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To improve prediction performance and reduce artifacts in Raman spectra, we developed an eXtreme Gradient Boosting (XGBoost) preprocessing method to preprocess the Raman spectra of glucose, glycerol and ethanol mixtures. To ensure the robustness and reliability of the XGBoost preprocessing method, an X-LR model (which combined XGBoost preprocessing and a linear regression (LR) model) and a X-MLP model (which combined XGBoost preprocessing and a multilayer perceptron (MLP) model) were developed. These two models were used to quantitatively analyze the concentrations of glucose, glycerol and ethanol in the Raman spectra of mixed solutions. The proportion map of hyperparameters was firstly used to narrow down the search range of hyperparameters in the X-LR and the X-MLP models. Then the correlation coefficients (R 2 ), root mean square of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used to evaluate the models' performance. Experimental results indicated that the XGBoost preprocessing method achieved higher accuracy and generalization capability, with better performance than those of other preprocessing methods for both LR and MLP models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Ivonescimab is a humanized IgG1 bispecific anti-PD-1/VEGF antibody. This study aimed to evaluate the safety and tolerance of ivonescimab combined with etoposide and carboplatin as first-line treatment in patients with extensive-stage small cell lung cancer (ES-SCLC) and explore the primary efficacy of this regimen., Methods: Eligible patients received intravenous ivonescimab 3 mg/kg, 10 mg/kg, or 20 mg/kg every 3 weeks combined with etoposide and carboplatin for up to 4 cycles, followed by ivonescimab as maintenance. The primary endpoints were safety and objective response rate (ORR)., Results: Between April 23, 2021 and December 2, 2021, 35 patients were enrolled. At data cutoff (October 25, 2023), the median follow-up was 13.3 months (range, 0.3-28.5). For all patients, the confirmed ORR and disease control rate were 80% and 91.4%, respectively. The ORR was 66.7%, 90.9%, and 76.2% at the dose of 3 mg/kg, 10 mg/kg, and 20 mg/kg, respectively. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 21 patients (60%), and the most frequent toxicities were decreased neutrophil count (n=8, 22.9%), decreased white blood cell count (n=5, 14.3%), and anemia (n=5, 14.3%). Grade ≥3 TRAEs occurred in 66.7%, 54.5%, and 61.9% of patients in 3, 10, and 20 mg/kg groups, respectively. TRAEs leading to death were reported in 2 patients (5.7%). Adverse events with potential immunologic etiology, most of them grade 1 or 2, occurred in 14 patients (40.0%)., Conclusions: Ivonescimab in combination with etoposide and carboplatin was well-tolerated and showed promising antitumor activity in ES-SCLC., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: This pharmacovigilance analysis was conducted to assess the safety signals of FMS-related tyrosine kinase 3 (FLT3) inhibitors in a real-world setting using the United States Food and Drug Administration Adverse Event Reporting System (FAERS)., Design: We analyzed adverse event (AE) reports related to FLT3 inhibitors submitted to the FAERS database from the first quarter of 2015 to the fourth quarter of 2022. Disproportionality analysis was used to identify AEs of FLT3 inhibitors in the FAERS database., Results: A total of 55,393 AE reports were identified, of which 5938, 44,013, and 5442 were attributed to midostaurin, sorafenib, and gilteritinib, respectively, as primary suspects. Compared to the full database, significant safety signals at the system organ class level were observed for midostaurin (blood and lymphatic system disorders and hepatobiliary disorders), sorafenib (skin and subcutaneous tissue disorders and hepatobiliary disorders), and gilteritinib (investigations, blood and lymphatic system disorders, infections and infestations, and hepatobiliary disorders). All the drugs studied were associated with hepatobiliary disorders. The most prominent AEs associated with midostaurin, sorafenib, and gilteritinib were cytopenia, palmar-plantar erythrodysesthesia syndrome, and increased blast cell count, respectively. Compared with chemotherapy, midostaurin and gilteritinib showed a higher risk of electrocardiogram QT prolongation, gastrointestinal hemorrhage, cerebral hemorrhage, and increased white blood cell count. Gilteritinib had the highest overall death percentage (30.28%), whereas sorafenib had the lowest (23.06%)., Conclusion: Mining AE signals using the FAERS database provides a method for analyzing the safety of FLT3 inhibitors in post-marketing. We found several significant AE signals that corresponded to previous studies; however, some AE signals were not mentioned in the drug instructions. Our study could provide a direction for follow-up real-world studies to verify the results further., (© The Author(s), 2024.)

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV., Competing Interests: Declaration of competing interest All authors assert that there are no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Near-infrared (NIR) spectroscopy has been widely utilized to predict multi-constituents of corn in agriculture. However, directly extracting constituent information from the NIR spectra is challenging due to many issues such as broad absorption band, overlapping and non-specific nature. To solve these problems and extract implicit features from the raw data of NIR spectra to improve performance of quantitative models, a one-dimensional shallow convolutional neural network (CNN) model based on an eXtreme Gradient Boosting (XGBoost) feature extraction method was proposed in this paper. The leaf node feature information in the XGBoost was encoded and reconstructed to obtain the implicit features of raw data in the NIR spectra. A two-parametric Swish (TSwish or TS) activation function was proposed to improve the performance of CNN, and the elastic net (EN) was also applied to avoid the overfitting problem of the CNN model. Performance of the developed XGBoost-CNN-TS-EN model was evaluated using two public NIR spectroscopy datasets of corn and soil, and the obtained determination coefficients (R 2 ) for moisture, oil, protein, and starch of the corn on test set were 0.993, 0.991, 0.998, and 0.992, respectively, with that of the soil organic matter being 0.992. The XGBoost-CNN-TS-EN model exhibits superior stability, good prediction accuracy, and generalization ability, demonstrating its great potentials for quantitative analysis of multi-constituents in spectroscopic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Observational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections., Methods: Utilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research., Results: The bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%, 41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD., Conclusion: Our study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Hao, Zhang, Wang and Xia.)

