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Triple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous and invasive subtype of breast cancer with very limited effective modalities of treatment. Degrading the critical transcription regulator cyclin-dependent kinase 9 (CDK9) by proteolysis targeting chimeras (PROTACs) has shown promising potential for treating TNBC. However, to date, CDK9-targeting PROTACs for oral administration in treatment of cancers have not been reported. We herein present the design, synthesis, and extensive biological evaluation of a series of novel PROTACs as orally bioavailable, potent and selective degraders of CDK9 for targeting transcription regulation in triple-negative breast cancer. The developed compound 29 exhibited a desired potency (DC 50  = 3.94 nM) with high efficacy (D max  = 96 %) on CDK9 degradation, and effectively inhibited the proliferation of TNBC MDA-MB-231 cells. Mechanistic investigations revealed that compound 29 is a bona fide CDK9 degrader and can substantially downregulate the downstream targets c-Myc and MCL-1. Furthermore, compound 29 displayed favorable oral bioavailability in mice, and oral administration of degrader 29 significantly depleted CDK9 protein in TNBC tumor tissues and exhibited tumor growth inhibition in TNBC xenograft mice models. Collectively, our work established that degrader 29 is a highly potent and selective degraders of CDK9 with satisfactory oral bioavailability, which holds promising potential for the treatment of TNBC., 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 Inc. All rights reserved.)

This study aims to investigate the associations of caring for grandchildren and/or great-grandparents with depressive symptoms, as well as life satisfaction in Chinese grandparents, and analyze the moderating roles of urban-rural residence and social participation. A nationally representative sample of 2973 grandparents in families with great-grandparents and grandchildren were selected from the 2018 China Health and Retirement Longitudinal Study (CHARLS). The Center for Epidemiologic Studies Depression (CESD-10) and the single-item were used to measure depressive symptoms and life satisfaction. Social participation included participation in social and intellectual activities. The binary logistic regression model was employed to explore the relationship between caring and depressive symptoms, as well as life satisfaction in the whole participants, different urban-rural residence, and social participation groups, respectively. Caring was associated with depressive symptoms and life satisfaction (p < 0.05). A significant interaction existed between caring and urban-rural residence for depressive symptoms (interaction p = 0.029) and life satisfaction (interaction p = 0.027). Significant interactions were also found among caring, urban-rural residence, and social activities with depressive symptoms (interaction p = 0.025). In urban, caring for both was negatively related to depressive symptoms for the non-social activists, while in rural, caring for great-grandparents was positively associated with depressive symptoms for social activists (p < 0.05). Any new policy design related to preventing and reducing the possibility of mental disorders in Chinese grandparents should be tailored to heterogeneous subgroups who live in different rural-urban and social activities participation., (© 2024 Family Process Institute.)

DnaJ proteins, also known as HSP40s, play a key role in plant growth and development, and response to environmental stress. However, little comprehensive research has been conducted on the DnaJ gene family in maize. Here, we identify 91 ZmDnaJ genes from maize, which are likely distributed in the chloroplast, nucleus, and cytoplasm. Our analysis revealed that ZmDnaJs were classified into three types, with conserved protein motifs and gene structures within the same type, particularly among members of the same subfamily. Gene duplication events have likely contributed to the expansion of the ZmDnaJ family in maize. Analysis of cis-regulatory elements in ZmDnaJ promoters suggested involvement in stress responses, growth and development, and phytohormone sensitivity in maize. Specifically, four cis-acting regulatory elements associated with stress responses and phytohormone regulation indicated a role in adaptation. RNA-seq analysis showed constitutive expression of most ZmDnaJ genes, some specifically in pollen and endosperm. More importantly, certain genes also responded to salt, heat, and cold stresses, indicating potential interaction between stress regulatory networks. Furthermore, early responses to heat stress varied among five inbred lines, with upregulation of almost tested ZmDnaJ genes in B73 and B104 after 6 h, and fewer genes upregulated in QB1314, MD108, and Zheng58. After 72 h, most ZmDnaJ genes in the heat-sensitive inbred lines (B73 and B104) returned to normal levels, while many genes, including ZmDnaJ55, 79, 88, 90, and 91, remained upregulated in the heat-tolerant inbred lines (QB1314, MD108, and Zheng58) suggesting a synergistic function for prolonged protection against heat stress. In conclusion, our study provides a comprehensive analysis of the ZmDnaJ family in maize and demonstrates a correlation between heat stress tolerance and the regulation of gene expression within this family. These offer a theoretical basis for future functional validation of these genes.

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

Background: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance., Methods: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses. We systematically assessed the tumor microenvironment using the NanoString GeoMx digital spatial profiler, single-cell RNA-seq and multiplex immunohistochemistry in ESCC. Finally, we evaluated the associations between HLA-A-positive tertiary lymphoid structures (TLSs) and patients' responses to ICB in 60 ESCC patients., Results: Tumor infiltrating B lymphocytes and several immune-related gene signatures, such as the antigen presenting machinery (APM) signature, are significantly elevated in ICB treatment responders. Multiplex immunohistochemistry identified the presence of HLA-A + TLSs and showed that TLS-resident cells increasingly express HLA-A as TLSs mature. Most TLS-resident HLA-A + cells are tumor-infiltrating T (TIL-T) or tumor-infiltrating B (TIL-B) lymphocytes. Digital spatial profiling of spatially distinct TIL-T lymphocytes and single-cell RNA-seq data from 60 ESCC tumor tissues revealed that CXCL13-expressing exhausted TIL-Ts inside TLSs are reactivated with elevated expression of the APM signature as TLSs mature. Finally, we demonstrated that HLA-A + TLSs and their major cellular components, TIL-Ts and TIL-Bs, are associated with a clinical benefit from ICB treatment for ESCC., Conclusions: HLA-A + TLSs are present in ESCC tumor tissues. TLS-resident TIL-Ts with elevated expression of the APM signature may be reactivated. HLA-A + TLSs and their major cellular components, TIL-Ts and TIL-Bs, may serve as biomarkers for ICB-treated ESCC patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, effective therapies for TNBC are very limited and remain a significant unmet clinical need. Targeting the transcription-regulating cyclin-dependent kinase 9 (CDK9) has emerged as a promising avenue for therapeutic treatment of TNBC. Herein, we report the design, synthesis, optimization, and evaluation of a new series of aminopyrazolotriazine compounds as orally bioavailable, potent, and CDK9/2 selectivity-improved inhibitors, enabling efficacious inhibition of TNBC cell growth, as well as notable antitumor effect in TNBC models. The compound C35 demonstrated low-nanomolar potency with substantially improved CDK9/2 selectivity, downregulated the CDK9-downstream targets ( e.g. , MCL-1), and induced apoptosis in TNBC cell lines. Moreover, with the desired oral bioavailability, oral administration of C35 could significantly suppress the tumor progression in two TNBC mouse models. This study demonstrates that target transcriptional regulation is an effective strategy and holds promising potential as a targeted therapy for the treatment of TNBC.

