Plasma proteometabolome in lung cancer: exploring biomarkers through bidirectional Mendelian randomization and colocalization analysis.

Unlike other cancers with widespread screening (breast, colorectal, cervical, prostate, and skin), lung nodule biopsies for positive screenings have higher morbidity with clinical complications. Development of non-invasive diagnostic biomarkers could thereby significantly enhance lung cancer management for at-risk patients. Here, we leverage Mendelian Randomization (MR) to investigate the plasma proteome and metabolome for potential biomarkers relevant to lung cancer. Utilizing bidirectional MR and co-localization analyses, we identify novel associations, highlighting inverse relationships between plasma proteins SFTPB and KDELC2 in lung adenocarcinoma (LUAD) and positive associations of TCL1A with lung squamous cell carcinoma (LUSC) and CNTN1 with small cell lung cancer (SCLC). Additionally, our work reveals significant negative correlations between metabolites such as theobromine and paraxanthine, along with paraxanthine-related ratios, in both LUAD and LUSC. Conversely, positive correlations are found in caffeine/paraxanthine and arachidonate (20:4n6)/paraxanthine ratios with these cancer types. Through single-cell sequencing data of normal lung tissue, we further explore the role of lung tissue-specific protein SFTPB in carcinogenesis. These findings offer new insights into lung cancer etiology, potentially guiding the development of diagnostic biomarkers and therapeutic approaches.

Elevated incidence of somatic mutations at prevalent genetic sites.

The common loci represent a distinct set of the human genome sites that harbor genetic variants found in at least 1% of the population. Small somatic mutations occur at the common loci and non-common loci, i.e. csmVariants and ncsmVariants, are presumed with similar probabilities. However, our work revealed that within the coding region, common loci constituted only 1.03% of all loci, yet they accounted for 5.14% of TCGA somatic mutations. Furthermore, the small somatic mutation incidence rate at these common loci was 2.7 times that observed in the non-common. Notably, the csmVariants exhibited an impressive recurrent rate of 36.14%, which was 2.59 times of the ncsmVariants. The C-to-T transition at the CpG sites accounted for 32.41% of the csmVariants, which was 2.93 times for the ncsmVariants. Interestingly, the aging-related mutational signature contributed to 13.87% of the csmVariants, 5.5 times that of ncsmVariants. Moreover, 35.93% of the csmVariants contexts exhibited palindromic features, outperforming ncsmVariant contexts by 1.84 times. Notably, cancer patients with higher csmVariants rates had better progression-free survival. Furthermore, cancer patients with high-frequency csmVariants enriched with mismatch repair deficiency were also associated with better progression-free survival. The accumulation of csmVariants during cancerogenesis is a complex process influenced by various factors. These include the presence of a substantial percentage of palindromic sequences at csmVariants sites, the impact of aging and DNA mismatch repair deficiency. Together, these factors contribute to the higher somatic mutation incidence rates of common loci and the overall accumulation of csmVariants in cancer development.

Genome-wide chromatin accessibility reveals transcriptional regulation of heterosis in inter-subspecific hybrid rice.

The utilization of rice heterosis is essential for ensuring global food security; however, its molecular mechanism remains unclear. In this study, comprehensive analyses of accessible chromatin regions (ACRs), DNA methylation, and gene expression in inter-subspecific hybrid and its parents were performed to determine the potential role of chromatin accessibility in rice heterosis. The hybrid exhibited abundant ACRs, in which the gene ACRs and proximal ACRs were directly related to transcriptional activation rather than the distal ACRs. Regarding the dynamic accessibility contribution of the parents, paternal ZHF1015 transmitted a greater number of ACRs to the hybrid. Accessible genotype-specific target genes were enriched with overrepresented transcription factors, indicating a unique regulatory network of genes in the hybrid. Compared with its parents, the differentially accessible chromatin regions with upregulated chromatin accessibility were much greater than those with downregulated chromatin accessibility, reflecting a stronger regulation in the hybrid. Furthermore, DNA methylation levels were negatively correlated with ACR intensity, and genes were strongly affected by CHH methylation in the hybrid. Chromatin accessibility positively regulated the overall expression level of each genotype. ACR-related genes with maternal Z04A-bias allele-specific expression tended to be enriched during carotenoid biosynthesis, whereas paternal ZHF1015-bias genes were more active in carbohydrate metabolism. Our findings provide a new perspective on the mechanism of heterosis based on chromatin accessibility in inter-subspecific hybrid rice.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms.