Introduction: Recently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children., Methods: Adverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline., Results: A total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with "general disorders and administration site conditions" and "gastrointestinal disorders," while minocycline was more frequently linked to "skin and subcutaneous tissue disorders" and "gastrointestinal disorders." Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48-42.67), although it remained unclear whether the discoloration was permanent., Conclusion: Our findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiao, Chen, Wang, Liu, Guo, Gu, Ding, Zhang and Mei.)

Purpose: To report the comparison of the therapeutic effects of lens capsular flap transplantation (LCT) and autologous retinal transplantation (ART) in refractory macular hole (MH) treatment., Methods: Thirty-one patients (31 eyes) with refractory MH were retrospectively reviewed. The patients were divided into two groups based on the surgical procedures: the LCT group (13 eyes) and the ART group (18 eyes). Patients were monitored for a minimum of 6 months. Best corrected visual acuity (BCVA), hole closure rate, postoperative central foveolar thickness (CFT), and some complications (e.g. graft loss or dislocation, postoperative retinal detachment, or postoperatively elevated intraocular pressure) were the primary outcome measures., Results: The mean preoperative MH diameter was 1104 ± 287 μm in the LCT group and 1066 ± 297 μm in the ART group (t = 0.353, P = 0.727). The MH was closed in 12 patients (92.3%) of the LCT group and 17 patients (94.4%) of the ART group (χ 2  = 0.057, P = 0.811); the MHs of 10 patients (76.9%) in the LCT group and 11 patients (61.1%) in the ART group were completely closed (χ 2  = 0.864, P = 0.353). The BCVA improved from 2.3 ± 1.0 logMAR preoperatively to 1.3 ± 0.9 logMAR postoperatively in the LCT group and 2.3 ± 0.9 logMAR preoperatively to 1.0 ± 0.6 logMAR postoperatively in the ART group (postoperative BCVA vs preoperative BCVA in the LCT group: t = 4.374, P = 0.001; postoperative BCVA vs preoperative BCVA in the ART group: t = 5.899, P = 0.000018). The visual improvement was 1.3 ± 0.9 logMAR in the ART group and 1.0 ± 0.8 logMAR in the LCT group (t = - 1.033, P = 0.310). The postoperative CFT was 139.7 ± 48.3 μm in the LCT and 199.2 ± 25.1 μm in the ART group (t = - 4.062, P = 0.001). Graft dislocation emerged in 2 patients (15.4%) in the LCT group and 1 patient (5.6%) in the ART group., Conclusions: Applications of LCT and ART may both enhance anatomical and visual outcomes in refractory MH cases. The ART group exhibited a more optimal postoperative CFT than the LCT group one., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 μm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 μPa/Hz 1/2 @1 kHz. We successfully used such acoustic sensor to measure acetylene (C 2 H 2 ) concentration in the PAS. The sensitivity of PAS for C 2 H 2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Epilepsy is a neural network disorder caused by uncontrolled neuronal hyperexcitability induced by an imbalance between excitatory and inhibitory networks. Abnormal synaptogenesis plays a vital role in the formation of overexcited networks. Recent evidence has confirmed that thrombospondin-1 (TSP-1), mainly secreted by astrocytes, is a critical cytokine that regulates synaptogenesis during epileptogenesis. Furthermore, numerous studies have reported that TSP-1 is also involved in other processes, such as angiogenesis, neuroinflammation, and regulation of Ca 2+ homeostasis, which are closely associated with the occurrence and development of epilepsy. In this review, we summarize the potential contributions of TSP-1 to epilepsy development., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors have reformed the treatment landscape for various malignancies and improved prognosis of patients. However, they also lead to events that although rare may prove to be fatal., Research Design and Methods: Data from July 2014 to June 2022 based on FDA Adverse Event Reporting System (FAERS) were analyzed. The signal index reporting odds ratio (ROR) was used to evaluate the correlation between cardiac AEs and given medications. The indications and the median time to onset (TTO) of different PD-1/PD-L1 inhibitors were compared., Results: Cardiac AEs are rare but may be fatal with particular profiles in primary tumor, onset time, and especially gender. We identified 11,538 reports that were related to cardiotoxicity of PD-1/PD-L1 inhibitors, in which 178 different preferred terms (PTs) were distinguished, and nivolumab reported the most PTs with signal. All targeted medications showed signals in myocardial disorders and pericardial disorders, which tend to occur in the first 1-2 months. Non-small cell neoplasm was the top and common indication during anti-PD-1 or anti-PD-L1 therapy with cardiotoxicity., Conclusions: This study could help early diagnosis and surveillance of ICIs-related cardiotoxicity.

