Search

Objective To establish and forensically verify a 42 microhaplotypes （mircohaps, MHs） multiplex assay system based on next-generation sequencing （NGS）, and to explore the application value of this system in the practice of forensic genetics. Methods A total of 42 highly polymorphic MHs were selected from previous studies, and sequenced by the MiSeq FGxTM platform to verify the repeata-bility, sensitivity, specificity, stability, and mixture analysis ability of the detection system. Through population genetic investigation of 102 unrelated Chinese Han individuals in Liyang City, Jiangsu Province, China, the application value of this system in forensic genetics was evaluated. Results The sequencing repeatability of the 42-plex MHs assay was 100% and the sensitivity was as low as 0.062 5 ng. The system had the ability to withstand the interference of indigo （≤2 500 ng/μL）, humic acid （≤9 ng/μL）, hemoglobin（≤20 μmol）, and urea （≤200 ng/μL） and to detect mixtures of 2 people （1∶19）， 3 people （1∶1∶9） and 4 people （1∶1∶1∶9）. Based on 102 individual data, the combined power of discrimination and the combined power of exclusion were 1-3.45×10-30 and 1-3.77×10-11, respectively, and the average effect value of alleles was 2.899. Conclusion The 42-plex MHs assay was successfully established in this study and this system has high repeatability and sensitivity, good anti-jamming ability and mixture analysis ability. The 42 MHs are highly polymorphism and have good application value in individual identification and paternity testing.

Abstract Background Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. Methods qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. Results The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. Conclusions The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. Methods The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. Results In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84–0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84–0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. Conclusion This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.

Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Abstract Background Subglottic Stenosis (SGS), with increasing numbers of studies, is the most specific and common clinical type of Laryngotracheal Stenosis (LTS). There is rapid publication turnover with newer management introduced and expanding research field. To our knowledge, there is no bibliometric analysis of SGS yet. Methods In August 2022, we performed a thorough search in the Web of Science Core Collection database using the word “subglottic stenosis,” and “SGS.” The 580 articles were arranged based on correlation. The collected articles were then analyzed with an assessment of relevant factors. Meanwhile, we analyzed the top 100 most-cited articles on SGS. Results The frequency of publication on SGS has increased substantially over time. The USA has contributed the most articles (n = 301). Vanderbilt University published most of the articles among other institutions (n = 18). Laryngoscope topped the list of journals and has published 89 SGS-related articles. Research hotspots shift from surgical treatment to conservative management. Conclusions The SGS-related literature has grown rapidly in recent years. This study represents the first bibliometric analysis of scientific articles on SGS. Areas to improve in SGS research can be identified after this analysis of the most impactful articles on this topic.

Abstract Impaired fatty acid oxidation (FAO) is a prominent feature of metabolic remodeling observed in pathological myocardial hypertrophy. Hepatocyte nuclear factor 4alpha (HNF4α) is closely associated with FAO in both cellular processes and disease conditions. Pellino 1 (Peli1), an E3 ligase containing a RING-like domain, plays a crucial role in catalyzing polyubiquitination of various substrates. In this study, we aimed to investigate the involvement of HNF4α and its ubiquitination, facilitated by Peli1, in FAO during pressure overload-induced cardiac hypertrophy. Peli1 systemic knockout mice (Peli1KO) display improved myocardial hypertrophy and cardiac function following transverse aortic constriction (TAC). RNA-seq analysis revealed that changes in gene expression related to lipid metabolism caused by TAC were reversed in Peli1KO mice. Importantly, both HNF4α and its downstream genes involved in FAO showed a significant increase in Peli1KO mice. We further used the antagonist BI6015 to inhibit HNF4α and delivered rAAV9-HNF4α to elevate myocardial HNF4α level, and confirmed that HNF4α inhibits the development of cardiac hypertrophy after TAC and is essential for the enhancement of FAO mediated by Peli1 knockout. In vitro experiments using BODIPY incorporation and FAO stress assay demonstrated that HNF4α enhances FAO in cardiomyocytes stimulated with angiotension II (Ang II), while Peli1 suppresses the effect of HNF4α. Mechanistically, immunoprecipitation and mass spectrometry analyses confirmed that Peli1 binds to HNF4α via its RING-like domain and promotes HNF4α ubiquitination at residues K307 and K309. These findings shed light on the underlying mechanisms contributing to impaired FAO and offer valuable insights into a promising therapeutic strategy for addressing pathological cardiac hypertrophy.

