Integration of network pharmacology and experimental verification to reveal the active components and molecular mechanism of modified Danzhi Xiaoyao San in the treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

Flexible X-ray Imaging and Stable Information Storage of SrF2:Eu Based on Radio-Photoluminescence.

X-ray imaging has garnered widespread interest in biomedical diagnosis and nondestructive detection. The exploration of radio-photoluminescence has hastened the advancement of X-ray information storage. However, significant challenges persist in achieving the prolonged imaging of curved objects without attenuation. Here, europium-doped strontium fluoride (SrF2:Eu) is meticulously created to exhibit a linear response to an extensive range of X-ray doses (maximum dose > 5000 Gy), showcasing excellent X-ray information reading/erasing reusability properties (10 cycles). This is accompanied by a red-to-blue emission transition under UV excitation, sustaining for 150 days without attenuation. To elucidate the phenomena of irradiated photoluminescent discoloration and the reversible X-ray storage of SrF2:Eu, we propose an electron-vacancy trap (valence conversion) mechanism, information stably retained by the SrF2:Eu-based device under ambient conditions due to high energy barriers. The time-lapse readout capability is further demonstrated for three-dimensional imaging of curved objects (10 lp mm-1) based on SrF2:Eu embedded within a polydimethylsiloxane (SrF2:Eu@PDMS). The SrF2:Eu demonstrates time-lapse imaging, reversible radio-photoluminescence, and recoverable X-ray storage, offering a promising avenue for optical information encryption and anticounterfeiting applications.

Protective effects of atractylenolide III on oxygen-glucose-deprivation/reperfusion-induced injury in HT22 cells.

BACKGROUND: Atractylenolide III (ATL III) is a natural bioactive compound, that possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, whether ATL III can protect against neuronal injury induced by cerebral ischemia/reperfusion (I/R) have not yet been studied. This study aimed to investigate the protective effects of ATL III on neuronal injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model in HT22 cells. METHODS: Establishment of OGD/R model to induce HT22 cell injury in vitro. Cell viability, live-dead cell staining, oxidative stress levels, and pro-inflammatory cytokine levels were detected using kits. Cell apoptosis was observed by flow cytometry, and the expression of Bax, Bcl-2, and Caspase-3 proteins was detected by western blot. RESULTS: ATL III significantly alleviates OGD/R-induced cell injury, as evidenced by the increased cell viability and reduced apoptosis rate. ATL III increased the levels of superoxide dismutase (SOD) and glutathione (GSH), while reducing malondialdehyde (MDA), reactive oxygen species (ROS), and the levels of TNF-α, IL-1ß, and IL-6. The protein expression of Bax and Caspase-3 was downregulated, while Bcl-2 expression was upregulated by ATL III. CONCLUSION: ATL III as a potential therapeutic agent for reducing neuronal injury by mitigating oxidative stress, apoptosis, and inflammation.

Textured Perovskite/Silicon Tandem Solar Cells Achieving Over 30% Efficiency Promoted by 4-Fluorobenzylamine Hydroiodide.

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

Modified Danzhi XiaoyaoSan inhibits neuroinflammation via regulating TRIM31/NLRP3 inflammasome in the treatment of CUMS depression.