Surface acoustic wave (SAW) technology has been widely used to manipulate microparticles and biological species, based on acoustic radiation force (ARF) and drag force induced by acoustic streaming, either by standing SAWs (SSAWs) or travelling SAWs (TSAWs). These acoustofluidic patterning functions can be achieved within a polymer chamber or a glass capillary with various cross-sections positioned along the wave propagating paths. In this paper, we demonstrated that microparticles can be aligned, patterned, and concentrated within both circular and rectangular glass capillaries using TSAWs based on a piezoelectric thin film acoustic wave platform. The glass capillary was placed at different angles along with the interdigital transducer directions. We systematically investigated effects of tilting angles and wave characteristics using numerical simulations in both circular and square shaped capillaries, and the patterning mechanisms were discussed and compared with those agitated under the SSAWs. We then experimentally verified the particle patterns within different glass capillaries using thin film ZnO SAW devices on aluminum (Al) sheets. Results show that the propagating SAWs can generate acoustic pressures and patterns in the fluid due to the diffractive effects, drag forces and ARF, as functions of the SAW device's resonant frequency and tilting angle. We demonstrated potential applications using this multiplexing, integrated, and flexible thin film-based platform, including patterning particles (1) inside multiple and successively positioned circular tubes; (2) inside a solidified hydrogel in the glass capillary; and (3) by wrapping a flexible ZnO/Al SAW device around the glass capillary., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occurrence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague‒Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis., Competing Interests: Declaration of competing interest There are no conflicts of interest in connection with this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A high sensitivity and ultra-low concentration range photoacoustic spectroscopy (PAS) gas detection system, which was based on a novel trapezoid compound ellipsoid resonant photoacoustic cell (TCER-PAC) and partial least square (PLS), was proposed to detect acetylene (C 2 H 2 ) gas. In the concentration range of 0.5 ppm ∼ 10.0 ppm, the limit of detection (LOD) values of TCER-PAC-based PAS system without data processing was 66.4 ppb, which was lower than that of the traditional trapezoid compound cylindrical resonant photoacoustic cell (TCCR-PAC). The experimental results indicated that the TCER-PAC had higher sensitivity than of TCCR-PAC. Within the concentration range of 12.5 ppb ∼ 125.0 ppb, the LOD and limit of quantification (LOQ) of TCER-PAC-based PAS system combined with PLS regression algorithm were 1.1 ppb and 3.7 ppb, respectively. The results showed that higher detection sensitivity and lower LOD were obtained by PAS system with TCER-PAC and PLS than that of TCCR-PAC-based PAS system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Populations of Eurasian otters Lutra lutra , one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Raman spectroscopy has gained popularity in analyzing blood glucose levels due to its non-invasive identification and minimal interference from water. However, the challenge lies in how to accurately predict blood glucose concentrations in human blood using Raman spectroscopy. This paper researches a novel integrated machine learning algorithm called Bagging-ABC-ELM. The optimal input weights and biases of extreme learning machine (ELM) model are obtained by artificial bee colony (ABC) algorithm. The bagging algorithm is used to obtain a better the stability of the model and higher performance than ELM algorithm. The results show that the mean value of coefficient of determination is 0.9928, and root mean square error is 0.1928. Compared to other regression models, the Bagging-ABC-ELM model exhibited superior prediction accuracy, robustness, and generalization capability. The Bagging-ABC-ELM model presents a promising alternative for analyzing blood glucose levels in clinical and research settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, we reported the complete genome sequence of Shewanella oncorhynchi for the first time. S. oncorhynchi Z-P2 is a bacterium that produces the siderophore putrebactin. Its genome consists of a circular chromosome of 5,034,612 bp with a G + C content of 45.4%. A total of 4544 protein-coding genes, 109 tRNAs and 31 rRNAs were annotated by the RAST. Five non-ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene clusters were identified by the antiSMASH analysis. The pan-genome analysis of Z-P2 and 10 Shewanella putrefaciens revealed 9228 pan-gene clusters and 2681 core gene clusters, with Z-P2 having 618 unique gene clusters. Additionally, the gene cluster involved in putrebactin biosynthesis in Z-P2 was annotated, and the mechanism of putrebactin biosynthesis was analyzed. The putrebactin produced by Z-P2 was detected using UPLC-MS analysis, with an [M + H] + molecular ion at m / z 373.21. These findings provide valuable support for further research on the genetic engineering of putrebactin biosynthetic genes of Z-P2 and their potential applications.

Choroidal neovascularization (CNV) is characterized by the infiltration of immune cells, particularly neutrophils. Neutrophil extracellular trap (NET) facilitates the angiogenesis of pulmonary endothelial cells via activating Toll-like receptor 4 (TLR4). TLR4 promotes the expression of transcription factor hypoxia inducible factor-1α (HIF-1α), which promotes inflammation and angiogenesis via the up-regulation of metalloproteinase-9 (MMP-9) and interleukin-1β (IL-1β). In the present study, we aimed to identify the formation of NET and its role in CNV. Our results showed that NET levels were increased in a mouse laser-induced CNV model via oxidative stress, whereas the inhibition of NET alleviated CNV. In vitro, NET activated the TLR4/HIF-1α pathway in human choroidal endothelial cells (HCECs). Additionally, NET increased the transcription and expression of MMP-9 and IL-1β in HCECs via activating the TLR4/HIF-1α pathway. Meanwhile, NET promoted the inflammatory response accompanied by the proliferation, migration and tube formation of HCECs in a MMP-9- and IL-1β-dependent manner. In conclusion, NET was up-regulated in CNV and promoted the formation of CNV via activating the TLR4/HIF-1α pathway in choroidal endothelial cells. Our data uncovered the novel role of NET in promoting the formation of CNV. The underlying mechanism of NET could be targeted to delay the process of CNV., (© 2023 Federation of European Biochemical Societies.)

Religious wildlife release is prevalent worldwide, especially in Asia countries. It is one of the anthropogenic pathways to cause biological invasions. Religious fish release is common on the Qinghai-Tibetan Plateau, yet few studies have assessed the influences of religious fish release on local species. In Yushu, a city on the Qinghai-Tibetan Plateau, we interviewed local people, conducted fish trap surveys in local rivers, and examined the diet of Eurasian otters Lutra lutra using a fecal DNA metabarcoding approach. We found that fish release started at least in 1980-1990s in Yushu. Tibetan residents released fish in large amounts and released fish were usually exotic commercial fish purchased from market. Despite such long-term and intensive fish release activities, released fish were few in local rivers. On the other hand, Eurasian otters mainly prey on fish and released fish accounted for ~20% of relative read abundance of prey DNA in otters' diet, indicating their high preference on released fish. Our study suggested that religious fish release may provide additional food resources for otters, whereas otters, as a top predator in local rivers, may deplete non-native fish once they were released and, therefore, reduce the probability of colonization of released fish, although further studies are required to assess otters' impact. Our study revealed otters' diet in Yushu, providing basic information for local otter management and conservation. Furthermore, it represents a case showing that native predators prey on religious released animals, implying a probable direction for controlling invasive species through native predator conservation., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19 F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

