The persistent use of solid fuel for domestic energy in South Africa's low-income settlements remains a critical air quality concern, posing severe health risks to vulnerable populations. Previous interventions have focused on a top-down approach of total fuel replacement, which frequently fails as households revert to coal and wood due to economic volatility and high electricity costs. The Semi-Continuous Coal Stove (SCCS), co-developed by North-West University and New Dawn Engineering (Pty) Ltd., offers a pragmatic alternative. However, while the SCCS performs exceptionally well in laboratory settings, its success in reducing real-world exposure depends on overcoming intricate social and behavioural barriers that lab tests cannot simulate. This study evaluates the impact of the SCCS through a socio-technical framework, utilising an unsupervised field trial in the Metsimaholo township in the Northern Free State. The novelty of this research lies in its integrated socio-technical evaluation of the Semi-Continuous Coal Stove (SCCS) as a realistic transition pathway. A dual-methodology approach was employed: qualitative assessments of socioeconomic profiles and user perceptions, and quantitative monitoring of indoor air quality PM 2.5 and CO during stove operation. The social findings reveal that households are experiencing significant economic challenges, including 38% unemployment and 41% relying on government pensions and grants. Although all houses are connected to the electricity grid, fuel stacking is practised for cooking and heating due to cost factors. Wood (63%), gas (40%), and coal (17%) are the most used energy sources. The SCCS significantly reduces indoor PM 2.5 and CO exposures by more than 50% during operational and burnout phases compared to traditional stoves. The SCCS ignition phase resulted in increased concentrations between 15% and 40%. About 50% of the participants found the stove easy to use, while the other 50% faced difficulties, particularly with ignition. Overall, the SCCS operational characteristics were viewed favourably by more than 90% of the households. The SCCS serves as a pragmatic transition pathway for coal-supplied communities, offering a realistic means to reduce indoor pollutant exposure. The study establishes a compelling case for a broader rollout on the South African Highveld to meet national clean air targets. • Solid fuel stacking is practised due to affordability. • Stove use proficiency is essential for successful improved cookstove interventions. • The SCCS demonstrated improvements in indoor air quality. • Households perceive the SCCS as a preferred alternative to conventional cookstoves. • The SCCS is a viable technology for solid fuel-burning low-income households

Green hydrogen in the Netherlands: A systemic assessment of status and barriers

Pathways for coal-fired power plants green production process transition

The historical context of gender-affirming healthcare (GAH) in Morocco presents a paradox. While Casablanca emerged as a global hub for such medical procedures from the 1950s to the 1970s, access to care was not available to local Moroccan citizens. Currently, transgender and gender non-conforming (TGNC) individuals experience what can be described as a "ban by silence." Although there is no explicit legal prohibition against GAH, its accessibility is effectively undermined by institutional neglect, inadequate medical education, and pervasive socio-religious biases among healthcare providers. This research aims to generate empirical evidence to inform advocacy and programming related to TGNC healthcare rights. This qualitative participatory action research study is grounded in in-depth, semi-structured interviews with 13 TGNC individuals who have sought GAH in Morocco. Participants were recruited in collaboration with a local transgender activist to foster trust within the community. A thematic analysis of the interviews was conducted to identify significant barriers and personal experiences related to accessing care. This analysis was further contextualized through a comparative review of informal care networks in Egypt and Lebanon. The findings indicate a complete absence of GAH within both the public and private healthcare sectors in Morocco. The healthcare environment is characterized by hostility, with inadequately trained providers often refusing care, attempting conversion therapy, or erroneously citing legal prohibitions. Consequently, participants are compelled to resort to unsafe, unregulated hormone therapies without medical oversight, such as the use of birth control pills. Systemic discrimination in education and employment results in considerable economic precarity, with many individuals engaging in survival sex work. Compounded by familial rejection and social stigma, these conditions render life in Morocco untenable, compelling migration as the sole viable option for safety and access to essential medical care. The legislative void in Morocco operates as a "ban by silence," a phenomenon that remains underrepresented in academic literature. This study seeks to address this gap by documenting the lived experiences of TGNC individuals navigating this de facto prohibition. The research advances a participant-led call for urgent reform, prioritizing three key areas: the establishment of legal and accessible pathways for medical transition; mandatory training for medical staff to eliminate discrimination; and the creation of affirming mental health services. Future research should continue to illuminate these invisible barriers to dismantle the systemic neglect that denies TGNC Moroccans their right to health. • Morocco’s ‘ban by silence’ effectively restricts healthcare access for transgender individuals. • State neglect forces TGNC people to seek care through unsafe and unregulated medical networks. • Providers often deny care by citing non-existent and inaccurate legal prohibitions. • Migration is seen as the only way to safely obtain essential medical care and safety.