The NLRP3 inflammasome is critically involved in the development of depression. The E3 ubiquitin ligase TRIM31 negatively regulates this process by promoting the degradation of NLRP3 through the ubiquitin-proteasome pathway. Modified Danzhi Xiaoyaosan (MDZXYS) has shown good therapeutic effect in both preclinical and clinical depression treatments, yet the underlying mechanisms of its antidepressant effects are not fully understood. In the present study, we aimed to explore the antidepressant mechanisms of MDZXYS, focusing on NLRP3 activation and ubiquitin-mediated degradation. We employed rats with depression induced by chronic unpredictable mild stress (CUMS) and conducted various behavioral tests, including the sucrose preference, forced swimming, and open field tests. Neuronal damage in CUMS-treated rats was assessed using Nissl staining. We measured proinflammatory cytokine levels using ELISA kits and analyzed NLRP3/TRIM31 protein expression via Western blotting and immunofluorescence staining. Our results disclosed that MDZXYS reversed CUMS-induced depression-like behaviors in rats, reduced proinflammatory cytokine levels (IL-1ß), and ameliorated neuronal damage in the prefrontal cortex. Additionally, CUMS activated the NLRP3 inflammasome in the prefrontal cortex and upregulated the protein expression of TRIM31. After MDZXYS administration, the expression of NLRP3 inflammasome-associated proteins was reduced, while the expression level of TRIM31 was further increased. Through co-localized immunofluorescence staining, we observed a significant elevation in the co-localization expression of NLRP3 and TRIM31 in the prefrontal cortex of the MDZXYS group. These findings suggest that inhibiting NLRP3 inflammasome-mediated neuroinflammation by modulating the TRIM31signaling pathway may underlie the antidepressant effects of MDZXYS, and further support targeting NLRP3 as a novel approach for the prevention and treatment of depression.

Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice.

OBJECTIVE AND DESIGN: Mast cells (MCs), as the fastest immune responders, play a critical role in the progression of neuroinflammation-related diseases, especially in depression. Quercetin (Que) and kaempferol (Kae), as two major diet-derived flavonoids, inhibit MC activation and exhibit significant antidepressant effect due to their anti-inflammatory capacity. The study aimed to explore the mechanisms of inhibitory effect of Que and Kae on MC activation, and whether Que and Kae suppress hippocampal mast cell activation in LPS-induced depressive mice. SUBJECTS AND TREATMENT: In vitro assays, human mast cells (HMC-1) were pretreated with Que or Kae for 1 h, then stimulated by phorbol 12-myristate 13-acetate (PMA) and 2,5-di-t-butyl-1,4-benzohydroquinone (tBHQ) for 3 h or 12 h. In vivo assays, Que or Kae was administered by oral gavage once daily for 14 days and then lipopolysaccharide (LPS) intraperitoneally injection to induce depressive behaviors. METHODS: The secretion and expression of TNF-α were determined by ELISA and Western blotting. The nuclear factor of activated T cells (NFAT) transcriptional activity was measured in HMC-1 stably expressing NFAT luciferase reporter gene. Nuclear translocation of NFATc2 was detected by nuclear protein extraction and also was fluorescently detected in HMC-1 stably expressing eGFP-NFATc2. We used Ca2+ imaging to evaluate changes of store-operated calcium entry (SOCE) in HMC-1 stably expressing fluorescent Ca2+ indicator jGCamP7s. Molecular docking was used to assess interaction between the Que or Kae and calcium release-activated calcium modulator (ORAI). The  hippocampal mast cell accumulation and activation  were detected by toluidine blue staining and immunohistochemistry with ß-tryptase. RESULTS: In vitro assays of HMC-1 activated by PtBHQ (PMA and tBHQ), Que and Kae significantly decreased expression and secretion of TNF-α. Moreover, NFAT transcriptional activity and nuclear translocation of NFATc2 were remarkably inhibited by Que and Kae. In addition, the Ca2+ influx mediated by SOCE was suppressed by Que, Kae and the YM58483 (ORAI inhibitor), respectively. Importantly, the combination of YM58483 with Que or Kae had no additive effect on the inhibition of SOCE. The molecular docking also showed that Que and Kae both exhibit high binding affinities with ORAI at the same binding site as YM58483. In vivo assays, Que and Kae significantly reversed LPS-induced depression-like behaviors in mice, and inhibited hippocampal mast cell activation  in LPS-induced depressive mice. CONCLUSIONS: Our results indicated that suppression of SOCE/NFATc2 pathway-mediated by ORAI channels may be the mechanism of inhibitory effect of Que and Kae on MC activation, and also suggested Que and Kae may exert the antidepressant effect through suppressing hippocampal mast cell activation.

Pan-cancer analysis of the prognostic and immunological role of FKBP4.