Chrysanthemum morifolium ranks among the four highest-selling cut flowers worldwide. Gene editing is an important tool to research gene function, but efficient and precise genome-editing tools are not available for chrysanthemum. Here, we established a CRISPR/Cas9-mediated gene-editing system to explore gene functions and enhance the breeding of chrysanthemum. We used the Golden Gate Assembly system to construct CRISPR/Cas9 vectors for dual targeting of the Phytoene Dehydro (PDS) gene. To test the accuracy of sgRNA design, we initially used the transient CRISPR/Cas9 editing in plants (TCEP) method. Target gene expression in nine plants subjected to transient transfection was 19.1%–52% of the normal level, confirming the feasibility of target gene knockout. We carried out stable transformation; PCR and sequencing of the target sites showed that four of eight albino plants obtained had been stably edited at the target sites. We further assessed the editing efficiency of the system by targeting another gene, CmTGA1, chosen because of its potential importance in Chrysanthemum White Rust (CWR) disease progression. Our data indicates that combining transient and stable transformation improves the efficiency and success rate of genome fixed-point editing. The effective, heritable CRISPR/Cas9-mediated genome-editing system we have established here lays the foundation for functional gene studies and genetic improvement of C. morifolium.

Geo-decentralized federated learning (FL) can empower fully distributed model training for future large-scale 6G networks. Without the centralized parameter server, the peer-to-peer model synchronization in geo-decentralized FL would incur excessive communication overhead. Some existing studies optimized synchronization interval for communication efficiency, but may not be applicable to latency-constrained geo-decentralized FL. This paper first proposes the synchronization interval optimization for latency-constrained geo-decentralized FL. The problem is formulated to maximize the model training accuracy within a time window under communication/computation constraints. We mathematically derive the convergence bound by jointly considering data heterogeneity, network topology and communication/computation resources. By minimizing the convergence bound, we optimize the synchronization interval based on the approximated system consistency metric. Extensive experiments on MNIST, Fashion-MNIST and CIFAR10 datasets validate the superiority of the proposed approach by achieving up to 30% higher accuracy than the state-of-the-art benchmarks.

The development of offshore wind power is a crucial step in China’s energy transition and the achievement of carbon peaking and carbon neutrality goals. This paper first introduces a wireless communication technology for independent networking. Its applicability in the field of relay protection is analyzed, and a security encryption scheme for its use in relay protection services is designed. Considering the primary wiring form and protection function configuration of offshore wind power, a multi-terminal wireless differential protection method suitable for offshore wind power collection lines is proposed, achieving synchronization error less than 3° and typical delay of wireless self-organizing network communication less than 12ms. Utilizing multi-terminal data synchronization technology and differential protection algorithms, a scheme for fault isolation and recovery of non-faulty wind turbines is established, thereby achieving minimal range isolation of offshore wind power collection line faults and precise fault section location. The action time of multi-terminal differential protection is less than 40ms. Finally, experimental results confirm that this technology’s various metrics satisfy the demands of engineering applications and hold promotional value, offering a reference for the practical application of wireless communication technology in offshore wind power collection line protection services.

Abstract Purpose This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. Methods This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study’s primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. Results The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P

The AMB-rotor system is complex and has strong coupling characteristics, which allows multi-harmonic disturbances to enter the system through different ways to produce vibrations with rich spectrum components, which has a great influence on the improvement of micro-vibration accuracy of the rotor system. To further achieve active control of the micro-vibration in the AMB-rotor system, firstly, the mechanism of multi-source disturbance is analyzed according to the working principle of the AMB-rotor system, and the mathematical and physical relationship between the mechanism of disturbance generation and the inducement is deeply studied. Then, the structure of a novel adaptive notch filter, the method of adaptive frequency estimation and analysis of harmonic current suppression in the AMB system are presented. Finally, simulation and experimental research using an MSCMG system demonstrate the feasibility of the proposed method regarding the elimination of harmonic control current.

