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In this work, Mg/Al composite plates with different thickness ratios were prepared by the asymmetrical rolling process with differential temperature rolls and isothermal symmetrical rolling. Microstructural evolution and mechanical properties of matrix and composite materials with different thicknesses were analyzed. Influence of thickness ratios on the coordinated deformability of heterogeneous metals and interface toughness under the action of temperature gradient and shear force was investigated. Results show that the relative deformation rates of matrix and composite materials converge gradually under the influence of work hardening of Mg/Al layer. The Mg layer is mainly DRXed grains and texture intensity gradually weakens with increasing thickness ratio. The Al layer is mostly dominated by subgrains and deformed grains, which have a strong correlation with thickness ratio. Strength and plasticity of composites first increase and then decrease with increasing thickness ratio. Fracture of composite plate occurs in intermetallic compounds (IMCs). Thickness of IMCs has a strong positive correlation with thickness ratio. When the thickness ratio of AZ31B/Al6061 for 5, the relative thickness of IMCs is the largest and the relative bonding strength is the smallest. When the thickness ratio of AZ31B/Al6061 for 3, there is no element aggregation in IMCs, and the comprehensive mechanical properties of composite plate are comparatively better.

In this work, a new strategy for achieving ultrahigh strength in the coarse-grained Mg-Gd binary alloy via utilizing recrystallization texture hardening and maximizing precipitation strengthening has been reported. Forging at a much high temperature suppresses dynamic precipitation, enabling the super-saturation of Gd atoms in Mg matrix. This facilitates the formation of fully recrystallized grains with strong texture and induces an exceptionally high precipitation hardening in the following ageing. Therefore, the forged Mg-13Gd sample exhibited extraordinary tensile yield strength (TYS) of ∼430 MPa, in which ageing-induced TYS increment exceeds ∼210 MPa, as the highest record so far in precipitation-hardened Mg communities. These results provide important theoretical guidance for fabricating the large section and high-strength Mg components for industrial applications.

Abstract Background Prostate cancer ranks among the six most lethal malignancies worldwide. Telomerase, a reverse transcriptase enzyme, plays a pivotal role in extending cellular telomeres and is intimately associated with cell proliferation and division. However, the interconnection between prostate cancer and telomerase-related genes (TEASEs) remains unclear. Methods Somatic mutations and copy number alterations of TEASEs were comprehensively analyzed. Subsequently, the transcripts of prostate cancer patients in TCGA and GEO databases were integrated to delineate new molecular subtypes. Followed by constructing a risk model containing nine characteristic genes through Lasso regression and Cox prognostic analysis among different subtypes. Various aspects including prognosis, tumor microenvironment (TME), landscape of immunity, tumor mutational burden (TMB), stem cell correlation, and median inhibitory concentration amongst different risk groups were compared. Finally, the expression, prognosis, and malignant biological behavior of ZW10 interactor (ZWINT) in vitro was explored. Results TEASEs exhibited a notably high mutation frequency. Three distinct molecular subtypes and two gene subclusters based on TEASEs were delineated, displaying significant associations with prognosis, immune function regulation, and clinical characteristics. Low-risk patients demonstrated superior prognosis and better response to immunotherapy. Conversely, high-risk patients exhibited higher TMB and stronger stem cell correlations. It was also found that the patients’ sensitivity to chemotherapy agents was impacted by the risk score. Finally, ZWINT’s potential as a novel diagnostic and prognostic biomarker for prostate cancer was validated. Conclusions TEASEs play a pivotal role in modulating immune regulation and immunotherapeutic responses, thereby significantly impacting the diagnosis, prognosis, and treatment strategies for affected patients.