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

Insights into heterosis from histone modifications in the flag leaf of inter-subspecific hybrid rice.

BACKGROUND: Inter-subspecific hybrid rice represents a significant breakthrough in agricultural genetics, offering higher yields and better resilience to various environmental stresses. While the utilization of these hybrids has shed light on the genetic processes underlying hybridization, understanding the molecular mechanisms driving heterosis remains a complex and ongoing challenge. Here, chromatin immunoprecipitation-sequencing (ChIP-seq) was used to analyze genome-wide profiles of H3K4me3 and H3K27me3 modifications in the inter-subspecific hybrid rice ZY19 and its parents, Z04A and ZHF1015, then combined them with the transcriptome and DNA methylation data to uncover the effects of histone modifications on gene expression and the contribution of epigenetic modifications to heterosis. RESULTS: In the hybrid, there were 8,126 and 1,610 different peaks for H3K4me3 and H3K27me3 modifications when compared to its parents, respectively, with the majority of them originating from the parental lines. The different modifications between the hybrid and its parents were more frequently observed as higher levels in the hybrid than in the parents. In ZY19, there were 476 and 84 allele-specific genes with H3K4me3 and H3K27me3 modifications identified, representing 7.9% and 12% of the total analyzed genes, respectively. Only a small portion of genes that showed differences in parental H3K4me3 and H3K27me3 modifications which demonstrated allele-specific histone modifications (ASHM) in the hybrid. The H3K4me3 modification level in the hybrid was significantly lower compared to the parents. In the hybrid, DNA methylation occurs more frequently among histone modification target genes. Additionally, over 62.58% of differentially expressed genes (DEGs) were affected by epigenetic variations. Notably, there was a strong correlation observed between variations in H3K4me3 modifications and gene expression levels in the hybrid and its parents. CONCLUSION: These findings highlight the substantial impact of histone modifications and DNA methylation on gene expression during hybridization. Epigenetic variations play a crucial role in controlling the differential expression of genes, with potential implications for heterosis.

Venetoclax overcomes resistance to all-trans retinoic acid in a variant acute promyelocytic leukemia with TNRC18::RARA fusion.

Acute promyelocytic leukemia (APL) is generally driven by PML::RARA, but approximately 2% of variant APL patients do not contain this fusion gene and pose challenges in diagnosis and treatment. Here, we reported an aggressive APL patient with variant TNRC18::RARA fusion gene, who was resistant to standard differentiation induction therapy consisting of all-trans retinoic acid (ATRA) and arsenic trioxide but achieved complete remission with venetoclax plus ATRA. Mechanistically, venetoclax possesses synergistic effects in ATRA-induced TNRC18::RARA-positive cell differentiation.

Anomalous far-field polarization around bound states in the continuum in non-Bravais lattices.

It is generally believed that at-Γ bound states in the continuum (BICs) are enclosed by a linearly polarized vortex in momentum space when the structures have mirror (σz) symmetry, in-plane inversion (I) symmetry, and time reversal symmetry (T). Here, we reveal an anomalous situation in which at-Γ BICs can be enclosed by linearly and elliptically polarized far-field even when the σz, I, and T symmetries are all maintained in non-Bravais lattices, which is radically different from previous cognition. Asymmetric, diatomic structures are designed to elaborate this intriguing phenomenon. By controlling the geometric parameters or refractive indexes of the two meta-atoms, the far-field polarization around the at-Γ BICs gradually deviates from linear polarization and approaches circular polarization. Our findings reveal that non-Bravais lattices can provide a novel platform to manipulate the far-field polarization, showing important applications in quantum entanglement, structured light, and radiation modulation.

Fabrication of A Multi-functional Separator Incorporating Crown ether- Polyoxometalate Supramolecular Compound for Lithium-Sulfur Batteries.