Lung adenocarcinoma (LUAD) is one of the most aggressive types of lung cancer. The prognosis of LUAD patients remains poor, and the overall efficacy of gemcitabine-based chemotherapy is still unsatisfactory. Long noncoding RNAs (lncRNAs) play important roles in several cancer types by interacting with multiple proteins, RNA, and DNA. However, the relationship between lncRNA dysregulation and gemcitabine resistance in LUAD has not been fully elucidated. In this study, lncRNA CYTOR expression and its association with the prognosis of LUAD patients are assessed by quantitative RT-PCR and Kaplan-Meier survival analysis. In vitro and in vivo functional studies are conducted to evaluate the biological functions of CYTOR in LUAD. The underlying mechanism regarding the tumor-promoting effects of CYTOR is explored using RNA immunoprecipitation, biotin-labelled RNA pulldown, luciferase reporter assays, and western blot analysis. We identify that CYTOR is an oncogenic lncRNA and is apparently upregulated in LUAD by analysing TCGA-LUAD data. High CYTOR expression is a poor prognostic factor for LUAD. Functional studies reveal that CYTOR confers LUAD cells with stronger resistance to gemcitabine treatment and upregulates the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. Mechanically, CYTOR acts as a competitive endogenous RNA (ceRNA) to absorb miR-125a-5p, weakens the antitumor function of miR-125a-5p, and ultimately upregulates ANLN and RRM2 expressions. Taken together, this study explains the mechanism of lncRNA in the gemcitabine resistance of LUAD and formulates a theoretical framework for the in depth study of LUAD.

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts. In addition, AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase (circ-DHPS) in PCa cells, which can be transported to osteoblasts by exosomes. Circ-DHPS acts as a competitive endogenous RNA (ceRNA) against endogenous miR-214-3p to promote C-C chemokine ligand 5 (CCL5) levels in osteoblasts. Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment. Thus, blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

Abstract Acute pancreatitis (AP) is a severe gastrointestinal inflammatory disease with increasing mortality and morbidity. Glycyrrhiza glabra, commonly known as Liquorice, is a widely used plant containing bioactive compounds like Glycyrrhizin, which possesses diverse medicinal properties such as anti-inflammatory, antioxidant, antiviral, and anticancer activities. The objective of this study is to investigate the active components, relevant targets, and underlying mechanisms of the traditional Chinese medicine Glycyrrhiza glabra in the treatment of AP. Utilizing various computational biology methods, we explored the potential targets and molecular mechanisms through Glycyrrhizin supplementation. Computational results indicated that Glycyrrhizin shows promising pharmacological potential, particularly with mitogen-activated protein kinase 3 (MAPK3) protein (degree: 70), forming stable complexes with Glycyrrhizin through ionic and hydrogen bonding interactions, with a binding free energy (ΔGbind) of -33.01 ± 0.08 kcal/mol. Through in vitro experiments, we validated that Glycyrrhizin improves primary pancreatic acinar cell injury by inhibiting the MAPK/STAT3/AKT signaling pathway. Overall, MAPK3 emerges as a reliable target for Glycyrrhizin’s therapeutic effects in AP treatment. This study provides novel insights into the active components and potential targets and molecular mechanisms of natural products.

The nuclear criticality safety issue in spent fuel reprocessing facilities is closely related to the main process and is almost equally important. It is closely related to the design and operation of reprocessing facilities. The requirement of nuclear criticality safety greatly restricts the operational capacity of the spent fuel reprocessing process, thereby affecting the economic efficiency of reprocessing. In the post-processing process, both multiphase uranium-plutonium mixed systems and multi body interaction systems are involved. The system characteristics are complex, and experimental simulation is difficult, which greatly restricts the further improvement of the production and operation capabilities of the pilot plant. However, due to the criticality safety challenges caused by reactivity changes such as the non-uniformity, dynamic complexity, and instability of the solution in the reactor under boiling nitric acid during the dissolution process, it has become a key research topic in various countries. According to the criticality safety problem of nuclear fuel dissolution process, the criticality effect of nitric acid concentration was studied. The criticality experiment data of nuclear fuel dissolution process were obtained by keeping the concentration of nitric acid in the same fuel concentration. Four experiments were conducted with different concentrations of nitric acid. During the experiment, the subcritical extrapolation method, reactivity interpolation method, and stable power method were used to complete the criticality experiment. The experimental results show that with the increase of nitric acid concentration, the relative deviation of the criticality experiment data is 0.068%, and the relative deviation between the criticality experiment results and the theoretical calculated values is 0.39%. The research results show that the reactivity of the system gradually increases as the concentration of nitric acid decreases. Therefore, it is necessary to consider the reactivity changes caused by changes in the criticality safety of the spent fuel dissolution process, and high attention is needed. According to the agreement between the experiment and the theoretical calculation, it is appropriate to use the Monte Carlo code MONK to calculate and analyze the acidity effect of the solid-liquid two-phase solution system, which can be used as a nuclear criticality safety control engineering design process for the solid-liquid two-phase nuclear fuel dissolution system. This series of experiment data can be used for calculation, verification, and safety evaluation of critical analysis under solid-liquid coexistence conditions of nuclear fuel. This paper results provide data support for improving the criticality safety control level of critical post-processing equipment.