ACE2 acts as a tumor suppressor in breast cancer by inhibiting progression via the TGF-β1/Smad pathway and potentiating immune checkpoint blockade.

The fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, plays a crucial role in various cancers. This study investigates its expression and functional role in bladder cancer (BCa). Analysis of TCGA data and validation in BCa cell lines revealed that FTO is significantly overexpressed in bladder cancer tissues and is associated with poor overall and disease-free survival. Functional assays demonstrated that knockdown of FTO markedly increased global m6A RNA methylation and suppressed the proliferation, migration, invasion, and colony formation of BCa cells in vitro. Furthermore, FTO depletion significantly inhibited tumor growth and experimental liver colonization in nude mouse xenograft models. Mechanistically, transcriptomic analysis of FTO-high patient tissues and FTO-knockdown cells revealed a strong association between FTO and epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) pathways. Consequently, FTO knockdown impaired the self-renewal capacity of BCa cells and downregulated the expression of key stemness genes (CD133, CD44, Nanog, OCT4). These findings suggest FTO is a critical oncoprotein that promotes bladder cancer progression and stemness-associated phenotypes, highlighting its potential as a therapeutic target and prognostic marker.

The decarbonisation of the electricity grid requires large scale deployment of renewable generation. Yet, most renewable generation is intermittent, and therefore large-scale energy storage may be needed to ensure supply availability. To guide future policies and system planning, it is important to know how much storage the future net-zero energy system will need. Previous attempts to estimate storage requirements have either focused on systems entirely supplied by renewables, or did not consider the increased demand due to expected electrification. In this work, we explore how much energy storage the future energy system in the United Kingdom may require and how much this requirement depends on future levels of demand, and the share of dispatchable generation in the grid, such as biomass or nuclear. We perform a simulation of energy flows for a typical year, for a range of energy mix scenarios, and two parameters – storage efficiency and renewable curtailment allowance. Our results anticipate a storage requirement for the UK ranging from 109 GWh to 9 TWh. Less storage is needed when a higher share of dispatchable generation is available, even if electricity demand is higher. Allowing for more renewable curtailment and less efficient storage may also reduce the requirements for storage capacity, at the expense of more energy dissipation. Highlights • We investigate energy storage requirements under energy transition pathways. • The UK will require 109GWh to 9TWh of energy storage depending on pathway. • The amount and type of dispatchable generation influence storage requirements. • Storage needs are much lower than in 100%-renewable scenarios. • VRE curtailment has a significant influence on storage requirements.

Injectable and transient hydrogel with programmable lifetime by endogenous coordination crosslinking and enzymatic de-crosslinking.

• An integrated framework combining energy modelling, sustainability, and synergy analyses enables comprehensive planning for the renewable energy transition. • Cuba can achieve 93% of its electricity from renewable sources by 2050 (13,000 GWh of solar energy and 11,000 GWh of wind energy). • Green hydrogen production can generate cross-sectoral benefits: synthesising fertilisers from ammonia reduces dependence on agricultural imports. • The Integrated SuWi Doughnut analysis confirms the achievements in social sustainability but identifies a critical gap in renewable energy. • The analytical methodology is replicable in countries that depend on fossil fuels and face challenges in sectoral integration. The global transition to renewable energy systems is imperative for climate sustainability. However, nations face significant challenges, including financial constraints, grid vulnerabilities, and dependence on fossil fuels. This study evaluates the feasibility of a 100% renewable electricity scenario for Cuba by 2050, employing a multidisciplinary framework integrating energy modelling (CUBALINDA), sustainability threshold quantification (Integrated SuWi Doughnut Approach), and cross-sectoral impact analysis (Dynamic Synergy Analysis). Using CUBALINDA—an adaptation of the LINDA framework calibrated for Cuban conditions—a backcasting scenario was constructed based on solar PV, wind energy, and Power-to-X technologies, supplemented by energy storage and green hydrogen production to address renewable intermittency. The Integrated SuWi Doughnut Approach reveals that while Cuba meets all social sustainability thresholds, it currently operates outside environmental limits regarding renewable energy share and ecological footprint. The Dynamic Synergy Analysis demonstrates that ammonia derived from green hydrogen could replace fertiliser imports, increase agricultural production, and reduce dependence on food imports. Cuba's energy transition is technically feasible but requires coherent policies, intersectoral integration, and substantial infrastructure investments. Green hydrogen yields significant collateral benefits, fostering energy sovereignty and agricultural revitalisation. By 2050, solar photovoltaic and wind will dominate the energy mix (93% renewable share), progressively replacing fossil fuels with sustainable biofuels and e-fuels. Critical challenges include grid modernisation, seasonal supply-demand imbalances, and financing for hydrogen infrastructure, all of which require coordinated policy interventions and innovative financing mechanisms. This study provides a replicable framework for integrated energy-sustainability planning, emphasising the need for decomposition and resilience analyses to optimise transition pathways.