Raman spectroscopy, with its advantages of non-contact nature, rapid detection, and minimum water interference, is promising for non-invasive blood detection or diagnosis in clinic applications. However, there is a critical issue that how to accurately analyze blood composition by Raman spectroscopy. In this study, we apply extreme learning machine (ELM) algorithm and a multivariate calibration regression model to analyze the results from Raman spectroscopy and determine the component's concentrations in blood samples, including glucose, cholesterol, and triglyceride. Self-adaption differential evolution artificial bee colony (SADEABC) algorithm was further applied to increase the data's accuracy and robustness. The obtained data for coefficient of determination, root mean square error of calibration, root mean square error of prediction, and relative percent deviation, were 0.9822, 0.3993, 0.3827, and 6.6679 for glucose, 0.9786, 0.2104, 0.2088 and 5.9533 for cholesterol, and 0.9921, 0.2744, 0.3433 and 10.5075 for triglyceride, respectively. Results demonstrated that the model based on SADEABC-ELM show much better prediction data than those models based on the ELM and ABC-ELM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In chemometrics, calibration model adaptation is desired when training- and test-samples come from different distributions. Domain-invariant feature representation is currently a successful strategy to realize model adaptation and has received wide attention. The paper presents a nonlinear unsupervised model adaptation method termed as domain adaption regularization-based kernel partial least squares regression (DarKPLS). DarKPLS aims to minimize the source and target distributions in a low-dimensional latent space projected from the reproducing kernel Hilbert space (RKHS) generated with the labeled source data and unlabeled target data. Specially, the distributional means and variances between source and target latent variables are aligned in the RKHS. By extending existing domain invariant partial least square regression (di-PLS) with the projected maximum mean discrepancy (PMMD) to reduce the mean discrepancy in the RKHS further, DarKPLS could realize fine-grained domain alignment that further improves the adaptation performance. DarKPLS is applied to the γ-polyglutamic acid fermentation dataset, tobacco dataset and corn dataset, and it demonstrates improved prediction results in comparison with No adaptation partial least squares (PLS), null augmented regression (NAR), extended linear joint trained framework (ExtJT), scatter component analysis (SCA) and domain-invariant iterative partial least squares (DIPALS)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tree peony is a "spring colored-leaf" plant which has red leaves in early spring, and the red color of the leaves usually fades in late spring. Flavonols are one subgroup of flavonoids, and they affect the plant organs' color as co-pigments of anthocyanins. To investigate the color variation mechanism of leaves in tree peony, PqMYBF1 , one flavonol biosynthesis-related MYB gene was isolated from Paeonia qiui and characterized. PqMYBF1 contained the SG7 and SG7-2 motifs which are unique in flavonol-specific MYB regulators. Subcellular localization and transactivation assay showed that PqMYBF1 localized to the nucleus and acted as a transcriptional activator. The ectopic expression of PqMYBF1 in transgenic tobacco caused an observable increase in flavonol level and the anthocyanin accumulation was decreased significantly, resulting in pale pink flowers. Dual-luciferase reporter assays showed that PqMYBF1 could activate the promoters of PqCHS , PqF3H, and PqFLS . These results suggested that PqMYBF1 could promote flavonol biosynthesis by activating PqCHS, PqF3H, and PqFLS expression, which leads metabolic flux from anthocyanin to flavonol pathway, resulting in more flavonol accumulation. These findings provide a new train of thought for the molecular mechanism of leaf color variation in tree peony in spring, which will be helpful for the molecular breeding of tree peony with colored foliage.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder of the synovial joints. Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii Hook F (TwHF) that has been proven to be effective in treating RA. However, the underlying molecular mechanism of celastrol in the treatment of RA remains unknown. This study explored the protective effect of celastrol against RA and the specific mechanisms of celastrol in vitro and in vivo., Methods: A chicken type II collagen (CII)-induced arthritis (CIA) mouse model was used to explore the anti-arthritic effects of celastrol, and paw swelling degree, the poly-arthritis index score and serum cytokine levels were determined. Pathological morphology was observed using hematoxylin and eosin (H&E) staining. The influences of celastrol on the proliferation of tumor necrosis factor-α (TNF-α)-induced fibroblast-like synoviocytes (FLSs) were tested by Cell Counting Kit-8 (CCK-8) assays and5-ethynyl-2'-deoxyuridine (EdU) staining assays. The level of autophagy was detected by transmission electron microscopy (TEM). Furthermore, the PI3K/AKT/mTOR pathway and the status of autophagy in the CIA model and FLSs were also detected by western blot and immunofluorescence staining., Results: The results showed that celastrol decreased arthritis severity and inhibited TNF-α-induced FLSs proliferation. Additionally, celastrol decreased the secretion of pro-inflammatory cytokines. Moreover, celastrol increased autophagosome levels and LC3B protein expression in TNF-α-treated FLSs. Furthermore, celastrol increased the protein expression of LC3-II and Beclin-1 and decreased the phosphorylation degree of mTOR and AKT., Conclusion: In conclusion, our findings confirmed that celastrol ameliorates RA via the up-regulation of autophagy by inhibiting the PI3K/AKT/mTOR axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Fyn, a non-receptor tyrosine kinase, plays an important role in microglial-mediated neuroinflammation and may serve as a candidate therapeutic target for neuropsychiatric diseases. In this study, we discovered that chrysin, a natural flavonoid compound, suppressed the activation of Fyn kinase and further alleviated neuroinflammation-induced neuron damage and behavior deficits. Functionally, chrysin improved lipopolysaccharide (LPS)-induced memory impairment and depressive behaviors in mice, it also protected against LPS-induced neuronal degeneration and loss and synaptic defects in mice. Our study demonstrated that chrysin inhibited the activation of microglia and reduced the expression of NLRP3 and IL-1β. Furthermore, our data indicated that chrysin blocked phosphorylation of Fyn and activation of NF-κB. Transfection with siRNA-Fyn validated that knockdown of Fyn partly abolished the inhibitory effect of chrysin on the expression of the NLRP3 inflammasome and NF-κB activation. Taken together, our findings revealed that chrysin alleviated LPS-induced neuron damage and behavioral deficits by inhibiting the expression of the NLRP3 inflammasome and NF-κB pathway, which might be mediated by inhibition of Fyn., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Antifouling and antibacterial surfaces that can prevent nonspecific biological adhesion are important to support a myriad of biomedical applications. In this study, we have used an innovative photopolymerization technology to develop sulfur-containing polymer-grafted antifouling and antibacterial surfaces. The relationship between the hydrophilic property and the capability to resist protein and macrophage adsorption of the surface copolymer brushes was investigated. The sulfide monomer incorporated into the surface copolymer brushes can be further ionized to carry positive charges and impart antibacterial activity, leading to surfaces with dual antifouling and antibacterial functions. We believe that the reported sulfur-containing polymer brushes can be considered an emerging and important polymer for antifouling and antibacterial applications.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.

