Bu Shen Huo Xue Formula Provides Neuroprotection Against Spinal Cord Injury by Inhibiting Oxidative Stress by Activating the Nrf2 Signaling Pathway.

Purpose: Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF's therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets. Methods: The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence. Results: The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway. Conclusion: BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.

Distinct accumulation patterns, translocation efficiencies, and impacts of nano-fertilizer and nano-pesticide in wheat through foliar versus soil application.

The use of nano-chemicals in agriculture has been shown to enhance crop production through soil additions or foliar sprays. However, the accumulation pattern, translocation efficiency, mode of action of nanomaterials (NMs) via different application methods remain unclear. In this study, wheat was treated with CuO-NPs/CeO2-NPs (50 and 100 nm) for 21 days using soil and foliar application separately. Foliar spray resulted in higher accumulation and more efficient translocation of NMs compared to soil addition. Smaller NMs exhibited higher accumulation and transfer capabilities under the same application method. The accumulation of CuO-NPs was approximately 20 times greater than that of CeO2-NPs, particularly under the soil addition treatment. Scanning electron microscopy analysis demonstrated that NMs could directly enter wheat leaves via stomata during foliar application. Wheat growth was inhibited by roughly 15 % following CuO-NPs exposure, whereas no significant effects on growth were observed with CeO2-NPs. By integrating nontargeted metabolomics analysis with targeted physiological characteristics assessments, it was revealed that CuO-NPs mainly disturbed nitrogen metabolism pathways and induced oxidative damage. In contrast, CeO2-NPs enhanced carbohydrates related biological processes such as starch and sucrose metabolism, glycolysis, and TCA cycle, which are crucial for carbon metabolism. These findings suggest that the type of nanomaterial is a crucial factor to consider when evaluating their foliar or soil application in agriculture.

Mitochondrial non-energetic function and embryonic cardiac development.

The initial contraction of the heart during the embryonic stage necessitates a substantial energy supply, predominantly derived from mitochondrial function. However, during embryonic heart development, mitochondria influence beyond energy supplementation. Increasing evidence suggests that mitochondrial permeability transition pore opening and closing, mitochondrial fusion and fission, mitophagy, reactive oxygen species production, apoptosis regulation, Ca2+ homeostasis, and cellular redox state also play critical roles in early cardiac development. Therefore, this review aims to describe the essential roles of mitochondrial non-energetic function embryonic cardiac development.

Research advance in effects of solar radiation on litter decomposition in terrestrial ecosystems.

Litter decomposition significantly influences the carbon (C) dynamics of terrestrial ecosystems. Solar radiation is not only essential for photosynthetic C fixation and primary productivity, but also can directly or indirectly promote litter decomposition through photodegradation. Recently, photodegradation has been identified as a key factor driving litter decomposition and potentially impacts terrestrial C cycle. To enrich and develop the theory of litter decomposition, we summarized the mechanisms and main driving factors of photodegradation, and compared the responses of photodegradation to environment and climate changes at different scales. Photodegradation primarily includes photomineralization, photoinhibition, and photofaciliation, each affecting litter decomposition differently under various environmental conditions. Photodegradation is closely related to factors such as solar radiation, litter traits, temperature, moisture, microorganisms, and vegetation cover. The interactions among these factors complicate the patterns of photodegradation. Finally, we identified the main issues in litter photodegradation research and prospected future research directions. We emphasized the needs for in-depth exploration of photodegradation pathways and intrinsic mechanisms, quantification of its interactive effects with environmental factors, and optimization of traditional carbon turnover models.

Latitudinal responses of litter decomposition to solar radiation.