AbstractMicromelalopha sieversi (Staudinger, 1892) is a significant pest of Poplar trees in China. In this study, we used high-throughput sequencing to sequence the whole mitochondrial genome of M. sieversi. The length of the genome was 15,373 base pairs. The nucleotide composition was 39.8%, 11.5%, 8.0%, and 40.7% for A, C, G, and T, respectively. We used the maximum-likelihood method to construct a molecular phylogenetic tree based on complete mitogenome sequences of 19 Noctuoidea species as ingroups and five Geometroidea species as outgroups. The results indicate that the genus Micromelalopha is closely related to the genus Clostera in family Notodontidae.

The radiometric calibration technique of spaceborne synthetic aperture radar (SAR) aims to establish a constant relationship between the SAR target pulse response energy and the actual radar cross-section (RCS) of the ground. It is an essential technology for achieving quantitative observations of the Earth using radar. In this article, the process of in-orbit radiometric calibration campaign for the SuperView Neo-2 SAR satellite is introduced, which is the distributed X-band SAR satellite in the new generation of Chinese SiWei commercial remote sensing satellite system. More specifically, the initial step involves deriving the total transfer function of the SAR system using the radar equation and establishing a stable calibration constant model for the SAR system. Further, by using the obtained calibration constant to invert the RCS value of the corner reflectors in the Otog Banner calibration field, while validating and analyzing the absolute radiometric accuracy. Considering that the elevation antenna pattern (EAP) predominantly affects the consistency of image radiometric correction, the method of extracting EAP and beam center bias angle from the rainforest is presented. Finally, the quality validation of impulse response function is performed over the California calibration field, which can effectively guarantee the quality of SuperView Neo-2 SAR satellite products.

To separate and unwrap the residual topographical and deformation components from the wrapped phases are the key issues for persistent scatterer interferometric synthetic aperture radar (PS-InSAR) technique. The current methods, such as grid-search method based on the assumption that the deformation in time-domain is linear, or the least squares ambiguity decorrelation adjustment method that needs priori information to construct the pseudo-observations, etc., are still difficult to tradeoff accuracy against efficiency. In this article, we propose a new method to separate and unwrap the differential phases for PS-InSAR by dividing them into residual topographical phase and differential deformation phases and performing the phase unwrapping separately. First, we calculate phase ambiguities caused by residual topographical error by zero-temporal baseline combination and single parameter grid-search method. The calculated residual topographical error is used to separate the differential phases dominated by deformations from the original differential phases of PS-InSAR. Then, we proposed time-domain differentiation to unwrap differential phases dominated by deformations without any assumption of deformation model in time-domain. The performance of the proposed method is tested by both simulated and real datasets. The experimental results show that, compared with classic PS-InSAR, the accuracy of residual topographical error estimation is comparable; however, there is an accuracy improvement of 34.4% for the deformation parameter estimation and 35.7% for nonlinear deformation time-series extraction, as well as an improvement of 20–40 times in computational efficiency.

Triple-negative breast cancer (TNBC) is a special type of breast cancer in which ER, PR and HER2 are all negative, characterized by high malignancy, strong invasiveness, and high recurrence rate. It is critical to develop novel drugs for improved therapies for triple-negative breast cancers. Here, we unveiled the transcriptional landscape associated with triple-negative breast cancer and identified candidate drugs using a comprehensive connectivity map. The candidate components could induce reverse expressions of the TNBC gene expression signature and trigger transcriptional reprogramming with a positive impact on modulating chemoresistance and the survival probability of breast cancer patients. Our study also provided an example of drug discovery using in silico drug screening followed by further validations, illustrating an effective computational drug discovery strategy.