In this work, thermo-oxidative behavior, kinetic triplet, and free radical mechanism of ultraheavy oil during an in situ combustion (ISC) process were systematically surveyed via multiple thermal analysis techniques (TG/DTG/DSC/PDSC), model-free methods, and related mathematical simulation. First, specific mass loss, exothermic intensity, and corresponding temperature intervals were respectively determined in low-/high-temperature oxidation (LTO/HTO) regions. In addition, the comparison of atmospheric/pressurized differential scanning calorimetry (DSC/PDSC) experiments indicated that the pressurized conditions could obviously strengthen the oxidation progress with more heat emission. Then two model-free methods were contrastively employed for PDSC data to calculate LTO and HTO activation energy variations with the conversion rate. Moreover, the acceleratory rate model for LTO and the Sestak-Berggren model for HTO were accordingly picked as the most probable mechanism functions, which were later used to determine the simulated curves. Then, the simulations of α- T and dα/d T - T curves were respectively attained using Friedman equation in MATLAB software and contrasted with experimental data to validate the accuracy of the yielded kinetic triplet and forecast the combustion behavior. Further, the evolution pathways of the underlying oxidation mechanism was illustrated. This study updates the understanding of the nonisothermal combustion process, contributing to the subsequent numerical simulation and feasible investigation for in situ combustion implementation to enhance heavy oil recovery., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

G protein-coupled receptors (GPCRs), the largest family of human membrane proteins and an important class of drug targets, play a role in maintaining numerous physiological processes. Agonist or antagonist, orthosteric effects or allosteric effects, and biased signaling or balanced signaling, characterize the complexity of GPCR dynamic features. In this study, we first review the structural advancements, activation mechanisms, and functional diversity of GPCRs. We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years. Particularly, an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms. Finally, we highlight how the widespread GPCR-druggable allosteric sites can guide structure- or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family., (© 2024. The Author(s).)

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy., (© The Author(s) 2024. Published by Oxford University Press.)

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis., (© 2024. The Author(s).)

Background: Livable environment and ways, as the necessary conditions for the elderly to enjoy their old age, have a significant impact on their mental health and happiness. It's crucial to understand how living arrangements affect depressive symptoms in China. Studies on how various leisure activities modify this association are yet limited., Methods: This study relies on panel data derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), collected during waves spanning 2008/2009, 2011/2012, 2014, and 2018. The primary objective is to examine the relationship between living arrangements, leisure activities, and depressive symptoms of elderly individuals. Linear mixed-effects models were used to analyze the data., Results: A total of 26,342 observations aged 65 and over were included in this paper. Older adults living alone (β = 0.66, 95 % CI: 0.55, 0.76) or living in institutions (β = 0.69, 95 % CI: 0.40, 0.98) had more depressive symptoms than those living with family. Leisure activities were negatively associated with depressive symptoms (β = -0.16, 95 % CI: -0.18, -0.15). Moreover, there was significant interactions between living arrangements and leisure activities. No matter which kind of living arrangements, participating in physical, productive or social activity was associated with a lower risk of depressive symptoms., Limitations: Study design might introduce bias, and it cannot establish causality between the tested variables., Conclusions: Older adults living alone or in institutions have more possibility to develop depressive symptoms than those living with family, and such a relationship among Chinese older adults can be moderated by participating in leisure activities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Protein phosphorylation plays an important role in the signal transduction and is capable of regulation of cell activity. The death-associated protein kinase 1 (DAPK1), as a Ser/Thr kinase, interacts with calmodulin (CaM) to regulate apoptotic and autophagic signaling. Autophosphorylation of DAPK1 at Ser308 located at the autoregulatory domain (ARD) blocks CaM binding and inhibits kinase catalytic activity. However, the mechanism underlying the influence of Ser308 phosphorylation (pS308) on the DAPK1 activity remains unclear. Here, we performed multiple, microsecond length molecular dynamics (MD) simulations, the molecular mechanics generalized Born/surface area (MM-GBSA) binding free energy calculations, principal component analysis, and dynamic cross-correlation analysis to unravel the conformational dynamics and allostery of the DAPK1 - CaM interaction triggered by the pS308 at the ARD. MD simulations showed that pS308 affected the conformational stability of the DAPK1 - CaM complex. Further energetic and structural exploration revealed that pS308 weakened the association of the phosphorylated DAPK1 to CaM, which lowered the susceptibility of DAPK1 to be activated by CaM. This result can provide mechanistic insights into the molecular underpinning through which the DAPK1 kinase activity is modulated by the auto-phosphorylation.Communicated by Ramaswamy H. Sarma.

The increase of deoxynivalenol (DON) caused by Fusarium graminearum (F. graminearum) during the malting process is a serious safety problem. In our work, the inhibition mechanism of F. graminearum growth by g-C 3 N 4 homojunction and its application in barley malting were studied. The reason why the growth activity of F. graminearum decreased after photocatalysis by g-C 3 N 4 homojunction was that under visible light irradiation, a large amount of •O 2 - elicited by g-C 3 N 4 homojunction destroyed the cell structure of F. graminearum, leading to the deficiency of cell membrane selective permeability and serious disorder of intracellular metabolism. The application of photocatalysis technology in malting can effectively inhibit the growth of F. graminearum and the accumulation of ergosterol was reduced by 30.55 %, thus reducing the DON content in finished malt by 31.82 %. Meanwhile, the physicochemical indexes of barley malt after photocatalytic treatment still met the requirements of second class barley malt in Chinese light industry standard QB/T 1686-2008. Our work provides a new idea for the control of fungal contamination in barley malt., 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.)

Viruses rely completely on host translational machinery to produce the proteins encoded by their genes. Controlling translation initiation is important for gaining translational advantage in conflicts between the host and virus. The eukaryotic translation initiation factor 4E (eIF4E) has been reported to be hijacked by potyviruses for virus multiplication. The role of translation regulation in defence and anti-defence between plants and viruses is not well understood. We report that the transcript level of eIF6 was markedly increased in turnip mosaic virus (TuMV)-infected Nicotiana benthamiana. TuMV infection was impaired by overexpression of N. benthamiana eIF6 (NbeIF6) either transiently expressed in leaves or stably expressed in transgenic plants. Polysome profile assays showed that overexpression of NbeIF6 caused the accumulation of 40S and 60S ribosomal subunits, the reduction of polysomes, and also compromised TuMV UTR-mediated translation, indicating a defence role for upregulated NbeIF6 during TuMV infection. However, the polysome profile in TuMV-infected leaves was not identical to that in leaves overexpressing NbeIF6. Further analysis showed that TuMV NIb protein, the RNA-dependent RNA polymerase, interacted with NbeIF6 and interfered with its effect on the ribosomal subunits, suggesting that NIb might have a counterdefence role. The results propose a possible regulatory mechanism at the translation level during plant-virus interaction., (© 2024 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons 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.

This study presents the biomimetic design of the structure and controller of AutoLEE-II, a self-balancing exoskeleton developed to assist patients in performing multiple rehabilitation movements without crutches or other supporting equipment. Its structural design is founded upon the human body structure, with an eliminated axis deviation and a raised CoM of the exoskeleton. The controller is a physical parameter-independent controller based on the CoM modification. Thus, the exoskeleton can adapt to patients with different physical parameters. Five subjects underwent exoskeleton-assisted rehabilitation training experiments, including squatting, tilting, and walking trainings. The results showed that the exoskeleton can assist patients in completing various rehabilitation exercises and help them maintain their balance during the rehabilitation training. This helpful role of the exoskeleton in rehabilitation training is analyzed through an electromyography (EMG) data analysis. The findings revealed that wearing the exoskeleton can reduce the activity of the lower limb muscles by approximately 20-30% when performing the same rehabilitation exercises.