Photodegradation driven by solar radiation has been confirmed as an important driving factor for litter decomposition. However, previous single-site studies could not quantify the relative contribution of variation in solar radiation to litter decomposition. To address it, we conducted a field experiment in Heshan National Field Research Station of Forest Ecosystem, Guangdong (Heshan Station, south subtropical climate), Jigongshan Ecological Research Station, Xinyang, Henan (Jigongshan Station, north subtropical climate) and Daqinggou Ecological Research Station, Institute of Applied Ecology, Chinese Academy of Sciences (Daqinggou Station, temperate climate) at intervals of 10 degrees. We examined litter decomposition of Populus davidiana and Larix olgensis, two species with significant differences in initial litter quality through an in-situ spectral-attenuation experiment. Treatments included full-spectrum, No-UV-B (attenuating UV-B radiation <315 nm) and No-UV & Blue (attenuating all UV and blue wavelengths <500 nm). After nearly 1-year decomposition, litter dry mass remaining of P. davidiana and L. olgensis under full-spectrum treatment was lowest at Heshan (30.2% and 36.3%), and highest at Jigongshan (37.3% and 45.8%). Among all sites, litter dry mass remaining was lowest under the full-spectrum, and lower than that of No-UV-B and No-UV & blue. UV and blue light significantly increased litter mass loss of P. davidiana and L. olgensis, with contributions of 59.7% and 57.0% (Heshan), 46.4% and 42.1% (Jigongshan), and 39.0% and 45.9% (Daqinggou), respectively. The contribution of UV-A and blue light (315-500 nm) was greater than UV-B (280-315 nm); the cumulative irradiance, soil temperature and moisture were the main driving factors for litter photodegradation.

Vertically Oriented 2D Perovskite Layer with n = 1 Phase Enables Efficient and Stable Inverted Perovskite Solar Cells.

Surface passivation with 2D perovskites has been reported to be important for high-performance perovskite solar cells (PSCs). However, it is challenging to achieve a controlled growth of 2D perovskites, which typically feature random orientation and various n number. In this paper, we fabricate a 2D layer with a highly ordered orientation and pure n = 1 phase on top of the perovskite film using the organic spacer molecule 7-fluoro-1,2,3,4-tetrahydroisoquinolinehydrochloride (7-FTH). The formed 2D perovskites feature a highly ordered orientation normal to the substrate and a pure n = 1 phase, which efficiently passivates surface defects of the as-prepared perovskite films and improves the energy level alignment between the perovskite film and electron transport layer. Consequently, the modified PSCs achieve a champion power conversion efficiency (PCE) of 24.65% with improved VOC and fill factor. After being stored in an N2 glovebox for 1200 h and kept in ambient air (room temperature and relative humidity of 50-70%) for 840 h, the modified devices retain 93% and 95% of its initial PCE, respectively.

The development and validation of a prognostic prediction modeling study in acute myocardial infarction patients after percutaneous coronary intervention: hemorrhea and major cardiovascular adverse events.

Background: Percutaneous coronary intervention (PCI) is one of the most important diagnostic and therapeutic techniques in cardiology. At present, the traditional prediction models for postoperative events after PCI are ineffective, but machine learning has great potential in identification and prediction of risk. Machine learning can reduce overfitting through regularization techniques, cross-validation and ensemble learning, making the model more accurate in predicting large amounts of complex unknown data. This study sought to identify the risk of hemorrhea and major adverse cardiovascular events (MACEs) in patients after PCI through machine learning. Methods: The entire study population consisted of 7,931 individual patients who underwent PCI at Jiangsu Provincial Hospital and The Affiliated Wuxi Second People's Hospital from January 2007 to January 2022. The risk of postoperative hemorrhea and MACE (including cardiac death and in-stent restenosis) was predicted by 53 clinical features after admission. The population was assigned to the training set and the validation set in a specific ratio by simple randomization. Different machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), random forest (RF), and deep learning neural network (DNN), were trained to build prediction models. A 5-fold cross-validation was applied to correct errors. Several evaluation indexes, including the area under the receiver operating characteristic (ROC) curve (AUC), accuracy (Acc), sensitivity (Sens), specificity (Spec), and net reclassification improvement (NRI), were used to compare the predictive performance. To improve the interpretability of the model and identify risk factors individually, SHapley Additive exPlanation (SHAP) was introduced. Results: In this study, 306 patients (3.9%) experienced hemorrhea, 107 patients (1.3%) experienced cardiac death, and 218 patients (2.7%) developed in-stent restenosis. In the training set and validation set, except for previous PCI and statins, there were no significant differences. XGBoost was observed to be the best predictor of every event, namely hemorrhea [AUC: 0.921, 95% confidence interval (CI): 0.864-0.978, Acc: 0.845, Sens: 0.851, Spec: 0.837 and NRI: 0.140], cardiac death (AUC: 0.939, 95% CI: 0.903-0.975, Acc: 0.914, Sens: 0.950, Spec: 0.800 and NRI: 0.148), and in-stent restenosis (AUC: 0.915; 95% CI: 0.863-0.967, Acc: 0.834, Sens: 0.778, Spec: 0.902 and NRI: 0.077). SHAP showed that the number of stents had the greatest influence on hemorrhea, while age and drug-coated balloon were the main factors in cardiogenic death and stent restenosis (all P<0.05). Conclusions: The XGBoost model (machine learning) performed better than the traditional logistic regression model in identifying hemorrhea and MACE after PCI. Machine learning models can be used as a tool for risk prediction. The machine learning model described in this study can personalize the prediction of hemorrhea and MACE after PCI for specific patients, helping clinicians adjust intervenable features.