Liver stiffness measurement (LSM) is a key tool for risk stratification in MASLD, yet static thresholds fail to capture dynamic transition across risk strata. We aimed to characterize LSM-risk transitions and develop a time-updated, individualized model for predicting state transitions, liver-related events and death (LREs/death). In a real-world MASLD cohort, we applied a multi-state, time-homogeneous Markov model to quantify annual transition probabilities and mean state occupancy times across LSM-defined low-, intermediate-, and high-risk strata. A Markov model incorporating age, sex, type 2 diabetes (T2D), hypertension was used to generate individualized, time-updated risk trajectories and probabilities of LREs/death. Among 11,514 MASLD individuals with ≥2 VCTE assessments, the low-risk category demonstrated notable stability, with 92% remaining unchanged at 1 year and a mean occupancy time of 8.43 years (95%CI:7.94-8.95). Contrarily the intermediate-risk category was highly dynamic, with only 39% remaining unchanged after 1 year and a mean occupancy time of 0.92 years (95%CI:0.88-0.96). T2D, hypertension, obesity substantially shorten low-risk occupancy time, whereas antidiabetic medication was associated with more favorable transitions. Finally, we developed a dynamic, multi-state Markov model (DYNAMO) integrating longitudinal LSM-defined risk states with relevant covariates to generate individualized predictions of state transitions and risks of LREs/death. LSM-based strata in MASLD represent distinct and meaningful dynamic trajectory. In particular, the marked instability of the intermediate-risk state supports more frequent reassessment. By quantifying transition pathways, and time-updated risks of LREs/death, this model may inform the personalized surveillance intervals and risk-adapted management.

Gastric cancer (GC) is a leading cause of cancer-related mortality characterized by aggressive metastasis and limited therapeutic options. Kin of IRRE-like protein 1 (KIRREL1) is an emerging cell surface protein whose specific oncogenic role in GC remains largely unknown. Therefore, the intention of this study was to comprehensively investigate the clinical relevance, biological functions, and underlying molecular mechanisms of KIRREL1 in GC progression. The expression and prognostic value of KIRREL1 were evaluated using data from The Cancer Genome Atlas (TCGA) and in vitro experiments. Gain- and loss-of-function studies were performed in GC cell lines to assess the effects of KIRREL1 on proliferation, 5-FU chemosensitivity, migration, and invasion. Western blotting was used to examine the regulation of epithelial-mesenchymal transition (EMT) markers. KIRREL1 was significantly upregulated in GC tissues and cell lines, and its high expression was strongly correlated with poor progression-free, disease-specific, and overall survival in patients. Functionally, KIRREL1 overexpression promoted GC cell proliferation, migration, and invasion, whereas its knockdown had the opposite effects. Furthermore, KIRREL1 knockdown sensitized GC cells to 5-FU treatment. Mechanistically, KIRREL1 was found to positively regulate the expression of the key EMT markers Vimentin, MMP2, and MMP9. Our findings identify KIRREL1 as a novel oncogene that actively promotes GC proliferation, 5-FU chemoresistance, and metastasis via the EMT pathway. Importantly, this establishes KIRREL1 as both a robust prognostic biomarker and a targetable driver of malignancy. Future clinical perspectives should explore the development of specific KIRREL1 inhibitors to overcome chemoresistance and suppress metastatic dissemination.

The B-Z DNA transition provides a rigorous benchmark for all-atom DNA force fields because it arises from a finely balanced free-energy competition between conformational states with distinct backbone geometries, sugar-pucker preferences, ion organization, and hydration patterns. Using enhanced-sampling molecular dynamics simulations in the NPT ensemble over a broad pressure range, we show that the recently modified OL21-vdW7 force field correctly describes the thermodynamic preference between B-DNA and Z-DNA under multiple Z-DNA-stabilizing conditions, including elevated pressure, high salt concentration, and multivalent polycations. The resulting two-dimensional free-energy landscapes resolve the plausible transition pathway and quantify the associated thermodynamic and structural responses. In addition to reproducing established experimental stabilization trends, OL21-vdW7 yields a cooperative nucleation-propagation mechanism initiated by the formation of a minimal Z-DNA segment and a single B-Z junction. The pressure dependence of the transition reflects a negative volume change, whose magnitude is largest under low-salt conditions. Overall, these results demonstrate the transferability of OL21-vdW7 for duplex DNA and highlight B-Z transitions as a stringent test case for force-field development and validation.

