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Background: Postweaning is a pivotal period for brain development and individual growth. As an important chemical used in medicines, foods and beverages, sodium citrate (SC) is commonly available. Although some effects of SC exposure on individual physiology have been demonstrated, the potential long-lasting effects of postweaning dietary SC exposure on social behaviours are still elusive., Methods: Both postweaning male and female C57BL/6 mice were exposed to SC through drinking water for a total of 3 weeks. A series of behavioural tests, including social dominance test (SDT), social interaction test (SIT), bedding preference test (BPT) and sexual preference test (SPT), were performed in adolescence and adulthood. After these tests, serum oxytocin (OT) levels and gut microbiota were detected., Results: The behavioural results revealed that postweaning SC exposure decreased the social dominance of male mice in adulthood and female mice in both adolescence and adulthood. SC exposure also reduced the sexual preference rates of both males and females, while it had no effect on social interaction behaviour. ELISA results indicated that SC exposure decreased the serum OT levels of females but not males. 16S rRNA sequencing analysis revealed a significant difference in β-diversity after SC exposure in both males and females. The correlation coefficient indicated the correlation between social behaviours, OT levels and dominant genera of gut microbiota., Conclusion: Our findings suggest that postweaning SC exposure may have enduring and sex-dependent effects on social behaviours, which may be correlated with altered serum OT levels and gut microbiota composition., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Carbon emissions and water consumption are both important factors affecting sustainable development. Therefore, it is necessary to put them in the same research framework and investigate the synergy. In this study, the dynamic evolution characteristics of the synergistic effect of reducing carbon and saving water (RCSW) were analyzed. Then, taking the Yangtze River Delta Urban Agglomerations (YRDUA) as the research object, the influencing factors and specific paths of the synergistic effect were clarified. The results showed that the low-carbon emission efficiency (LCEE) had a stable synergy with the intensive utilization efficiency of water resources (IUEWR) in the YRDUA. Government financial expenditure, actual use of foreign capital, and population density were the most significant driving forces for the synergistic effect of RCSW, with q values of 0.561, 0.363, and 0.240, respectively. In addition, most of the interactions of the driving factors were nonlinear enhancement and double-factor enhancement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis., (© 2024. The Author(s).)

Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to device operating environment limitations and data privacy protection, it is frequently difficult to obtain sufficient high-quality labeled data from devices, resulting in an insufficient generalization ability of fault diagnosis model. Therefore, a high-performance federated learning framework is proposed in this work, which makes improvements in the procedure of model aggregation and local model training. In the model aggregation of central server, an optimization aggregation strategy in which forgetting Kalman filter (FKF) is combined with cubic exponential smoothing (CES) is proposed to improve the efficiency of federated learning. In the local model training of multiclient, a deep learning network combined with multiscale convolution, attention mechanism, and multistage residual connection is proposed, which is able to fully extract multiclient data features simultaneously. Meanwhile, experiments on two machinery fault datasets show that the proposed framework is capable of achieving high accuracy and strong generalization of fault diagnosis on the premise of protecting data privacy in actual industrial situations.

Introduction: Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI-ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear. Therefore, this study aimed to evaluate the protective effect of ondansetron, a 5-HT3 inhibitor, on TBI-ALI, and to explore whether the underlying mechanism is related to the regulation of TREM-1., Material and Methods: A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed., Results: TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue., Conclusions: Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

This study aims to investigate the role and mechanism of Gusong Qianggu Decoction(GSQG) in attenuating bone loss in ovariectomized mice by targeting the endoplasmic reticulum stress(ERS)-induced apoptosis of osteocytes. After the modeling of osteoporosis in mice with bilateral ovary removal(OVX), 60 mice were randomized by the random number method into six groups: sham,model, low-, medium-, and high-dose GSQG(GSQG-L, GSQG-M, and GSQG-H, respectively), and estradiol(E_2), with 10 mice in each group. The mice in each group were administrated with corresponding drugs by gavage one month after surgery and the administration lasted for 3 months. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum levels of osteocalcin(OCN), procollagen type Ⅰ N-terminal propeptide(PINP), carboxy-terminal cross-linked telopeptide of type Ⅰ collagen(CTX),and anti-tartarte acid phosphatase 5b(TRAcP-5b). Micro-CT was employed to observe the changes in bone microstructure of the distal femur. Hematoxylin-eosin(HE) staining was employed to observe the morphology of the bone tissue. RT-qPCR was conducted to determine the m RNA levels of tibial stem osteogenesis-associated genes [type Ⅰ collagen(Col-Ⅰ), alkaline phosphatase(ALP), Runtrelated transcription factor-2(Runx2), bone sialoprotein(BSP), and OCN] and bone-breaking related genes [tartrate-resistant acid phosphatase(TRAP), nuclear factor-activated T cell 1(NFATc1), and cathepsin K(CATK)]. TUNEL staining and immunohistochemistry were employed to detect the apoptosis of osteoblasts. Western blot was employed to measure the expression of ERS-related proteins glucose-regulated protein 78( Grp78), protein kinase RNA-like endoplasmic reticulum kinase( PERK), phosphorylated PERK(p-PERK),eukaryotic translation initiation factor 2 alpha(eIF2α), phosphorylated e IF2α(p-eIF2α), inositol-requiring enzyme 1 alpha(IRE1α), phosphorylated IRE1α(p-IRE1α), and activating transcription factor 6(ATF6) in the proximal tibial bone tissue. The results showed that GSQG significantly recovered the levels of OCN, PINP, TRAc P-5b, and CTX in the serum of ovariectomized mice, and Micro-CT showed that GSQG improved the bone microstructure of distal femur in a dose-dependent manner. Compared with the model group, GSQG widened and increased the bone trabeculae, restored the reticular structure with neat arrangement and enlarged interstitial gaps, and reduced the number of TUNEL-positive cells(P<0. 05, P<0. 01). Furthermore, GSQG down-regulated the expression levels of cysteine aspartate protease-3( caspase-3) and factor Bcl-2-associated X protein( Bax)(P< 0. 05,P<0. 01) and up-regulated the expression level of Bcl-2(P<0. 05, P<0. 01). The GSQG groups showed up-regulated m RNA levels of Col-Ⅰ, ALP, Runx2, BSP, and OCN(P< 0. 01) and down-regulated m RNA levels of TRAP, NFATc1, and CATK(P< 0. 05,P<0. 01). In addition, GSQG, especially GSQG-H, down-regulated the protein levels of Grp78, p-PERK, p-eIF2, p-IRE1α, and ATF6(P< 0. 05, P< 0. 01). In conclusion, GSQG can inhibit the apoptosis of osteocytes by inhibiting the Grp78/PERK/e IF2α/IRE1α/ATF6 signaling pathway in the proximal tibia tissue, thus reducing bone loss in ovariectomized mice.

Background: Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated., Purpose: This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis., Study Design: This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models., Methods: Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg body weight Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured MC3T3-E1(14) cells were exposed to H 2 O 2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis., Results: Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H 2 O 2 -induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor)., Conclusion: In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/AKT axis, offering a new therapeutic strategy for PMOP., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective. This study aims to leverage a deep learning approach, specifically a deformable convolutional layer, for staging cervical cancer using multi-sequence MRI images. This is in response to the challenges doctors face in simultaneously identifying multiple sequences, a task that computer-aided diagnosis systems can potentially improve due to their vast information storage capabilities. Approach. To address the challenge of limited sample sizes, we introduce a sequence enhancement strategy to diversify samples and mitigate overfitting. We propose a novel deformable ConvLSTM module that integrates a deformable mechanism with ConvLSTM, enabling the model to adapt to data with varying structures. Furthermore, we introduce the deformable multi-sequence guidance model (DMGM) as an auxiliary diagnostic tool for cervical cancer staging. Main results. Through extensive testing, including comparative and ablation studies, we validate the effectiveness of the deformable ConvLSTM module and the DMGM. Our findings highlight the model's ability to adapt to the deformation mechanism and address the challenges in cervical cancer tumor staging, thereby overcoming the overfitting issue and ensuring the synchronization of asynchronous scan sequences. The research also utilized the multi-modal data from BraTS 2019 as an external test dataset to validate the effectiveness of the proposed methodology presented in this study. Significance. The DMGM represents the first deep learning model to analyze multiple MRI sequences for cervical cancer, demonstrating strong generalization capabilities and effective staging in small dataset scenarios. This has significant implications for both deep learning applications and medical diagnostics. The source code will be made available subsequently., (© 2024 Institute of Physics and Engineering in Medicine.)