Inorganic electrides are considered potential superconductors due to the unique properties of their anionic electrons. However, most electrides require external high-pressure conditions to exhibit considerable superconducting transition temperatures ( T c ). Therefore, searching for superconducting electrides under low or moderate external pressures is of significant research interest and importance. In this work, a series of A 3 Hf 2 B 3 -type compounds (A = Mg, Ca, Sr, Ba; B = Si, Ge, Sn, Pb) were constructed and systematically studied based on density functional theory calculations. According to the analysis of the electronic structures and phonon dispersion spectrums, stable one-dimensional electrides Ca 3 Hf 2 Ge 3 , Ca 3 Hf 2 Sn 3 , and Sr 3 Hf 2 Pb 3 , were screened out. Interestingly, the superconductivity of these electrides were predicted from electron phonon coupling calculations. It is highlighted that Sr 3 Hf 2 Pb 3 showed the highest T c , reaching 4.02 K, while the T c values of Ca 3 Hf 2 Ge 3 and Ca 3 Hf 2 Sn 3 were 1.16 K and 1.04 K, respectively. Moreover, the T c value of Ca 3 Hf 2 Ge 3 can be increased to 1.96 K under 20 GPa due to the effect of phonon softening. This work enriches the types of superconducting electrides and has important guiding significance for the research on constructing electrides and related superconducting materials., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Physical aging is a long-lasting research hot spot in the glass community, yet its long-term effects remain unclear because of the limited experimental time. In this study, we discover the extraordinary aging effects in five typical lunar glassy particles with diameters ranging from about 20 to 53 micrometers selected from Chang'e-5 lunar regolith. It is found that geological time scales' aging can lead to unusually huge modulus enhancements larger than 73.5% while much weaker effects on hardness (i.e., varies decoupling evolutions of Young's modulus and hardness during aging) in these lunar glassy samples. Such extraordinary aging effects are primarily attributed to the natural selected complex glassy compositions and structures, consistent with high entropy and minor element doping criteria, prevailing under the special lunar conditions and the extensive aging time for the lunar glasses. This study offers valuable insights for developing high-performance and stable glassy materials for radiation protection and advanced space explorations.

Objective: Improving accuracy and safety of pedicle screw placement is of great clinical importance. Electronic conductivity device (ECD) can be a promising technique with features of affordability, portability, and real-time detection capabilities. This study aimed to validate the safety and effectiveness of a modified ECD., Methods: The ECD underwent a modification where six lamps of various colors, and it was utilized in a prospectively multicenter randomized controlled clinical trial involving 96 patients across three hospitals from June 2018 to December 2018. The trial incorporated a self-control randomization with an equal distribution of left or right side of vertebral pedicle among two groups: the free-hand group and the ECD group. A total of 496 pedicle screws were inserted, with 248 inserted in each group. The primary outcomes focused on the accuracy of pedicle screw placement and the frequency of intraoperative X-rays. Meanwhile, the secondary indicator measured the time required for pedicle screw placement. Results were presented as means ± SD. Paired samples t-test and χ 2 -test were used for comparison. Furthermore, an updated review was conducted, which included studies published from 2006 onwards., Results: Baseline patient characteristics were recorded. The primary accuracy outcome revealed a 96.77% accuracy rate in the ECD group, compared to a 95.16% accuracy rate in the free-hand group, with no significant differences noted. In contrast, ECD demonstrated a significant reduction in radiation exposure frequency when compared to the free-hand group (1.11 ± 0.32 vs. 1.30 ± 0.53; p < 0.001), resulting in a 14.6% reduction. Moreover, ECD displayed a decrease of 30.38% in insertion time (70.88 ± 30.51 vs. 101.82 ± 54.00 s; p < 0.001). According to the results of the 21 studies, ECD has been utilized in various areas of the spine such as the atlas, thoracic and lumbar spine, as well as sacral 2-alar-iliac. The accuracy of ECD ranged from 85% to 100%., Conclusion: The prospectively randomized trial and the review indicate that the use of ECD presents a secure and precise approach to the placement of pedicle screws, with the added benefit of reducing both procedure time and radiation exposure., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: To examine and quantify liver and kidney lesions and their response to anti-tumor necrosis factor (TNF) therapy in a TNF-Tg mouse model of rheumatoid arthritis (RA)., Methods: Female TNF-Tg (Tg3647) mice were used as the animal model for chronic RA. Ultrasound, immunofluorescence, histological staining, serology tests, and real-time RT-PCR were used to examine the pathological changes in the liver and kidney., Results: TNF-Tg mice showed a significant decrease in the body weight and a dramatic increase in the volumes of the gallbladder, knee cavity, and popliteal lymph nodes. The liver and kidneys of TNF-Tg mice showed increased chronic inflammation and accumulation of immune cells and fibrosis, compared to wild-type (WT) mice. Moreover, upregulation of inflammatory factors and impaired normal function were observed in the liver and kidneys of TNF-Tg mice. Inflammatory infiltration and fibrosis of the liver and kidneys of female TNF-Tg mice were improved after anti-TNF treatment, and better treatment effects were achieved at 4.5-month-old mice when they were received 8 weeks of intervention., Conclusions: We found that TNF drives the development of liver and kidney pathology in female TNF-Tg mice and that there are limitations to the loss of utility of anti-TNF for the prolonged treatment of RA-associated hepatic and renal injury. This study provides a reliable and clinically relevant animal model for further studies exploring the molecular mechanisms and drug discovery for hepatorenal pathologies in RA., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The dysfunction of immune cell development often impairs immunological homeostasis, thus causing various human diseases. Accumulating evidence shows that the development of different immune cells from hematopoietic stem cells are highly fine-tuned by different epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling and RNA-related regulations. Understanding how epigenetic regulators modulate normal development of immune cells contributes to the identification of new strategies for various diseases. Here, we review recent advances suggesting that epigenetic modulations can orchestrate immune cell development and functions through their impact on critical gene expression. We also discuss the aberrations of epigenetic modulations in immune cells that influence tumor progression, and the fact that underlying mechanisms affect how epigenetic drugs interfere with tumor progression in the clinic., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Two donor-acceptor acridone-based compounds, namely, 2-{10-[4-(diphenylamino)phenyl]acridin-9-ylidene}malononitrile (TPA-AD-DCN), C 34 H 22 N 4 , and 2-{10-[4-(9H-carbazol-9-yl)phenyl]acridin-9-ylidene}malononitrile (CzPh-AD-DCN), C 34 H 20 N 4 , have been synthesized in high yield and their structures determined. TPA-AD-DCN and CzPh-AD-DCN crystallized in the centrosymmetric space groups P-1 and P2 1 /c, respectively. Both molecules adopt a `butterfly-like' configuration of the common part of the structure and differences occur within the substituents on the acridine N atom. A Hirshfeld surface analysis showed that the H...H and C...H/H...C contacts constitute a high percentage of the intermolecular interactions. The optical and electrochemical properties, as well as theoretical calculations, of TPA-AD-DCN and CzPh-AD-DCN support the structural characterization of these materials. As crystallization-induced emission materials, TPA-AD-DCN and CzPh-AD-DCN are anticipated to be of potential use in the construction of promising optoelectronic materials.

Background: Since few studies have incorporated factors like stressors, coping styles, and academic burnout into the same model to analyze their impacts on depressive symptoms, this research attempts to establish an optimal structural model to explore the direct and indirect effects of these factors on depressive symptoms., Methods: A total of 266 postgraduates completed questionnaires regarding coping styles, academic burnout, stressors, and depressive symptoms. The path analysis was applied for investigating the roles of coping styles and academic burnout in mediating the relationship between stressors and depressive symptoms., Results: The total and direct effects of stressors on depressive symptoms were 0.53 and 0.31, respectively. The proportion of the direct effect of stressors on depressive symptoms to its total effect amounted to 58.50%. The indirect effects of academic burnout, positive coping style, and negative coping style on the association between stressors and depressive symptoms were 0.11, 0.04, and 0.03, taking up 20.75%, 7.55%, and 5.66% of the total effect, respectively. The serial indirect effect of positive coping style and academic burnout was 0.02, accounting for 3.77% of the total effect, while that of negative coping style and academic burnout was 0.02, taking up 3.77% of the total effect., Conclusions: Coping styles and academic burnout chain jointly mediate the relationship between stressors and depressive symptoms among postgraduates. Thus, encouraging postgraduates to tackle stress positively may reduce the likelihood of the development of academic burnout and further reduce depressive symptoms., Competing Interests: The authors declare there are no competing interests., (©2023 Shi et al.)

