Developing preclinical dog models for reconstructive severed spinal cord continuity via spinal cord fusion technique.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

Hierarchical superstructure aerogels for in situ biofluid metabolomics.

High-throughput biofluid metabolomics analysis for screening life-threatening diseases is urgently needed. However, the high salt content of biofluid samples, which introduces severe interference, can greatly limit the analysis throughput. Here, a new 3-D interconnected hierarchical superstructure, namely a "plasmonic gold-on-silica (Au/SiO2) double-layered aerogel", integrating distinctive features of an upper plasmonic gold aerogel with a lower inert silica aerogel was successfully developed to achieve in situ separation and storage of inorganic salts in the silica aerogel, parallel enrichment of metabolites on the surface of the functionalized gold aerogel, and direct desorption/ionization of enriched metabolites by the photo-excited gold aerogel for rapid, sensitive, and comprehensive metabolomics analysis of human serum/urine samples. By integrating all these unique advantages into the hierarchical aerogel, multifunctional properties were introduced in the SALDI substrate to enable its effective utilization in clinical metabolomics for the discovery of reliable metabolic biomarkers to achieve unambiguous differentiation of early and advanced-stage lung cancer patients from healthy individuals. This study provides insight into the design and application of superstructured nanomaterials for in situ separation, storage, and photoexcitation of multi-components in complex biofluid samples for sensitive analysis.

MYT1L deficiency impairs excitatory neuron trajectory during cortical development.

Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a proneural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 313,335 nuclei from the forebrains of wild-type and MYT1L-deficient mice at two developmental stages: E14 at the peak of neurogenesis and P21, when neurogenesis is complete, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportion of cortical excitatory neurons at E14 and P21. Significant changes in gene expression were largely concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.

Non-targeted metabolomics analysis of indoleamine 2,3-dioxygenase inhibitor treatment in a mouse model of early-stage lung adenocarcinoma.

Background: Lung adenocarcinoma is a common malignant tumor, and its early diagnosis and treatment are key to improving patient survival rates. However, due to the non-specific early symptoms, many patients are already at an advanced stage when diagnosed. Non-targeted metabolomics analysis, as a method for comprehensive analysis of metabolites in the body, has been shown to have potential in the early diagnosis of cancer. This study aims to identify early-stage lung adenocarcinoma-specific biomarkers using non-targeted metabolomics analysis in an established mouse model. The intervention mechanism of indoleamine 2,3-dioxygenase (IDO) inhibitor in early-stage lung adenocarcinoma is explored to provide evidence for clinical disease treatment. Methods: Twenty specific-pathogen-free-grade female Kunming mice were divided into control group, experimental group, Epacadostatlow group, and Epacadostathigh group. After modeling, immune therapy intervention (epacadostat) was administered to the mice, and plasma and urine samples were collected from all mice on day 7 and day 28. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed to identify potential biomarkers for diagnosing early-stage lung adenocarcinoma. Cluster analysis and correlation analysis were used to explore the differential expression patterns of metabolites in different samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify enriched pathways of differentially expressed metabolites. Results: A total of 348 metabolites were identified after merging the positive and negative ion modes. Among them, organic acids and derivatives (16.954%) and lipids and lipid-like molecules (15.517%) were the two major classes of metabolites in the early-stage lung adenocarcinoma mice. Anthranilic acid (vitamin L1), 1-methylhistidine, 12(R)-HETE, and hippuric acid were the major differentially expressed metabolites on both day 7 and day 28, and they showed correlations with each other. Metabolic pathway analysis revealed multiple dysregulated pathways in lung adenocarcinoma mice. Conclusions: UPLC-QTOF-MS analysis is a feasible method for identifying biomarkers of lung adenocarcinoma. Epacadostat, a novel and promising IDO inhibitor, may exert its therapeutic effect by modulating 1-methylhistidine and anthranilic acid (vitamin L1).

The evolution of Earth's surficial Mg cycle over the past 2 billion years.