Four new species and four newly recorded species of Omphale Haliday (Hymenoptera, Eulophidae) from China, with a key to Chinese species.

In this paper, four species of Omphale Haliday, O.longigena Li & Li, sp. nov., O.longitarsus Li & Li, sp. nov., O.rectisulcus Li & Li, sp. nov., and O.xanthosoma Li & Li, sp. nov., are described as new to science; four species, O.brevibuccata Szelényi, O.connectens Graham, O.melina Yefremova & Kriskovich, and O.obscura (Förster) are reported from China for the first time; and the male of O.melina is reported for the first time in the world. A key to all known species of the genus Omphale in China is provided.

Pattern dynamics of networked epidemic model with higher-order infections.

Current research on pattern formations in networked reaction-diffusion (RD) systems predominantly focuses on the impacts of diffusion heterogeneity between nodes, often overlooking the contact heterogeneity between individuals within nodes in the reaction terms. In this paper, we establish a networked RD model incorporating infection through higher-order interaction in simplicial complexes in the reaction terms. Through theoretical and numerical analysis, we find that these higher-order interactions may induce Turing instability in the system. Notably, the relationship between the size of the Turing instability range and the average 2-simplices degree within nodes can be approximated by a quadratic function. Additionally, as the average 2-simplices degree increases, the amplitude of the patterns exhibits three distinct trends: increasing, decreasing, and initially increasing then decreasing, while the average infection density increases consistently. We then provide a possible explanation for these observations. Our findings offer new insights into the effects of contact heterogeneity within nodes on networked pattern formations, thereby informing the development of epidemic prevention and control measures.

Telangiectasia Macularis Multiplex Acquisita and its Potential Association with Calcium Channel Blockers: A Retrospective Study of 46 Chinese Patients.

Telangiectasia macularis multiplex acquisita is an acquired cutaneous telangiectasis of unknown aetiology, and it lacks both effective and cost-efficient treatment. This study aims to identify a novel potential associated factor of the disease and explore feasible therapeutic interventions. In this retrospective case series study, 46 Chinese patients diagnosed with telangiectasia macularis multiplex acquisita between 1 January 2007 and 18 May 2023 were included. The median age of onset was 43 years (23 to 60 years), and the male to female ratio was 10.5:1. Besides previously reported associations including chronic liver disorders, alcohol consumption, and smoking, a potential association was found between use of calcium channel blockers and development of telangiectasia macularis multiplex acquisita. Twenty-two of 27 hypertensive patients took calcium channel blockers, with 17 followed up. Ten out of 17 displayed a range of improvements following the cessation of calcium channel blockers; 1 patient reported no lesion change post-discontinuation of calcium channel blockers; 1 patient continued their medication but showed partial improvement after 2 pulsed dye laser treatments; 1 patient observed lesion colour lightening without altering hypertensive medication or other specific treatments; and another 4 kept their previous hypertensive regimen due to blood pressure stability concerns, with no change in their lesions. The study proposes that cessation of calcium channel blockers can be a novel therapeutic approach for affected individuals.

Interference of skeleton photoperiod in circadian clock and photosynthetic efficiency of tea plant: in-depth analysis of mathematical model.