Objectives: Our previous studies revealed the significant roles of FK506-binding protein 4 (FKBP4) in tumorigenesis, however, there has been no pan-cancer analysis of FKBP4. Using bioinformatics, the current study reported the expression and prognostic role of FKBP4, and the correlation between FKBP4 and clinicopathological parameters, methylation, molecular network, immunological traits and drug sensitivity. Methods: RNA sequencing data, somatic mutation, and related clinical information were obtained from TCGA using UCSC Xena. The association between FKBP4 expression and clinical features was assessed using TISIDB. The relationships between FKBP4 expression and tumour stage, OS, DSS, DFS, and PFS were analysed using univariate cox regression analysis. The radar plots for TMB and MSI were obtained using "Fmsb" R package. UALCAN was used to explore the effect of FKBP4 methylation on tumour and normal samples. CBioportal was used to analyse copy number mutations in FKBP4 Gene expression and drug sensitivity data were downloaded from the CellMiner database. GO analysis was performed for the high and the low expression of FKBP4 compared with the median level of FKBP4 using clusterProfiler4.0. Results: FKBP4 expression is significantly upregulated in various types of cancers. Cox regression analysis showed that high FKBP4 levels were correlated with poor OS, DSS, DFS, and PFS in most patients with cancer. Methylation of FKBP4 DNA was upregulated in most cancers, and FKBP4 expression is positively associated with transmethylase expression. FKBP4 and its copy were significantly associated with the expression of immune-infiltrating cells, immune checkpoint genes, immune modulators, TMB, MMR, and MSI. FKBP4 expression levels significantly correlated with 16 different drug sensitivities (all p < 0.05). Conclusions: Our pan-cancer bioinformatic analysis revealed a potential mechanism underlying the effects of FKBP4 on the prognosis and progression of various cancers.

Naringenin protects against septic cardiomyopathy in mice by targeting HIF-1α.

Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.

Analysis of pollutant dispersion patterns in rivers under different rainfall based on an integrated water-land model.

In the context of rapid urban expansion, the interaction between humanity and nature has become more prominent. Urban land and rivers often exist as distinct entities with limited material exchange. However, during rainfall, these two systems interconnect, resulting in the transfer of land-derived pollutants into rivers. Such transfer significantly increases river pollutant levels, adversely affecting water quality. Therefore, developing a water quality simulation and prediction model is crucial. This model should effectively illustrate pollutant movement and dispersion during rain events. This study proposes a comprehensive model that merges the Storm Water Management Model (SWMM) with the Environmental Fluid Dynamics Code (EFDC). This integrated model assesses the spread and dispersion of pollutants, including Ammonia Nitrogen (NH3-N), Total Phosphorus (TP), Total Nitrogen (TN), and Chemical Oxygen Demand (COD), within urban water cycles for various rainfall conditions, thus offering critical theoretical support for managing the water environment. The application of this model under different rainfall intensities (light, moderate and heavy) provides vital insights. During light rainfall, the river's natural purification process can sustain surface water quality at Class IV. Moderate rainfall causes accumulation of pollutants, reducing water quality to Class V. Conversely, heavy rainfall rapidly increases pollutant concentrations due to higher inflow, pushing the river to a degraded Class V status, which is beyond its natural purification capacity, necessitating engineering solutions to reattain Class IV quality. Furthermore, pollutant accumulation in downstream river sections is more influenced by flow rate than by rainfall intensity. In summary, the SWMM-EFDC integrated model proves highly effective in predicting river water quality, thereby significantly aiding urban water pollution control.

Parkinson's severity diagnosis explainable model based on 3D multi-head attention residual network.

The severity evaluation of Parkinson's disease (PD) is of great significance for the treatment of PD. However, existing methods either have limitations based on prior knowledge or are invasive methods. To propose a more generalized severity evaluation model, this paper proposes an explainable 3D multi-head attention residual convolution network. First, we introduce the 3D attention-based convolution layer to extract video features. Second, features will be fed into LSTM and residual backbone networks, which can be used to capture the contextual information of the video. Finally, we design a feature compression module to condense the learned contextual features. We develop some interpretable experiments to better explain this black-box model so that it can be better generalized. Experiments show that our model can achieve state-of-the-art diagnosis performance. The proposed lightweight but effective model is expected to serve as a suitable end-to-end deep learning baseline in future research on PD video-based severity evaluation and has the potential for large-scale application in PD telemedicine. The source code is available at https://github.com/JackAILab/MARNet.