Sepsis is a life-threatening illness caused by the dysregulated host response to infection. Nevertheless, our current knowledge of the microbial landscape in the blood of septic patients is still limited. Next-generation sequencing (NGS) is a sensitive method to quantitatively characterize microbiomes at various sites of the human body. In this study, we analyzed the blood microbial DNA of 22 adult patients with sepsis and 3 healthy subjects. The presence of non-human DNA was identified in both healthy and septic subjects. Septic patients had a markedly altered microbial DNA profile compared to healthy subjects over α- and β-diversity. Unexpectedly, the patients could be further divided into two subgroups (C1 and C2) based on β-diversity analysis. C1 patients showed much higher bacteria, viruses, fungi, and archaea abundance, and a higher level of α-diversity (Chao1, Observed and Shannon index) than both C2 patients and healthy subjects. The most striking difference was seen in the case of Streptomyces violaceusniger , Phenylobacterium sp. HYN0004 , Caulobacter flavus , Streptomyces sp. 11-1-2 , and Phenylobacterium zucineum , the abundance of which was the highest in the C1 group. Notably, C1 patients had a significantly poorer outcome than C2 patients. Moreover, by analyzing the patterns of microbe-microbe interactions in healthy and septic subjects, we revealed that C1 and C2 patients exhibited distinct co-occurrence and co-exclusion relationships. Together, our study uncovered two distinct microbial signatures in the blood of septic patients. Compositional and ecological analysis of blood microbial DNA may thus be useful in predicting mortality of septic patients., 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.)

Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated., Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways., Results: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10 -6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10 -3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified., Conclusions: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby., Plain Language Summary: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer., (© 2023 American Cancer Society.)

Study Objectives: To investigate whether sleep traits are associated with the risk of biological aging using a case-control design with Mendelian randomization (MR) analyses., Methods: We studied 336 559 participants in the UK Biobank cohort, including 157 227 cases of accelerated biological aging and 179 332 controls. PhenoAge, derived from clinical traits, estimated biological ages, and the discrepancies from chronological age were defined as age accelerations (PhenoAgeAccel). Sleep behaviors were assessed with a standardized questionnaire. propensity score matching matched control participants to age-accelerated participants, and a conditional multivariable logistic regression model estimated odds ratio (OR) and 95% confidence intervals (95% CI). Causal relationships between sleep traits and PhenoAgeAccel were explored using linear and nonlinear MR methods., Results: A U-shaped association was found between sleep duration and PhenoAgeAccel risk. Short sleepers had a 7% higher risk (OR = 1.07; 95% CI: 1.03 to 1.11), while long sleepers had an 18% higher risk (OR = 1.18; 95% CI: 1.15 to 1.22), compared to normal sleepers (6-8 hours/day). Evening chronotype was linked to higher PhenoAgeAccel risk than morning chronotype (OR = 1.14; 95% CI: 1.10 to 1.18), while no significant associations were found for insomnia or snoring. Morning chronotype had a protective effect on PhenoAgeAccel risk (OR = 0.87, 95% CI: 0.79 to 0.95) per linear MR analysis. Genetically predicted sleep duration showed a U-shaped relationship with PhenoAgeAccel, suggesting a nonlinear association (pnonlinear < 0.001)., Conclusions: The study suggests that improving sleep can slow biological aging, highlighting the importance of optimizing sleep as an intervention to mitigate aging's adverse effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

N 6 -methyladenosine (m 6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m 6 A-associated single-nucleotide polymorphisms (m 6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m 6 A-SNPs and examined the association of these m 6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m 6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m 6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m 6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m 6 A modification site of AK9 and significantly reduced AK9 expression (β = -0.15, p = 2.78 × 10 -8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m 6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m 6 A modification., (© 2023 Wiley Periodicals LLC.)

Introduction: NBP is a compound isolated from celery seeds, which was approved by the National Medical Products Administration in 2002 for clinical treatment of ischemic stroke. However, in brain ischemia/reperfusion (I/R) injury, the related research on mitochondrial dynamics and its mechanism of action of NBP still need to be further studied. The aim of this study was to assess NBP on cerebral pathology in ischemic stroke in vivo , with a specific focus on the molecular mechanisms of how NBP promotes mitochondrial fusion. Methods: Male C57BL/6 mice were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Pre-ischemia, NBP was administered through intraperitoneal (i.p.) injection for 7 days. Results: Our findings demonstrated that NBP effectively reduced infarct volume, improved neurological dysfunction, enhanced cerebral blood flow, and promoted mitochondrial fusion in mice subjected to MCAO/R. More importantly, the pro-fusion effects of NBP were found to be linked to the activation of AMPK/Mfn1 pathway, and with the activation of neurological function, which was partially eliminated by inhibitors of AMPK. Discussion: Our results revealed that NBP is a novel mitochondrial fusion promoter in protecting against ischemic stroke through the AMPK-mediated Mfn1. These findings contribute to the understanding of novel mechanisms involved in the protection of neurological function following NBP treatment for ischemic stroke., 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 Zhu, Dong, Qin, Liu, Shi and Wan.)

Key Message: The transcriptome is beneficial for dissecting the mechanism of millet in response to low potassium stress and SiSnRK2.6 was identified as a potential target for improving low potassium stress tolerance. Foxtail millet (Setaria italica L.), which originated in China, has high nutrient utilization character. Nevertheless, the molecular mechanism of its tolerance to low potassium stress is largely unclear. In this research, the low potassium tolerant variety "Yugu28" was screened out by low potassium stress treatment, and the transcriptome of "Yugu28" under low potassium stress was comprehensively analyzed. A total of 4254 differentially expressed genes (DEGs) were identified, including 1618 up-regulated and 2636 down-regulated genes, respectively. In addition, there were 302 transcription factor (TF) genes in the DEGs and MYB TFs accounted for the highest proportion, which was 14.9%. After functional analysis of all DEGs, a total of 7 genes involved in potassium transport and potassium ion channels and 50 genes corresponding to hormones were screened. The expression levels of randomly selected 17 DEGs were verified by qRT-PCR and the results coincided well with the RNA-seq analysis, indicating the reliability of our transcriptome data. Moreover, one of the ABA signaling pathway genes, SiSnRK2.6, was identified and selected for further functional verification. Compared with the wild type, transgenic rice with ecotopic expression of SiSnRK2.6 showed remarkably increased root length and root number, indicating that overexpression of SiSnRK2.6 can enhance the resistance of transgenic plants to low potassium stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Our previous studies have confirmed that resveratrol (RSV) can prevent the development of osteoarthritis through a variety of mechanisms, such as apoptosis inhibition, autophagy induction and SIRT 1 activation. However, the pharmaceutical application of RSV is mainly limited by its low bioavailability. Here, we designed and synthesized RSV-loaded poly (D, l-lactide-coglycolide acid) (PLGA)-nanoparticles (NPs). The average particle size, polydispersity index and positive charge of RSV-loaded PLGA NPs were 50.40 nm, 0.217 and 12.57 mV, respectively. These nanoparticles had marked encapsulation efficiency (92.35 %) and drug loading (15.1 %) for RSV. It was found that RSV-loaded PLGA NPs not only inhibited the apoptosis of chondrocytes induced by IL-1, but also rescued GAG loss in vitro. Pharmacokinetic data showed that RSV-loaded PLGA NPs demonstrated a significantly profound and prolonged concentration profile in joint tissues, with quantifiable RSV concentrations over 35 days. The therapeutic effects of RSV-loaded PLGA NPs were then examined in rat osteoarthritis models. In vitro magnetic resonance imaging results showed that RSV-loaded PLGA NPs treatment dramatically reduced both T1ρ and T2 relaxation times at 4, 8, 12 weeks during administration, implying that cartilage destruction was alleviated. Histological assessments showed that RSV-loaded PLGA NPs significantly improved osteoarthritis symptoms. Gene expression analysis revealed that osteoarthritis mediator genes were downregulated in rats treated with RSV-PLGA NPs. Mechanistic studies indicated that RSV-loaded PLGA NPs inhibit apoptosis and promote autophagy. Collectively, this study demonstrates that intra-articular delivery of RSV via PLGA NPs might be an effective therapeutic approach for osteoarthritis., Competing Interests: The authors have declared that no conflict of interest exists., (© 2023 The Authors.)