Rice blast, caused by Magnaporthe oryzae, is one of the most destructive rice diseases. Developing blast-resistant rice cultivars represents the most economical and environmentally friend strategy for managing the disease. In our previous study, an isobaric tags for relative and absolute quantitation (iTRAQ)-based comparative protein quantification was carried out to investigate the resistance gene Piz-t gene-mediated resistance response to infection in two contrasting rice genotypes of the Piz-t transgenic Nipponbare line (NPB-Piz-t) and its wild-type Nipponbare (NPB). Here, from the comparisons of differentially expressed proteins (DEPs) of NPB-Piz-t to the avirulent isolate KJ201 (KJ201-Piz-t)and the virulent isolate RB22 (RB22-Piz-t) with mock-treated NPB-Piz-t (Mock-Piz-t), NPB to the virulent isolate KJ201(KJ201-NPB) and RB22 (RB22-NPB) with mock-treated NPB (Mock-NPB), 1, 1, and 6 common DEPs were, respectively, identified at 24, 48 and 72 h post-inoculation (hpi) in the susceptible comparisons of RB22-Pizt/Mock-Piz-t, KJ201-NPB/Mock-NPB, and RB22-NPB/Mock-NPB, involving in gi|54,290,836 and gi|59,800,021 were identified in the resistance comparison KJ201-Piz-t/Mock-Piz-t at 48 and 72 hpi respectively. Moreover, four genes of Os01g0138900 (gi|54,290,836), Os04g0659300 (gi|59,800,021), Os09g0315700 (gi|125,563,186) or Os04g0394200 (gi|21,740,743) were knocked out or overexpressed in NPB using gene over-expression and CRISPR/Cas9 technology, and results verified that the Os01g0138900 obviously affected the rice blast resistance. Further, expression and targeted metabolomics analysis illuminated the resistance response of cysteine-containing substances as gi|59,800,021 under blast infection. These results provide new targets for basal resistance gene identification and open avenues for developing novel rice blast resistant materials., (© 2023. Northwest A&F University (NWAFU).)

Small-molecule modulators of neurotensin receptor 1 (NTSR1), a class A G-protein-coupled receptor (GPCR), has emerged as promising therapeutic agent for psychiatric disorders and cancer. Interestingly, a chemical group substitution in NTSR1 modulators can launch different types of downstream regulation, highlighting the significance of deciphering the internal fine-tuning mechanism. Here, we conducted a synergistic application of a Gaussian accelerated molecular dynamics simulation, a conventional molecular dynamics simulation, and Markov state models (MSM) to investigate the underlying mechanism of 'driver chemical groups' of modulators triggering inverse signaling. The results indicated that the flexibility of the leucine moiety in NTSR1 agonists contributes to the inward displacement of TM7 through a loosely coupled allosteric pathway, while the rigidity of the adamantane moiety in NTSR1 antagonists leads to unfavorable downward transduction of agonistic signaling. Furthermore, we found that R322 6.54 , Y319 6.51 , F353 7.42 , R148 3.32 , S356 7.45 , and S357 7.46 may play a key role in inducing the activation of NTSR1. Together, our findings not only highlight the ingenious signal transduction within class A GPCRs but also lay a foundation for the development of targeted drugs harboring different regulatory functions of NTSR1.

In this work, high-performance two-dimensional (2D) graphene-based single-atom electrocatalysts (ZZ/ZA-MN x C y ) for the oxygen reduction reaction (ORR) were screened out using machine learning (ML). A model was built for the fast prediction of electrocatalysts and two descriptors valence electron correction (VEc) and degree of construction differences (DC) were proposed to improve the accuracy of the model prediction. Two evaluation criteria, high-performance catalyst retention rate r R and high-performance catalyst occupancy rate r O , were proposed to evaluate the accuracy of ML models in high-performance catalyst screening. The addition of VEc and DC in the model could change the mean absolute error (MAE test ) of the test set, the coefficient of determination ( R 2 test ) of the test set, r O , and r R from 0.334 V, 0.683, 0.222, and 0.360 to 0.271 V, 0.774, 0.421, and 0.671, respectively. The partially screened potential high-performance ORR electrocatalysts such as ZZ-CoN 4 and ZZ-CoN 3 C 1 were also further investigated using a Density Functional Theory (DFT) method, which confirmed the accuracy of the ML model (MAE = 0.157 V, R 2 = 0.821).

Objective: This study aims to verify the moderating roles of lifestyle factors and age between body mass index (BMI), BMI trajectory and depressive symptoms of Chinese adults through a prospective design., Methods: The participants who are 18 years old and above from the China Family Panel Studies (CFPS) were included in the 2016 baseline and 2018 follow-up research. BMI was calculated according to self-report weight (kilogram) and height (centimeter). Depressive symptoms were evaluated via the Center for Epidemiologic Studies Depression (CESD-20) scale. Inverse probability-of-censoring weighted estimation (IPCW) was used to check whether selection bias existed. Modified Poisson regression was performed to calculate prevalence and risk ratios as well as 95% confidence intervals., Results: After adjustment, it was found that the positive associations of persistent underweight (RR = 1.154, P < 0.001) and normal weight → underweight (RR = 1.143, P < 0.001) with 2018 depressive symptoms were significant among middle-aged people, while the negative association of persistent overweight/obesity (RR = 0.972, P < 0.001) was significant in young adults. Notably, smoking moderated the relationship between baseline BMI and subsequent depressive symptoms (interaction P = 0.028). Also, exercise regularly and exercise duration weekly moderated the relationships of baseline BMI (interaction P = 0.004 and 0.015) and trajectories of BMI (interaction P = 0.008 and 0.011) with depressive symptoms among Chinese adults, respectively., Conclusion: Weight management strategies for underweight and normal weight → underweight adults should pay attention to the role of exercise in maintaining normal weight and improving depressive symptoms., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However, reliable processes capable of controlling film composition have yet to be developed. In this work, the effect of precursor partial pressure and steric hindrance on the surface activity was presented and analyzed in detail, which led to the development of a component tailoring process for ALD composition control in intralayer for the first time. Further, a homogeneous organic/inorganic hybrid film was successfully grown. The component unit of the hybrid film under the joint action of EG and O plasma could achieve arbitrary ratios by controlling the EG/O plasma surface reaction ratio via varied partial pressures. Film growth parameters (growth rate per cycle and mass gain per cycle) and physical properties (density, refractive index, residual stress, transmission, and surface morphology) could be modulated as desired. Moreover, the hybrid film with low residual stress was effectively used in the encapsulation of flexible organic light-emitting diodes (OLEDs). Such a component tailoring process is an important step forward in ALD technology, and allowing for in-situ control of thin film components at the atomic level in intralayer.

Introduction: The critical challenge for periodontitis therapy is thoroughly eliminating the dental plaque biofilm, particularly penetrating the deep periodontal tissue. Regular therapeutic strategies are insufficient to penetrate the plaque without disturbing the commensal microflora of the oral cavity. Here, we constructed a Fe 3 O 4 magnetic nanoparticle loading minocycline (FPM NPs) to penetrate the biofilm physically and effectively eliminate periodontal biofilm., Methods: In order to penetrate and remove the biofilm effectively, Fe 3 O 4 magnetic nanoparticles were modified with minocycline using a co-precipitation method. The particle size and dispersion of the nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The antibacterial effects were examined to verify the magnetic targeting of FPM NPs. Confocal laser scanning microscopy was employed to check the effect of FPM + MF and develop the best FPM NPs treatment strategy. Additionally, the therapeutic effect of FPM NPs was investigated in periodontitis rat models. The expression of IL-1β, IL-6, and TNF-α in periodontal tissues was measured by qRT-PCR and Western blot., Results: The multifunctional nanoparticles exhibited intense anti-biofilm activity and good biocompatibility. The magnetic forces could pull FMP NPs against the biofilm mass and kill bacteria deep in the biofilms both in vivo and in vitro. The integrity of the bacterial biofilm is disrupted under the motivation of the magnetic field, allowing for improved drug penetration and antibacterial performance. The periodontal inflammation recovered well after FPM NPs treatment in rat models. Furthermore, FPM NPs could be monitored in real-time and have magnetic targeting potentials., Conclusion: FPM NPs exhibit good chemical stability and biocompatibility. The novel nanoparticle presents a new approach for treating periodontitis and provides experimental support for using magnetic-targeted nanoparticles in clinic applications., Competing Interests: The authors report no commercial, proprietary, or financial interest in the products or companies described in this article. The authors declare no competing financial interests., (© 2023 Tong et al.)

