Country-specific net-zero strategies of the pulp and paper industry.

The pulp and paper industry is an important contributor to global greenhouse gas emissions1,2. Country-specific strategies are essential for the industry to achieve net-zero emissions by 2050, given its vast heterogeneities across countries3,4. Here we develop a comprehensive bottom-up assessment of net greenhouse gas emissions of the domestic paper-related sectors for 30 major countries from 1961 to 2019-about 3.2% of global anthropogenic greenhouse gas emissions from the same period5-and explore mitigation strategies through 2,160 scenarios covering key factors. Our results show substantial differences across countries in terms of historical emissions evolution trends and structure. All countries can achieve net-zero emissions for their pulp and paper industry by 2050, with a single measure for most developed countries and several measures for most developing countries. Except for energy-efficiency improvement and energy-system decarbonization, tropical developing countries with abundant forest resources should give priority to sustainable forest management, whereas other developing countries should pay more attention to enhancing methane capture rate and reducing recycling. These insights are crucial for developing net-zero strategies tailored to each country and achieving net-zero emissions by 2050 for the pulp and paper industry.

Global iron and steel plant CO2 emissions and carbon-neutrality pathways.

The highly energy-intensive iron and steel industry contributed about 25% (ref. 1) of global industrial CO2 emissions in 2019 and is therefore critical for climate-change mitigation. Despite discussions of decarbonization potentials at national and global levels2-6, plant-specific mitigation potentials and technologically driven pathways remain unclear, which cumulatively determines the progress of net-zero transition of the global iron and steel sector. Here we develop a CO2 emissions inventory of 4,883 individual iron and steel plants along with their technical characteristics, including processing routes and operating details (status, age, operation-years etc.). We identify and match appropriate emission-removal or zero-emission technologies to specific possessing routes, or what we define thereafter as a techno-specific decarbonization road map for every plant. We find that 57% of global plants have 8-24 operational years, which is the retrofitting window for low-carbon technologies. Low-carbon retrofitting following the operational characteristics of plants is key for limiting warming to 2 °C, whereas advanced retrofitting may help limit warming to 1.5 °C. If each plant were retrofitted 5 years earlier than the planned retrofitting schedule, this could lead to cumulative global emissions reductions of 69.6 (±52%) gigatonnes (Gt) CO2 from 2020 to 2050, almost double that of global CO2 emissions in 2021. Our results provide a detailed picture of CO2 emission patterns associated with production processing of iron and steel plants, illustrating the decarbonization pathway to the net-zero-emissions target with the efforts from each plant.

PREDAC-CNN: predicting antigenic clusters of seasonal influenza A viruses with convolutional neural network.

Vaccination stands as the most effective and economical strategy for prevention and control of influenza. The primary target of neutralizing antibodies is the surface antigen hemagglutinin (HA). However, ongoing mutations in the HA sequence result in antigenic drift. The success of a vaccine is contingent on its antigenic congruence with circulating strains. Thus, predicting antigenic variants and deducing antigenic clusters of influenza viruses are pivotal for recommendation of vaccine strains. The antigenicity of influenza A viruses is determined by the interplay of amino acids in the HA1 sequence. In this study, we exploit the ability of convolutional neural networks (CNNs) to extract spatial feature representations in the convolutional layers, which can discern interactions between amino acid sites. We introduce PREDAC-CNN, a model designed to track antigenic evolution of seasonal influenza A viruses. Accessible at http://predac-cnn.cloudna.cn, PREDAC-CNN formulates a spatially oriented representation of the HA1 sequence, optimized for the convolutional framework. It effectively probes interactions among amino acid sites in the HA1 sequence. Also, PREDAC-CNN focuses exclusively on physicochemical attributes crucial for the antigenicity of influenza viruses, thereby eliminating unnecessary amino acid embeddings. Together, PREDAC-CNN is adept at capturing interactions of amino acid sites within the HA1 sequence and examining the collective impact of point mutations on antigenic variation. Through 5-fold cross-validation and retrospective testing, PREDAC-CNN has shown superior performance in predicting antigenic variants compared to its counterparts. Additionally, PREDAC-CNN has been instrumental in identifying predominant antigenic clusters for A/H3N2 (1968-2023) and A/H1N1 (1977-2023) viruses, significantly aiding in vaccine strain recommendation.