Objective: To investigate the correlation of peripheral blood platelet/lymphocyte ratio (PLR) with Treg and Th17 and its influence on prognosis in newly diagnosed multiple myeloma (MM)., Methods: One hundred thirty-five newly diagnosed multiple myeloma patients admitted to the Department of Hematology of Zhengzhou People's Hospital from June 2015 to October 2022 were selected as MM group. Clinical data included sex, age, immune typing, ISS stage, blood calcium (Ca), albumin (ALB), hemoglobin (Hb), PLR, LDH, β 2 microglobulin (β 2 -MG), Treg and Th17 levels. Sixty healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. PLR, Treg and Th17 levels in MM group and control group were compared. Pearson was used to analyze the correlation between PLR and Treg, Th17. The relationship between MM patients with different PLR and clinical features and prognosis was analyzed., Results: The PLR and Th17 of MM patients were significantly higher than that of control group, and Treg was significantly lower than that of control group ( P <0.05). In MM patients, PLR was negatively correlated with Treg ( r =-0.616), and PLR was positively correlated with Th17 ( r =0.555). Using mean PLR=132.72 as the boundary, 135 MM patients were divided into high PLR group ( n =54) and low PLR group ( n =81). In MM patients with high PLR, ISS stage, ALB and Treg were significantly higher than those in low PLR group, while Th17 was significantly lower than those in low PLR group ( P <0.05). By univariate and COX regression analysis, PLR was an independent prognostic risk factor for newly diagnosed MM patients ( P <0.05). MM patients with high PLR had better PFS and OS, and the difference was statistically significant compared with MM patients with low PLR ( P <0.05). 65 patients admitted from June 2015 to December 2018 were used as the training set, and 70 patients admitted from January 2019 to October 2022 were used as the validation set. The OS of MM patients with different PLR were compared respectively. The results showed that the conclusions of the training set and the validation set were consistent. PLR with high expression had higher OS ( P <0.01)., Conclusion: PLR is correlated with Treg and Th17 in newly diagnosed MM patients, and high PLR has better prognosis. PLR can be used to evaluate the prognosis of MM patients.

Chromobox protein homolog 2 (CBX2) exerts a multifaceted impact on the progression of aggressive cancers. The proteasome-dependent pathway is crucial for modulating CBX2 regulation, while the specific regulatory roles and mechanisms of deubiquitinating enzymes targeting CBX2 remain poorly understood. Mass spectrometry analysis identified ubiquitin-specific peptidase 27X (USP27X) as a deubiquitinating enzyme that targets CBX2. Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis. Furthermore, it has been revealed that glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 and leading to further stabilization of the CBX2 protein. Clinically, the co-expression of high levels of USP27X and CBX2 in breast cancer tissues is indicative of a poor prognosis for patients with this disease. These findings collectively underscore the critical regulatory role played by USP27X in modulating CBX2, thereby establishing the GSK3β-USP27X-CBX2 axis as a pivotal driver of malignant progression in breast cancer., (© 2023. The Author(s).)

Magnesium (Mg) batteries have garnered considerable interest because of their safety characteristics and low costs. However, the practical application of Mg batteries is hindered by the slow diffusion of Mg ions in the cathode materials. In this study, we prepared NiS 1.97 quantum dot composites with nitrogen doping and carbon coating (NiS 1.97 QDs@NC) using a one-step sulfurization process with NiO QDs/Ni@NC as the precursor. We applied the prepared NiS 1.97 QDs/Ni@NC-based cathodes to Mg batteries because of the large surface area of the quantum dot composite, which provided abundant intercalation sites. This design ensured efficient deintercalation of magnesium ions during charge-discharge processes. The fabricated NiS 1.97 QDs@NC displayed a high reversible Mg storage capacity of 259.1 mAh g -1 at 100 mA g -1 and a good rate performance of 96.0 mAh g -1 at 1000 mA g -1 . Quantum dot composites with large surface areas provide numerous embedded sites, which ensure effective deintercalation of Mg ions during cycling. Thus, the proposed cathode synthesis strategy is promising for Mg-ion-based energy storage systems.

Vinylene-linked covalent organic frameworks (COFs) have attracted enormous attention for photocatalytic H 2 evolution from water because of their fully conjugated structures, high chemical stabilities, and enhanced charge-carrier mobilities. In this work, two novel vinylene-linked COFs with tuned cyano contents were successfully synthesized and then employed as photocatalysts for H 2 generation. Notably, the photocatalytic H 2 production rate of the COF with the higher cyano content reached 73 μmol h -1 under visible light irradiation, which is 2.4 times higher than that with the lower content (30 μmol h -1 ). Both the experimental and computational results demonstrated that the rational design incorporating cyano groups into COF skeletons could precisely tune the corresponding energy levels, expand the visible-light absorption, and improve the photoinduced charge separation. This work not only provides a simple method for modulating the photocatalytic activities of COFs at the molecular level, but also affords interesting insights into the relationship between their structures and photocatalytic performance., (© 2023 Wiley-VCH GmbH.)