Abstract Background Non-small cell lung cancer (NSCLC) is a prevalent and heterogeneous disease with significant genomic variations between the early and advanced stages. The identification of key genes and pathways driving NSCLC tumor progression is critical for improving the diagnosis and treatment outcomes of this disease. Methods In this study, we conducted single-cell transcriptome analysis on 93,406 cells from 22 NSCLC patients to characterize malignant NSCLC cancer cells. Utilizing cNMF, we classified these cells into distinct modules, thus identifying the diverse molecular profiles within NSCLC. Through pseudotime analysis, we delineated temporal gene expression changes during NSCLC evolution, thus demonstrating genes associated with disease progression. Using the XGBoost model, we assessed the significance of these genes in the pseudotime trajectory. Our findings were validated by using transcriptome sequencing data from The Cancer Genome Atlas (TCGA), supplemented via LASSO regression to refine the selection of characteristic genes. Subsequently, we established a risk score model based on these genes, thus providing a potential tool for cancer risk assessment and personalized treatment strategies. Results We used cNMF to classify malignant NSCLC cells into three functional modules, including the metabolic reprogramming module, cell cycle module, and cell stemness module, which can be used for the functional classification of malignant tumor cells in NSCLC. These findings also indicate that metabolism, the cell cycle, and tumor stemness play important driving roles in the malignant evolution of NSCLC. We integrated cNMF and XGBoost to select marker genes that are indicative of both early and advanced NSCLC stages. The expression of genes such as CHCHD2, GAPDH, and CD24 was strongly correlated with the malignant evolution of NSCLC at the single-cell data level. These genes have been validated via histological data. The risk score model that we established (represented by eight genes) was ultimately validated with GEO data. Conclusion In summary, our study contributes to the identification of temporal heterogeneous biomarkers in NSCLC, thus offering insights into disease progression mechanisms and potential therapeutic targets. The developed workflow demonstrates promise for future applications in clinical practice.

The macroscopic finite element method (FEM) and the crystal plasticity finite element method (CPFEM) were combined to study the transverse difference of activation slip/twin system in wide AZ31 magnesium alloy plates during rolling. The macro-deformation and micro-texture evolution along the transverse direction of the plate during rolling were analyzed experimentally. The microscopic CPFEM was developed on the basis of the thermo-force coupling behavior during plate rolling obtained from macroscopic FEM. The CPFEM parameters were fitted by uniaxial compression experiments. This combination of two scale simulations accurately predicted the texture evolution during the rolling process and had been experimentally validated. Further examination of the deformation mechanism reveals that the transverse spread action of the plate is stronger at the edge region compared to center, and this transverse spread action has a more significant impact on the activation of the {10 1‾ 2} tension twin. The comparison of the activation and extension of pyramidal slip in granular and plate-like grains reveals that plate-like grains are more prone to generate slip bands through the grain, leading to cracking of the grain along the slip activation band and further formation of sub-grains.

Abstract Objective Chronic subjective tinnitus is a worldwide intractable problem. In our previous studies, customized music therapy combined with a follow‐up system can reduce tinnitus perception and improve anxiety/depression. This study aims to explore which characteristics of tinnitus patients are more likely to benefit from our therapy. Study Design This study included 1031 patients with chronic subjective tinnitus, all of whom completed customized music therapy with the follow‐up system. Population demographics, tinnitus characteristics, and tinnitus‐related scales at pretherapy and posttherapy were collected. Setting Huadong Hospital affiliated Fudan University, Department of Otorhinolaryngology–Head & Neck Surgery from 2018 to 2022. Methods A paired t test and the one‐way analysis of variance were utilized to the overall efficacy and stratified difference based on tinnitus duration/age/tinnitus frequency. Results There were significant statistical differences in the Tinnitus Handicap Inventory (THI), Tinnitus Loudness Visual Analog Scale (VAS), and Hospital Anxiety and Depression Scale (HADS)‐A/D scores between pretherapy and 3 months posttherapy. THI and HADS (A/D) scores decreased the most in the 1‐year duration tinnitus group. The most significant decrease in THI and VAS scores was observed in the 31‐ to 50‐year‐old tinnitus group. Patients with high‐frequency tinnitus and extended high‐frequency tinnitus had greater decreases generally than those with low‐frequency tinnitus though no significance. Conclusion Group with severe and prolonged tinnitus, shorter duration of tinnitus onset, and 31 to 50 years old benefit more from our therapy. Therefore, standardized personalized music and consulting and follow‐up systems while promoting early treatment can reduce tinnitus and its comorbidities.