Ferroptosis Contributes to Microvascular Dysfunction in Diabetic Retinopathy.

Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. Herein, the expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with quantitative RT-PCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including glutathione peroxidase 4, ferritin heavy chain 1, long-chain acyl-CoA synthetase 4, transferrin receptor protein 1, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.

The effect of top-down attention on empathy fatigue.

Prolonged exposure to others' suffering can lead to empathy fatigue, especially when individuals struggle to effectively regulate their empathic capacity. Shifting active attention away from emotional components toward cognitive components of others' suffering is an effective strategy for mitigating empathy fatigue. This research investigated how top-down attentional manipulation modulates empathy fatigue in both auditory (Study 1) and visual (Study 2) modalities. Participants completed two tasks in both studies: (i) the attention to cognitive empathy task (A-C task) and (ii) the attention to emotional empathy task (A-E task). Each task included three blocks (Time Block 1, Time Block 2, and Time Block 3) designed to induce empathy fatigue. Study 1 revealed that the A-C task reduced empathy fatigue and N1 amplitudes than the A-E task in Time Block 3, indicating that attention to cognitive empathy might decrease auditory empathy fatigue. Study 2 indicates that the A-C task caused a longer N2 latency than the A-E task, signifying a decelerated emotional empathic response when attention was on cognitive empathy in the visual modality. Overall, prioritizing cognitive empathy seems to conserve mental resources and reduce empathy fatigue. This research documented the relationship between top-down attention and empathy fatigue and the possible neural mechanism.

Integrated metabolome and transcriptome analyses reveal the molecular mechanism underlying dynamic metabolic processes during taproot development of Panax notoginseng.

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum.

BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

HBV DNA polymerase upregulates the transcription of PD-L1 and suppresses T cell activity in hepatocellular carcinoma.

BACKGROUND: In HBV-associated HCC, T cells often exhibit a state of functional exhaustion, which prevents the immune response from rejecting the tumor and allows HCC to progress. Moreover, polymerase-specific T cells exhibit more severe T-cell exhaustion compared to core-specific T cells. However, whether HBV DNA polymerase drives HBV-specific CD8+ T cell exhaustion in HBV-related HCC remains unclear. METHODS: We constructed a Huh7 cell line stably expressing HA-HBV-DNA-Pol and applied co-culture systems to clarify its effect on immune cell function. We also examined how HBV-DNA-Pol modulated PD-L1 expression in HCC cells. In addition, HBV-DNA-Pol transgenic mice were used to elucidate the underlying mechanism of HBV-DNA-Pol/PD-L1 axis-induced T cell exhaustion. RESULTS: Biochemical analysis showed that Huh7 cells overexpressing HBV-DNA-Pol inhibited the proliferation, activation, and cytokine secretion of Jurkat cells and that this effect was dependent on their direct contact. A similar inhibitory effect was observed in an HCC mouse model. PD-L1 was brought to our attention during screening. Our results showed that the overexpression of HBV-DNA-Pol upregulated PD-L1 mRNA and protein expression. PD-L1 antibody blockade reversed the inhibitory effect of Huh7 cells overexpressing HBV-DNA-Pol on Jurkat cells. Mechanistically, HBV-DNA-Pol interacts with PARP1, thereby inhibiting the nuclear translocation of PARP1 and further upregulating PD-L1 expression. CONCLUSIONS: Our findings suggest that HBV-DNA-Pol can act as a regulator of PD-L1 in HCC, thereby directing anti-cancer immune evasion, which further provides a new idea for the clinical treatment of liver cancer.

ATN-Res2Unet: an advanced deep learning network for the elimination of saturation artifacts in endoscopy optical coherence tomography.