In this study, convolutional neural network based on Gramian angular field (GAF-CNN) was firstly proposed. The 1-D Raman spectral data was converted into images and used for predicting the biochemical value of blood glucose. 106 sets of blood spectrums were acquired by Fourier transform (FT) Raman spectroscopy. Spectral data ranging from 800 cm -1 to 1800 cm -1 were selected for quantitative analysis of the blood glucose. Data augmentation was used to train neural networks and normalize the Raman spectra. And, we applied principal component analysis (PCA) for dimension reduction and information extraction. The root mean squared error of prediction (RMSEP) are 0.06570 (GADF) and 0.06774 (GASF), the determination coefficient of prediction (R 2 ) are 0.99929 (GADF) and 0.99925 (GASF), and the residual predictive deviation of prediction (RPD) are 37.56324 (GADF) and 36.43362 (GASF). GAF-CNN model performed better for predicting of glucose concentration. The GAF-CNN model can be used to establish a calibration model to predict blood glucose concentration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Adenosine and lactate accumulated in tumor microenvironment are two major causes of immunosuppression, their concurrent downregulation holds promise in effective cancer immunotherapy, but remains challenging. Here, a sub-6 nm MnFe 2 O 4 conjugated with dichloroacetic acid (DCA) nanoparticle is developed to modulate tumor glucose metabolism and ATP catabolism for reversing the tumor immunosuppressive microenvironment. The ultrasmall MnFe 2 O 4 -DCA nanoparticle can efficiently enter mitochondria and supply oxygen, improving the bioactivity of DCA to regulate glucose metabolism and reduce lactate production ca. 100 times higher than free DCA itself. Moreover, this design significantly downregulates CD39 and CD73 expression than DCA or MnFe 2 O 4 alone, which consequently decreases the extracellular ATP catabolism. The concurrent regulation of glucose metabolism and ATP catabolism leads to increased immunostimulatory ATP level and decreased immunosuppressive adenosine and lactate levels in tumor microenvironment, eventually amplified dendritic cells maturation, enhanced cytotoxic T lymphocyte response, and improved cancer immunotherapy efficacy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ultrasound imaging technology has the advantages of noninvasiveness, real-time, low price, and easy operation. It is one of the most used diagnostic tools for early detection and classification of premature ovarian failure. Although the rapid development of computer-aided diagnosis has provided a great help to the ultrasound diagnosis of premature ovarian failure, it still has many limitations and shortcomings, so this paper adopts transfer learning and feature fusion algorithms to improve the identification and prediction efficiency of premature ovarian failure. In this study, the POF group and the control group both adopted a unified scale. From the four aspects of sociological characteristics, past medical history, environmental factors, and living habits, a dedicated person asked and filled out the scale face to face. All patients participating in the experiment underwent ultrasound examinations. In this paper, the bottom-level feature fusion method is used to improve classification performance. The experiment uses 100 epochs. After each epoch training is completed, we used all the data and labels of the target domain to test. All experiments were performed five times, and the result is the average of five experiments. All the results of baseline and direct classification without migration use the average of five experimental results as the result. Migrating the features extracted by the InceptionV3 network has the best performance for predicting premature ovarian failure. Its classification accuracy is as high as 85.13%, and the F1 value is 0.78. The results show that the migration learning and feature fusion algorithms used in this paper can provide reliable predictive analysis and decision support for doctors in the diagnosis of premature ovarian failure., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Yuanyuan Zhang et al.)

The Chinese pangolin (Manis pentadactyla) is a critically endangered mammal with a highly specialized diet. To enhance nutritional knowledge of its diet, we analyzed the colony composition of a nest of Polyrhachis dives ants, which is the key natural prey in the Chinese pangolin's diet. In addition, we determined the nutrient composition of the total colony compared with adult ants. Nutrients quantified in this study included: crude protein, crude fat, carbohydrate, and amino acids, minerals, and vitamins, as well as formic acid and chitin, which have not been reported in previous diet studies. Our results showed that the colony consisted of adults (82%), pupae (10%), larvae (7%), and eggs (1%) (fresh mass). Both the total colony and adult ants, respectively, contained high concentrations of crude protein (62.97% and 64.68%), chitin (49.25% and 60.40%), crude fat (10.12% and 9.91%) (dry matter basis), and formic acid (2.06% and 3.07%) (fresh mass). This implies that Chinese pangolin might prefer prey with high protein, high chitin, low fat, and low formic acid content. Colony and adult ants differed in chemical composition in many aspects, thus it might be unsuitable to feed Chinese pangolin with only adult ants. Chitin and formic acid may play important roles in the diet and selectivity of Chinese pangolin. This study provides reference information that may be useful for developing better artificial diets with more comprehensive nutrient compositional data to meet the nutritional requirements of the Chinese pangolin under managed feeding programs., (© 2021 Wiley Periodicals LLC.)