Diffusible Capping Layer Enabled Homogeneous Crystallization and Component Distribution of Hybrid Sequential Deposited Perovskite.

Nowadays, the development of wide-bandgap perovskite by thermal evaporation and spin-coating hybrid sequential deposition (HSD) method has special meaning on textured perovskite/silicon tandem solar cells. However, the common issues of insufficient reaction caused by blocking of perovskite capping layer are exacerbated in HSD, because evaporated precursors are usually denser with higher crystallinity and the widely used additive-assisted microstructure is also difficult to access. Here, a facile "diffusible perovskite capping layer" (DPCL) strategy to solve this dilemma is presented. With DPCL, crystallization alleviation of perovskite and more diffusion channels of organic salts can be realized simultaneously, contributing to a homogenization process. The resultant perovskite films exhibit complete conversion, uniform crystallization, enhanced quality, and reduced defect, leading to obvious improvements in device efficiency, repeatability, and stability. This work offers a way to promote the development of textured tandems a step further.

Real-world experience with Deutetrabenazine management in patients with Huntington's disease using video-based telemedicine.

BACKGROUND: Huntington's disease (HD) is a rare progressive neurological disorder, and telemedicine has the potential to improve the quality of care for patients with HD. Deutetrabenazine (DTBZ) can reduce chorea symptoms in HD; however, there is limited experience with this medication in Asian countries. METHODS: Retrospective and prospective studies were employed to explore the feasibility and reliability of a video-based telemedicine system for HD patient care. Reliability was demonstrated through consistency between selected-item scores (SIS) and total motor scores (TMS) and the agreement of scores obtained from hospital and home videos. Finally, a single-centre real-world DTBZ management study was conducted based on the telemedicine system to explore the efficacy of DTBZ in patients with HD. RESULTS: There were 77 patients included in the retrospective study, and a strong correlation was found between SIS and TMS (r = 0.911, P < 0.0001), indicating good representativeness. There were 32 patients enrolled in the prospective study. The reliability was further confirmed, indicated by correlations between SIS and TMS (r = 0.964, P < 0.0001) and consistency of SIS derived from the in-person and virtual visits (r = 0.969, P < 0.0001). There were 17 patients included in the DTBZ study with a mean 1.41 (95% confidence interval, 0.37-2.46) improvement in chorea score and reported treatment success. CONCLUSIONS: A video-based telemedicine system is a feasible and reliable option for HD patient care. It may also be used for drug management as a supplementary tool for clinical visits.

Co-Fe-N@biochar anode for improvment the electricity generation performance of microbial fuel cell.

Microbial fuel cells (MFCs) can generate energy while processing organic pollutants, which has a great impact on environmental wastewater treatment applications. In this study, a gel polymer was formed by Co-Fe-N co-doping biochar (Co-Fe-N@BC), which was used as the anode material to improve the electricity generation performance of MFC. The Co-Fe-N@BC material prepared at 900℃ carbonised biomass into more graphitic carbon, and its total resistance (3.56 Ω) was significantly reduced. In the corresponding dual-chamber MFC, the current density was 2.81 A/m2, and the power density reached 1181 mW/m2 at maximum. Among the materials tested, the Co-Fe-N@BC anode MFC had the highest chemical oxygen demand removal rate and coulombic efficiency, reaching 91% and 13%, respectively. It is proved that MFC with Co-Fe-N@BC anode has the best electrochemical performance.

Co-production of 2,5-dihydroxymethylfuran and furfuralcohol from sugarcane bagasse via chemobiocatalytic approach in a sustainable system.