Background: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis)., Methods: In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or whole exome sequencing data. Cancer predisposing variants affecting 60 genes associated with well-established autosomal-dominant cancer-predisposition syndromes were characterised. Subsequent malignant neoplasms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 with modifications. Cause-specific late mortality was based on linkage with the US National Death Index and systematic cohort follow up. Fine-Gray subdistribution hazard models were used to estimate subsequent malignant neoplasm-related late mortality starting from the first biospecimen collection, treating non-subsequent malignant neoplasm-related deaths as a competing risk, adjusting for genetic ancestry, sex, age at diagnosis, and cancer treatment exposures. SJLIFE (NCT00760656) and CCSS (NCT01120353) are registered with ClinicalTrials.gov., Findings: 12 469 (6172 male and 6297 female) participants were included, 4402 from the SJLIFE cohort (median follow-up time since collection of the first biospecimen 7·4 years [IQR 3·1-9·4]) and 8067 from the CCSS cohort (median follow-up time since collection of the first biospecimen 12·6 years [2·2-16·6]). 641 (5·1%) of 12 469 participants carried cancer predisposing variants (294 [6·7%] in the SJLIFE cohort and 347 [4·3%] in the CCSS cohort), which were significantly associated with an increased severity of subsequent malignant neoplasms (CTCAE grade ≥4 vs grade <4: odds ratio 2·15, 95% CI 1·18-4·19, p=0·0085). 263 (2·1%) subsequent malignant neoplasm-related deaths (44 [1·0%] in the SJLIFE cohort; and 219 [2·7%] in the CCSS cohort) and 426 (3·4%) other-cause deaths (103 [2·3%] in SJLIFE; and 323 [4·0%] in CCSS) occurred. Cumulative subsequent malignant neoplasm-related mortality at 10 years after the first biospecimen collection in carriers of cancer predisposing variants was 3·7% (95% CI 1·2-8·5) in SJLIFE and 6·9% (4·1-10·7) in CCSS versus 1·5% (1·0-2·1) in SJLIFE and 2·1% (1·7-2·5) in CCSS in non-carriers. Carrying a cancer predisposing variant was associated with an increased risk of subsequent malignant neoplasm-related mortality (SJLIFE: subdistribution hazard ratio 3·40 [95% CI 1·37-8·43]; p=0·0082; CCSS: 3·58 [2·27-5·63]; p<0·0001)., Interpretation: Identifying participants at increased risk of subsequent malignant neoplasms via genetic counselling and clinical genetic testing for cancer predisposing variants and implementing early personalised cancer surveillance and prevention strategies might reduce the substantial subsequent malignant neoplasm-related mortality burden., Funding: American Lebanese Syrian Associated Charities and US National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Pesticides are applied widely to increase agricultural output and quality, however, this practice results in residual issues that not only harm the environment but also put people and animals' lives and health at risk. As a result, it is critical to find pesticide residues in a variety of sources, including crops, water supplies, and soil. Aptamers are more flexible in their synthesis and modification, have a high level of specificity, are inexpensive, and have good stability compared to conventional detection methods. They have therefore attracted a lot of interest in the industry. This study reviews the most recent aptasensor advancements in the detection of pesticide residues. Firstly, aptamers specifically binding to many pesticides are summarized. Secondly, the combination of aptasensors with colorimetric, fluorescent, surface enhanced Raman spectroscopy (SERS), resonance Light Scattering (RLS), chemiluminescence (CL), electrochemical, and electrochemiluminescence (ECL) technologies are systematically introduced, and their advantages and disadvantages are expounded. Importantly, the aptasensors for the detection of various pesticides (organochlorine, organophosphorus, neonicotinoids, carbamates, and pyrethroids) that have been developed so far are systematically analyzed and discussed. Finally, the furture prospects and challenges of the aptasensors are highlighted. It is expected to offer suggestions for the later creation of novel, highly effective and sensitive aptasensors for the detection of pesticide residues.

In this article, an adaptive iterative learning control scheme is presented for a class of nonlinear parametric strict-feedback systems with unknown state delays, aiming to achieve the point-wise tracking of desired trajectory in a finite interval. The appropriate Lyapunov-Krasovskii functions are established to compensate the influence of time-delay uncertainties on the control systems. As the main features, the proposed approach integrates the command filter into the backstepping procedure to avoid the differential explosion problem that may occur with the increase of system order, and introduces the hyperbolic tangent functions into the learning controller to handle the singularity problem thus maintaining the continuity of input signal. The results of theoretical analysis and numerical simulation demonstrate that the tracking errors at the entire period will converge to a compact set along the iteration axis. Compared with the existing works, the proposed control scheme is promising to manifest the better performance and practicability owing to the learning mechanism, the dynamic model, as well as the implementation of controller.

The gut microbiota plays a crucial role in regulating various host metabolic, immune, and neuroendocrine functions, and has a significant impact on human health. Several lines of evidence suggest that gut dysbiosis is associated with a variety of diseases, including cancer. The gut microbiota can impact the development and progression of cancer through a range of mechanisms, such as regulating cell proliferation and death, modulating the host immune response, and altering the host metabolic state. Gene regulatory programs are considered critical mediators between the gut microbiota and host phenotype, of which RNA N6-methyladenosine (m6A) modifications have attracted much attention recently. Aberrant m6A modifications have been shown to play a crucial role in cancer development. This review aims to provide an overview of the diverse roles of gut microbiota and RNA m6A modifications in cancer and highlight their potential interactions in cancer development., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Shrine et al. 1 conducted the largest multi-ancestry genome-wide meta-analysis of lung function and identified 1,020 signals associated with lung function. These provide novel insights into the genetic underpins of lung function and may inform better clinical management of respiratory disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Newborns have a high incidence of nosocomial infection (NI). We conducted a logistic regression to analyze different incubator standards and other risk factors for newborn NI, which could better help clinical choice of incubator standard., Methods: Newborns with complete necessary clinical data were included. We collected the demographic and incubator data of 76 patients (40 uninfected and 36 infected) at the Heping Hospital Affiliated to Changzhi Medical College. An analysis of variance, Pearson correlation matrix analysis, and logistic regression analysis were conducted to explore the different incubator standards and other risk factors for neonatal hospital infections. In addition, 4 machine-learning algorithms were used to predict neonatal hospital infections., Results: We found differences in the gestational age, incubator type, paternal age, and maternal age between the 2 groups. The correlation analysis only revealed a correlation between paternal age and maternal age. The logistic regression showed that gestational age [odds ratio (OR)= 0.77574, 95% confidence interval (CI): 0.583513-0.996354] and the new standard incubator (OR =0.011639, 95% CI: 0.000958-0.067897) may be protective factors for infant infection during hospitalization. Among the extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and decision tree (DT) algorithms, XGBoost had the best performance in terms of accuracy, sensitivity, specificity, and precision., Conclusions: We found early gestational age and incubator standards may be risk factors for the NIs of newborns, which might help clinicians to improve the health and safety standards for incubators. XGBoost can be used to predict newborn NIs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-171/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Importance: Certain cancer therapies are risk factors for epigenetic age acceleration (EAA) among survivors of childhood cancer, and EAA is associated with chronic health conditions (CHCs). However, small numbers of younger survivors (aged <20 years) previously evaluated have limited the ability to calculate EAA among this age group., Objective: To evaluate the change rate of epigenetic age (EA) and EAA in younger compared with older survivors and the possible association of EAA with early-onset obesity (aged <20 years), severity/burden of CHCs, and late mortality (>5 years from cancer diagnosis)., Design, Setting, and Participants: Study participants were from the St Jude Lifetime Cohort, initiated in 2007 with ongoing follow-up. The present study was conducted from April 17, 2022, to March 23, 2023. Survivors in this cohort of European ancestry with DNA methylation data were included. Cross-sectional annual changes in EA and EAA were compared across 5 different chronologic age groups: age 0 to 9 (children), 10 to 19 (adolescents), 20 to 34 (younger adults), 35 to 49 (middle-aged adults), and greater than or equal to 50 (older adults) years. Logistic regression evaluated the association between EAA and early-onset obesity or severity/burden of CHCs. Cox proportional hazards regression assessed the association between EAA and late mortality., Main Outcomes and Measures: Early-onset obesity, severity/burden of CHCs (graded using the Common Terminology Criteria for Adverse Events (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into high vs low severity/burden based on frequency and grade), and late mortality were the outcomes based on follow-up until April 2020. Expanded DNA methylation profiling increased the number of survivors younger than 20 years (n = 690). Epigenetic age was calculated primarily using the Levine clock, and EAA was derived from least squares regression of EA against chronologic age and was standardized to a z score (Levine EEA)., Results: Among 2846 participants (median age, 30.3 [IQR, 9.3-41.5] years; 53% males), the cross-sectional annual change in EA&#95;Levine was higher in children (1.63 years) and adolescents (1.14 years), and the adjusted least-squares mean of Levine EEA was lower in children (-0.22 years) and older adults (-1.70 years). Each 1-SD increase in Levine EEA was associated with increased risk of developing early-onset obesity (odds ratio [OR], 1.46; 95% CI, 1.19-1.78), high severity/burden of CHCs (OR, 1.13; 95% CI, 1.03-1.24), and late mortality (hazard ratio, 1.75; 95% CI, 1.35-2.26)., Conclusions and Relevance: The findings of this study suggest that EAA measured in children and adolescent survivors of childhood cancer is associated with early-onset obesity, severity/burden of all CHCs, and late mortality. Evaluating EAA may help identify survivors of childhood cancer at increased risk for early-onset obesity, morbidity in general, and mortality.