Paeonia qiui is a wild species of tree peony native to China. Its leaves are purplish red from the bud germination to the flowering stage, and anthocyanin is the main pigment in purplish red leaves. However, the anthocyanin synthesis regulation mechanism in tree peony leaves remains unclear. In this study, an R2R3-MYB, PqMYB113 was identified from the leaves of P. qiui . Phylogenetic analysis revealed that PqMYB113 clustered with Liquidambar LfMYB113 and grape VvMYBA6. Subcellular location analysis showed that PqMYB113 was located in the cell nucleus. The transient reporter assay suggested that PqMYB113 was a transcriptional activator. The overexpression of PqMYB113 in Arabidopsis thaliana and tobacco ( Nicotiana tabacum ) resulted in increased anthocyanin accumulation and the upregulation of CHS , F3H , F3'H , DFR , and ANS . The dual luciferase reporter assay showed that PqMYB113 could activate the promoters of PqDFR and PqANS . Bimolecular fluorescence complementation assays and yeast two-hybrid assays suggested that PqMYB113 could form a ternary MBW complex with PqbHLH1 and PqWD40 cofactors. These results provide insight into the regulation of anthocyanin biosynthesis in tree peony leaves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Duan, Huo, Li, Wang, Zhang, Niu and Luo.)

In this paper, a one-dimensional shallow convolutional neural network structure combined with elastic nets (1D-SCNN-EN) was firstly proposed to predict the glucose concentration of blood by Raman spectroscopy. A total of 106 different blood glucose spectra were obtained by Fourier transform (FT) Raman spectroscopy. The one-dimensional shallow convolutional neural network, with elastic nets added to the full connected layer, was presented to capture multiple deep features and reduce the complexity of the model. The 1D-SCNN-EN model has a better performance than conventional approaches (partial least squares and support vector machine). The root mean squared error of calibration (RMSEC), the root mean squared error of prediction (RMSEP), the determination coefficient of prediction (R P 2 ), and the residual predictive deviation of prediction (RPD) were 0.10262, 0.11210, 0.99403, and 12.94601, respectively. The experiment results showed that the 1D-SCNN-EN model has a higher prediction accuracy and stronger robustness than the other regression models. The overall studies indicated that the 1D-SCNN-EN model looked promising for predict the glucose concentration of blood by Raman spectroscopy when the sample size is small., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Immunogenic cell death (ICD) is a promising strategy in cancer immunotherapy to induce high immunogenicity and activate the immune system. However, its efficacy is counteracted by the concurrent exposure of phosphatidylserine (PS), an immunosuppressive signal on the surface of cancer cells. Here we report the synthesis of a bimetallic metal-organic framework (MOF) nanoparticle containing Gd 3+ and Zn 2+ (Gd-MOF-5) that can be used as an immunomodulator to downregulate the immunosuppressive PS signal and an ICD inducer to upregulate immunostimulatory signals. Gd 3+ inhibits PS externalization via inhibiting the activity of scramblase, an enzyme to transfer PS to the outer leaflet of plasma membrane. Moreover, intracellular Zn 2+ overload activates endoplasmic reticulum stress for ICD induction. In combination with an immune checkpoint inhibitor (PD-L1 antibody, denoted as aPDL1), Gd-MOF-5 activated potent immune response and effectively inhibited primary and distal tumor growth in a bilateral 4T1 tumor model. This work presents a new strategy using designed MOF materials to modulate the cell signalling and immunosuppressive microenvironment to improve the outcome of cancer immunotherapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

When fourier transform infrared spectroscopy (FTIR) techniques combined with multivariate calibration are used to measure the key process features or analyte concentrations during batch process, model adaption is indispensable for maintaining the predictability of a primary calibration model in new secondary batches. Many model adaption methods conforming to the actual application scenario of batch process have been proposed. Here we report on a novel standard-free model adaption method without reference measurement called variable selection strategy with self-organizing maps (VSSOM). It uses self-organizing maps (SOM) to classify the whole spectral variables into multiple classes according to the spectra from primary batch and secondary batch, respectively; and the corresponding primary feature subsets and secondary feature subsets are formed firstly. Secondly, candidate feature subsets without empty elements are generated by operating intersection between any primary feature subsets and any secondary feature subsets. Thirdly, the candidate feature subset with minimum root mean square error of cross-validation (RMSECV) for the primary calibration set is selected as the optimal feature subset. In this manner, the optimal feature subset can be identified from the candidate feature subsets. In other words, VSSOM aims to create a stable and consistent feature subset across different batches provided that it selects better features within the intersection sets between primary feature subsets and any secondary feature subsets. Two batch process datasets (γ-polyglutamic acid fermentation and paeoniflorin extraction) are presented for comparing the VSSOM method with No transfer partial least squares (PLS), boxcar signal transfer (BST), successive projection algorithm (SPA), transfer component analysis (TCA) and domain-invariant iterative partial least squares (DIPALS). Experimental results show that VSSOM has superior performance and comparable prediction performance in all the scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Xenon is an inert gas with stable chemical properties which is used as an anesthetic. Recent in vitro and in vivo findings indicate that xenon also elicits an excellent neuroprotective effect in subanesthetic concentrations. The mechanisms underlying this primarily involve the attenuation of excitotoxicity and the inhibition of N-methyl-d-aspartic acid (NMDA) receptors and NMDA receptor-related effects, such as antioxidative effects, reduced activation of microglia, and Ca 2+ -dependent mechanisms, as well as the interaction with certain ion channels and glial cells. Based on this strong neuroprotective role, a large number of experimental and clinical studies have confirmed the significant therapeutic effect of xenon in the treatment of neurological diseases. This review summarizes the reported neuroprotective mechanisms of xenon and discusses its possible therapeutic application in the treatment of various neurological diseases., (© 2021 Wiley Periodicals LLC.)