Abstract Background Pre-exposing plants to abiotic stresses can induce stress memory, which is crucial for adapting to subsequent stress exposure. Although numerous genes involved in salt stress response have been identified, the understanding of memory responses to salt stress remains limited. Results In this study, we conducted physiological and transcriptional assays on maize plants subjected to recurrent salt stress to characterize salt stress memory. During the second exposure to salt stress, the plants exhibited enhanced salt resistance, as evidenced by increased proline content and higher POD and SOD activity, along with decreased MDA content, indicative of physiological memory behavior. Transcriptional analysis revealed fewer differentially expressed genes and variations in response processes during the second exposure compared to the first, indicative of transcriptional memory behavior. A total of 2,213 salt stress memory genes (SMGs) were identified and categorized into four response patterns. The most prominent group of SMGs consisted of genes with elevated expression during the first exposure to salt stress but reduced expression after recurrent exposure to salt stress, or vice versa ([+ / −] or [− / +]), indicating that a revised response is a crucial process in plant stress memory. Furthermore, nine transcription factors (TFs) (WRKY40, WRKY46, WRKY53, WRKY18, WRKY33, WRKY70, MYB15, KNAT7, and WRKY54) were identified as crucial factors related to salt stress memory. These TFs regulate over 53% of SMGs, underscoring their potential significance in salt stress memory. Conclusions Our study demonstrates that maize can develop salt stress memory, and the genes identified here will aid in the genetic improvement of maize and other crops.

The present study aimed to investigate the impact of hydrogen (H2) on chronic intermittent hypoxia (CIH)-induced cardiac hypertrophy in mice by modulating iron metabolism. C57BL/6N mice were randomly allocated into four groups: control (Con), CIH, CIH + H2, and H2. The mice were exposed to CIH (21–5% FiO2, 3 min/cycle, 8 h/d), and received inhalation of a hydrogen–oxygen mixture (2 h/d) for 5 weeks. Cardiac and mitochondrial function, levels of reactive oxygen species (ROS), and iron levels were evaluated. The H9C2 cell line was subjected to intermittent hypoxia (IH) and treated with H2. Firstly, we found H2 had a notable impact on cardiac hypertrophy, ameliorated pathological alterations and mitochondrial morphology induced by CIH (p < 0.05). Secondly, H2 exhibited a suppressive effect on oxidative injury by decreasing levels of inducible nitric oxide synthase (i-NOS) (p < 0.05) and 4-hydroxynonenal (4-HNE) (p < 0.01). Thirdly, H2 demonstrated a significant reduction in iron levels within myocardial cells through the upregulation of ferroportin 1 (FPN1) proteins (p < 0.01) and the downregulation of transferrin receptor 1 (TfR1), divalent metal transporter 1 with iron-responsive element (DMT1(+ire)), and ferritin light chain (FTL) mRNA or proteins (p < 0.05). Simultaneously, H2 exhibited the ability to decrease the levels of Fe2+ and ROS in H9C2 cells exposed to IH (p < 0.05). Moreover, H2 mediated the expression of hepcidin, hypoxia-inducible factor-1α (HIF-1α) (p < 0.01), and iron regulatory proteins (IRPs), which might be involved in the regulation of iron-related transporter proteins. These results suggested that H2 may be beneficial in preventing cardiac hypertrophy, a condition associated with reduced iron toxicity.

Abstract Background Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL). Methods Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered. Results The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation. Conclusions The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.

Abstract This study aimed to investigate the relationship between the dietary approaches to stop hypertension (DASH) dietary patterns and bone mineral density (BMD) in adults residing in the United States. To achieve this, data from the National Health and Nutrition Examination Survey (NHANES) database for 2011–2018 were utilized. This study utilized the NHANES database from 2011 to 2018, with a sample size of 8,486 US adults, to investigate the relationship between the DASH diet and BMD. The DASH diet was assessed based on nine target nutrients: total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium and potassium. The primary outcome measures were BMD values at the total BMD, thoracic spine, lumbar spine, and pelvis. Multivariable linear models were employed to analyze the association between the DASH diet and BMD. Interaction tests, subgroup, and sensitivity analysis were also followed. A negative correlation was observed between the DASH diet and total BMD (OR: − 0.003 [95%CI: − 0.005, − 0.001), pelvic (OR: − 0.005 [95%CI: − 0.007, − 0.002]), and thoracic BMD (OR: − 0.003 [95%CI: − 0.005, − 0.001]). However, the DASH diet does not appear to have a particular effect on lumbar spine BMD (OR: − 0.002 [95%CI: − 0.004, 0.001]). Similarly, when the DASH diet was categorized into tertiles groups, the relationship with total BMD, pelvic BMD, thoracic BMD, and lumbar spine BMD remained consistent. Furthermore, we performed a sensitivity analysis by converting BMD to Z-scores, and the results remained unchanged. Subgroup analyses and interaction tests indicated no significant dependence of BMI, gender, smoking, hypertension, and diabetes on the observed association (all p for interactions > 0.05). The DASH diet has been identified as potentially reducing total BMD, while specifically impacting thoracic and pelvic BMD. However, it appears to have no significant effect on lumbar spine BMD.