The surficial cycling of Mg is coupled with the global carbon cycle, a predominant control of Earth's climate. However, how Earth's surficial Mg cycle evolved with time has been elusive. Magnesium isotope signatures of seawater (δ26Mgsw) track the surficial Mg cycle, which could provide crucial information on the carbon cycle in Earth's history. Here, we present a reconstruction of δ26Mgsw evolution over the past 2 billion years using marine halite fluid inclusions and sedimentary dolostones. The data show that δ26Mgsw decreased, with fluctuations, by about 1.4‰ from the Paleoproterozoic to the present time. Mass balance calculations based on this δ26Mgsw record reveal a long-term decline in net dolostone burial (NDB) over the past 2 billion years, due to the decrease in dolomitization in the oceans and the increase in dolostone weathering on the continents. This underlines a previously underappreciated connection between the weathering-burial cycle of dolostone and the Earth's climate on geologic timescales.

Association of body temperature and mortality in critically ill patients: an observational study using two large databases.

BACKGROUND: Body temperature (BT) is routinely measured and can be controlled in critical care settings. BT can impact patient outcome, but the relationship between BT and mortality has not been well-established. METHODS: A retrospective cohort study was conducted based on the MIMIC-IV (N = 43,537) and eICU (N = 75,184) datasets. The primary outcome and exposure variables were hospital mortality and first 48-h median BT, respectively. Generalized additive models were used to model the associations between exposures and outcomes, while adjusting for patient age, sex, APS-III, SOFA, and Charlson comorbidity scores, temperature gap, as well as ventilation, vasopressor, steroids, and dialysis usage. We conducted subgroup analysis according to ICU setting, diagnoses, and demographics. RESULTS: Optimal BT was 37 °C for the general ICU and subgroup populations. A 10% increase in the proportion of time that BT was within the 36-38 °C range was associated with reduced hospital mortality risk in both MIMIC-IV (OR 0.91; 95% CI 0.90-0.93) and eICU (OR 0.86; 95% CI 0.85-0.87). On the other hand, a 10% increase in the proportion of time when BT < 36 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.08; 95% CI 1.06-1.10) and eICU (OR 1.18; 95% CI 1.16-1.19). Similarly, a 10% increase in the proportion of time when BT > 38 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.09; 95% CI 1.07-1.12) and eICU (OR 1.09; 95% CI 1.08-1.11). All patient subgroups tested consistently showed an optimal temperature within the 36-38 °C range. CONCLUSIONS: A BT of 37 °C is associated with the lowest mortality risk among ICU patients. Further studies to explore the causal relationship between the optimal BT and mortality should be conducted and may help with establishing guidelines for active BT management in critical care settings.

Evaluating Losses from Water Scarcity and Benefits of Water Conservation Measures to Intercity Supply Chains in China.

The severe water scarcity in China poses significant economic risks to its agriculture, energy, and manufacturing sectors, which can have a cascading effect through the supply chains. Current research has assessed water scarcity losses for global countries and Chinese provinces by using the water scarcity risk (WSR) method. However, this method involves subjective functions and parameter settings, and it fails to capture the adaptive behaviors of economies to water scarcity, compromising the reliability of quantified water scarcity loss. There is a pressing need for a new method to assess losses related to water scarcity. Here, we develop an agent-based complex network model to estimate the inter-regional and intersectoral impacts of water scarcity on both cities and basins. Subsequently, we evaluate the supply chain-wide economic benefits of four different water conservation measures as stipulated by the 14th Five-Year Plan for the Construction of a Water-Saving Society. These measures include increasing the utilization rate of recycled water in water-scarce cities, reducing the national water consumption per industrial value-added, and implementing agricultural and residential water conservation measures. Results show that direct losses constitute only 9% of the total losses from water scarcity. Approximately 37% of the losses can be attributed to interregional impacts. Among the water-scarce cities, Qingdao, Lanzhou, Jinan, and Zhengzhou pose a significant threat to China's supply chains. Agricultural water conservation yields the highest amount of water savings and economic benefits, while residential water conservation provides the highest economic benefit per unit of water saved. The results provide insights into managing water scarcity, promoting cross-regional cooperation, and mitigating economic impacts.