Endoscopic optical coherence tomography (OCT) possesses the capability to non-invasively image internal lumens; however, it is susceptible to saturation artifacts arising from robust reflective structures. In this study, we introduce an innovative deep learning network, ATN-Res2Unet, designed to mitigate saturation artifacts in endoscopic OCT images. This is achieved through the integration of multi-scale perception, multi-attention mechanisms, and frequency domain filters. To address the challenge of obtaining ground truth in endoscopic OCT, we propose a method for constructing training data pairs. Experimental in vivo data substantiates the effectiveness of ATN-Res2Unet in reducing diverse artifacts while preserving structural information. Comparative analysis with prior studies reveals a notable enhancement, with average quantitative indicators increasing by 45.4-83.8%. Significantly, this study marks the inaugural exploration of leveraging deep learning to eradicate artifacts from endoscopic OCT images, presenting considerable potential for clinical applications.

K2CO3-Catalyzed (3 + 2) Cycloaddition Reaction of N-2,2,2-Trifluoroethylisatin Ketimines with Azodicarboxylates: Access to Spirooxindoles Containing Trifluoromethyl-1,2,4-triazolines.

Potassium carbonate-catalyzed (3 + 2) cycloaddition reaction between N-2,2,2-trifluoroethylisatin ketimines and azodicarboxylates has been developed, constructing a series of novel N-heterocycle infused spirooxindoles in good to excellent yields (up to 98%) under milder conditions. The presence of both biologically active oxindole and trifluoromethyl-1,2,4-triazoline moieties in these novel spirocyclic compounds would provide new lead structures in the discovery of heterocyclic compounds with potential pharmaceutical activities.

Microglial purinergic signaling in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease. The prevalent features of AD pathogenesis are the appearance of ß-amyloid (Aß) plaques and neurofibrillary tangles, which cause microglial activation, synaptic deficiency, and neuronal loss. Microglia accompanies AD pathological processes and is also linked to cognitive deficits. Purinergic signaling has been shown to play a complex and tight interplay with the chemotaxis, phagocytosis, and production of pro-inflammatory factors in microglia, which is an important mechanism for regulating microglia activation. Here, we review recent evidence for interactions between AD, microglia, and purinergic signaling and find that the purinergic P2 receptors pertinently expressed on microglia are the ionotropic receptors P2X4 and P2X7, and the subtypes of P2YRs expressed by microglia are metabotropic receptors P2Y2, P2Y6, P2Y12, and P2Y13. The adenosine P1 receptors expressed in microglia include A1R, A2AR, and A2BR. Among them, the activation of P2X4, P2X7, and adenosine A1, A2A receptors expressed in microglia can aggravate the pathological process of AD, whereas P2Y2, P2Y6, P2Y12, and P2Y13 receptors expressed by microglia can induce neuroprotective effects. However, A1R activation also has a strong neuroprotective effect and has a significant anti-inflammatory effect in chronic neuroinflammation. These receptors regulate a variety of pathophysiological processes in AD, including APP processing, Aß production, tau phosphorylation, neuroinflammation, synaptic dysfunction, and mitochondrial dysfunction. This review also provides key pharmacological advances in purinergic signaling receptors.

Decreasing Greenhouse Gas Emissions from the Municipal Solid Waste Sector in Chinese Cites.

Municipal solid waste (MSW) management systems play a crucial role in greenhouse gas (GHG) emissions in China. Although the government has implemented many policies to improve the MSW management system, the impact of these improvements on city-level GHG emission reduction remains largely unexplored. This study conducted a comprehensive analysis of both direct and downstream GHG emissions from the MSW sector, encompassing sanitary landfill, dump, incineration, and biological treatment, across 352 Chinese cities from 2001 to 2021 by adopting inventory methods recommended by the Intergovernmental Panel on Climate Change (IPCC). The results reveal that (1) GHG emissions from the MSW sector in China peaked at 70.6 Tg of CO2 equiv in 2018, followed by a significant decline to 47.6 Tg of CO2 equiv in 2021, (2) cities with the highest GHG emission reduction benefits in the MSW sector were historical emission hotspots over the past 2 decades, and (3) with the potential achievement of zero-landfilling policy by 2030, an additional reduction of 203.7 Tg of CO2 equiv is projected, with the emission reduction focus toward cities in South China (21.9%), Northeast China (17.8%), and Southwest China (17.3%). This study highlights that, even without explicit emission reduction targets for the MSW sector, the improvements of this sector have significantly reduced GHG emissions in China.

Development and validation of the parental health literacy scale for children with asthma (PHLSCA).

OBJECTIVE: This study aimed to develop and validate an instrument to assess the health literacy of parents of children with asthma in a Chinese context. METHODS: The preliminary Parental Health Literacy Scale for Children with Asthma (PHLSCA) was developed based on a literature review and refined to 45 items through two rounds of expert consultation using the Delphi method. A total of 481 parents of children with asthma were recruited from seven hospitals across four provinces in China between February and April 2019. Principal component analysis (PCA) and confirmatory factor analysis were conducted to evaluate the structural and construct validity of the scale. RESULTS: The development and validation processes led to a 38 items scale comprising three subscales, namely: Health Knowledge (11 items), Health Skills (19 items) and Health Behavior (8 items). The scale demonstrated good reliability, with an internal consistency of Cronbach's α = 0.956 and a split-half reliability of r = 0.887 (p < 0.01). The Item Content Validity Index (I-CVI) ranged from 0.81 to 1.00, and the Scale-CVI was 0.842. The correlation coefficients and factor analysis results indicated good construct validity, with the factors explaining 59.33% to 62.90% of the variance in each subscale. CONCLUSIONS: The final version of the questionnaire (PHLSCA) has been demonstrated to be a valid and reliable tool for assessing the health literacy of parents of Chinese children with asthma.

The influence of aggressive exercise on responses to self-perceived and others' pain.

Previous studies have reported relationships between exercise and pain. However, little is known about how aggressive exercise modulates individuals' responses to their own and others' pain. This present study addresses this question by conducting 2 studies employing event-related potential (ERP). Study 1 included 38 participants whose self-perceived pain was assessed after intervention with aggressive or nonaggressive exercises. Study 2 recruited 36 participants whose responses to others' pain were assessed after intervention with aggressive or nonaggressive exercise. Study 1's results showed that P2 amplitudes were smaller, reaction times were longer, and participants' judgments were less accurate in response to self-perceived pain stimuli, especially to high-pain stimuli, after intervention with aggressive exercise compared to nonaggressive exercise. Results of study 2 showed that both P3 and LPP amplitudes to others' pain were larger after intervention with aggressive exercise than with nonaggressive exercise. These results suggest that aggressive exercise decreases individuals' self-perceived pain and increases their empathic responses to others' pain.

MSC microvesicles loaded G-quadruplex-enhanced circular single-stranded DNA-9 inhibits tumor growth by targeting MDSCs.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. RESULTS AND CONCLUSION: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.

Forecasting the trend of tuberculosis incidence in Anhui Province based on machine learning optimization algorithm, 2013-2023.

Tuberculosis has been one of the most common communicable diseases raising global concerns. Accurately predicting the incidence of Tuberculosis remains challenging. Here we constructed a time-series analysis and fusion tool using multi-source data, and aimed to more accurately predict the incidence trend of tuberculosis of Anhui Province from 2013 to 2023. Random forest algorithm (RF), Feature Recursive Elimination (RFE) and Least absolute shrinkage and selection operator (LASSO) were implemented to improve the derivation of features related to infectious diseases and feature work. Based on the characteristics of infectious disease data, a model of RF-RFE-LASSO integrated particle swarm optimization multiple inputs long short term memory recurrent neural network (RRL-PSO-MiLSTM) was created to perform more accurate prediction. Results showed that the PSO-MiLSTM achieved excellent prediction results compared with common single-input and multi-input time-series models (test set MSE:42.3555, MAE: 59.3333, RMSE: 146.7237, MAPE: 2.1133, R2: 0.8634). PSO-MiLSTM enriches and complements the methodological research content of calibrating the time-series predictive analysis of infectious diseases using multi-source data, and can be used as a brand-new benchmark for the analysis of influencing factors and trend prediction of infectious diseases at the public health level in the future, as well as providing a reference for incidence rate prediction of infectious diseases.