The circadian system of plants is a complex physiological mechanism, a biological process in which plants can adjust themselves according to the day and night cycle. To understand the effects of different photoperiods on the biological clock of tea plants, we analyzed the expression levels of core clock genes (CCA1, PRR9, TOC1, ELF4) and photosynthesis-related genes (Lhcb, RbcS, atpA) under normal light (light/dark = 12 h/12 h, 12L12D) and took the cost function defined by cycle and phase errors as the basic model parameter. In the continuous light environment (24 h light, 24L), the peak activity and cycle of key genes that control the biological clock and photosynthesis were delayed by 1-2 h. Under a skeleton photoperiod (6L6D, 3L3D), the expression profiles of clock genes and photosynthesis-related genes in tea plants were changed and stomatal opening showed a circadian rhythm. These observations suggest that a skeleton photoperiod may have an effect on the circadian rhythm, photosynthetic efficiency and stomatal regulation of tea plants. Our study and model analyzed the components of circadian rhythms under different photoperiodic pathways, and also revealed the underlying mechanisms of circadian regulation of photosynthesis in tea plants.

A Study of the Diversity Patterns of Desert Vegetation Communities in an Arid Zone of China.

The Gobi Desert ecosystem is currently experiencing the impacts of persistent climate warming and extreme weather. However, the relative influences of factors such as soil, climate, and spatial variables on the ß-diversity of desert plants and their key components have not been systematically studied. In this research, the Dunhuang North Mountain and Mazong Mountain areas were selected as study areas, with a total of 79 plant community plots systematically established. The aim was to explore intercommunity ß-diversity and its components and to analyze the interrelationships with climate factors, soil factors, and geographic distance. The results indicate that (1) there is a geographic decay pattern and significant differences among plant communities in the Dunhuang North Mountain and Mazong Mountain areas, with ß-diversity primarily driven by replacement components. (2) Climate, soil, and geographic distance significantly influence ß-diversity and its replacement components, with climate factors exerting the greatest influence and geographic distance the least. (3) Multiple regression analysis (MRM) reveals differential effects of climate factors, soil factors, and geographic distance on ß-diversity and its replacement components, with climate and soil factors exerting a much greater influence than geographic distance. In summary, the ß-diversity of plant communities and their replacement components in the Dunhuang North Mountain and Mazong Mountain areas result from the combined effects of habitat filtering and dispersal limitation, with habitat filtering having a greater impact, while environmental heterogeneity is an important factor influencing species differences in this region.

Oxymatrine inhibits migration and invasion of esophageal squamous cell carcinoma cell lines via the MEK1/ERK/ß-catenin pathway.

Esophageal, cancer is a prevalent malignant tumour of the digestive system in China, and esophageal squamous cell carcinoma (ESCC) accounts for 90 % of all esophageal cancer cases. Currently, the primary treatment involves surgical resection combined with postoperative radiotherapy. In this study, we used two ESCC cell lines to determine whether oxymatrine (OMT) inhibits ESCC, whether the mechanism involves the MEK1/ERK/ß-catenin pathway, and how OMT modulates this pathway to affect the development of ESCC. The effects of OMT treatment were monitored with Cell Counting Kit-8 (CCK-8) assays as well as with clony formation, migration and invasion, wound healing, Hoechst 33258, and Western blot analyses. The relationship between OMT and the target was also evaluated by molecular docking and cell stability experiments. These findings suggest that ESCC development and metastasis may be inhibited by OMT and that OMT targets MEK1 through the ERK/ß-catenin/EMT pathway to suppress ESCC cell migration and invasion. In addition, in vivo studies confirmed that OMT can inhibit the growth of ESCC cell lines in NOG mice without causing damage to other organs. In conclusion, in vitro experiments, revealed that OMT prevents the migration and invasiveness of ESCC cells by inhibiting the ERK/ß-catenin/EMT pathway and thus targeting MAP2K1 (MEK1) in ESCC.

Plant diversity increases diversity and network complexity rather than alters community assembly processes of leaf-associated fungi in a subtropical forest.

Plant diversity significantly impacts ecosystem processes and functions, yet its influence on the community assembly of leaf fungi remains poorly understood. In this study, we investigated leaf epiphytic and endophytic fungal communities in a Chinese subtropical tree species richness experiment, ranging from 1 to 16 species, using amplicon sequencing to target the internal transcribed spacer 1 region of the rDNA. We found that the community assembly of epiphytic and endophytic fungi was predominantly governed by stochastic processes, with a higher contribution of dispersal limitation on epiphytic than on endophytic fungal communities but a higher contribution of selection on endophytic than on epiphytic fungal communities. The plant-epiphytic fungus interaction network was more complex (e.g., more highly connected and strongly nested but less specialized and modularized) than the plant-endophytic fungus interaction network. Additionally, tree species richness was positively correlated with the network complexity and diversity of epiphytic (α-, ß- and γ-diversity) and endophytic (ß- and γ-diversity) fungi, but was not associated with the contribution of the stochastic and deterministic processes on the community assembly of epiphytic and endophytic fungi. This study highlights that tree species diversity enhances the diversity and network complexity, rather than alters the ecological processes in community assembly of leaf-associated fungi.