Recently, research on polyoxometalates (POMs) has gained significant momentum. Owing to their properties as electronic sponges, POMs catalyst harbor substantial potential in lithium-sulfur battery research. However, POMs undergo a transformation into reduced heteropoly blue (HPB) during electrochemical reactions, which then dissolve into the electrolyte, resulting in catalyst loss. In this research, we amalgamated 18-crown-6 (CR6) with K3PW12O40, (KPW), synthesized a novel POM-based supramolecular compound, and integrated it with graphene oxide (GO) to fabricate a multi-functional composite polypropylene (PP) separator KPW-CR6/GO/PP. The crown ether array was employed to immobilize POM and construct ion transport channels, thereby enhancing the Li+ migration rate and capturing polysulfides. Subsequently, leveraging the stable structure and redox properties of POM, the polysulfide is catalyzed to transform and inhibit the shuttle effect, thereby protecting the Li anode. The lithium-sulfur batteries with the Crown ether-POM supramolecular compound separators, exhibit enhanced capacity and stability (1073.3 mAh g-1 at 1.0 C, and 81.5% retention rate after 250 cycles). The battery (S loading: 3.2 mg cm-2) presents an initial specific discharge capacity of 543.4 mAh g-1 at 0.5 C, with 89.8% of the capacity retained after 160 cycles. This underlines the practical application potential of Crown ether-POM supramolecular materials in Li-S batteries.

Metabolic profile of follicular fluid in patients with ovarian endometriosis undergoing IVF: a pilot study.

RESEARCH QUESTION: What are the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing IVF? DESIGN: This was an exploratory cohort study on endometriosis. In total, 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy, and 23 controls matched in terms of age and body mass index (women with infertility due to male or tubal factors) were enrolled in this study. All patients underwent IVF treatment with a gonadotrophin-releasing hormone antagonist protocol, and follicular fluid was collected at oocyte retrieval. The metabolomics of follicular fluid samples was analysed using an ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was selected by performing stepwise logistic regression analysis with backward elimination. RESULTS: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with sensitivity of 94.7% and specificity of 95.7%. Enrichment analysis via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in eight metabolic pathways. CONCLUSION: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of follicular fluid in patients with ovarian endometriosis. These findings may provide a new basis for better understanding of how diseases progress, and for the discovery of new biomarkers.

Enhancing selection of alcohol consumption-associated genes by random forest.

Machine learning methods have been used in identifying omics markers for a variety of phenotypes. We aimed to examine whether a supervised machine learning algorithm can improve identification of alcohol-associated transcriptomic markers. In this study, we analysed array-based, whole-blood derived expression data for 17 873 gene transcripts in 5508 Framingham Heart Study participants. By using the Boruta algorithm, a supervised random forest (RF)-based feature selection method, we selected twenty-five alcohol-associated transcripts. In a testing set (30 % of entire study participants), AUC (area under the receiver operating characteristics curve) of these twenty-five transcripts were 0·73, 0·69 and 0·66 for non-drinkers v. moderate drinkers, non-drinkers v. heavy drinkers and moderate drinkers v. heavy drinkers, respectively. The AUC of the selected transcripts by the Boruta method were comparable to those identified using conventional linear regression models, for example, AUC of 1958 transcripts identified by conventional linear regression models (false discovery rate < 0·2) were 0·74, 0·66 and 0·65, respectively. With Bonferroni correction for the twenty-five Boruta method-selected transcripts and three CVD risk factors (i.e. at P < 6·7e-4), we observed thirteen transcripts were associated with obesity, three transcripts with type 2 diabetes and one transcript with hypertension. For example, we observed that alcohol consumption was inversely associated with the expression of DOCK4, IL4R, and SORT1, and DOCK4 and SORT1 were positively associated with obesity, and IL4R was inversely associated with hypertension. In conclusion, using a supervised machine learning method, the RF-based Boruta algorithm, we identified novel alcohol-associated gene transcripts.

Simultaneous Detection of Ochratoxin A and Aflatoxin B1 Based on Stable Tuning Fork-shaped DNA Fluorescent Aptasensor.