AbstractWe performed the first sequencing of the complete mitogenome of Botyodes diniasalis by high-throughput sequencing. A circular DNA molecule of 15,219 bp in size, encoding 2 rRNAs, 22 tRNAs, and 13 PCGs, contains a non-coding AT-rich region. The overall nucleotide composition of the genome is A (39.5%), T (41.3%), C (11.3%), and G (7.8%). Phylogenetic analysis based on mitogenomic data suggest that the species B. diniasalis has a close evolutionary relationship with B. principalis in Margaroniini. The complete mitogenome of B. diniasalis will serve as a valuable resource for future studies on evolution, taxonomy, genetic conservation, and utilization of Botyodes.

Abstract Cognitive disorders, including dementia, Parkinson's and Alzheimer's disease, pose significant public health issues. Preventing/delaying their onset is essential as effective medical treatments are unavailable. Nuts contain bioactive compounds, including fatty acids, macronutrients such as proteins and dietary fibers, micronutrients, and polyphenols; these act synergistically preventing age‐related diseases. Epidemiological investigations have established that high nut consumption reduces cognitive impairment risk, suggesting it is useful for cognitively impaired individuals; however, clinical data on the effects of nut consumption on cognitive function are lacking. This review summarized nut consumption effects on oxidative stress, inflammatory response, and gut microbiota. Nuts reduce oxidative stress; their active substances, including glansreginin A, proanthocyanidins, quercetin, and nut oil, have significant anti‐inflammatory effects. Furthermore, they comprise complex mixtures, which synergistically induce beneficial changes in the intestinal microbial community.

Abstract Structural variants (SVs), accounting for a larger fraction of the genome than SNPs/InDels, are an important pool of genetic variation, enabling environmental adaptations. Here, we perform long-read sequencing data of 320 Tibetan and Han samples and show that SVs are highly involved in high-altitude adaptation. We expand the landscape of global SVs, apply robust models of selection and population differentiation combining SVs, SNPs and InDels, and use epigenomic analyses to predict enhancers, target genes and biological functions. We reveal diverse Tibetan-specific SVs affecting the regulatory circuitry of biological functions, including the hypoxia response, energy metabolism and pulmonary function. We find a Tibetan-specific deletion disrupts a super-enhancer and downregulates EPAS1 using enhancer reporter, cellular knock-out and DNA pull-down assays. Our study expands the global SV landscape, reveals the role of gene-regulatory circuitry rewiring in human adaptation, and illustrates the diverse functional roles of SVs in human biology.

Abstract Seed germination is a complex process regulated by internal and external factors. Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous signaling molecule, playing an important role in regulating seed germination under normal and stressful conditions. In this review, we aim to provide a comprehensive overview on melatonin's effects on seed germination on the basis of existing literature. Under normal conditions, exogenous high levels of melatonin can suppress or delay seed germination, suggesting that melatonin may play a role in maintaining seed dormancy and preventing premature germination. Conversely, under stressful conditions (e.g., high salinity, drought, and extreme temperatures), melatonin has been found to accelerate seed germination. Melatonin can modulate the expression of genes involved in ABA and GA metabolism, thereby influencing the balance of these hormones and affecting the ABA/GA ratio. Melatonin has been shown to modulate ROS accumulation and nutrient mobilization, which can impact the germination process. In conclusion, melatonin can inhibit germination under normal conditions while promoting germination under stressful conditions via regulating the ABA/GA ratios, ROS levels, and metabolic enzyme activity. Further research in this area will deepen our understanding of melatonin's intricate role in seed germination and may contribute to the development of improved seed treatments and agricultural practices.