At the beginning of the ''Disease X'' outbreak, drug discovery and development are often challenged by insufficient and unbalanced data. To address this problem and maximize the information value of limited data, we propose a drug screening model, LGCNN, based on convolutional neural network (CNN), which enables rapid drug screening by integrating features of drug molecular structures and drug-target interactions at both local and global (LG) levels. Experimental results show that LGCNN exhibits better performance compared to other state-of-the-art classification methods under limited data. In addition, LGCNN was applied to anti-SARS-CoV-2 drug screening to realize therapeutic drug mining against COVID-19. LGCNN transcends the limitations of traditional models for predicting interactions between single drug targets and shows new advantages in predicting multi-target drug-target interactions. Notably, the cross-coronavirus generalizability of the model is also implied by the analysis of targets, drugs, and mechanisms in the prediction results. In conclusion, LGCNN provides new ideas and methods for rapid drug screening in emergency situations where data are scarce.

A wide width is one of the fundamental requirements for magnesium alloy sheets to fulfill the lightweight needs of the aerospace and rail transportation industries. Nevertheless, ensuring the dimensional integrity of wide-format magnesium alloy sheets is a challenge in most manufacturing facilities. Simultaneously, processing operations are susceptible to encountering production issues, including but not limited to significant loss of raw materials, elevated costs, environmental contamination, and safety risks. Therefore, to fulfill the operational demands of the hot rolling finishing line for wide sheets made of magnesium alloy, the present study employed ultrasonic-assisted shearing (UAS) to carry out a high-temperature shearing test investigation on the AZ31B magnesium alloy sheet. In this research, we employed scanning electron microscopy, optical microscopy, and a micro-hardness tester to investigate the relationship between ultrasonic amplitude and fracture behavior, deformation mechanism, and mechanical properties of magnesium alloy sheets following exposure to ultrasonic vibration. The fracture morphology of the sheet fracture demonstrates that the behavior of the magnesium alloy sheet fractures under ultrasonic vibration changes from ductile fracture under conventional shearing to brittle fracture under ultrasonic-assisted shearing. The primary cause of this transformation between ductile and brittle is the effect of ultrasonic vibration on the material's internal energy. High-energy ultrasonic amplitude action causes magnesium to absorb a significant amount of ultrasonic energy. This results in an increase in the number of dynamic re-crystallization grains in the material organization, a decrease in the number of twins, and significant refinement of the grains. The sheet's hardness also changes along the rolling and normal directions, with a uniform distribution. The magnesium alloy sheet's fracture quality is optimal when the ultrasonic amplitude is 10 μm in the UAS process. This treatment results in notable enhancements in the section's straightness and brightness. Our study aims to advance the mass manufacturing of wide-format magnesium alloy sheets by investigating a cost-effective and high-yield technique for shearing magnesium alloy sheets.

Low absolute strength becomes one major obstacle for the wider applications of low/no rare-earth (RE) containing Mg alloys. This review firstly demonstrates the importance of grain refinement in improving strength of Mg alloys by comprehensively comparing with other strategy, e.g., precipitation strengthening. Dynamic recrystallization (DRX) plays a crucial role in refining grain size of Mg wrought alloys. Therefore, secondly, the DRX models, grain nucleation mechanisms and the related grain refinement abilities in Mg alloys are summarized, including phase boundary, twin boundary and general boundary induced recrystallization. Thirdly, the newly developed low-RE containing Mg alloy, e.g., Mg-Ce, Mg-Nd and Mg-Sm based alloys, and the RE-free Mg alloys, e.g., Mg-Al, Mg-Zn, Mg-Sn and Mg-Ca based alloy, are reviewed, with the focus on enhancing the mechanical properties mainly via the grain refinement strategy. At the last section, the perspectives and outstanding issues concerning high-performance Mg wrought alloys are also proposed. This review is meant to promote the deep understanding on the critical role of grain refinement in Mg alloys and provide reference for the development of other high strength and low-cost Mg alloys which are fabricated by the conventional extrusion/rolling processing.

Extruded magnesium alloy bars are susceptible to uneven microstructure after the heat treatment process, which is characterised by coarse grain size in the surface, thus affecting the further processing properties of the overall bars. In this paper a new cyclic rotating-bending (CRB) process is proposed to improve the microstructure by achieving a gradient plastic deformation of the bars from the surface to the core. The paper is based on finite element simulations to qualitatively and quantitatively investigate the plastic strain distribution and evolution in the middle radial section of the bar under different CRB processes. In addition, the influence on the microstructure distribution under the processes is also further clarified. The results show that during CRB deformation, the plastic strain in the middle radial section of AZ31B magnesium alloy bars gradually decreases from the surface to the core radially, and the plastic strain in the surface is significantly positively correlated with the bending angle and the period of rotation. When the bending angle reaches 150°–170° and the period of rotation reaches 30 r, the section of the bars is fully plastic deformed. Simultaneously, compared to the initial microstructure, significant twinning deformation occurs in the surface of the bars after different CRB processes, which further promotes grain refinement.

ObjectivesInflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach.MethodsSingle nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion.ResultsFrom a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis.ConclusionsChanges in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.

To investigate the effects of differential temperature on microstructure, interfacial morphology and mechanical properties of Mg/Al composite plates, asymmetric rolling was used to prepare Mg/Al composite plates. The results show that the shear deformation induced slip system at interface is less and the degree of dislocation accumulation is higher in isothermal rolling compared to differential temperature rolling. This results in a higher degree of subgrain in each layer and higher tensile and yield strength of composite plate. However, the plate is prone to stress concentration at interface, which severely reduces elongation and bond strength. The differential temperature rolling can better promote the recrystallization of magnesium alloy and grain refinement of aluminum alloy at interface by introducing temperature gradient. This reduces the occurrence of stress concentrations at interface, resulting in higher elongation and bond strength of composite plate.

A new Mg–Sm–Ce–Mn-based alloying system with a large miscibility gap was uncovered, and multi-solute co-segregations at high-angular grain boundaries (HAGBs), dislocations and low-angular grain boundaries (LAGBs) are obtained after the proper extrusion process. During following long-term thermal exposure, the solute along HAGBs gradually evolves into nano-precipitates, while the precipitation process along LAGBs is obviously suppressed due to the intrinsically low-energy character, and numerous G. P. zones and γ” phases are formed in deformed regions, which always keep the limited size and reticular distribution. Consequently, the bimodal-grain structure is thermally stable, and the excellent high-temperature strength can be well maintained.

Abstract Backgrounds Tinnitus is a meaningless sound signal perceived by the patients in the absence of auditory stimuli. Due to the complex etiology and unclear mechanism, specific therapies for tinnitus are still in the exploratory stage. In recent years, personalized and customized music therapy has been proposed as an effective method for tinnitus treatment. The aim of this study was to explore the efficacy of customized therapy with a well-designed follow-up system in the treatment of tinnitus through a large sample one arm study and to identify the relevant factors affecting the treatment outcome. Methods The study investigated a total of 615 patients with unilateral or bilateral chronic tinnitus who received personalized and customized music therapy for 3 months. A complete follow-up system was designed by the professionals. Questionnaires of Tinnitus Handicap Inventory (THI), Hospital Anxiety and Depression Scale (HADS) and Visual Analogue Scale (VAS) were used to evaluate the therapeutic effects and relevant factors affecting the efficacy of therapy. Results The results showed a decreasing trend in THI and VAS scores after 3 months of therapy, with statistically significant differences between pre- and post-therapy time points (P

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6A shows a definite cell-specific methylation profile and m6A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway.

The influence of temperature and strain rate on the deformation behavior of twin-roll casting AZ31 alloy has been examined as a function of stress state using notched and un-notched tensile specimens. Failure behavior during the physical tension was carried out using FEM simulations with different fracture criteria. Using a combined experimental-FEM investigation, the applicability of each fracture criterion was verified to serve the prediction for the crack initiation under multiaxial stress state. Results show that the critical fracture strain presents a clear exponential relationship with stress triaxiality and strain rate, and a linear relationship with temperature. Through the quantitative analysis of the relationship, a mathematical model can be well established. After comparison and verification, the fracture model can accurately predict the forming limit during the plastic deformation of twin-roll casted AZ31 magnesium alloy under complex stress state, and the classical Cockcroft & Latham criterion is the most suitable criterion for predicting the related crack initiation.