Superconducting Electride Li9S with a Transition Temperature above the McMillan Limit.

An electride, characterized by unique interstitial anionic electrons (IAEs), offers promising avenues for modulating its superconductivity. The pressure-dependent coupling between IAEs and orbital electrons significantly affects the superconducting transition temperature (Tc). However, existing research has predominantly concentrated on pressures within 300 GPa. To advance the understanding, we propose investigating the Li-S system under ultrahigh pressure to unveil novel electride superconductors. Five stable Li-rich electrides with diverse IAE topologies, including one Li7S, three Li9S, and one Li12S phases, are identified through structural search calculations. Among the Li9S phases, in the C2/c phase (600 GPa), the IAEs are connected to the S atomic extra-nuclear electrons with the unconventional d orbital attribute due to the extreme pressure, while two low-pressure R-3 (25 GPa) and C2/m (400 GPa) phases have interconnected IAEs. Due to its unique IAE attributes, C2/c Li9S exhibits the highest Tc of 53.29 K at 600 GPa. Its superconductivity results from the coupling of the S d, Li p electrons, and IAEs with the low-frequency phonons associated with the attraction between IAEs and the Li-S framework. Our work enhances insights into IAEs within electrides and their role in facilitating superconductivity.

Efficacy and safety of tegoprazan for duodenal ulcers in Chinese patients: a multicenter, randomized, double-blind, non-inferiority, phase III study.

OBJECTIVE: Tegoprazan represents a newly developed potassium-competitive acid blocker utilized for the treatment of acid-related disorders. The present study aimed to explore the therapeutic effectiveness of tegoprazan in Chinese individuals with duodenal ulcers (DU). METHODS: In the current multicenter, randomized, double-blind, double-dummy, parallel-group, non-inferiority, phase III clinical trial, individuals with DU underwent randomization 1:1 to be administered tegoprazan 50 mg or lansoprazole 30 mg once daily. The primary efficacy endpoint was the 6-week cumulative endoscopic ulcer healing rate. Secondary endpoints included 4-week endoscopic ulcer healing rate and relief of DU-related gastrointestinal symptoms at weeks 2, 4, and 6. Safety analysis encompassed adverse events (AEs) and laboratory indexes. RESULTS: The 6-week cumulative endoscopic ulcer healing rates were 96.9% (188/194) and 99.0% (189/191) in the tegoprazan and lansoprazole groups, respectively, indicating a difference of -2.0% (95% confidence interval (CI) = -4.9 to 0.8) in the full analysis set (FAS). The corresponding healing rates were 98.4% (185/188) and 99.5% (183/184) in the per-protocol set, respectively, indicating a difference of -1.1% (95% CI = -3.1 to 1.0). The 4-week healing rates in the tegoprazan and lansoprazole groups were 89.2% (173/194) and 88.5% (169/191) in the FAS, respectively, with a difference of 0.7% (95% CI = -5.6 to 7.0). Treatment-related AEs, all mild-to-moderate, were reported in 38.2% (78/204) and 48.2% (94/195) of participants in the tegoprazan and lansoprazole groups, respectively. CONCLUSIONS: Tegoprazan 50 mg once daily is effective and non-inferior to lansoprazole 30 mg once daily in Chinese patients with DU, showing a promising safety and tolerability profile. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT05010954.

Single-cell sequencing analysis revealed that NEAT1 was a potential biomarker and therapeutic target of prostate cancer.