Since the product contains no carbon-based substances and can be driven by non-carbon-based electricity, electrocatalytic water splitting is considered to be among the most effective strategies for alleviating the energy crisis and environmental pollution. This process helps lower greenhouse gas emissions while also supporting the shift toward renewable energy sources. The anodic oxygen evolution reaction (OER) involves a more complex multi-electron transfer process, which is the principal limiting factor in overall water splitting. Extensive research has demonstrated that the controlled design of effective electrocatalysts can address this limitation. In this study, a previously unreported covalent organic framework material (COF-IM) was synthesized via a post-synthetic modification strategy. Notably, COF-IM contains imidazole nitrogen metal active sites. Transition metal-coordinated COF-IM@Co can function as a highly effective electrocatalyst, exhibiting a lower overpotential (403.8 mV@10 mA cm−2) in alkaline electrolytes, thereby highlighting its potential for practical applications in energy conversion technologies. This study offers new perspectives on the design and synthesis of COFs, while also making substantial contributions to the advancement and application of OER electrocatalysts.

To address the limitations of traditional footstep vibration signal localization algorithms, such as limited accuracy, single feature extraction, and cumbersome parameter adjustment, a motion target localization method for step vibration signals based on deep learning is proposed. Velocity vectors are used to describe human motion and adapt it to the nonlinear motion and complex interactions of moving targets. In the feature extraction stage, a one-dimensional residual convolutional neural network is constructed to extract the time–frequency domain features of the signals, and a channel attention mechanism is introduced to enhance the model’s focus on different vibration sensor signal features. Furthermore, a bidirectional long short-term memory network is built to learn the temporal relationships between the extracted signal features of the convolution operation. Finally, regression operations are performed through fully connected layers to estimate the position and velocity vectors of the moving target. The dataset consists of footstep vibration signal data from six experimental subjects walking on four different paths and the actual motion trajectories of the moving targets obtained using a visual tracking system. Experimental results show that compared to WT-TDOA and SAE-BPNN, the positioning accuracy of our method has been improved by 37.9% and 24.8%, respectively, with a system average positioning error reduced to 0.376 m.

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood–brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignant skin tumor. Early and precise diagnosis of tumor staging is crucial for long-term outcomes. While pathological diagnosis has traditionally served as the gold standard, the assessment of differentiation levels heavily depends on subjective judgments. Therefore, how to improve the diagnosis accuracy and objectivity of pathologists has become an urgent problem to be solved. We used multispectral imaging (MSI) to enhance tumor classification. The hematoxylin and eosin (H&E) stained cSCC slides were from Shanghai Ruijin Hospital. Scale-invariant feature transform was applied to multispectral images for image stitching, while the adaptive threshold segmentation method and random forest segmentation method were used for image segmentation, respectively. Synthetic pseudo-color images effectively highlight tissue differences. Quantitative analysis confirms significant variation in the nuclear area between normal and cSCC tissues (p < 0.001), supported by an AUC of 1 in ROC analysis. The AUC within cSCC tissues is 0.57. Further study shows higher nuclear atypia in poorly differentiated cSCC tissues compared to well-differentiated cSCC (p < 0.001), also with an AUC of 1. Lastly, well differentiated cSCC tissues show more and larger keratin pearls. These results have shown that combined MSI with imaging processing techniques will improve H&E stained human cSCC diagnosis accuracy, and it will be well utilized to distinguish histopathological staging features.

In the PUREX (the plutonium uranium reduction extraction) process, a plutonium barrier unit (1BXX) is used to achieve deep plutonium stripping. According to the operating experience of the French reprocessing plant, after the separation of uranium and plutonium in the first cycle (1B + 1BXX), the plutonium barrier unit has excellent stripping effect, such that the removal of plutonium from uranium can already be achieved in the first cycle, and the second cycle only needs to focus on the removal of neptunium from uranium in order to obtain a qualified uranium product. In recent decades, China has also been actively conducting research on the plutonium barrier unit process to reduce the plutonium concentration in the primary uranium product in the first cycle to avoid the need to remove neptunium and plutonium at the same time in the second cycle, and to improve the efficiency and feasibility of reprocessing. Due to the lack of design basis for plutonium barriers to achieve deep plutonium stripping at present, this study conducts a basic study on the plutonium barrier unit, aiming to provide data for the optimization of plutonium barriers in the actual reprocessing process at a later date. In this work, a kinetic study on the reduction and stripping of trace plutonium from dibutyl phosphate-containing organic phases was carried out first, and the kinetic equations for the reduction and stripping of Pu(IV) by U(IV) under flow process conditions were obtained. The effects of U(IV) addition on the extraction loss of U(IV) and the concentration distribution of U(IV) at various stages were investigated by process simulation. Additionally, the oxidation of U(IV) under process conditions was investigated to clarify the process chemistry of U(IV) oxidation and to provide a reference for the oxidation consumption of U(IV). Finally, the process parameters of the plutonium barrier unit were preliminarily designed based on the above research.