2,5-Dihydroxymethylfuran and furfuryl alcohol serve as versatile building-blocks in pharmaceuticals, polymers, and value-added intermediates. To develop an efficient and sustainable method for their production from biomass, a combined approach using deep eutectic solvent Citric acid:Betaine (CTA:BT) for bagasse catalysis and recombinant E. coli SCFD23 for bioreduction of bagasse-derived 5-hydroxymethylfurfural and furfural was devised. Bagasse was effectively transformed into 5-hydroxymethylfurfural (48 mM) and furfural (14 mM) in CTA:BT (8 wt%)-water at 170 °C for 30 min. Bioreduction of 5-hydroxymethylfurfural and furfural by SCFD23 cell co-expressing formate dehydrogenase and NAD(P)H-dependent aldehyde reductase (SsCR) yielded 2,5-dihydroxymethylfuran (90.0 % yield) and furfuryl alcohol (99.0 % yield) in 6 h, using biomass-derived formic acid, xylose and glucose as co-substrates. Molecular docking confirmed the stable binding and reductase activity of SsCR with the biomass-derived 5-hydroxymethylfurfural and furfural. An efficient and eco-friendly chemobiological approach was applied for co-production of 2,5-dihydroxymethylfuran and furfuryl alcohol from biomass in one-pot two-step reaction.

Application of tangent-arc technology for deep inspiration breath-hold radiotherapy in left-sided breast cancer.

Objective: To explore the advantages of dosimetry and the treatment efficiency of tangent-arc technology in deep inspiration breath-hold radiotherapy for breast cancer. Methods: Forty patients with left-sided breast cancer who were treated in our hospital from May 2020 to June 2021 were randomly selected and divided into two groups. The first group's plan was a continuous semi-arc that started at 145° ( ± 5°) and stopped at 325° ( ± 5°). The other group's plan, defined as the tangent-arc plan, had two arcs: the first arc started at 145° ( ± 5°) and stopped at 85° ( ± 5°), and the second arc started at 25° ( ± 5°) and stopped at 325° ( ± 5°). We compared the target dose, dose in organs at risk (OARs), and treatment time between the two groups. Results: The target dose was similar between the continuous semiarc and tangent-arc groups. The V5 of the right lung was significantly different between the two groups (Dif 5.52, 95% confidence interval 1.92-9.13, t=3.10, P=0.004), with the patients in the continuous semi-arc and tangent-arc groups having lung V5 values of (9.16 ± 1.62)%, and (3.64 ± 0.73)%, respectively. The maximum dose to the spinal cord was (1835.88 ± 222.17) cGy in the continuous semi-arc group and (599.42 ± 153.91) cGy in the tangent-arc group, yielding a significant difference between the two groups (Dif 1236.46, 95% confidence interval 689.32-1783.6, t=4.57, P<0.001). The treatment times was (311.70 ± 60.45) s for patients in the continuous semi-arc group and (254.66 ± 40.73) s for patients in the tangent-arc group, and there was a significant difference in the mean number of treatment times between the two groups (Dif 57.04, 95% confidence interval 24.05-90.03, t=3.5, P=0.001). Conclusion: Both the continuous semi-arc and tangent-arc plans met the clinical prescription dose requirements. The OARs received less radiation with the tangent-arc plan than the continuous semi-arc plan, especially for the lung (measured as V5) and the spinal cord (measured as the maximum dose). Tangent-arc plan took significantly less time than the continuous semi-arc, which can greatly improve treatment efficiency. Therefore, tangent-arc plans are superior continuous semi-arc plans for all cases.

Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages.

OBJECTIVES: About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. MATERIALS AND METHODS: We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. RESULTS: We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22-26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. CONCLUSION: Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.

Identification of novel key markers that are induced during traumatic brain injury in mice.

Background: Traumatic brain injury (TBI) has emerged as an increasing public health problem but has not been well studied, particularly the mechanisms of brain cellular behaviors during TBI. Methods: In this study, we established an ischemia/reperfusion (I/R) brain injury mice model using transient middle cerebral artery occlusion (tMCAO) strategy. After then, RNA-sequencing of frontal lobes was performed to screen key inducers during TBI. To further verify the selected genes, we collected peripheral blood mononuclear cells (PBMCs) from TBI patients within 24 h who attended intensive care unit (ICU) in the Affiliated Hospital of Yangzhou University and analyzed the genes expression using RT-qPCR. Finally, the receiver operator characteristic (ROC) curves and co-expression with cellular senescence markers were applied to evaluate the predictive value of the genes. Results: A total of six genes were screened out from the RNA-sequencing based on their novelty in TBI and implications in apoptosis and cellular senescence signaling. RT-qPCR analysis of PBMCs from patients showed the six genes were all up-regulated during TBI after comparing with healthy volunteers who attended the hospital for physical examination. The area under ROC (AUC) curves were all >0.7, and the co-expression scores of the six genes with senescence markers were all significantly positive. We thus identified TGM1, TGM2, ATF3, RCN3, ORAI1 and ITPR3 as novel key markers that are induced during TBI, and these markers may also serve as potential predictors for the progression of TBI.