High Selectivity Cofactor NADH Regeneration Organic Iridium Complexes Used for High-Efficiency Chem-Enzyme Cascade Catalytic Hydrogen Transfer.

Our research demonstrated that novel pentamethylcyclopentadienyl (Cp*) iridium pyridine sulfonamide complex PySO2NPh-Ir (7) could highly specifically catalyze nicotinamide adenine dinucleotide (NAD+) into the corresponding reducing cofactor NADH in cell growth media containing various biomolecules. The structures and catalytic mechanism of 7 were studied by single-crystal X-ray, NMR, electrochemical, and kinetic methods, and the formation of iridium hydride species Ir-H was confirmed to be the plausible hydride-transfer intermediate of 7. Moreover, benefiting from its high hydrogen-transfer activity and selectivity for NADH regeneration, 7 was used as an optimal metal catalyst to establish a chem-enzyme cascade catalytic hydrogen-transfer system, which realized the high-efficiency preparation of l-glutamic acid by combining with l-glutamate dehydrogenase (GLDH).

Graphene/Heterojunction Composite Prepared by Carbon Thermal Reduction as a Sulfur Host for Lithium-Sulfur Batteries.

An interlayer nanocomposite (CC@rGO) consisting of a graphene heterojunction with CoO and Co9S8 was prepared using a simple and low-cost hydrothermal calcination method, which was tested as a cathode sulfur carrier for lithium-sulfur batteries. The CC@rGO composite comprises a spherical heterostructure uniformly distributed between graphene sheet layers, preventing stacking the graphene sheet layer. After the introduction of cobalt heterojunction on a graphene substrate, the Co element content increases the reactive sites of the composite and improves its electrochemical properties to some extent. The composite exhibited good cycling performance with an initial discharge capacity of 847.51 mAh/g at 0.5 C and a capacity decay rate of 0.0448% after 500 cycles, which also kept 452.91 mAh/g at 1 C and in the rate test from 3 C back to 0.1 C maintained 993.27 mAh/g. This article provides insight into the design of cathode materials for lithium-sulfur batteries.

Early zygotic gene product Dunk interacts with anillin to regulate Myosin II during Drosophila cleavage.

Drosophila melanogaster cellularization is a special form of cleavage that converts syncytial embryos into cellular blastoderms by partitioning the peripherally localized nuclei into individual cells. An early event in cellularization is the recruitment of nonmuscle myosin II ("myosin") to the leading edge of cleavage furrows, where myosin forms an interconnected basal array before reorganizing into individual cytokinetic rings. The initial recruitment and organization of basal myosin are regulated by a cellularization-specific gene, dunk, but the underlying mechanism is unclear. Through a genome-wide yeast two-hybrid screen, we identified anillin (Scraps in Drosophila), a conserved scaffolding protein in cytokinesis, as the primary binding partner of Dunk. Dunk colocalizes with anillin and regulates its cortical localization during the formation of cleavage furrows, while the localization of Dunk is independent of anillin. Furthermore, Dunk genetically interacts with anillin to regulate the basal myosin array during cellularization. Similar to Dunk, anillin colocalizes with myosin since the very early stage of cellularization and is required for myosin retention at the basal array, before the well-documented function of anillin in regulating cytokinetic ring assembly. Based on these results, we propose that Dunk regulates myosin recruitment and spatial organization during early cellularization by interacting with and regulating anillin.

Femtosecond-laser-based full-field three-dimensional imaging with phase compensation.

Coherence scanning interferometer (CSI) enables 3D imaging with nanoscale precision. However, the efficiency of such a system is limited because of the restriction imposed by the acquisition system. Herein, we propose a phase compensation method that reduces the interferometric fringe period of femtosecond-laser-based CSI, resulting in larger sampling intervals. We realize this method by synchronizing the heterodyne frequency with the repetition frequency of the femtosecond laser. The experimental results show that our method can keep the root-mean-square axial error down to 2 nm at a high scanning speed of 6.44 µm per frame, which enables fast nanoscale profilometry over a wide area.