Background: Long non-coding RNAs (lncRNAs) play an important role in the immune regulation of gastric cancer (GC). However, the clinical application value of immune-related lncRNAs has not been fully developed. It is of great significance to overcome the challenges of prognostic prediction and classification of gastric cancer patients based on the current study.Methods: In this study, the R package ImmLnc was used to obtain immune-related lncRNAs of The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) project, and univariate Cox regression analysis was performed to find prognostic immune-related lncRNAs. A total of 117 combinations based on 10 algorithms were integrated to determine the immune-related lncRNA prognostic model (ILPM). According to the ILPM, the least absolute shrinkage and selection operator (LASSO) regression was employed to find the major lncRNAs and develop the risk model. ssGSEA, CIBERSORT algorithm, the R package maftools, pRRophetic, and clusterProfiler were employed for measuring the proportion of immune cells among risk groups, genomic mutation difference, drug sensitivity analysis, and pathway enrichment score.Results: A total of 321 immune-related lncRNAs were found, and there were 26 prognostic immune-related lncRNAs. According to the ILPM, 18 of 26 lncRNAs were selected and the risk score (RS) developed by the 18-lncRNA signature had good strength in the TCGA training set and Gene Expression Omnibus (GEO) validation datasets. Patients were divided into high- and low-risk groups according to the median RS, and the low-risk group had a better prognosis, tumor immune microenvironment, and tumor signature enrichment score and a higher metabolism, frequency of genomic mutations, proportion of immune cell infiltration, and antitumor drug resistance. Furthermore, 86 differentially expressed genes (DEGs) between high- and low-risk groups were mainly enriched in immune-related pathways.Conclusion: The ILPM developed based on 26 prognostic immune-related lncRNAs can help in predicting the prognosis of patients suffering from gastric cancer. Precision medicine can be effectively carried out by dividing patients into high- and low-risk groups according to the RS.

Atractylodes species are widely distributed across East Asia and are cultivated as medicinal herbs in China, Japan, and Korea. Their unclear morphological characteristics and low levels of genetic divergence obscure the taxonomic relationships among these species. In this study, 24 plant samples were collected representing five species of Atractylodes located in China; of these, 23 belonged to members of the A. lancea complex. High-throughput sequencing was used to obtain the concatenated nrDNA sequences (18S-ITS1-5.8S-ITS2-28S) and plastid genomes. The concatenated nrDNA sequence lengths for all the Atractylodes species were 5,849 bp, and the GC content was 55%. The lengths of the whole plastid genome sequences ranged from 152,138 bp (A. chinensis) to 153,268 bp (A. lancea), while their insertion/deletion sites were mainly distributed in the intergenic regions. Furthermore, 33, 34, 36, 31, and 32 tandem repeat sequences, as well as 30, 30, 29, 30, and 30 SSR loci, were detected in A. chinensis, A. koreana, A. lancea, A. japonica, and A. macrocephala, respectively. In addition to these findings, a considerable number of heteroplasmic variations were detected in the plastid genomes, implying a complicated phylogenetic history for Atractylodes. The results of the phylogenetic analysis involving concatenated nrDNA sequences showed that A. lancea and A. japonica formed two separate clades, with A. chinensis and A. koreana constituting their sister clade, while A. lancea, A. koreana, A. chinensis, and A. japonica were found based on plastid datasets to represent a mixed clade on the phylogenetic tree. Phylogenetic network analysis suggested that A. lancea may have hybridized with the common ancestor of A. chinensis and A. japonica, while ABBA–BABA tests of SNPs in the plastid genomes showed that A. chinensis was more closely related to A. japonica than to A. lancea. This study reveals the extensive discordance and complexity of the relationships across the members of the A. lancea complex (A. lancea, A. chinensis, A. koreana, and A. japonica) according to cytonuclear genomic data; this may be caused by interspecific hybridization or gene introgression.

The low microalloying content and high yield strength of 365 MPa have been achieved simultaneously in extruded Mg–Ce–Al alloy which is mainly ascribed to the unexpected grain refinement (mean size of ∼420 nm). It is found that adding tiny Al (0.05 wt.%) into Mg–0.2 wt.% Ce alloy can promote the formation of Ce–Al-enriched segregation along dislocations and grain boundaries which can effectively counterbalance the thermally activated dislocation recovery and thus guarantee grain refinement. The ultra-fined grains are mainly related to both linear and planar cosegregation of solutes, rather than the traditional planar segregations and/or nanoprecipitations at grain boundaries.

Abstract Background Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method. Methods Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients. Results Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes. Conclusions For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence.