Tuning fork, consisting of two fork arms and a fork handle, has a stable and rigid structure. Inspired by this structure, a tuning fork-shaped DNA (TF-DNA) fluorescence aptasensor was constructed to detect ochratoxin A (OTA) and aflatoxin B1 (AFB1). A TF-DNA double-stranded structure capable of attaching both OTA aptamer labeled with the FAM fluorescent group (FAM-Apt) and AFB1 aptamer labeled with the ROX fluorescent group (ROX-Apt) was designed and linked to magnetic beads. This TF-DNA double-stranded structure can provide a stable platform for dual-target detection. In the presence of OTA and AFB1, FAM-Apt and ROX-Apt preferentially bound to them and detached from the TF-DNA double-stranded structure. Dual-signal fluorescent probes were collected from the supernatant by magnetic separation, and achieved fluorescence enhancement at 520 nm and 607 nm, respectively. The linear ranges are 0.05 ng/mL to 100 ng/mL for OTA and 0.1 ng/mL to 100 ng/mL for AFB1, and the detection limits are 0.015 ng/mL and 0.045 ng/mL, respectively. The developed sensor has the advantages of simple and fast preparation, good specificity and reproducibility, which is promising for the simultaneous determination of multiple hazardous substances in food.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Use of new-media health information among the elderly and its effect on their health and health management.

BACKGROUND: The aim of this study to explore the use of new-media health information and its influence on their health and health management. METHODS: A total of 208 elderly people in Qiqihar City were selected as the survey objects, and a questionnaire was used to investigate their access to health information through new-media platforms. We analyze the factors ( e.g., education、pre-retirement occupation, etc.) in the use of health information on new-media platforms. RESULTS: Monthly income, educational level, pre-retirement occupation and attention of the new-media of the elderly had significant effects on health information acquisition (p < 0.05). CONCLUSION: The use of new-media health information among the elderly was diversified and had an impact on their health management. We should standardize the management of new-media health information dissemination platforms and publicize the use of new-media health information in a targeted way, to improve the self-health management of the elderly and reduce their burden on the national medical system.

The effectiveness of evidence-based nursing intervention for nasal irrigation after endoscopic sinus surgery in patients with chronic rhinosinusitis: a randomized controlled trial.

OBJECTIVES: To evaluate its effect of an evidence-based nursing program for nasal irrigation after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS). METHODS: A total of 66 patients with CRS were randomly divided into two groups, for which the experimental group received evidence-based nasal irrigation nursing, and the control group received conventional nursing. Differences in Sino-Nasal Outcome Test-20 (SNOT-20), visual analogue scale (VAS), Lund-Mackay CT, Endoscopic Lund Kennedy Score (LKES) and overall efficacy were assessed between the two groups. RESULTS: 2, 4 and 12 weeks after the intervention, the scores of SNOT-20, VAS, Lund-Mackay CT and LKES in the two groups were significantly lower than those before the surgery (P < 0.05). Compared with the control group, the scores were significantly lower in the experimental group (P < 0.05). 12 weeks after the intervention, the overall effective rate of treatment in the experimental group was 90.62%, while the control group was 16.43%, but the difference was not statistically significant in treatment effect (P > 0.05). CONCLUSIONS: The implementation of nasal irrigation evidence-based nursing program for patients with CRS after endoscopic sinus surgery can promote postoperative nasal mucosal recovery, improve treatment efficiency, and help improve patient comfort, quality of life and other subjective feelings. TRIAL REGISTRATION: The study was registered retrospectively with reference number ChiCTR2300075484 on 06/09/2023, available at: https://www.chictr.org.cn .

Ehrlichia chaffeensis Etf-3 Induces Host RAB15 Upregulation for Bacterial Intracellular Growth.

Ehrlichia chaffeensis infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, E. chaffeensis resides in membrane-bound inclusions, E. chaffeensis-containing vesicles (ECVs), which have early endosome-like characteristics and fuse with early autophagosomes but not lysosomes, to evade host innate immune microbicidal mechanisms and obtain nutrients for bacterial intracellular growth. The mechanisms exploited by E. chaffeensis to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied. Here, we demonstrate that E. chaffeensis type IV secretion system (T4SS) effector Etf-3 induces RAB15 upregulation in host cells and that RAB15, which is localized on ECVs, inhibits ECV fusion with lysosomes and induces autophagy. We found that E. chaffeensis infection upregulated RAB15 expression using qRT-PCR, and RAB15 was colocalized with E. chaffeensis using confocal microscopy. Silence of RAB15 using siRNA enhanced ECV maturation to late endosomes and fusion with lysosomes, as well as inhibited host cell autophagy. Overexpression of Etf-3 in host cells specifically induced RAB15 upregulation and autophagy. Our findings deepen the understanding of E. chaffeensis pathogenesis and adaptation in hosts as well as the function of RAB15 and facilitate the development of new therapeutics for HME.