Introduction: The validity of adjusting dialysate bicarbonate based on pre-hemodialysis (HD) serum bicarbonate is unclear. There are no studies of the impact of dialysate sodium on blood pH., Aims: To understand the impact of dialysate bicarbonate and sodium on blood pH., Methods: Two hundred arterialized blood samples were obtained on the third session of HD with four configurations of dialysate: sodium (140, 137 mEq/L) and bicarbonate (38, 32 mEq/L)., Results: The correlation between pre-HD serum bicarbonate and pH was modest (r = 0.6). A lower dialysate sodium (p = 0.035) and a higher bicarbonate (p = 0.02) associated with a higher post-HD blood pH. The frequency of pre-HD blood pH of <7.4 and a post-HD blood pH of >7.5 did not differ for samples with serum bicarbonate <22, 22-26, or >26 mEq/L., Discussion/conclusions: Adjusting dialysate buffer based on pre-HD serum bicarbonate is unnecessary. A higher bicarbonate and lower dialysate sodium associate with post-HD alkalemia., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

High nutritional value and the development of efficient biotechnological methods of controlled production have made black porgy ( Acanthopagrus schlegelii ) an economically important fish in Chinese aquaculture in recent years. However, aquaculture production of the species faces multiple issues associated with reduced growth rate, low reproduction ability, and high mortality during production, which are associated with the species' limited tolerance to low temperatures. To date, comprehensive information on the genetic-based mechanisms of cold tolerance and adaptation to low temperature in the species are still unavailable. In this study, the HiSeq™2500 (Illumina) sequencing platform was used to analyze the transcriptomic profile of the liver tissue in the black porgy subjected to different extents of cold shock, including a control temperature group (AS, T = 15 °C), an intermediate temperature group (AL1, T = 10 °C), and an acute low-temperature stress group (AL2, T = 5 °C). For this purpose, three standardized cDNA libraries of AS, AL1, and AL2 were established. We obtained 43,258,908, 48,239,072, and 38,983,833 clean reads from the AS group, AL1 group, and AL2 group, respectively. After pairwise comparison, 70 differentially expressed genes (DEGs) were identified in the examined fish groups. Among them, 60 genes were found to be significantly differentially expressed after trend analysis. GO annotation and enrichment results showed that they were mainly enriched into three categories: biological processes (12 subcategories), molecular functions (7 subcategories), and cellular components (7 subcategories). KEGG analysis results indicated that all significantly differentially expressed genes were annotated to 102 signaling pathways, including biological rhythm, cholesterol metabolism, glycerolipid metabolism, animal autophagy, FoxO signaling pathway, steroid biosynthesis, and regulation of adipocyte lipolysis and apoptosis. Four of them, namely: G6PC, GPX1, GCK, and HSPE1 were randomly selected for further qRT-PCR verification of data reliability obtained by RNA-Seq technology. In this study, we found that environmental acute cold stress mainly affected the black porgy's biological processes related to metabolism, apoptosis, and signal transduction. The data that we have reported provides baseline information for further studies concerning the genetic responses of the black porgy under cold stress conditions, the improvement of its aquaculture production, and other economically important matters regarding their limited tolerance to cold shock.

Background: Ectopic ossification is an important cause of disability in patients with ankylosing spondylitis (AS). Whether fibroblasts can transdifferentiate into osteoblasts and contribute to ossification remains unknown. This study aims to investigate the role of stem cell transcription factors (POU5F1, SOX2, KLF4, MYC, etc.) of fibroblasts in ectopic ossification in patients with AS., Methods: Primary fibroblasts were isolated from the ligaments of patients with AS or osteoarthritis (OA). In an in vitro study, primary fibroblasts were cultured in osteogenic differentiation medium (ODM) to induce ossification. The level of mineralization was assessed by mineralization assay. The mRNA and protein levels of stem cell transcription factors were measured by real-time quantitative PCR (q-PCR) and western blotting. MYC was knocked down by infecting primary fibroblasts with lentivirus. The interactions between stem cell transcription factors and osteogenic genes were analysed by chromatin immunoprecipitation (ChIP). Recombinant human cytokines were added to the osteogenic model in vitro to evaluate their role in ossification., Results: We found that MYC was elevated significantly in the process of inducing primary fibroblasts to differentiate into osteoblasts. In addition, the level of MYC was remarkably higher in AS ligaments than in OA ligaments. When MYC was knocked down, the expression of the osteogenic genes alkaline phosphatase (ALP) and bone morphogenic protein 2 (BMP2) was decreased, and the level of mineralization was reduced significantly. In addition, the ALP and BMP2 were confirmed to be the direct target genes of MYC. Furthermore, interferon-γ (IFN-γ), which showed high expression in AS ligaments, was found to promote the expression of MYC in fibroblasts in the process of ossification in vitro., Conclusions: This study demonstrates the role of MYC in ectopic ossification. MYC may act as the critical bridge that links inflammation with ossification in AS, thus providing new insights into the molecular mechanisms of ectopic ossification in AS., (© 2023. The Author(s).)

During fixed orthodontic treatment, white spot lesions are prevalent issues associated with cariogenic bacteria. This study aims to construct an orthodontic adhesive containing nanoparticles of amorphous calcium phosphate-polydopamine-Ag (NPA) fillers to combat white spot lesions. The NPA fillers were prepared and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The biocompatibility of the fillers was evaluated. A colony counting test evaluated the antibacterial property of the fillers against Streptococcus mutans (S. mutans) . NPA fillers were mixed with orthodontic adhesive (Transbond XT) at different weight ratios (0, 0.1, 0.2, 0.3, and 0.5 wt.%). The shear bond strength and antibacterial properties were then further investigated. The results showed that NPA was prepared successfully, with good antibacterial properties. The cell survival rate of all groups of fillers was higher than 70%, showing good biocompatibility. Moreover, the shear bond strength of the orthodontic adhesive with 0.2 wt.% NPA fillers was 11.89 ± 1.27 MPa, meeting the minimal clinical bond strength requirements of 7.8 MPa. Furthermore, the orthodontic adhesive resin blocks and the extract displayed good antibacterial properties, with the number of colonies decreasing significantly ( p < 0.001). Taken together, we think that an orthodontic adhesive with NPA may have a good application potential for the prevention and treatment of white spot lesions.

Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology., (© 2023. The Author(s).)

Transparent electrodes (TEs) are important components in organic optoelectronic devices. ITO is the mostly applied TE material, which is costly and inferior in mechanical performance, and could not satisfy the versatile need for the next generation of transparent optoelectronic devices. Recently, many new TE materials emerged to try to overcome the deficiency of ITO, including graphene, ultrathin metal, and oxide-metal-oxide structure. By finely control of the fabrication techniques, the main properties of conductivity, transmittance, and mechanical stability, have been studied in the literatures, and their applicability in the potential optoelectronic devices has been reported. Herein, in this work, we summarized the recent progress of the TE materials applied in optoelectronic devices by focusing on the fabrication, properties, such as Graphene, ultra-thin metal film, and metal oxide and performance. The advantages and insufficiencies of these materials as TEs have been summarized and the future development aspects have been pointed out to guide the design and fabrication TE materials in the next generation of transparent optoelectronic devices.