Background: Remarkably, the anti-cancer efficacy of immunotherapy in lung adenocarcinoma (LUAD) has been demonstrated. However, predicting the beneficiaries of this expensive treatment is still a challenge., Materials and Methods: A group of patients (N = 250) diagnosed with LUAD and receiving immunotherapy were retrospectively studied. They were randomly divided into a training dataset (80%) and a test dataset (20%). The training dataset was utilized to train neural network models to predict patients' objective response rate (ORR), disease control rate (DCR), responders (progression-free survival time > 6 months), and overall survival (OS) possibility, which were validated by both the training and test datasets and packaged into a tool later., Results: In the training dataset, the tool scored 0.9016 area under the receiver operating characteristic (AUC) curve on ORR judgment, 0.8570 on DCR, and 0.8395 on responder prediction. In the test dataset, the tool scored 0.8173 AUC on ORR, 0.8244 on DCR, and 0.8214 on responder determination. As for OS prediction, the tool scored 0.6627 AUC in the training dataset and 0.6357 in the test dataset., Conclusions: This immunotherapy efficacy predictive tool for LUAD patients based on neural networks could predict their ORR, DCR, and responder well., 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 © 2023 Li, Fu, Gao, Lu, Jin, Qin, Zhang, Wu, Li and Wang.)

Background: DNA methylation (DNAm) plays an important role in lipid metabolism, however, no epigenome-wide association study (EWAS) of lipid levels has been conducted among childhood cancer survivors. Here, we performed EWAS analysis with longitudinally collected blood lipid data from survivors in the St. Jude lifetime cohort study., Methods: Among 2052 childhood cancer survivors of European ancestry (EA) and 370 survivors of African ancestry (AA), four types of blood lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG), were measured during follow-up beyond 5-years from childhood cancer diagnosis. For the exposure EWAS (i.e., lipids measured before blood draw for DNAm), the DNAm level was an outcome variable and each of the blood lipid level was an exposure variable; vice versa for the outcome EWAS (i.e., lipids measured after blood draw for DNAm)., Results: Among EA survivors, we identified 43 lipid-associated CpGs in the HDL (n = 7), TC (n = 3), and TG (n = 33) exposure EWAS, and 106 lipid-associated CpGs in the HDL (n = 5), LDL (n = 3), TC (n = 4), and TG (n = 94) outcome EWAS. Among AA survivors, we identified 15 lipid-associated CpGs in TG exposure (n = 6), HDL (n = 1), LDL (n = 1), TG (n = 5) and TC (n = 2) outcome EWAS with epigenome-wide significance (P < 9 × 10 -8 ). There were no overlapping lipids-associated CpGs between exposure and outcome EWAS among EA and AA survivors, suggesting that the DNAm changes of different CpGs could be the cause or consequence of blood lipid levels. In the meta-EWAS, 12 additional CpGs reached epigenome-wide significance. Notably, 32 out of 74 lipid-associated CpGs showed substantial heterogeneity (P het  < 0.1 or I 2  > 70%) between EA and AA survivors, highlighting differences in DNAm markers of blood lipids between populations with diverse genetic ancestry. Ten lipid-associated CpGs were cis-expression quantitative trait methylation with their DNAm levels associated with the expression of corresponding genes, out of which seven were negatively associated., Conclusions: We identified distinct signatures of DNAm for blood lipids as exposures or outcomes and between EA and AA survivors, revealing additional genes involved in lipid metabolism and potential novel targets for controlling blood lipids in childhood cancer survivors., (© 2023. The Author(s).)

Background/objective: The third-generation epidermal growth factor receptor ( EGFR ) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR -mutated non-small cell lung cancer (NSCLC). Thus, detection of the EGFR T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting EGFR T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs., Methods: A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples., Results: The results showed that the sensitivity and the specificity of EGFR T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of EGFR T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher EGFR T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% ( P = 0.016) or average value of 3.16% ( P = 0.010)., Conclusion: Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of EGFR T790M in the plasma samples of NSCLC patients., Competing Interests: Author GY was employed by Shanghai Yuanqi Biomedical Technology Co., Ltd. The remaining 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 © 2023 Zhang, Hu, Wang, Song, Hu, Ma, Yang, Li, Qin, Wang, Lv, Li, Zhang, Zhang, Wu, Yao and Zhang.)

A large number of studies in recent years indicate that osteocytes are the orchestrators of bone remodeling by regulating both osteoblast and osteoclast activities. Oxidative stress-induced osteocyte apoptosis plays critical roles in the pathological processes of postmenopausal osteoporosis. Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis. However, whether resveratrol regulates osteocyte apoptosis via autophagy remains largely unknown. The effects of resveratrol on regulating osteocyte apoptosis and autophagy were analyzed both in vivo and in vitro. In vitro, cultured MLO-Y4 cells were exposed to H 2 O 2 with or without resveratrol. In vivo, an ovariectomy-induced osteoporosis model was constructed in rats with or without daily intraperitoneal injection of 10 mg/kg body weight resveratrol. It was found that resveratrol attenuated H 2 O 2 -induced apoptosis through activating autophagy in cultured MLO-Y4 cells, which was mediated by the dissociation of Beclin-1/Bcl-2 complex in AMPK/JNK1-dependent pathway, ultimately regulating osteocytes function. Furthermore, it was shown that resveratrol treatment reduced osteocytes oxidative stress, inhibited osteocytes apoptosis and promoted autophagy in ovariectomized rats. Our study suggests that resveratrol protects against oxidative stress by restoring osteocytes autophagy and alleviating apoptosis via AMPK/JNK1 activation, therefore dissociating Bcl-2 from Beclin-1., (© 2023. The Author(s).)

Background: Auxin performs important functions in plant growth and development processes, as well as abiotic stress. Small auxin-up RNA (SAUR) is the largest gene family of auxin-responsive factors. However, the knowledge of the SAUR gene family in foxtail millet is largely obscure., Results: In the current study, 72 SiSAUR genes were identified and renamed according to their chromosomal distribution in the foxtail millet genome. These SiSAUR genes were unevenly distributed on nine chromosomes and were classified into three groups through phylogenetic tree analysis. Most of the SiSAUR members from the same group showed similar gene structure and motif composition characteristics. Analysis of cis-acting elements showed that many hormone and stress response elements were identified in the promoter region of SiSAURs. Gene replication analysis revealed that many SiSAUR genes were derived from gene duplication events. We also found that the expression of 10 SiSAURs was induced by abiotic stress and exogenous hormones, which indicated that SiSAUR genes may participated in complex physiological processes., Conclusions: Overall, these results will be valuable for further studies on the biological role of SAUR genes in foxtail development and response to stress conditions and may shed light on the improvement of the genetic breeding of foxtail millet., (© 2023. The Author(s).)

Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10 -3 ) after adjusting for plurality, sex and other potential confounding factors. In particular, blastocyst-stage embryo transfer was associated with shorter LTL (beta, -0.54, P = 2.69 × 10 -3 ) in children conceived by ART. The association was validated in 586 children conceived by ART from five centers using different LTL quantification methods (that is, WGS or qPCR). Blastocyst-stage embryo transfer resulted in shorter telomere lengths in mice at postnatal day 1 (P = 2.10 × 10 -4 ) and mice at 6 months (P = 0.042). In vitro culturing of mice embryos did not result in shorter telomere lengths in the late cleavage stage, but it did suppress telomerase activity in the early blastocyst stage. Our findings demonstrate the need to evaluate the long-term consequences of ART, particularly for aging-related phenotypes, in children conceived by ART., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: At present, immunotherapy is a very promising treatment method for lung cancer patients, while the factors affecting response are still controversial. It is crucial to predict the efficacy of lung squamous carcinoma patients who received immunotherapy., Methods: In our retrospective study, we enrolled lung squamous carcinoma patients who received immunotherapy at Beijing Chest Hospital from January 2017 to November 2021. All patients were grouped into two cohorts randomly, the training cohort (80% of the total) and the test cohort (20% of the total). The training cohort was used to build neural network models to assess the efficacy and outcome of immunotherapy in lung squamous carcinoma based on clinical information. The main outcome was the disease control rate (DCR), and then the secondary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)., Results: A total of 289 patients were included in this study. The DCR model had area under the receiver operating characteristic curve (AUC) value of 0.9526 (95%CI, 0.9088-0.9879) in internal validation and 0.9491 (95%CI, 0.8704-1.0000) in external validation. The ORR model had AUC of 0.8030 (95%CI, 0.7437-0.8545) in internal validation and 0.7040 (95%CI, 0.5457-0.8379) in external validation. The PFS model had AUC of 0.8531 (95%CI, 0.8024-0.8975) in internal validation and 0.7602 (95%CI, 0.6236-0.8733) in external validation. The OS model had AUC of 0.8006 (95%CI, 0.7995-0.8017) in internal validation and 0.7382 (95%CI, 0.7366-0.7398) in external validation., Conclusions: The neural network models show benefits in the efficacy evaluation of immunotherapy to lung squamous carcinoma patients, especially the DCR and ORR models. In our retrospective study, we found that neoadjuvant and adjuvant immunotherapy may bring greater efficacy benefits to patients., 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, Ma, Fu, Gao, Qin, Wu, Zhang, Wang, Pan and Liu.)

Background: Mosaic chromosomal alterations (mCAs) detected from blood-derived DNA are large structural alterations of clonal haematopoietic origin and are associated with various diseases, such as haematological malignancies, infections, and solid cancers. We aimed to investigate whether mCAs contribute to the risk of lung cancer and modify the effect of polygenic risk score (PRS) on lung cancer risk prediction., Methods: The blood-derived DNA of patients with lung cancer and cancer-free controls with Chinese ancestry from the Nanjing Lung Cancer Cohort (NJLCC) study were genotyped with a Global Screening Array, and mCAs were detected with the Mosaic Chromosomal Alterations (MoChA) pipeline. mCA call sets of individuals with European ancestry were obtained from the prospective cohort UK Biobank (UKB) study, including documented incident lung cancer. All patients with lung cancer from the NJLCC study (aged 15 years or older at diagnosis) were histopathologically confirmed as new lung cancer cases by at least two pathologists and were free of chemotherapy or radiotherapy before diagnosis. Participants with incident lung cancer (aged 37-73 years at assessment) diagnosed after recruitment to the UKB were identified through linkage to national cancer registries. Logistic regression and Cox proportional hazard models were applied to evaluate associations between mCAs and risk of lung cancer in the NJLCC (logistic regression) and UKB (Cox proportional hazard model) studies., Findings: The NJLCC study included 10 248 individuals (6445 [62·89%] men and 3803 [37·11%] women; median age 60·0 years [IQR 53·0-66·0]) with lung cancer and 9298 individuals (5871 [63·14%] men and 3427 [36·86%] women; median age 60·0 years [52·0-65·0]) without lung cancer recruited from three sub-regions (north, central, and south) across China between April 15, 2003, and Aug 18, 2017. The UKB included 450 821 individuals recruited from 22 centres across the UK between March 13, 2006, and Nov 1, 2010, including 2088 individuals with lung cancer (1075 [51·48%] men and 1013 [48·52%] women; median age 63·0 years [IQR 59·0-66·0]), and 448 733 participants were free of lung cancer (204 713 [45·62%] men and 244 020 [54·38%] women; median age 58·0 years [IQR 50·0-63·0]). Compared with non-carriers of mosaic losses, carriers had a significantly increased risk of lung cancer in the NJLCC (odds ratio [OR] 1·81, 95% CI 1·43-2·28; p=6·69 × 10 -7 ) and UKB (hazard ratio [HR] 1·40, 95% CI 1·00-1·95; p=0·048) studies. This increased risk was even higher in patients with expanded cell fractions of mCAs (ie, cell fractions ≥10% vs cell fractions <10%) in the NJLCC (OR 1·61 [95% CI 1·26-2·08] vs 1·03 [0·83-1·26]; p for heterogeneity test=6·41 × 10 -3 ). A significant multiplicative interaction was observed between PRS and mosaic losses on the risk of lung cancer in both the NJLCC (interaction p value=0·030) and UKB (p=0·043). Compared with non-carriers of mosaic loss abnormalities with low genetic risk, participants with expanded mosaic losses (cell fractions ≥10%) and high genetic risk had around a six-times increased risk of lung cancer in the NJLCC study (OR 6·40 [95% CI 3·22-12·69]), and an almost four-times increased risk of lung cancer (HR 3·75 [95% CI 1·86-7·55]) in the UKB study. The additive interaction also contributed a 3·67 (95% CI 0·49-6·85) relative excess risk of developing lung cancer in the NJLCC study, and a 2·15 (0·12-4·19) relative excess risk in the UKB study., Interpretation: mCAs act as a new endogenous indicator for the risk of lung cancer and might be jointly used with PRS to optimise personalised risk stratification for lung cancer., Funding: National Natural Science Foundation of China, Outstanding Youth Foundation of Jiangsu Province, Natural Science Foundation of Jiangsu Province, and Postdoctoral Science Foundation of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We present the largest whole-genome sequencing (WGS) study of non-small cell lung cancer (NSCLC) to date among 6,004 individuals of Chinese ancestry, coupled with 23,049 individuals genotyped by SNP array. We construct a high-quality haplotype reference panel for imputation and identify 20 common and low-frequency loci (minor allele frequency [MAF] ≥ 0.5%), including five loci that have never been reported before. For rare loss-of-function (LoF) variants (MAF < 0.5%), we identify BRCA2 and 18 other cancer predisposition genes that affect 5.29% of individuals with NSCLC, and 98.91% (181 of 183) of LoF variants have not been linked previously to NSCLC risk. Promoter variants of BRCA2 also have a substantial effect on NSCLC risk, and their prevalence is comparable with BRCA2 LoF variants. The associations are validated in an independent case-control study including 4,410 individuals and a prospective cohort study including 23,826 individuals. Our findings not only provide a high-quality reference panel for future array-based association studies but depict the whole picture of rare pathogenic variants for NSCLC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that play critical roles in cytokine-mediated regulation of homeostasis and inflammation. However, relationships between their immune phenotypic characteristics and HCC remain largely unexplored., Approach and Results: We performed single-cell RNA sequencing analysis on sorted hepatic ILC cells from human patients with HCC and validated using flow cytometry, multiplex immunofluorescence staining, and functional experiments. Moreover, we applied selection strategies to enrich ILC populations in HCC samples to investigate the effects of B cells on the immune reaction of inducible T cell costimulator (ICOS) + ILC2 cells. Dysregulation of ILCs was manifested by the changes in cell numbers or subset proportions in HCC. Seven subsets of 3433 ILCs were identified with unique properties, of which ICOS + ILC2a were preferentially enriched in HCC and correlated with poor prognosis. Mechanistically, we report that B cells, particularly resting naïve B cells, have a previously unrecognized function that is involved in inflammatory differentiation of ILC2 cells. B cell-derived ICOSL signaling was responsible for exacerbating inflammation through the increased production of IL-13 in ICOS + ILC2a cells. Heat shock protein 70 (HSP70) genes Heat Shock Protein Family A Member 1A (HSPA1A) and Heat Shock Protein Family A Member 1B (HSPA1B) were highly expressed in ILC2s in late-stage HCC, and targeting to ICOS and its downstream effector HSP70 in ILC2s suppressed tumor growth and remodeled the immunosuppressive tumor microenvironment., Conclusions: This in-depth understanding sheds light on B cell-driven innate type 2 inflammation and provides a potential strategy for HCC immunotherapy., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Immunotherapy has shown great promise in treating various types of malignant tumors. However, some patients with gastrointestinal cancer have been known to experience rapid disease progression after treatment, a situation referred to as hyperprogressive disease (HPD). This minireview focuses on the definitions and potential mechanisms of HPD, natural disease progression in gastrointestinal malignancies, and tumor immunological microenvironment., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The development of high-efficiency and low-cost oxygen reduction electrocatalysts have become an urgent need to push fuel cells into practical application. Herein, an effective electrocatalyst Co/NC was successfully constructed, which was derived from abundant peanut shells, obtained by doping with cobalt ions and pyrolyzing in NH 3 atmosphere. Due to the abundant Co-N active sites triggered by Co-N heteroatomic interface, the prepared electrocatalysts present excellent oxygen reduction reaction (ORR) performance with more positive half-wave potential (E 1/2  = 0.83 V), incremental limiting current density (J L  = 5.45 mA cm -2 ), higher durability and stronger resistance to methanol, which is superior to that of Pt/C (E 1/2  = 0.81 V and J L  = 5.19 mA cm -2 ). This work proposes a potential strategy to synthesize efficient ORR electrocatalysts to instead of Pt-based catalysts., 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 Inc. All rights reserved.)