Host Cells Upregulate Phosphate Transporter PIT1 to Inhibit Ehrlichia chaffeensis Intracellular Growth.

Ehrlichia chaffeensis infects and proliferates inside monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. After internalization, E. chaffeensis resides in specialized membrane-bound inclusions, E. chaffeensis-containing vesicles (ECVs), to evade from host cell innate immune responses and obtain nutrients. However, mechanisms exploited by host cells to inhibit E. chaffeensis growth in ECVs are still largely unknown. Here we demonstrate that host cells recognize E. chaffeensis Ech_1067, a penicillin-binding protein, and then upregulate the expression of PIT1, which is a phosphate transporter and transports phosphate from ECVs to the cytosol to inhibit bacterial growth. We found that host cells upregulate the PIT1 expression upon E. chaffeensis infection using transcriptome sequencing, qRT-PCR and Western blotting, and PIT1 is localized on the ECV membrane in infected THP-1 cells using confocal microscopy. Silence of PIT1 using shRNA enhances E. chaffeensis intracellular growth. Finally, we found that E. chaffeensis Ech_1067 induces the upregulation of PIT1 expression through the MyD88-NF-κB pathway using recombinant protein for stimulation and siRNA for silence. Our findings deepen the understanding of the innate immune responses of host cells to inhibit bacterial intracellular growth and facilitate the development of new therapeutics for HME.

Exploring potential neuroimaging biomarkers for the response to non-steroidal anti-inflammatory drugs in episodic migraine.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. METHODS: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. RESULTS: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. CONCLUSIONS: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.

Ensemble and Pre-Training Approach for Echo State Network and Extreme Learning Machine Models.

The echo state network (ESN) is a recurrent neural network that has yielded state-of-the-art results in many areas owing to its rapid learning ability and the fact that the weights of input neurons and hidden neurons are fixed throughout the learning process. However, the setting procedure for initializing the ESN's recurrent structure may lead to difficulties in designing a sound reservoir that matches a specific task. This paper proposes an improved pre-training method to adjust the model's parameters and topology to obtain an adaptive reservoir for a given application. Two strategies, namely global random selection and ensemble training, are introduced to pre-train the randomly initialized ESN model. Specifically, particle swarm optimization is applied to optimize chosen fixed and global weight values within the network, and the reliability and stability of the pre-trained model are enhanced by employing the ensemble training strategy. In addition, we test the feasibility of the model for time series prediction on six benchmarks and two real-life datasets. The experimental results show a clear enhancement in the ESN learning results. Furthermore, the proposed global random selection and ensemble training strategies are also applied to pre-train the extreme learning machine (ELM), which has a similar training process to the ESN model. Numerical experiments are subsequently carried out on the above-mentioned eight datasets. The experimental findings consistently show that the performance of the proposed pre-trained ELM model is also improved significantly. The suggested two strategies can thus enhance the ESN and ELM models' prediction accuracy and adaptability.

[Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children].

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Spidroin-mimetic Engineered Protein Fibers with High Toughness and Minimized Batch-to-batch Variations through ß-sheets Co-assembly.

Synthetic spidroin fibers have not yet attained the same level of toughness and stability as natural spider silks due to the complexity of composition and hierarchical structure. Particularly, understanding the intricate interactions between spidroin components in spider fiber is still elusive. Herein, we report modular design and preparation of spidroin-mimetic fibers composed of a conservative C-terminus spidroin module, two different natural ß-sheets modules, and a non-spidroin random-coil module. The resulting fibers exhibit a toughness of ~200 MJ/m3, reaching the highest value among the reported artificial spider silks. The interactions between two components of recombinant spidroins facilitate the intermolecular co-assembly of ß-sheets, thereby enhancing the mechanical strength and reducing batch-to-batch variability in the dual-component spidroin fibers. Additionally, the dual-component spidroin fibers offer potential applications in implantable or even edible devices. Therefore, our work presents a generic strategy to develop high-performance protein fibers for diverse translations in different scenarios.