Calcium (Ca 2+ ) signaling plays an important role in the regulation of many cellular functions. Ca 2+ -binding protein calmodulin (CaM) serves as a primary effector of calcium function. Ca 2+ /CaM binds to the death-associated protein kinase 1 (DAPK1) to regulate intracellular signaling pathways. However, the mechanism underlying the influence of Ca 2+ on the conformational dynamics of the DAPK1-CaM interactions is still unclear. Here, we performed large-scale molecular dynamics (MD) simulations of the DAPK1-CaM complex in the Ca 2+ -bound and-unbound states to reveal the importance of Ca 2+ . MD simulations revealed that removal of Ca 2+ increased the anti-correlated inter-domain motions between DAPK1 and CaM, which weakened the DAPK1-CaM interactions. Binding free energy calculations validated the decreased DAPK1-CaM interactions in the Ca 2+ -unbound state. Structural analysis further revealed that Ca 2+ removal caused the significant conformational changes at the DAPK1-CaM interface, especially the helices α1, α2, α4, α6, and α7 from the CaM and the basic loop and the phosphate-binding loop from the DAPK1. These results may be useful to understand the biological role of Ca 2+ in physiological processes., 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 Li, Li, Li, Yang, Bai, Chen, Chen and Mao.)

Study Design: A retrospective case-control study., Objective: To evaluate whether Ponte osteotomy improves thoracic kyphosis and to determine its clinical efficacy in hypokyphotic adolescent idiopathic scoliosis (AIS)., Methods: Eighty consecutive Lenke type 1 AIS patients with hypokyphotic curves who underwent posterior spinal fusion by one spine surgeon at a single institution were recruited. According to whether Ponte osteotomy was performed, the patients were divided into two groups. The preoperative, immediate, one-year postoperative, and two-year postoperative radiographs were analyzed. The demographic characteristics, surgical information, radiographic parameters, Scoliosis Research Societye-22 (SRS-22) questionnaire, and complications were compared., Results: The sagittal alignment and coronal alignment were both improved in the Ponte group and the control group postoperatively. There was no significant difference in the preoperative parameters between the two groups, except the TL/L, CB, and LL. Significant differences were found in the MT (15.18° ± 2.84° vs. 20.33° ± 3.75°, P < 0.001) and TK (24.23° ± 2.71° vs. 19.93° ± 2.38°, P < 0.001) at the two-year follow-up. The Ponte group had a longer operation time and more intraoperative blood loss. No significant difference was observed between the groups in the SRS-22 scores at the final follow-up., Conclusions: Ponte osteotomy could obtain better coronal correction and sagittal contour restoration in AIS patients with hypokyphosis. However, Ponte osteotomies might lead to more intraoperative blood loss and longer operation time. Moreover, no discrepancy was found in the postoperative health-related quality of life of the included patients. Therefore, we considered that the Ponte osteotomy may be an alternative method to restore the desired thoracic kyphosis, which needs further study., (© 2022. The Author(s).)

Utilization of rice blast-resistance ( R ) genes is the most economical and environmentally friendly method to control blast disease. However, rice varieties with R genes influence the outcome of genetic architectures of Magnaporthe oryzae ( M. oryzae ), and mutations in avirulence ( AVR ) genes of M. oryzae may cause dysfunction of the corresponding R genes in rice varieties. Although monitoring and characterizing rice R genes and pathogen AVR genes in field populations may facilitate the implementation of effective R genes, little is known about the changes of R genes over time and their ultimate impact on pathogen AVR genes. In this study, 117 main cultivated rice varieties over the past five decades and 35  M. oryzae isolates collected from those diseased plants were analyzed by PCR using gene-specific markers of the nine R genes and six primer pairs targeting the coding sequence or promoter of AVR genes, respectively. The R genes Pigm, Pi9 , Pi2 , Piz-t , Pi-ta , Pik, Pi1 , Pikp, and Pikm were identified in 5, 0, 1, 4, 18, 0, 2, 1, and 0 cultivars, respectively. Significantly, none of these R genes had significant changes that correlated to their application periods of time. Among the four identified AVR genes, AVR-Pik had the highest amplification frequency (97.14%) followed by AVR-Pita (51.43%) and AVR-Pi9 (48.57%); AVR-Piz-t had the lowest frequency (28.57%). All these AVR genes except AVR-Pi9 had 1-2 variants. Inoculation mono-genic lines contained functional genes of Pi2/9 and Pik loci with 14 representative isolates from those 35 ones revealed that the presence of certain AVR-Piz-t , AVR-Pita variants, and AVR-Pik-E + AVR-Pik-D in M. oryzae populations, and these variants negated the ability of the corresponding R genes to confer resistance. Importantly, Pi2, Pi9, and Pigm conferred broad-spectrum resistance to these local isolates. These findings reveal that the complex genetic basis of M. oryzae and some effective blast R genes should be considered in future rice blast-resistance breeding programs., 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. The reviewer YD declared a shared affiliation with several of the authors, DT, XY, ZC, and XG, to the handling editor., (Copyright © 2022 Tian, Deng, Yang, Li, Li, Zhou, Chen, Guo, Su, Luo and Yang.)

Black porgy is an important marine aquaculture fish species whose production is at the fifth position in all kinds of marine-cultured fishes in China. In this study, Illumina high-throughput sequencing technology was used to sequence the total RNA of black porgy. Sixty-one candidate SNPs (Single Nucleotide Polymorphism) were screened out and genotyped through GATK4 (Genome Analysis ToolKit) software and MALDI-TOF MS (Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry). The experimental results showed that a total of sixty SNPs were successfully genotyped, with a success rate of 98.36%. The results of principal component analysis and correlation analysis of growth traits showed that body weight was the first principal component, with a cumulative contribution rate of 74%. There were significant correlations ( p < 0.05) or extremely significant correlations ( p < 0.01) between different growth traits. The results of genetic parameter analysis and association analysis showed that scaffold12-12716321, scaffold13-4787950, scaffold2-13687576 and scaffold290-11890 were four SNPs that met the requirement of polymorphic information content and conformed to the Hardy-Weinberg equilibrium. There were significant differences between their genotype and the phenotype of growth traits. The four SNP molecular markers developed in this research will lay a foundation for further exploration of molecular markers related to the growth traits of black porgy and will provide a scientific reference for the further study of its growth mechanisms. At the same time, these molecular markers can be applied to the production practices of black porgy, so as to realize selective breeding at the molecular level and speed up the breeding process.