Objective: Although our previous genome-wide association study (GWAS) has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer (NSCLC), the causal variants remain unclear. The aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in NSCLC., Methods: CCK-8, colony formation, EdU incorporation, Transwell, and quantitative real-time polymerase chain reaction assays were applied to examine variant function. The tumor xenograft model was used to examine variant function in vivo . Caspase-8 activity assays, flow cytometry analysis, and co-immunoprecipitation assays were used to explore the molecular mechanism., Results: The missense variant rs3769823 (A > G), which caused the substitution of lysine with arginine at amino acid 14 in caspase-8 (caspase-8K14R), was identified as a potential causal candidate in 2q33.1. Compared with the wild type caspase-8 (caspase-8WT) group, the caspase-8K14R group had higher expression of caspase-8 and cleaved caspase-8. Caspase-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in vitro . Moreover, caspase-8K14R repressed lung cancer cell growth in vivo . Mechanistically, caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and FADD., Conclusions: These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway, leading to a decreased risk of NSCLC., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2022 Cancer Biology & Medicine.)

Ultrathin films of intrinsic magnetic topological insulator MnBi 2 Te 4 exhibit fascinating quantum properties such as the quantum anomalous Hall effect and the axion insulator state. In this work, we systematically investigate the evolution of the electronic structure of MnBi 2 Te 4 thin films. With increasing film thickness, the electronic structure changes from an insulator type with a large energy gap to one with in-gap topological surface states, which is, however, still in drastic contrast to the bulk material. By surface doping of alkali-metal atoms, a Rashba split band gradually emerges and hybridizes with topological surface states, which not only reconciles the puzzling difference between the electronic structures of the bulk and thin-film MnBi 2 Te 4 but also provides an interesting platform to establish Rashba ferromagnet that is attractive for (quantum) anomalous Hall effect. Our results provide important insights into the understanding and engineering of the intriguing quantum properties of MnBi 2 Te 4 thin films.

Background: Adult survivors of childhood cancer are at increased risk of cardiac late effects., Methods: Using whole-genome sequencing data from 1870 survivors of European ancestry in the St. Jude Lifetime Cohort (SJLIFE) study, genetic variants were examined for association with ejection fraction (EF) and clinically assessed cancer therapy-induced cardiac dysfunction (CCD). Statistically significant findings were validated in 301 SJLIFE survivors of African ancestry and 4020 survivors of European ancestry from the Childhood Cancer Survivor Study. All statistical tests were 2-sided., Results: A variant near KCNK17 showed genome-wide significant association with EF (rs2815063-A: EF reduction = 1.6%; P = 2.1 × 10-8) in SJLIFE survivors of European ancestry, which replicated in SJLIFE survivors of African ancestry (EF reduction = 1.5%; P = .004). The rs2815063-A also showed a 1.80-fold (P = .008) risk of severe or disabling or life-threatening CCD and replicated in 4020 Childhood Cancer Survivor Study survivors of European ancestry (odds ratio = 1.40; P = .04). Notably, rs2815063-A was specifically associated among survivors exposed to doxorubicin only, with a stronger effect on EF (3.3% EF reduction) and CCD (2.97-fold). Whole blood DNA methylation data in 1651 SJLIFE survivors of European ancestry showed statistically significant correlation of rs2815063-A with dysregulation of KCNK17 enhancers (false discovery rate <5%), which replicated in 263 survivors of African ancestry. Consistently, the rs2815063-A was associated with KCNK17 downregulation based on RNA sequencing of 75 survivors., Conclusions: Leveraging the 2 largest cohorts of childhood cancer survivors in North America and survivor-specific polygenomic functional data, we identified a novel risk locus for CCD, which showed specificity with doxorubicin-induced cardiac dysfunction and highlighted dysregulation of KCNK17 as the likely molecular mechanism underlying this genetic association., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Our previous study confirmed that polydatin (PD) can alleviate sepsis-induced multiorgan dysfunction (in the vascular endothelium, kidney, and small intestine) by activating Sirt1 and that PD protects against traumatic brain injury in rats via increased Sirt1 and inhibition of the p38-mediated mitogen-activated protein kinase (MAPK) pathway. We aim to investigate whether PD may also attenuate sepsis-associated encephalopathy (SAE)., Methods: In this study, we constructed an SAE mouse model by cecal ligation and puncture (CLP) and measured Sirt1 protein activity, p38 phosphorylation, brain tissue pathological damage, pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), mitochondrial function (mitochondrial membrane potential, ATP content, and reactive oxygen species), neurological function, and animal survival time. Sirt1 selective inhibitor Ex527 and p38 inhibitor SB203580 were used to explore the possible mechanism of PD in SAE., Results: We confirmed that PD inhibits neuroinflammation evidenced by reduced proinflammatory cytokines. In addition, PD protects mitochondria as demonstrated by restored mitochondrial membrane potential and adenosine triphosphate (ATP) content, and decreased reactive oxygen species (ROS) level. As we expected, p38 inhibition reduces neuroinflammation and mitochondrial damage. In contrast, Sirt1 inhibition aggravates cerebral cortex mitochondrial damage and neuroinflammation and promotes phosphorylation of p38. Mechanistically, PD treatment suppressed p38 phosphorylation and consequently reduced the neuroinflammatory response, and these effects were blocked by the Sirt selective inhibitor Ex527., Conclusions: This study, to the best of our knowledge, is the first to demonstrate that PD alleviates SAE, at least partially, by upregulating Sir1-mediated neuroinflammation inhibition and mitochondrial function protection., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Super-enhancers (SEs) are important transcriptional regulators in tumorigenesis; however, the functional characterization and clinical significance of SEs in lung adenocarcinoma (LUAD) remain unclear. By using H3K27ac ChIP-seq data of two LUAD cell lines and eight lung tissues, we detected 1045 cancer-specific and 5032 normal-specific SEs. Compared to normal-specific SEs, cancer-specific SEs have different regulatory mechanisms where associated target genes were enriched in critical tumor-related pathways and tended to be regulated by transcription factors of Fos Proto-Oncogene, AP-1 Transcription Factor Subunit and Jun Proto-Oncogene, AP-1 Transcription Factor Subunit families. By using expression data of 513 LUAD and 57 adjacent samples from The Cancer Genome Atlas and 80 tumor-normal paired LUAD samples from the Nanjing Lung Cancer Cohort study, we performed differential expression analysis of target genes for SEs and defined 243 crucial SEs. Unsupervised clustering of crucial SEs revealed two subtypes with different levels of genomic aberrations (i.e., mutation and copy number alteration) and clinical outcomes (progression-free interval: p = 0.030; disease-free interval: p = 0.047). In addition, patients with adverse clinical outcomes were more sensitive to three small molecule inhibitors (bortezomib, doxorubicin, and etoposide), and their targets (PSMB5 and TOP2A) also have elevated expression levels among these patients. Taken together, our findings provided a comprehensive characterization of SEs in LUAD and emphasized their clinical significance in LUAD therapy., (© 2022 Wiley Periodicals LLC.)