Associations between perceived and actual risk of HIV infection and HIV prevention services uptake among men who have sex with men in Shandong province, China: a cross-sectional study.

BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Comparing expert elicitation and model-based probabilistic technology cost forecasts for the energy transition.

We conduct a systematic comparison of technology cost forecasts produced by expert elicitation methods and model-based methods. Our focus is on energy technologies due to their importance for energy and climate policy. We assess the performance of several forecasting methods by generating probabilistic technology cost forecasts rooted at various years in the past and then comparing these with observed costs in 2019. We do this for six technologies for which both observed and elicited data are available. The model-based methods use either deployment (Wright's law) or time (Moore's law) to forecast costs. We show that, overall, model-based forecasting methods outperformed elicitation methods. Their 2019 cost forecast ranges contained the observed values much more often than elicitations, and their forecast medians were closer to observed costs. However, all methods underestimated technological progress in almost all technologies, likely as a result of structural change across the energy sector due to widespread policies and social and market forces. We also produce forecasts of 2030 costs using the two types of methods for 10 energy technologies. We find that elicitations generally yield narrower uncertainty ranges than model-based methods. Model-based 2030 forecasts are lower for more modular technologies and higher for less modular ones. Future research should focus on further method development and validation to better reflect structural changes in the market and correlations across technologies.

Formononetin Induces Ferroptosis in Activated Hepatic Stellate Cells to Attenuate Liver Fibrosis by Targeting NADPH Oxidase 4.

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl4-induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP+/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.

Changes in the Objective Vision Quality of Adolescents in a Mesopic Visual Environment After Wearing Orthokeratology Lenses: A Prospective Study.

PURPOSE: This study aimed to investigate changes in objective vision quality in mesopic environments in teenagers with myopia after wearing orthokeratology (OK) lenses. METHODS: This prospective clinical study included 45 patients (80 eyes) who received OK lenses at the First Affiliated Hospital of Jinan University from March 2021 to September 2021. An Optical Path Difference-Scan III refractive power/corneal analyzer was used to determine the corneal topographic parameters (corneal e, corneal Q, surface asymmetry index (SAI), and surface regularity index (SRI)), higher-order aberrations (HOAs), axial length (AL) change, lens decentration, induced astigmatism, target power, and Strehl ratio (SR) in a mesopic visual environment after wearing OK lenses for 6 months. In addition, corneal morphological parameters, HOAs, and SR were analyzed in a mesopic visual environment. Finally, we investigated the correlations among corneal morphology, HOAs, AL change, lens decentration, induced astigmatism, and SR. RESULTS: The SAI value was significantly higher ( P <0.01), and the corneal e was significantly lower ( P <0.01), in a mesopic visual environment after wearing OK lenses for 1 week than baseline. A significant increase was observed in total HOAs and spherical aberrations, compared with before the OK lenses were worn ( P <0.01). In addition, SR in the mesopic visual environment decreased significantly after wearing the lenses ( P <0.01). No significant differences were observed ( P >0.05) among the 1-week, 1-month, 3-month, and 6-month follow-up findings. After 6 months, AL and lens decentration did not differ significantly compared with before ( P >0.05), whereas induced astigmatism significantly increased ( P <0.05). Negative correlations were observed between corneal Q, SAI, SRI, HOAs, induced astigmatism, and SR, and positive correlations were found between corneal e, AL change, lens decentration, and SR, after wearing OK lenses. KEY POINTS: • Wearing orthokeratology lenses significantly altered corneal morphology and HOAs in myopic teenagers within 1 week. • The changes that we observed in the eyes of adolescents with myopia after wearing orthokeratology lenses decreased vision quality in mesopic environments. • Strehl ratio is significantly correlated with multiple parameters, including HOAs, AL change, and lens decentration. CONCLUSIONS: In teenagers with myopia wearing OK lenses, significant changes in vision quality and corneal morphology were observed, leading to increased aberrations and affecting optical imaging quality. Furthermore, SR is significantly correlated with multiple parameters, including HOAs, AL change, and lens decentration. REGISTRATION NUMBER: This study is registered with the United States Clinical Trials Registry under registration number NCT04929119.