A new bin size index method for statistical analysis of multimodal datasets from materials characterization.

This paper presents a normalized standard error-based statistical data binning method, termed "bin size index" (BSI), which yields an optimized, objective bin size for constructing a rational histogram to facilitate subsequent deconvolution of multimodal datasets from materials characterization and hence the determination of the underlying probability density functions. Totally ten datasets, including four normally-distributed synthetic ones, three normally-distributed ones on the elasticity of rocks obtained by statistical nanoindentation, and three lognormally-distributed ones on the particle size distributions of flocculated clay suspensions, were used to illustrate the BSI's concepts and algorithms. While results from the synthetic datasets prove the method's accuracy and effectiveness, analyses of other real datasets from materials characterization and measurement further demonstrate its rationale, performance, and applicability to practical problems. The BSI method also enables determination of the number of modes via the comparative evaluation of the errors returned from different trial bin sizes. The accuracy and performance of the BSI method are further compared with other widely used binning methods, and the former yields the highest BSI and smallest normalized standard errors. This new method particularly penalizes the overfitting that tends to yield too many pseudo-modes via normalizing the errors by the number of modes hidden in the datasets, and also eliminates the difficulty in specifying criteria for acceptable values of the fitting errors. The advantages and disadvantages of the new method are also discussed.

Integrated analysis of FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer and anti-proliferation of T lymphocyte.

Background: Solute Carrier Family 3 Member 2 (SLC3A2) is a member of the solute carrier family that plays pivotal roles in regulation of intracellular calcium levels and transports L-type amino acids. However, there are insufficient scientific researches on the prognostic and immunological roles of SLC3A2 in breast cancer (BC) and whether everolimus regulates novel SLC3A2 related molecular mechanism in the immuno-oncology context of the tumor microenvironment (TME), therefore, we see a necessity to conduct the current in silico and biological experimental study. Methods: Using diverse online databases, we investigated the role of SLC3A2 in therapy response, clinicopathological characteristics, tumor immune infiltration, genetic alteration, methylation and single cell sequencing in BC. WB, Co-IP, cell proliferation assay, Edu staining, ROS and GSH assay and in vivo tumor xenograft assays were performed to verify FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer. Co-cultures and IL-9 ELISA were performed to demonstrate the T lymphocyte function. Results: We demonstrated that SLC3A2 was aberrantly expressed among various BC cohorts. Our results also suggested that SLC3A2 expression was associated with chemotherapeutic outcome in BC patients. Our results further indicated that SLC3A2 was associated with tumor infiltration of cytotoxic T cell but not other immune cells among BC TME. The alterations in SLC3A2 gene had a significant correlation to relapse free survival and contributed a significant impact on BC tumor mutational burden. Finally, SLC3A2 was illustrated to be expressed in diverse BC cellular populations at single cell level, and negatively linked to angiogenesis, inflammation and quiescence, but positively correlated with other functional phenotypes. Noteworthily, everolimus (a targeted therapy drug for BC) related protein, FK506-binding protein 1A (FKBP1A) was found to bind with SLC3A2, and negatively regulated SLC3A2 expression during the processes of everolimus inducing ferroptosis of BC cells and promoting anti-proliferation of Th9 lymphocytes. Conclusions: Altogether, our study strongly implies that SLC3A2 is an immuno-oncogenic factor and FKBP1A/SLC3A2 axis would provide insights for a novel immunotherapy approach for the treatment of BC in the context of TME.