BACKGROUND: Prostate cancer (PCa) usually manifests atypical symptoms in the early stage, and once symptoms appear, most PCa patients have developed to the advanced stage, failing to undergo radical surgery. In this study, PCa occurrence-related biomarkers were explored based on single-cell RNA sequencing (scRNA-seq) data. METHODS: scRNA-seq data of prostate normal (Normal), benign prostatic hyperplasia (BPH), and PCa (Tumor) samples were acquired from the Gene Expression Omnibus (GEO). Cellular subsets associated with PCa occurrence were obtained using cell annotation. Additionally, the mRNA expression of nuclear enriched abundant transcript 1 (NEAT1) was detected by quantitative real-time PCR (qRT-PCR). The effects of NEAT1 on cell proliferation and apoptosis were analyzed by 5-ethynyl-2-deoxyuridine (EdU) and flow cytometry. Subsequently, cell-derived xenograft (CDX) models were constructed and divided into the LV-NC and LV-shNEAT1 groups. After the tumor tissues of CDX model mice in each group were extracted, the cell growth and Ki67 expression were observed separately using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). RESULTS: Ten cellular subsets were obtained via cell annotation, and significantly differential changes were observed between Basal intermediate and Luminal during the course of BPH to PCa. NEAT1-Luminal was highly recruited in the Tumor group with low stemness and high malignancy scores. Matrix metallopeptidase 7 (MMP7)- keratin 17 (KRT17)-Basal intermediate had high ratios in the Tumor group with low stemness and high malignancy scores. The results of pseudotime analysis revealed that NEAT1-Luminal in the Tumor group were consistently distributed with tumor stage cells. In vitro assays showed that NEAT1 expression was elevated in PCa cells, and NEAT1 knockdown could inhibit cell proliferation and induce apoptosis. CDX assays indicated that silencing NEAT1 could reduce the growth rate of PCa tumor volume in CDX model mice. H&E staining results showed that nuclei of tumor cells were reduced and exhibited lighter color in the LV-shNEAT1 group compared with the LV-NC group. IHC results showed that Ki67 positivity was significantly lower in the LV-shNEAT1 group than in the LV-NC group. CONCLUSION: NEAT1 expression is increased in PCa, and NEAT1 can be a potential biomarker and therapeutic target for PCa.

Drug Repurposing Using Molecular Network Analysis Identifies Jak as Targetable Driver in Necrobiosis Lipoidica.

Drug repurposing is an attractive strategy for therapy development, particularly in rare diseases where traditional drug development approaches may be challenging owing to high cost and small numbers of patients. In this study, we used a drug identification and repurposing pipeline to identify candidate targetable drivers of disease and corresponding therapies through application of causal reasoning using a combination of open-access resources and transcriptomics data. We optimized our approach on psoriasis as a disease model, demonstrating the ability to identify known and, to date, unrecognized molecular drivers of psoriasis and link them to current and emerging therapies. Application of our approach to a cohort of tissue samples of necrobiosis lipoidica (an unrelated; rare; and, to date, molecularly poorly characterized cutaneous inflammatory disorder) identified a unique set of upstream regulators, particularly highlighting the role of IFNG and the Jak-signal transducer and activator of transcription pathway as a likely driver of disease pathogenesis and linked it to Jak inhibitors as potential therapy. Analysis of an independent cohort of necrobiosis lipoidica samples validated these findings, with the overall agreement of drug-matched upstream regulators above 96%. These data highlight the utility of our approach in rare diseases and offer an opportunity for drug discovery in other rare diseases in dermatology and beyond.

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 µg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 µg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 µg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 µg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 µg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

Design and Simulation for Minimizing Non-Radiative Recombination Losses in CsGeI2Br Perovskite Solar Cells.

CsGeI2Br-based perovskites, with their favorable band gap and high absorption coefficient, are promising candidates for the development of efficient lead-free perovskite solar cells (PSCs). However, bulk and interfacial carrier non-radiative recombination losses hinder the further improvement of power conversion efficiency and stability in PSCs. To overcome this challenge, the photovoltaic potential of the device is unlocked by optimizing the optical and electronic parameters through rigorous numerical simulation, which include tuning perovskite thickness, bulk defect density, and series and shunt resistance. Additionally, to make the simulation data as realistic as possible, recombination processes, such as Auger recombination, must be considered. In this simulation, when the Auger capture coefficient is increased to 10-29 cm6 s-1, the efficiency drops from 31.62% (without taking Auger recombination into account) to 29.10%. Since Auger recombination is unavoidable in experiments, carrier losses due to Auger recombination should be included in the analysis of the efficiency limit to avoid significantly overestimating the simulated device performance. Therefore, this paper provides valuable insights for designing realistic and efficient lead-free PSCs.