Ethnopharmacological Relevance: Cholestatic liver disease (CLD) is mainly characterized by cholestasis. If not treated, it will deteriorate to cholestatic hepatitis, liver fibrosis, liver cirrhosis, and even liver failure. CLD has a high clinical incidence, and limited treatment with single therapy. In the long-term clinical exploration, traditional Chinese medicine (TCM) has been corroborated with unique therapeutic effects on the CLD process., Aim of This Review: This paper summarizes the effective single and compound TCMs for the treatment of CLD. According to 4 important clinical stages of CLD: cholestasis, hepatitis, liver fibrosis, liver cirrhosis, pharmacological effects and mechanisms of 5 typical TCM examples are reviewed, aims to provide basis for clinical drug selection in different processes of CLD., Materials and Methods: Relevant scientific articles regarding therapeutic effects of TCM for the CLD were collected from different databases. We collated three single herbs including Artemisia scoparia Waldst. et Kit. or Artemisia capillaris Thunb. (Artemisiae Scopariae Herba, Yin Chen in Chinese), Paeonia lactiflora Pall. or Paeonia veitchii Lynch. (Paeoniae radix rubra, Chi Shao in Chinese), Poria cocos (Schw.) Wolf (Poria, Fu Ling in Chinese), and two compound herbs of Huang Qi Decoction (HQD) and Yin Chen Hao Decoction (YCHD) to studied and analyzed., Results: We proposed five promising TCMs treatments for the important developmental stages of CLD. Among them, Yin Chen is an essential medicine for protecting liver and gallbladder, and its TCM prescription is also a promising strategy for cholestasis. Based on clinical evidence, high-dose application of Chi Shao is a clinical special treatment of cholestasis hepatitis. Fu Ling can regulate immune cells and increase antibody levels in serum, which is expected to be an emerging therapy to prevent cholestatic liver fibrosis to cirrhosis. HQD can be used as routine clinical medicine for liver fibrosis. In addition, YCHD can exert better comprehensive advantages with multiple components, can treat the whole course of CLD and prevent it from developing to the end-stage., Conclusion: Yin Chen, Chi Shao, Fu Ling, HQD and YCHD have shown good clinical efficacy in controlling the development of CLD. Clinically, it is easier to curb the development of CLD by adopting graded diagnosis and treatment measures. We suggest that CLD should be risk stratified in clinical treatment to ensure personalized treatment for patients, so as to slow down the development of the disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Aucklandiae Radix (AR) and Vladimiriae Radix (VR) were used to treat gastrointestinal, liver and gallbladder diseases at practice. In most conditions, VR was used to be a substitute of AR or a local habit may attribute to the same main active ingredients Costunolide and Dehydrocostus lactone, which presented many similar pharmacological activities. However, other different lactone compounds in AR and VR also play a role in disease treatment, so the difference in therapeutic effects of AR and VR in related diseases needs to be further studied., Aims of the Study: Revealing the differences between the chemical compounds of the total lactone extracts of AR and VR (TLE of AR and VR) and the differences in the protective effects of cholestatic liver injury to ensure rational use of AR and VR., Study Design and Methods: The macroporous adsorption resin was used to purify and enrich the lactone compounds to obtain the total lactone extracts of AR and VR. HPLC-PDA was used to obtain the data to establish chemical fingerprint and chemometric analysis to compare similarities and differences between TLE of AR and VR. The pharmacodynamic experiment revealed how TLE of AR and VR to show protect effects on cholestatic liver injury., Results: Similarity analysis results showed TLE of AR and VR had a high similarity (>0.9). Nevertheless, difference analysis results showed 4 compounds, Costunolide, Dehydrocostus lactone, 3β-acetoxy-11β-guaia-4 (15), 10 (14)-diene-12,6α-olide and vladinol F may contribute to the differences between them. The pharmacodynamics experiments results showed the TLE of AR and VR affected the different liver cholate-associated transporters mRNA expression (TLE of AR up-regulated CYP7A1, TLE of VR down-regulated FXR and BSEP), the TLE of AR and VR had an effect to regulate biochemical indicators (AST, ALT, ALP, TBA) of liver function, and TLE of VR was better than TLE of AR in reducing the expression of inflammatory factors (IL-6 and IL-1β)., Conclusion: The liver protection of AR and VR have been confirmed, but the differences of material basis and mechanism of drug efficacy needed further study to guarantee formulation research and provide theoretical references for clinical rational applications of AR and VR., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Low-temperature-deposited, transparent, high-barrier-performance atomic layer deposition (ALD) Al 2 O 3 films are widely utilized to protect organic optoelectronic devices. However, because the internal compression residual stresses result in poor mechanical properties, these films are unable to realize independent encapsulation. In this work, we propose a pre-bending and substrate thermal expansion process to fabricate low-residual-stress ALD-Al 2 O 3 films by multistep adjustment of mechanical equilibrium homeostasis, compare and analyze the key properties of the films to determine the optimal processing conditions, and adjust the surface area differences between the film and the substrate to acquire a flat-bottom encapsulation substrate. Therefore, fewer cracks form in ALD-Al 2 O 3 deposited at 40 °C, and no significant increase in the water-vapor-transmission rate (WVTR) occurred after multiple bending processes at a 3 mm radius. Furthermore, both the bending radius for the first crack generation and crack saturation density were optimal, resulting in excellent mechanical stability, and a bending radius of 1 mm was achieved. Finally, we confirm the feasibility of the monolayer ALD-Al 2 O 3 prepared by our process for applications in OLEDs. The encapsulated OLED maintained 94% of its initial efficiency after 10 days of bending in a harsh environment at 30 °C and 90% relative humidity.

Study Design: Retrospective study., Objective: The aim of this study was to assess long-term radiographic and clinical outcomes in Lenke 5C adolescent idiopathic scoliosis (AIS) patients after posterior selective fusion., Methods: Lenke 5C AIS patients who underwent posterior selective thoracolumbar/lumbar (TL/L) fusion in our hospital from January 2007 to January 2010 were recruited. Radiographic parameters were measured preoperatively and at the 3-month, 1-year, 2-year, 5-year, and 10-year follow-ups. The SRS-22 (Scoliosis Research Society) questionnaire was used to assess the clinical outcomes., Results: We included 37 patients who underwent posterior selective TL/L fusion surgery in our study, and the mean follow-up time was 11.26 ± 0.85 years. The average preoperative Cobb angles of the thoracic and TL/L curves were 24.0 ± 9.0° and 45.4 ± 6.3°, respectively, which were corrected to 12.2° and 12.4° at the 3-month follow-up postoperatively, with correction losses of 2.2° and 1.5° at the 10-year follow-up. In the sagittal plane, the degree of thoracic kyphosis (TK) gradually increased over the follow-up period. The proximal junctional angle (PJA) also gradually increased from 6.7 ± 4.6 to 13.7 ± 5.6 during the follow-up period. For the clinical outcomes, correction surgery improved the SRS-22 scores in each domain, especially in the self-image domain., Conclusions: Posterior selective TL/L fusion can effectively correct spinal deformities, leading to stable outcomes for 10 years postoperatively. During the follow-up period, the degree of TK presented an increasing trend that remained almost constant after the 1-year follow-up. Moreover, the variation in the PJA was highly significant in the postoperative period, and it showed an increasing trend until the 2-year follow-up.

The blocking of gastric mucosal intestinal metaplasia (IM) has been considered to be the pivotal method to control the occurrence of gastric cancer. However, there is still a lack of effective therapeutic agent. Here, we developed mucus-penetrating liposome system by covering surface with polyethylene glycol (PEG) chains (hydrophilic and electroneutral mucus-inert material) to co-delivery candidate drugs combination. Then studied the impact on the transmucus performance of different conformations, which were constructed by controlling the density of PEG chains on the surface. The results showed that the particle size of 5%PEG-Lip was less than 120 nm, the polydispersity index was less than 0.3, and the surface potential tended to be neutral. The D value (long chain spacing) of 5% PEG-Lip was 3.25 nm, which was close to the R F value (diameter of spherical PEG long chain group without external force interference) of 3.44 nm, and the L value (extended length) was slightly larger than 3.44 nm. In this case, PEG showed mushroom-brush transitional conformation on the surface of liposomes. This conformation was not only promoted stable delivery, but also shielded the capture of mucus more favorably, leading to a more unrestricted transportation in mucus. The further in vivo experimental results demonstrated the rapid distribution of liposomes, which gradually appeared both in the superficial and deep glandular of mucosa and gland cells at 1 h and absorbed into the cell cytoplasm at 6 h. The 5% PEG-Lip with the mushroom-brush transitional configuration recalled abnormal organ index and improved inflammation and intestinal metaplasia. The modified PEG conformation assay presented here was more suitable for liposomes. This PEG-modified liposome system has potential of mucus-penetrating and provides a strategy for local treatment of gastric mucosal intestinal metaplasia., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To test the feasibility and effectiveness of a multifaceted intervention administered through school-based health centers (SBHCs) to improve asthma control for children in high-poverty schools with not well controlled asthma., Methods: Students 4-14 years old with persistent asthma were enrolled from three SBHCs. The centers' advanced practice providers received training on evidence-based asthma guidelines. Students randomized to the intervention received directly observed therapy of their asthma controller medication, medication adjustments as needed by the centers' providers, and daily self-management support. Students randomized to usual care were referred back to their primary care provider (PCP) for routine asthma care., Results: We enrolled 29 students. Students in the intervention group received their controller medication 92% of days they were in school. Ninety-four percent of follow-up assessments were completed. During the study, 11 of 12 intervention students had a step-up in medication; 2 of 15 usual care students were stepped up by their PCP. Asthma Control Test scores did not differ between groups, although there were significant improvements from baseline to the 7 month follow-up within each group (both p  < .01). Both FEV 1 % predicted and FEV 1 /FVC ratio significantly worsened in the usual care group (both p  = .001), but did not change in the intervention group ( p  = .76 and .28 respectively)., Conclusions: Our pilot data suggest that a multifaceted intervention can be feasibly administered through SBHCs in communities with health disparities. Despite the small sample size, spirometry detected advantages in the intervention group. Further study is needed to optimize the intervention and evaluate outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT03032744.