As one of the key ways to realize the industrialization and green development of construction, prefabricated construction is conducive to saving resources and energy and improving labor productivity and quality. Aiming to solve the problem of the lack of standardization in the design of prefabricated residential buildings, which leads to the components not being universally used and the industrial characteristics not being fully embodied, while excessive standardization leads to a lack of personalization and flexibility, the modular design theory is applied to the standardized design of prefabricated residential buildings in this study. The application route of modular design theory in the standardized design is constructed, that is, “system decomposition—module design—module combination”. Taking residential buildings within a height of 54 m as an example, each basic functional module is standardized and combined into standard plans. At the same time, the functional space module design based on modular coordination and the module combination design based on the trinity of “modulus, pattern, and mode” are discussed. This research is of great significance for giving full play to the comprehensive benefits of prefabricated concrete structures in quality improvement, cost reduction, and rapid assembly.

As a key component of the ecosystem, soil seed banks (SSBs) play a vital role in the evolution and renewal of plant communities. Although the pattern and mechanisms of influence of SSBs along the altitudinal gradient have been reported, most studies have focused on forest, grassland and alpine meadow ecosystems. The pattern and factors of SSBs across the altitudinal gradient in sedge peatlands remain largely unknown. Through vegetation surveys and seed germination experiments, we studied the changes in aboveground vegetation and SSBs in sedge peatlands at altitudes ranging from 300 m to 1300 m in the Changbai Mountains, China, and discussed the direct and indirect effects of climatic factors, soil properties and aboveground vegetation on SSBs. The results showed that the richness and density of the SSBs of sedge peatlands decreased with the altitude. Similarly, aboveground vegetation richness and density declined with altitude. A Spearman correlation analysis showed that SSB richness and density were mainly correlated with mean annual temperature, soil total phosphorus and ammonia nitrogen and the plant composition and richness of aboveground vegetation. A structural equation model analysis showed that climatic factors and aboveground vegetation directly affected seed bank richness, while soil properties indirectly affected it by directly affecting aboveground vegetation. Climatic factors, soil properties and aboveground vegetation directly affected SSB density, and soil properties indirectly affected it by directly affecting aboveground vegetation. This finding enhances our understanding of the altitude patterns of the SSBs in sedge peatlands and the response to future climate and environmental changes.

In the present study, an acid catalyst (UiO-66-SO3H) with Brønsted and Lewis acid sites was synthesised for the preparation of highly efficient biodiesel from oleic acid and methanol using chlorosulphonic acid sulfonated metal–organic frameworks (UiO-66) prepared with acetic acid as a moderator. The prepared catalysts were characterised using XRD, SEM, FT-IR and BET. The catalytic efficiency of the sulfonated catalysts was significantly improved and successful sulfonation was demonstrated by characterisation techniques. Biodiesel was synthesised by the one-pot method and an 85.0% biodiesel yield was achieved under optimum conditions of the reaction. The esterification reaction was determined to be consistent with a proposed primary reaction and the kinetics of the reaction was investigated. A reusability study of the catalyst (UiO-66-SO3H) was also carried out with good reproducibility. In conclusion, the present study provides some ideas for the synthesis of catalysts with high catalytic activity for the application in the catalytic preparation of biodiesel.

Exchange programs have been found to have a positive impact on regional economic growth, university cooperation, and student academic, and professional development. However, there has been limited analysis of the factors that influence the quality of these programs. In this study, a mixed-methods approach was used to examine regional exchange programs in China. Qualitative research was conducted using Octopus Big Data Crawler software, Timdream.org software, and 33 interviews to develop a questionnaire that covers student expectations, service quality, and satisfaction. Using SPSS 22 and Amos 21, the study analyzed the interactive relationships among expectations, perceived service quality, and satisfaction in the context of regional education integration based on a sample of 246 questionnaires. The results demonstrate that perceived service quality plays an intermediary role in the relationship between expectations and satisfaction, with students' perceptions of learning quality and interpersonal quality at the receiving university influencing their satisfaction levels. This study provides important insights into the factors that impact the quality of regional exchange programs in China.

BackgroundIt remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM.Methods and findingsThis open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection.ConclusionsThe combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity.Trial registrationClinicalTrials.gov Identifier: NCT03493048.