbacks can significantly improve the accuracy of weather and air-quality forecasts and that forest-fire plume-rise calculations within an online coupled model change the predicted fire plume dispersion and emissions, the latter through changing the meteorology driving fire intensity and fuel consumption.

Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most severe neurological disorders, with a high mortality rate and severe disabling functional sequelae. Systemic inflammation following hemorrhagic stroke may play an important role in mediating intracranial and extracranial tissue damage. Previous studies showed that various systemic inflammatory biomarkers might be useful in predicting clinical outcomes. Anti-inflammatory treatment might be a promising therapeutic approach for improving the prognosis of patients with aSAH. This review summarizes the complicated interactions between the nervous system and the immune system.

There is an urgent need for the identification as well as clinicopathological and functional characterization of potent prognostic biomarkers and therapeutic targets in acute myeloid leukemia (AML). Using immunohistochemistry and next-generation sequencing, we investigated the protein expression as well as clinicopathological and prognostic associations of serine protease inhibitor Kazal type 2 (SPINK2) in AML and examined its potential biological functions. High SPINK2 protein expression was an independent adverse biomarker for survival and an indicator of elevated therapy resistance and relapse risk. SPINK2 expression was associated with AML with an NPM1 mutation and an intermediate risk by cytogenetics and European LeukemiaNet (ELN) 2022 criteria. Furthermore, SPINK2 expression could refine the ELN2022prognostic stratification. Functionally, an RNA sequencing analysis uncovered a potential link of SPINK2 with ferroptosis and immune response. SPINK2 regulated the expression of certain P53 targets and ferroptosis-related genes, including SLC7A11 and STEAP3, and affected cystine uptake, intracellular iron levels and sensitivity to erastin, a specific ferroptosis inducer. Furthermore, SPINK2 inhibition consistently increased the expression of ALCAM, an immune response enhancer and promoter of T-cell activity. Additionally, we identified a potential small-molecule inhibitor of SPINK2, which requires further characterization. In summary, high SPINK2 protein expression was a potent adverse prognostic marker in AML and might represent a druggable target.

Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3β (S9):GSK-3β ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3β activity without an apparent change in post-injury tauopathy in rTg4510 mice.

Molecules involved in drug resistance can be targeted for better therapeutic efficacies. Research on midkine (MDK) has escalated in the last few decades, which affirms a positive correlation between disease progression and MDK expression in most cancers and indicates its association with multi-drug resistance in cancer. MDK, a secretory cytokine found in blood, can be exploited as a potent biomarker for the non-invasive detection of drug resistance expressed in various cancers and, thereby, can be targeted. We summarize the current information on the involvement of MDK in drug resistance, and transcriptional regulators of its expression and highlight its potential as a cancer therapeutic target.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.