Molecular conformations play a critical role in determining molecular properties, such as membrane permeability, binding affinity, and ultimately therapeutic efficacy. Experimental and computational approaches can characterize conformations and provide insight into why certain conformations are thermodynamically preferred over others. However, examining conformations alone may not fully explain why subtle differences, such as a single LEU-to-ILE mutation in a bicyclic peptide, can produce markedly distinct conformational ensembles. Analyzing the transition pathways between conformations further reveals the mechanisms that shape these ensembles. Here, we introduce a deep learning model, termed ICoN-v1, trained in molecular dynamics simulation data to learn the underlying physics that governs cyclic peptide conformational dynamics. We examined hexacyclic peptides with Nuclear magnetic resonance (NMR)-determined structures, and MYC-targeting bicyclic peptides, which are stereo-diversified or have a single LEU-to-ILE mutation. By following the minimum-energy pathway in the latent space constructed by ICoN-v1, conformational transition paths, led by various sets of concerted backbone and sidechain torsional rotations moving in sequence between energy minima, are efficiently generated. Notably, smooth transition pathways that are absent from molecular dynamic output can be observed using ICoN-v1. Our results identify various sets of concerted torsional motions that are nonlinearly combined during conformational transitions and reveal the key residues governing each stage of the transition, thereby elucidating how the observed conformations are generated and informing molecular design.

Integrative Single-Cell and Bulk Transcriptomics Analysis Reveals Cellular Heterogeneity, Immune Microenvironment Dynamics, and Prognostic Signatures in Oral Squamous Cell Carcinoma.

The absence of pressure-induced amorphization in NH4F stands in stark contrast to the behavior of ice, despite their isostructural characteristics. In this study, we developed a deep potential model for NH4F and constructed its phase diagram. Our molecular dynamics simulations reveal that the transitions from Phases Ih and Ic to Phase II proceed via an intermediate Phase IV (NaCl-type). Within this Phase IV lattice, NH4+ ions undergo active rotation, enabling a transient reconfiguration of the hydrogen-bond (HB) network. This intermediate rotator phase acts as a structural buffer, effectively releasing the topological constraints of the parent HB network and allowing the system to dynamically explore the transition pathway to the product phase. In contrast, the lack of such a dynamic intermediate in molecular ice necessitates rigid network preservation, which typically fails to find a viable crystalline pathway and triggers a collapse into high-density amorphous (HDA) ice upon low-temperature compression. Our findings elucidate how the emergence of an intermediate rotator phase prevents amorphization in the NH4F systems.

Curative-intent surgery is the standard treatment for node-negative, early-stage rectal cancer. Although distant recurrence is uncommon in this setting, it carries a markedly poor prognosis. There is limited understanding of tumour biology linked to this aggressive cancer and no biomarkers to aid clinical practice. The aim of this pilot study was to demonstrate feasibility to identify putative prognostic biomarkers of distant metastasis following curative-intent surgery for early rectal cancer. Treatment-naïve patients who developed distant metastases after total mesorectal excision for Stage I/IIA rectal cancer were identified from our centre over a 7-year period. A cohort matched for clinicopathological features without subsequent metastasis was used as control. Formalin-fixed paraffin embedded primary tumour was laser microdissected and proteins extracted for mass-spectrometry based proteomics. Separately, intratumoural CD3+, CD3+CD8+ and CD3+CD8- T cells densities were measured using immunohistochemistry. In our cohort, the frequency of distant metastasis was 8.4%. 5,473 proteins were quantified in all samples, with 69 proteins differentially expressed between primary tumours with or without subsequent distant metastasis. TGF-β signaling, epithelial-mesenchymal transition, and coagulation pathways were enriched in primary tumours that developed distant metastases. Total T cells and CD8- T cell densities were lower in both the epithelium and stroma of patients with distant metastasis. CD8+ T cell density was also lower in the tumour epithelial regions of patients who developed distant metastases. We demonstrated feasibility to detect putative protein and T cell infiltrate biomarkers of distant metastasis in early-stage rectal cancer. A multi-centre validation study is now required to identify higher risk patients where adjuvant chemotherapy may improve outcomes.