Liposome-tethered supported lipid bilayer platform for capture and release of heterogeneous populations of circulating tumor cells.

Because of scarcity, vulnerability, and heterogeneity in the population of circulating tumor cells (CTCs), the CTC isolation system relying on immunoaffinity interaction exhibits inconsistent efficiencies for all types of cancers and even CTCs with different phenotypes in individuals. Moreover, releasing viable CTCs from an isolation system is of importance for molecular analysis and drug screening in precision medicine, which remains a challenge for current systems. In this work, a new CTC isolation microfluidic platform was developed and contains a coating of the antibody-conjugated liposome-tethered-supported lipid bilayer in a developed chaotic-mixing microfluidic system, referred to as the "LIPO-SLB" platform. The biocompatible, soft, laterally fluidic, and antifouling properties of the LIPO-SLB platform offer high CTC capture efficiency, viability, and selectivity. We successfully demonstrated the capability of the LIPO-SLB platform to recapitulate different cancer cell lines with different antigen expression levels. In addition, the captured CTCs in the LIPO-SLB platform can be detached by air foam to destabilize the physically assembled bilayer structures due to a large water/air interfacial area and strong surface tension. More importantly, the LIPO-SLB platform was constructed and used for the verification of clinical samples from 161 patients with different primary cancer types. The mean values of both single CTCs and CTC clusters correlated well with the cancer stages. Moreover, a considerable number of CTCs were isolated from patients' blood samples in the early/localized stages. The clinical validation demonstrated the enormous potential of the universal LIPO-SLB platform as a tool for prognostic and predictive purposes in precision medicine.

Photo- or Electrochemical Cyclization of Dienes with Diselenides to Access Seleno-Benzo[b]azepines.

A cascade selenylation/cyclization of dienes with diselenides has been realized under visible-light irradiation or electrolysis conditions. Employing O2 or electricity as a "green" oxidant, this protocol provides a green and efficient method for an array of biologically important seleno-benzo[b]azepine derivatives in moderate to good yields. The direct sunlight irradiation and gram-scale reaction render the approach practical and attractive.

AcrNET: predicting anti-CRISPR with deep learning.

MOTIVATION: As an important group of proteins discovered in phages, anti-CRISPR inhibits the activity of the immune system of bacteria (i.e. CRISPR-Cas), offering promise for gene editing and phage therapy. However, the prediction and discovery of anti-CRISPR are challenging due to their high variability and fast evolution. Existing biological studies rely on known CRISPR and anti-CRISPR pairs, which may not be practical considering the huge number. Computational methods struggle with prediction performance. To address these issues, we propose a novel deep neural network for anti-CRISPR analysis (AcrNET), which achieves significant performance. RESULTS: On both the cross-fold and cross-dataset validation, our method outperforms the state-of-the-art methods. Notably, AcrNET improves the prediction performance by at least 15% regarding the F1 score for the cross-dataset test problem comparing with state-of-art Deep Learning method. Moreover, AcrNET is the first computational method to predict the detailed anti-CRISPR classes, which may help illustrate the anti-CRISPR mechanism. Taking advantage of a Transformer protein language model ESM-1b, which was pre-trained on 250 million protein sequences, AcrNET overcomes the data scarcity problem. Extensive experiments and analysis suggest that the Transformer model feature, evolutionary feature, and local structure feature complement each other, which indicates the critical properties of anti-CRISPR proteins. AlphaFold prediction, further motif analysis, and docking experiments further demonstrate that AcrNET can capture the evolutionarily conserved pattern and the interaction between anti-CRISPR and the target implicitly. AVAILABILITY AND IMPLEMENTATION: Web server: https://proj.cse.cuhk.edu.hk/aihlab/AcrNET/. Training code and pre-trained model are available at.

MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain.

In vitro studies indicate the neurodevelopmental disorder gene myelin transcription factor 1-like (MYT1L) suppresses non-neuronal lineage genes during fibroblast-to-neuron direct differentiation. However, MYT1L's molecular and cellular functions in the adult mammalian brain have not been fully characterized. Here, we found that MYT1L loss leads to up-regulated deep layer (DL) gene expression, corresponding to an increased ratio of DL/UL neurons in the adult mouse cortex. To define potential mechanisms, we conducted Cleavage Under Targets & Release Using Nuclease (CUT&RUN) to map MYT1L binding targets and epigenetic changes following MYT1L loss in mouse developing cortex and adult prefrontal cortex (PFC). We found MYT1L mainly binds to open chromatin, but with different transcription factor co-occupancies between promoters and enhancers. Likewise, multiomic data set integration revealed that, at promoters, MYT1L loss does not change chromatin accessibility but increases H3K4me3 and H3K27ac, activating both a subset of earlier neuronal development genes as well as Bcl11b, a key regulator for DL neuron development. Meanwhile, we discovered that MYT1L normally represses the activity of neurogenic enhancers associated with neuronal migration and neuronal projection development by closing chromatin structures and promoting removal of active histone marks. Further, we showed that MYT1L interacts with HDAC2 and transcriptional repressor SIN3B in vivo, providing potential mechanisms underlying repressive effects on histone acetylation and gene expression. Overall, our findings provide a comprehensive map of MYT1L binding in vivo and mechanistic insights into how MYT1L loss leads to aberrant activation of earlier neuronal development programs in the adult mouse brain.

Proliferative ability of circulating tumor cells is a prognostic factor in Early-Stage lung adenocarcinoma.

INTRODUCTION: Circulating tumor cells (CTCs) and their proliferative ability in lung adenocarcinoma (LUAD) were not well-investigated. We developed a protocol combining an efficient viable CTC isolation and in-vitro cultivation for the CTC enumeration and proliferation to evaluate their clinical significance. METHOD: The peripheral blood of 124 treatment-naïve LUAD patients were processed by a CTC isolation microfluidics, DS platform, followed by in-vitro cultivation. LUAD-specific CTCs were defined by immunostaining of DAPI+/CD45-/(TTF1/CK7)+ and were enumerated upon isolation and after 7-day cultivation. The CTC proliferative ability was evaluated by both the cultured number and the culture index, a ratio of cultured CTC number to the initial CTC number in 2 mL of blood. RESULT: All but two LUAD patients (98.4%) were detected with at least one CTC per 2 mL of blood. Initial CTC numbers did not correlate with metastasis (75 ± 126 for non-metastatic, 87 ± 113 for metastatic groups; P = 0.203). In contrast, both the cultured CTC number (mean: 28, 104, and 185 in stage 0/I, II/III, and IV; P < 0.001), and the culture index (mean: 1.1, 1.7 and 9.3 in stage 0/I, II/III, and IV; P = 0.043) were significantly correlated with the stages. Overall survival analysis within the non-metastatic group (N = 53) showed poor prognosis for patients with elevated cultured counts (cutoff ≥ 30; P = 0.027). CONCLUSION: We implemented a CTC assay in clinical LUAD patients with a high detection rate and cultivation capability. Cultured CTC count and proliferative ability, rather than the crude CTC numbers, highly associated with cancer prognosis.

Significantly Enhanced Robustness of K Isotope Analysis by Collision Cell MC-ICP-MS and Its Application to the Returned Lunar Samples by China's Chang'e-5 Project.