The temporal and spatial development law of regional geohazards is the result of the joint action of internal and external geological forces, which are relatively stable within a large area. Therefore, the source, magnitude and occurrence time of earthquakes are the main factors affecting the temporal and spatial development law of regional geohazards. In order to study the impact of "5·12" Wenchuan earthquake on the spatial and temporal development of geohazards in Sichuan Province, based on the data of landslide, collapse, debris flow, earthquake and rainfall from 1998 to 2018, the spatial and temporal characteristics of major geohazards in Sichuan Province around the Wenchuan earthquake were analyzed by mathematical statistics and spatial analysis methods, The results show that: ① Activity in major disasters in Sichuan Province shows cycles, under normal circumstances, it presents a small cycle of about 3 years, after the earthquake geohazards increased year by year, to the peak of 4a, then decreased year by year; the impact is not obvious after 8 years; ② The relative intensity of major geohazards has little change after the earthquake, but the activity and intensity of geohazards are not corresponding before the earthquake. In the geomorphic division, the largest number of geohazards is in Sichuan Basin, and the most active is in Northwest Sichuan Plateau. Compared with that before the earthquake, the occurrence of geohazards in the quaternary system is higher than that in the hard rock area. The geohazards in the tectonic zones have obvious zoning characteristics. The earthquake intensity of the Yangtze quasi-platform is much greater than that of the Songpan-Ganzi geosynclinal fold system before and after the earthquake, but the disaster activity is obviously weaker than that of the Songpan-Ganzi geosynclinal fold system, and the basic structural units have similar characteristics.

Geological hazards in plateau mountainous areas are the greatest hazards to traffic lines, and the key to effectively avoid risks is to grasp the engineering geological factors and inducing factors of geological hazards along the high way. Based on the geographical, geological, meteorological, remote sensing and field investigation, the paper systematically studies the influencing factors of the landslide and collapse in the belt area along the Jinxiao Highway in the plateau of Aba Prefecture in western Sichuan. The results indicate that: (1)the cleavage transformation of the carbonaceous mudstone, silty mudstone and siltstone in the zone, as well as The Himalayan period tectonic movement and frequent seismic activity intensified the fracture of rock mass, provided the material source for the landslide and collapse in the area and created favorable conditions for shaping the topography of the alpine valley; (2)concentrated rainfall in the region from June to September is the main factor triggering landslides and collapses; (3)high mountains, valleys, high-angle slopes and other terrain and geomorphology background and slope foot excavation are also an important factor that triggeringcollapse, landslides;(4)seasonal freezing-thawing accelerates the bedrock weathering failure and promotes the formation of landslides and rockfalls.

Introduction: The prediction of the impact of olfactory impairment on cognitive decline in older adults has been different among different age groups. Objective: This meta-analysis sought to estimate the predictive power of olfactory impairment on cognitive decline during follow-up in older adults of different ages. Material and methods: A medical literature search was carried out using these databases for eligible studies: MEDLINE, COCHRANE and EMBASE. Studies recording olfaction and cognition detection at the beginning and end of the follow-up were included in the preliminary screening. The medical records of older adults without cognitive impairment at the beginning of the follow-up were taken into account in this analysis. Raw data was extracted in order to estimate the relative risk and the corresponding 95% confidence interval (95% CI). Subgroup analysis of age was performed to eliminate the effect of age on the results. Statistical heterogeneity was measured using the I2 index and Cochran's Q test. Results: Eight studies were enrolled in this analysis (3237 events and 13165 participants), and the pooled relative risk for the 70–80 years old subgroup was 2.00 (95% CI = 1.79–2.23). Conclusion: Relatively, there is a higher risk of cognitive impairment at the end of follow-up in younger adults with olfactory impairment at the beginning of follow-up. The length of follow-up has a little effect on the relative risk.

Atractylodes japonica Koidz. ex Kitam. is a perennial herbal plant, and its dried rhizomes have been widely used as traditional medicine in China and Japan. In this study, we assembled and annotated the complete chloroplast (cp) genome sequence of A. japonica using the high-throughput sequencing approach. The cp genome of A. japonica is 153,208 bp in length with the overall GC content of 37.7%, including two inverted repeat (IR) regions of 25,147 bp, which was separated by a large single-copy (LSC) region of 84,255 bp and a small single-copy (SSC) region of 18,659 bp. 113 unique genes were annotated in the genome, including 80 protein-coding genes, 29 represented tRNA genes, and four denoted rRNA genes. A maximum-likelihood phylogenetic analysis with 38 complete cp sequences showed that Atractylodes formed a monophyletic clade, and A. japonica and A. koreana formed a subclade in Atractylodes. This study provides the chloroplast genome structure features and phylogenetic relationship of A. japonica.