In this paper, a reagent-free simultaneous and direct detection method of three analytes in human blood based on Fourier-transform Raman (FT-Raman) spectroscopy with 1064 nm laser radiation was proposed for the first time. A total of 161 human blood samples were characterized by FT-Raman spectroscopy under the excitation laser source of 1064 nm. In order to achieve a robust regression model, the Nonlinear Iterative Partial Least Squares (NIPALS) with orthogonal signal correction (OSC) algorithm and sample set partition based on a joint x-y distance (SPXY) is used to establish multivariate calibration models. The root means square error of cross-validation (RMSECV), root mean square error of prediction (RMSEP), correlation coefficients (R 2 ) and ratio of performance to deviation (RPD) were 0.34255 mg/dL, 0.3662 mg/dL, 0.99982 and 56.3524 for glucose, 0.33656 mg/dL, 0.75736 mg/dL, 0.99967 and 34.9169 for total cholesterol (TC), and 0.29956 mg/dL, 0.27469 mg/dL, 0.99998 and 173.5098 for triglycerides (TG), respectively. The analysis results showed that the proposed method could be able to accurately predict the concentration of glucose, TC and TG in blood. This method can instantaneous multi-component detection on whole blood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neuroinflammation is a major pathophysiological contributor to the progression of the central nervous system disorders. Bavachin is a natural product belonging to the flavonoid class. The anti-neuroinflammatory effect and the molecular mechanisms are not well understood. In this study, we found bavachin can exert anti-neuroinflammatory effect via inhibition of nuclear factor-kappa B (NF-κB) signaling. We found that bavachin can obviously upregulate the expression of A20 (TNFAIP3) in microglial cells. Further studies suggested siRNA-A20 knockdown treatment can attenuate the inhibitory effects of bavachin on neuroinflammation. We further found bavachin can increase the interaction of ubiquitin-editing enzyme A20 complex including A20, Tax1-binding protein 1 (TAX1BP1) and Itch, the subsequently downregulated the K63-ubiquitination of TNF receptor associated factor 6 (TRAF6) and NF-κB signaling pathway. Altogether, our results indicated that bavachin exerted anti-neuroinflammatory effects through inhibition of NF-κB signaling mediated by regulation of ubiquitin-editing enzyme A20 complex. Our finding has important clinical significance for the potential application of bavachin in the treatment of neurological disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent studies have verified that inducing reactive oxygen species (ROS) is one of the gemcitabine anti-tumor mechanisms of action. Human carbonyl reductase 1 (CBR1) plays an important role in protecting cells against oxidative damage. However, it is unclear whether CBR1 is involved in pancreatic cancer (PC) progression and resistance to gemcitabine. Based on the GEPIA database, we analyzed tumor tissue samples from PC patients using immunohistochemistry (IHC) and revealed that CBR1 was highly expressed in PC tissues and that this was significantly correlated with the clinicopathological features of PC. Genetic inhibition of CBR1 suppressed PC cell proliferation by regulating ROS generation. Furthermore, gemcitabine upregulated CBR1 expression, which could limit the anti-tumor activity of gemcitabine, and attenuation of CBR1 enhanced gemcitabine sensitivity in vitro and in vivo. Additionally, we report that chrysin directly binds to CBR1, which inhibited its enzymatic activity both at the molecular and cellular levels. Inhibition of CBR1 by chrysin increased cellular ROS levels and led to ROS-dependent autophagy, which resulted in the degradation of ferritin heavy polypeptide 1 (FTH1) and an increase in the intracellular free iron level that participates in ferroptosis in PC cells. Finally, our results showed that chrysin enhanced PC sensitivity to gemcitabine by inducing ferroptotic death in vitro and in vivo. Collectively, these findings indicate that CBR1 is a potential therapeutic target for PC treatment. In addition, we elucidated a novel mechanism underlying the anti-tumor effects of chrysin., (Copyright © 2021 Elsevier Inc. All rights reserved.)

According to the classical pharmacophore fusion strategy, a series of 6-arylureido-4-anilinoquinazoline derivatives ( Compounds 7a - t ) were designed, synthesized, and biologically evaluated by the standard CCK-8 method and enzyme inhibition assay. Among the title compounds, Compounds 7a , 7c , 7d , 7f , 7i , 7o , 7p , and 7q exhibited promising anti-proliferative bioactivities, especially Compound 7i , which had excellent antitumor activity against the A549, HT-29, and MCF-7 cell lines (IC 50 = 2.25, 1.72, and 2.81 μM, respectively) compared with gefitinib, erlotinib, and sorafenib. In addition, the enzyme activity inhibition assay indicated that the synthesized compounds had sub-micromolar inhibitory levels (IC 50 , 11.66-867.1 nM), which was consistent with the results of the tumor cell line growth inhibition tests. By comparing the binding mechanisms of Compound 7i (17.32 nM), gefitinib (25.42 nM), and erlotinib (33.25 nM) to the EGFR, it was found that Compound 7i could extend into the effective region with a similar action conformation to that of gefitinib and interact with residues L85, D86, and R127, increasing the binding affinity of Compound 7i to the EGFR. Based on the molecular hybridization strategy, 14 compounds with EGFR inhibitory activity were designed and synthesized, and the action mechanism was explored through computational approaches, providing valuable clues for the research of antitumor agents based on EGFR inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Xue, Liu, Wang, Yan, Liu, Wang, Shi, Cao, Zhang and Zhang.)