Stable K isotope ratios, an emerging research tool for a wide range of problems, can be measured precisely with high sensitivity by using collision cell multicollector ICP mass spectrometers (CC-MC-ICP-MS). However, it has been shown that the accuracy of K isotope analysis by CC-MC-ICP-MS could be compromised severely by trace-level Ca contaminants, although the cause of such an effect remains poorly understood. Here, we report that the influence of Ca on K isotope analysis by CC-MC-ICP-MS can be dramatically reduced if D2 rather than H2 (the default gas) is used as the reaction gas that goes into the collision cell. This indicates the generation of positively charged calcium-hydride molecules in the collision cell. Usage of D2 as reaction gas circumvents the Ca-induced inaccuracy issues during K isotope analysis because 40CaD+ does not interfere with 41K+ as 40CaH+ does; as such, the robustness of K isotope analysis by CC-MC-ICP-MS is significantly enhanced. This improved method is verified by K isotope analysis of seven geostandards, and applied to China's Chang'e-5 lunar return samples at submicrogram K consumption, revealing significant K isotope variability within a 17 mg lunar basalt fragment.

Identification of the Key Active Pharmaceutical Ingredients of Yishen Qutong Granule, A Chinese Medicine Formula, In The Treatment of Primary Lung Cancer.

BACKGROUND: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional Chinese medicine (TCM) reportedly has potential therapeutic effects against LC. OBJECTIVE: This study aimed to investigate the antitumor efficacy of Yishen Qutong granule (YSQTG) in primary LC treatment, to identify its key active pharmaceutical ingredients (APIs), and to explore its possible mechanism of action. METHODS: The antitumor role of YSQTG was validated via cell function assays and a xenograft tumor model. Then, high-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to determine the objective precipitation components of YSQTG, followed by target prediction through reference to databases. Subsequently, the proportion of the predicted targets that underwent actual changes was identified via RNA-sequencing. Enrichment analysis was performed to explore the possible mechanisms of action. Hub genes were screened, and western blotting was used to verify their protein expression levels to identify the core target. Molecular docking between the active compounds and the verified core target was performed, combined with an evaluation of the potential efficacy of candidate compounds using meta-analysis to screen the candidate key APIs. RESULTS: Experiments confirmed that YSQTG could inhibit LC cell proliferation, induce apoptosis in vitro, and inhibit lung tumor growth in vivo. HPLC-MS, RNA-seq, and enrichment analysis showed that oxidative stress-related pathways were the possible mechanism of YSQTG in primary LC treatment. Western blot verification indicated that heme oxygenase 1 (HMOX1, HO-1) could be the core target. Molecular docking and meta-analysis suggested that genistein and quercetin were the candidate key APIs. CONCLUSION: YSQTG and its active ingredients, genistein and quercetin, may have therapeutic effects against LC through their action on the downregulation of oxidative stress-related HMOX1 protein expression.

Decoupling and scenario analysis of economy-emissions pattern in China's 30 provinces.

The tension between reducing CO2 emissions and economic growth has become increasingly prominent in recent years, while China is vigorously promoting ecological civilization to achieve sustainable development. However, the factors influencing China's current economic emission nexus at the regional and provincial levels and the sustainability of the strong decoupling state remain unclear. We analyze the decoupling of emissions at the national and provincial levels of the Chinese economy from the perspective of historical patterns and current drivers from 1997 to 2019. Also, we developed three scenarios (i.e., pessimistic, median, and optimistic scenarios) to analyze the impact of decoupling relationship changes. We find that China's national decoupling relationship has eased since 1997, but it has not yet reached the ideal state, with provinces mainly exhibiting weak decoupling. The EKC hypothesis is tested for the whole country and 30 provinces and finds that 15 provinces have two turning points, 13 provinces have one turning point, and the others have no turning point. Based on the scenario analysis, the total emissions in the pessimistic scenario (S1) without any improvement of decoupling would increase by 73.97% compared to the level of 2019. However, the total emissions in the optimistic scenario (S3), in which all provinces obtained strong decoupling, are almost half of the level of 2019. This is mainly from the reduction of emissions in the western less developed regions (e.g., Shanxi, Inner Mongolia, and Xinjiang) and developed coastal regions (e.g., Jiangsu and Shandong). On the basis of the results of factor analysis, we put forward policy recommendations for expanding electrification, optimizing industrial structure, and promoting technological innovation.