Carbon nanotubes (CNTs), which possess their characteristic structural, electrical, and chemical properties, have become flexible nanomaterials in the theranostics of cancer. They can deliver drugs precisely to their intended target due to their high surface area, tunable surface chemistry, and biological intactness through their ability to cross biological barriers and enhance imaging, as well as enabling new forms of treatment, including photothermal therapy and photodynamic therapy. The clinical efficacy of these light-based modalities is, however, limited because the shallow penetration of the light in the near-infrared (NIR) light can diminish the efficacy of treatment on tumours that are deep-seated. The physicochemical properties that predispose CNTs to be useful in treating the human body also provoke valid questions about the safety of this approach in the long-term, especially concerning carcinogenic effects. This review has critically discussed the dual nature of CNTs in oncology, synthesizing the current developments in the therapeutic applications of CNTs, and describes mechanistic insights about their toxicity. CNTs are used to enhance cancer therapy in terms of their application as drug carriers, radiosensitizers, and immune modulators, and comment on their diagnostic application in multimodal imaging. The CNT/PEI/durvalumab nanoagent systems are among them, and they are preclinical studies that have been carried out primarily on animal models. On the other hand, this review evaluates the increasing evidence that links CNT exposure to oxidative stress, mitochondrial malfunctioning, inflammation, epithelial-mesenchymal transition (EMT), and endothelial leakiness pathways that have been implicated in tumorigenesis and metastasis. The review outlines the significance of standardization of functionalization procedures, strict toxicological testing, and the long-term biocompatibility by comparison of therapeutic benefits and biological risks. These risks and benefits have to be weighed to provide a way of balancing the safety of CNT-based nanotechnologies to leap clinical oncology using the resulting experimental models to guide researchers, clinicians, and regulatory officials.

Chronic infection with the hepatitis B virus (HBV) remains a major global health burden and depends on efficient viral replication, including the assembly of the viral capsid during the HBV life cycle. Capsid assembly proceeds through transient oligomeric intermediates, among which the formation of hexameric units is thought to underlie the energetic bottleneck associated with nucleation during capsid assembly. Despite extensive experimental and computational work, the structural and energetic determinants of hexamer closure remain incompletely understood at the molecular level. Here, we employ a multistage computational approach to investigate the open-to-closed transition of the HBV capsid hexamer in the apo system, in which targeted molecular dynamics is employed to generate diverse open-to-closed transition pathways. These pathways are subsequently refined and sampled by using path-based free-energy methods to construct multidimensional free-energy landscapes of hexamer closure. Across independently sampled pathways, we observe diverse transition routes, while a conserved steric rearrangement in the gate region emerges as the dominant rate-limiting feature. These results provide a qualitative characterization of hexamer closure energetics and establish a general framework for studying complex conformational transitions in large, flexible biomolecular assemblies.

• Impact of natural resources, social factors and energy transition in Bangladesh. • NRR and economic factors are analyzed using ARDL, ECM and prediction methods. • All the variables are stationary and show long-run cointegration and relationships. • Natural and economic factors, show positive association with the energy transition. • Policymakers should focus on the multi-scale impacts of energy changeover. Realizing affordable and clean energy requires a global transition away from reliance on fossil fuels toward sustainable energy sources; however, the significance of natural resource rents (NRR) in this transition remains surprisingly underexplored. The aim of this study is toward analyzing the impact of eight natural resource factors in the Bangladesh perspective, and this study covers the period 1980–2022. Additionally, the ARDL model is employed. We employed different types of regression model evaluation metrics (i.e., RMSE, MAE, and MAPE) to solve the desired problem at hand. The outcomes show that (i) all the variables at the first difference represent the cointegration test, while the bounds test outcomes confirm that there is long-run cointegration and relationships among energy transition, energy import, natural gas, total natural resources, oil, and forest rents. (ii) The natural resource rents and economic growth factors show a positive relationship with energy transition in Bangladesh between 0.55% and 3.90% in the short run and between 0.05% and 7.69% in the long run. This suggests that even a 1% change in resource rent and economic growth factors can still lead to optimistic growth, driven by rapid economic growth and the intense use of natural resources, which provides advanced development for its energy sector. (iii) The prediction results provide RMSE higher than MAE, while MAPE for energy transition is calculated at 1.45%, suggesting that energy transition processing in Bangladesh can be properly adopted. Finally, based on a comprehensive analysis of Bangladesh’s energy transition, resource rents, and economic factors, the study suggests its contributions to resource governance and plans evidence-based pathways for rent management, import structure, and renewable energy transition with long-run environmental stability.

Strengthening regional energy–economic resilience in China: Digital innovation and energy efficiency pathways for sustainable transition