Background: The aim of the present study was to confirm the role of Brachyury in breast cancer and to verify whether four types of machine learning models can use Brachyury expression to predict the survival of patients., Methods: We conducted a retrospective review of the medical records to obtain patient information, and made the patient's paraffin tissue into tissue chips for staining analysis. We selected 303 patients for research and implemented four machine learning algorithms, including multivariate logistic regression model, decision tree, artificial neural network and random forest, and compared the results of these models with each other. Area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the results., Results: The chi-square test results of relevant data suggested that the expression of Brachyury protein in cancer tissues was significantly higher than that in paracancerous tissues (P=0.0335); patients with breast cancer with high Brachyury expression had a worse overall survival (OS) compared with patients with low Brachyury expression. We also found that Brachyury expression was associated with ER expression (P=0.0489). Subsequently, we used four machine learning models to verify the relationship between Brachyury expression and the survival of patients with breast cancer. The results showed that the decision tree model had the best performance (AUC = 0.781)., Conclusions: Brachyury is highly expressed in breast cancer and indicates that patients had a poor prognosis. Compared with conventional statistical methods, decision tree model shows superior performance in predicting the survival status of patients with breast cancer., (© 2021 The Author(s).)

Exercise can enhance motivation to change lifestyle behaviors, improve aerobic fitness, improve physical function, control fatigue, and enhance quality of life. Studies have demonstrated the benefits to be gained from physical exercise, highlighting the importance of popularizing the concept of physical exercise for individuals and making professional exercise-treatment programs available to patients with cancer. However, the correlation between physical exercise and carcinogenesis is easily overlooked, and exercise interventions are not routinely provided to patients with cancer, especially those with advanced cancer. In this article, we present a literature review of the effects of exercise on cancer development and progression and give recent evidence for the type of exercise best suited for different types of cancer and in different disease stages. Moreover, the molecular mechanisms about regulating metabolism and systemic immune function in cancer are summarized and discussed. In conclusion, physical exercise should be considered as an important intervention for preventing and treating cancer and its complications., (Copyright © 2020. Production and hosting by Elsevier B.V.)

Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo . Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.

As a hallmark for cancer treatment, PARP inhibitors can effectively kill tumor cells with a mechanism termed as synthetic lethality, and are used to treat various cancers including ovarian, breast, prostate, pancreatic and others with DNA repair defects. However, along with the clinical trials progressing, the limitations of PARP-1 inhibitors became apparent such as limited activity and indications. Studies have shown that a molecule that is able to simultaneously restrict two or more targets involving in tumors is more effective in preventing and treating cancers due to the enhancing synergies. In order to make up for the shortcomings of PARP inhibitors, reduce the development cost and overcome the pharmacokinetic defects, multiple works were carried out to construct dual targeting PARP inhibitors for cancer therapy. Herein, they were summarized briefly.

Background: Oxidative stress plays an important role in the pathogenesis of asthma. Glutathione (GSH) is considered to be one of the most important antioxidants. Our study systematically investigated the effect of the GSH alternative, glutathione ethyl ester (GSH-EE), on airway hyper-responsiveness (AHR) in mice., Methods: Sixty-three male specific pathogen-free mice were used. Asthma was induced using a single dose of ovalbumin (OVA). The normal group (n=15) received vehicle only [Al(OH)3 in saline]. Then, 48 mice were divided into two groups, including a control group who received sodium phosphate buffer (pH =7.4), and the GSH-EE group who received 0.1% GSH-EE. AHR was measured 2, 6, and 12 hours after exposure to nebulized OVA (0.01%). The animals were then sacrificed, and lung tissue and the bronchi-alveolar lavage fluid (BALF) were harvested. Factors involved in the antioxidant response to asthma were then measured in these tissues, including thiol content (from GSH and protein), γ-glutamylcysteine synthetase (γ-GCS) activity and expression, and nuclear factor-erythroid-2-related factor (Nrf2) expression., Results: The GSH-EE group showed a significant attenuation of AHR (P<0.01) 2 hours after OVA challenge, and significantly enhanced thiol contents by approximately 45% (P<0.05) at 2 and 6 hours after the last OVA challenge, compared to the control group. γ-GCS activity was also higher in the GSH-EE group compared to the control group at different time points (P<0.01). γ-GCSh and Nrf2 protein expression increased in the GSH-EE group and the control group compared with the normal group, but there was no statistically significant difference (P>0.05) between the GSH-EE group and the control group., Conclusions: GSH-EE supplementation can prevent AHR in asthmatic mice during the early stages. It may function by serving as a precursor for GSH biosynthesis and by protecting sulfhydryl groups from oxidation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7114). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Paired-like homeodomain transcription factor 1 (PITX1) participates in miscellaneous biological processes including cell growth, development, progression and invasion in various malignant tumors. However, the analysis of the association between PITX1 expression and the survival in breast cancer remains unclear., Methods: Clinical prognostic parameters and survival data related to PITX1 in breast cancer patients were performed using the bioinformatic analysis including Oncomine, Bc-GenExMiner v4.3, PrognoScan and UCSC Xena., Results: We found that PITX1 gene expression was significantly higher in different histological classification of breast cancer. The Scarff-Bloom-Richardson (SBR) grade, Nottingham prognostic index (NPI), estrogen receptor (ER) negative, epidermal growth factor receptor-2 (HER2) positive, lymph node positive, triple-negative status and basal-like status were positively correlated with PITX1 level, except for patients' age and the progesterone receptor (PR) status. We have found that the increased PITX1 expression correlated with worse relapse-free survival, disease specific survival and overall survival. PITX1 was positively correlated with metastatic relapse-free survival and distant metastasis-free survival. We also confirmed positive correlation between PITX1 and the nucleotide-binding oligomerization domain 2 (NOD2)., Conclusion: The lower expression of PITX1 was associated with better clinical prognostic parameters and clinical survival in breast cancer according to the bioinformatic analysis., (© 2020 The Author(s).)