Background and Objective: Preoperative imaging diagnosis of axillary lymph node (ALN) metastasis is particularly important for breast cancer patients. This paper focuses on developing non-invasive and automatic schemes for accurate localization and classification (metastasis prediction) of ALN via contrast-enhanced computed tomography (CECT) image and deep learning models., Methods: Based on a two-stage strategy, a novel detection neural network is proposed, where the convolutional block attention module is utilized to extract spacial information and the bottleneck feature fusion module is designed for feature fusion in different scales., Results: Owing to the two embedded modules, the proposed convolutional neural network (CNN) model outperforms Faster R-CNN, YOLOv3, and EfficientDet in the sense that the achieved mAP is 0.454, higher than 0.247, 0.335, and 0.329, respectively. In particular, considering the function of classification only, the proposed model reaches the best performance on most indices (accuracy of 0.968, positive predictive value of 0.972, negative predictive value of 0.966, specificity of 0.983), compared with the methods that have been frequently adopted to predict ALN. In addition, the proposed CNN model has the function of locating ALN, which is lacking in existing models., Conclusions: In this paper, a supervised deep learning method is proposed to detect ALN in CECT images. The positive effect of new added modules are verified, and the benefits of spatial information in ALN detection are confirmed. Further, the two subtasks called localization and classification are evaluated separately, where the proposed model achieves the best performance on most indices. The source code mentioned in this article will be released later., (Copyright © 2022. Published by Elsevier B.V.)

Background: Epigenetic alterations have been shown to contribute immensely to human carcinogenesis. Dynamic and reversible N6-methyladenosine (m6A) RNA modification regulates gene expression and cell fate. However, the reasons for activation of KIAA1429 (also known as VIRMA, an RNA methyltransferase) and its underlying mechanism in lung adenocarcinoma (LUAD) remain largely unexplored. In this study, we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD., Methods: Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase. The in vitro and in vivo functions of KIAA1429 were investigated. Transcriptome sequencing, methylated RNA immunoprecipitation sequencing (MeRIP-seq), m6A dot blot assays and RNA immunoprecipitation (RIP) were performed to confirm the modified gene mediated by KIAA1429. RNA stability assays were used to detect the half-life of the target gene., Results: Copy number amplification drove higher expression of KIAA1429 in LUAD, which was correlated with poor overall survival. Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD. Mechanistically, the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays. We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner. Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2, the m6A "reader")-dependent BTG2 mRNA stability and promoted the expression of BTG2; thus, participating in the tumorigenesis of LUAD., Conclusions: Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis, which may provide a novel view on the targeted molecular therapy of LUAD., (© 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: Immunotherapy represented by immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with non-oncogenic advanced non-small cell lung cancer (NSCLC). While lung cancer is most prevalent in elderly patients, these patients are rarely included in pivotal clinical trial studies. We aimed to describe the efficacy and safety of immunotherapy for elderly patients in the "real-world"., Methods: The data of older NSCLC patients and younger patients who received immunotherapy between July 2018 to October 2021 were retrospectively analyzed and the objective response rate (ORR) and progression-free survival (PFS) in different age groups (less than 60 years old was defined as the young group, 60 years-74 years old was the young old group, 75 years old and above was the old old group) were compared. And the impact of different clinical characteristics on treatment response and prognosis were analyzed in each age subgroup., Results: A total of 21 young patients, 70 young old patients and 15 old old patients were included in this study, with ORR of 33.3%, 52.8% and 53.3%, respectively, without statistically significant difference (P=0.284). The median PFS was 9.1 mon, 7.6 mon and 10.9 mon, respectively, without statistically significant difference (P=0.654). Further analysis of the predictors of immunotherapy in each subgroup revealed that patients in the young old group and young group who received immunotherapy in the first line had a longer PFS. The difference of the incidence of adverse events was not statistically significant among the three groups (P>0.05)., Conclusions: The efficacy and safety of immunotherapy in elderly patients were similar to those in younger patients, and PFS was superior in the first-line immunotherapy. Further prospective studies are still needed to explore predictors of immunotherapy in elderly NSCLC patients.

Precise control of the structure of crystalline materials is an efficient strategy to manipulate the fundamental performance of solids. In metal-organic framework (MOF) materials, this control can be realized by reversible cation-exchange through chemically driven changes in the crystalline state. Herein, we reported that the reversible structural transformations between an anionic Zn-MOF ( 1 ) and a topologically equivalent bimetallic Zn/Co-MOF ( 2 ) were accomplished. Both MOFs powders and their hybrid composites were used as positive electrode materials to assemble triboelectric nanogenerators (TENGs). The results demonstrated that the output performance of the Zn/Co-MOF-TENG was effectively improved because the introduction of Co ions makes electron transfer easier. Moreover, the output performance of the TENGs based on MOF@PVDF (PVDF = polyvinylidene fluoride) composite films showed that the Zn/Co-MOF@PVDF-TENG possessed much higher output than these corresponding film-based and MOF-based TENGs. As a practical application, the superior output of Zn/Co-MOF@PVDF-TENG was used to light an ultraviolet lamp plate for the [2 + 2] photochemical cycloaddition of organometallic macrocycles.

Background: Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA., Methods: Genome-wide association studies of EAA based on multiple epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) were performed. MethylationEPIC BeadChip array and whole-genome sequencing data were generated with blood-derived DNA from participants in the St. Jude Lifetime Cohort Study (discovery: 2138 pre-existing and 502 newly generated data, all survivors; exploratory: 282 community controls). Linear regression models were fit for each epigenetic age against the allelic dose of each genetic variant, adjusting for age at sampling, sex, and cancer treatment exposures. Fixed-effects meta-analysis was used to combine summary statistics from two discovery data sets. LD (Linkage disequilibrium) score regression was used to estimate single-nucleotide polymorphism (SNP)-based heritability., Results: For EAA-Horvath, a genome-wide significant association was mapped to the SELP gene with the strongest SNP rs732314 (meta-GWAS: β=0.57, P=3.30×10 -11 ). Moreover, the stratified analysis of the association between rs732314 and EAA-Horvath showed a substantial heterogeneity between children and adults (meta-GWAS: β=0.97 vs. 0.51, I 2 =73.1%) as well as between survivors with and without chest/abdominal/pelvic-RT exposure (β=0.64 vs. 0.31, I 2 =66.3%). For EAA-Hannum, an association was mapped to the HLA locus with the strongest SNP rs28366133 (meta-GWAS: β=0.78, P=3.78×10 -11 ). There was no genome-wide significant hit for EAA-PhenoAge or EAA-GrimAge. Interestingly, among community controls, rs732314 was associated with EAA-Horvath (β=1.09, P=5.43×10 -5 ), whereas rs28366133 was not associated with EAA-Hannum (β=0.21, P=0.49). The estimated heritability was 0.33 (SE=0.20) for EAA-Horvath and 0.17 (SE=0.23) for EAA-Hannum, but close to zero for EAA-PhenoAge and EAA-GrimAge., Conclusions: We identified novel genetic variants in the SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer. The new genetic variants in combination with other replicated known variants can facilitate the identification of survivors at higher risk in developing accelerated aging and potentially inform drug targets for future intervention strategies among vulnerable survivors., (© 2022. The Author(s).)

Here, a tetrakaidecahedron-shaped Cu four-core supramolecule was designed to overcome the defects of supramolecules for lithium-ion batteries. With multiple metal centers, conductive ligands and abundant hydrogen bonds, this novel electrode shows excellent rate capability (459.4 mA h g -1 at 2000 mA g -1 ) and cyclicality (494.5 mA h g -1 after 700 cycles).