The essential oil from Vladimiriae Radix (VEO) is a medicinal natural product with anti-ulcer activity. A novel gastroretentive drug delivery system was developed by preparing the hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex incorporated into chitosan nanoparticles (V-CD/NPs), to improve the bioavailability of VEO and its protective effect on gastric mucosa. The optimum preparation process of V-CD/NPs was obtained by Plackett-Burman and Box-Behnken response surface methodology. The resulting V-CD/NPs gained a suitable positive potential and small particle size, and showed stability in simulated gastric fluid, whose morphology and in vitro drug release profiles had a pH-sensitivity. Besides, V-CD/NPs was proved to strongly bind with mucin, and in vivo imaging revealed that it could be retained in the stomach for more than 8 h. The results of drug concentration in gastric tissues showed that the sequential loading of inclusion complex/nanoparticles promoted the local absorption of VEO in gastric tissues, which was favorable to reach the effective therapeutic concentration in the lesioned mucosa area. In comparison to VEO and V-CD, the callback effect of V-CD/NPs on 1L-1β, 1L-6, TNF-α, NF-κB, MDA and SOD was comparable to cimetidine, and V-CD/NPs outperformed in gastric mucosal protection. Therefore, the gastroretentive drug delivery system developed in our study effectively enhanced the anti-ulcer activity of VEO, which could be a promising strategy for the prevention and treatment of the acute gastric mucosal injury., (Copyright © 2021. Published by Elsevier B.V.)

Papillary thyroid carcinoma (PTC) is a highly heterogeneous malignancy with diverse prognoses. Ferroptosis is a new type of cell death dependent on iron. Nevertheless, the predictive ability of ferroptosis-related genes for PTC is unclear. Based on the mRNA expression information from The Cancer Genome Atlas, we compared tumor and normal tissues in terms of the gene expression, for identifying differentially expressed genes (DEGs). Then, the risk score of a 5-gene signature was calculated and a prognostic model was established to test the predictive value of this gene signature by virtue of the LASSO Cox regression. The 5 genes were validated in PTC tissues by RT-qPCR.At last, functional analysis was implemented to investigate the underlying mechanisms. We found a total of 45 ferroptosis-related genes expressed differentially between tumor and normal tissues. 6 DEGs exhibited a significant relevance to the overall survival (OS) ( P < 0.05). We classified patients into group with high risk and group with low risk based on the median risk score of a 5-gene signature. Patients in the group with low risk presented a remarkably higher OS relative to the group with high risk ( P < 0.01). The Cox regression analysis displayed the independent predictive ability of the risk score. The receiver operating characteristic analysis helped to validate the predictive power owned by the gene signature. After validation, the 5 genes were abnormally expressed between PTC and normal tissues. Functional analysis showed two groups had different immune status. A new ferroptosis-related gene signature can predict the outcomes of PTC patients.

Background: Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous malignant cancer with poor prognosis. Pyroptosis is defined as a novel inflammation-dependent programmed cell death. However, the pyroptosis-associated gene expression in HNSCC and their relationship with prognosis are still indistinct., Material and Methods: We acquired the mRNA expression information of HNSCC patients from publicly available TCGA and GEO databases. We compared the tumor issues and adjacent normal tissues in terms of the gene expression for the purpose of identifying differentially expressed genes (DEGs). Based on these genes, we established a risk signature by the LASSO Cox regression in the TCGA cohort and validated the results in a GEO cohort. We also verified the levels of relevant mRNA expression in the model by RT-qPCR analysis. Eventually, functional enrichment approach was carried out to explore the potential mechanisms., Results: Our team found a total of 18 differentially expressed genes (DEGs) between the HNSCC and healthy samples, and 4 DEGs displayed a remarkable association with the overall survival (OS) (P < 0.05). A 4-gene signature was constructed, presenting beneficial forecast power in both TCGA and GEO cohorts. Our team categorized patients into a group with high risk and another group with low risk as per the average risk value of the 4-gene feature. The individuals in the low risk group displayed a notably greater OS compared with the high risk one (P < 0.01). The Cox regression study demonstrated the independent forecast capability of the risk score. The receiver operating characteristic approach facilitated the verification of the forecast function of the gene signature. Posterior to verification, 4 genes were aberrantly expressed in the HNSCC and healthy samples. Functional study displayed that these groups presented diverse immunity conditions., Conclusion: Pyroptosis-associated genes are pivotal for the prognosis of HNSCC and can serve as potential therapeutic targets., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Qian et al.)

This study aimed to investigate the applicability of carbon nanoparticle tracers in the lateral neck lymph nodes of CN1bx patients with papillary thyroid carcinoma surgery. 73 patients with papillary thyroid carcinoma at our hospital between January 2019 to December 2019 were suspected metastasis in the lateral neck lymph node before surgical treatment. During the operation, carbon nanoparticle tracers were used as black staining tracers for the lateral neck lymph nodes to detect metastasis in each Compartment of the neck. The lateral Compartment is defined as level ll-V The black-stained lymph nodes, dyed by Carbon nanoparticle tracers, and non-dyed lymph nodes were compared. Post-surgery paraffin pathology was adopted as the gold standard to calculate the predictive performance of the carbon nanoparticle tracers in detecting lymph node biopsy metastasis. 59 of the patients (80.8%) had lateral neck metastasis. The black-stained lymph nodes, dyed by Carbon nanoparticle tracers, in Compartment IV exhibited the highest proportions in the case number submitted for detection and in lymph nodes metastasis, followed by Compartment III. The metastasis rate of the dyed lymph nodes in areas III and IV was significantly higher than that of non-dyed lymph nodes (P < 0.05). The sensitivity and accuracy of the dyed lymph node biopsy in Compartments III-IV were 90% and 93.2%, respectively. This predictive performance was similar to that Compartments ll-V combined. In conclusion, when carbon nanoparticle tracers are used for lymph node biopsy, high sensitivity and accuracy are obtained in lateral neck compartments III-IV, making these compartments ideal for lymph node biopsy.

This study aimed to investigate the clinical efficacy of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. A total of 100 patients with hypoparathyroidism after total thyroidectomy were erolled, they were divided into the observation group (n=50), Salvia miltiorrhiza and Rhizoma chuanxiong preparation were added on the basis of traditional treatment. The control group (n=50), were treated with traditional treatment. To analyze the therapeutic effect of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. After follow-up, the recovery time of parathyroid function in the observation group was significantly shorter than the control (P<0.05). No permanent hypoparathyroidism in the observation group and 4 cases in the control, which was statistically significant (P<0.05). The serum PTH in the observation group was significantly higher than the control on the 7th, 30th day, 3rd and 6th month. The level of serum calcium in the observation group was significantly higher than the control on the 3rd, 7th and 30th day (P<0.05). Salvia miltiorrhiza and Rhizoma chuanxiong preparation has obvious effects on the treatment of hypoparathyroidism and has low adverse reactions, which is worthy of clinical application.