Atractylodes koreana (Nakai) Kitam is a perennial herb of Asteraceae, mainly distributed in China and Korea, which is the main adulterant of traditional herbal medicine ‘Cangzhu’. In the present study, we reported the complete chloroplast (cp) genome of A. koreana with the total length of 153,232 bp, which is consisted of four regions, including one large single copy (LSC) region of 84,250 bp, one small single copy (SSC) region of 18,690 bp, and two inverted repeat regions (IRa and IRb) of 25,146 bp. The GC content of the complete cp genome is 37.7%. A total of 110 unique genes were annotated, comprising 79 protein-coding genes, 27 transfer RNA (tRNA) genes and four ribosome RNA (rRNA) genes. Moreover, nine protein-coding genes contained one intron and three protein-coding genes (clpP, ycf3, and rps12) contained two introns. The phylogenetic analysis indicated that A. koreana is a sister group of A. chinensis and A. lancea.

With the widespread use of traditional medicine around the world, the safety and efficacy of traditional herbal patent medicine have become an increasing concern to the public. However, it is difficult to supervise the authenticity of herbal materials in mixed herbal products according to the current quality standards, especially for traditional herbal patent medicine, with a distinct variance in the dosage of herbal materials. This study utilized the shotgun metabarcoding approach to analyze the biological ingredients of Fuke Desheng Wan (FKDSW), which is an effective traditional herbal product for the treatment of dysmenorrhea. Six herbal materials were collected, and a lab-made mock FKDSW sample was produced to establish a method for the authentication assessment of biological ingredients in traditional herbal patent medicine based on shotgun metabarcoding. Furthermore, four commercial FKDSW samples were collected to verify the practicality of the shotgun metabarcoding approach. Then, a total of 52.16 Gb raw data for 174 million paired-end reads was generated using the Illumina NovaSeq sequencing platform. Meanwhile, 228, 23, and 14 operational taxonomic units (OTUs) were obtained for the ITS2, matK, and rbcL regions, respectively, after bioinformatic analysis. Moreover, no differences were evident between the assembly sequences obtained via shotgun metabarcoding and their corresponding reference sequences of the same species obtained via Sanger sequencing, except for part of the ITS2 and matK assembly sequences of Paeonia lactiflora Pall., Saussurea costus (Falc.) Lipsch. and Bupleurum chinense DC. with 1–6 different bases. The identification results showed that all six prescribed ingredients were successfully detected and that the non-authentic ingredient of Bupleuri Radix (Chaihu, Bupleurum chinense DC. or Bupleurum scorzonerifolium Willd.) was found in all the commercial samples, namely Bupleurum falcatum L. Here, 25 weed species representing 16 genera of ten families were detected. Moreover, 26 fungal genera belonging to 17 families were found in both lab-made and commercial FKDSW samples. This study demonstrated that the shotgun metabarcoding approach could overcome the biased PCR amplification and authenticate the biological ingredients of traditional herbal patent medicine with a distinct variance in the dosage of the herbal materials. Therefore, this provides an appropriate evaluation method for improving the safety and efficacy of traditional herbal patent medicine.

As one of the high-incidence diseases in the world, pharyngitis seriously affects the lives of those with the condition. Qingguo Wan is a herbal medicine used for treating pharyngitis, and its quality evaluation is currently only accomplished via traditional identification. However, precise identification becomes challenging with fake products on the market or fungal contamination during the production process. This study used the Illumina NovaSeq platform for targeting the ITS2, psbA-trnH, matK, and rbcL sequences to survey the species composition of lab-made and commercial samples. The results showed that a total of 34.56 Gb of raw data that was obtained represented more than 0.23 billion reads. After assembly, annotation, and operational taxonomic unit clustering, 103, 12, 10, and 12 OTUs were obtained, which belonged to the ITS2, psbA-trnH, matK, and rbcL sequences of the mock lab-made and commercial samples. The analytical results indicated that the sequences of all the prescription ingredients were successfully obtained in the two lab-made samples. The positive control medicinal Panax quinquefolius L. sequence was obtained in HSZY175, while Scutellaria baicalensis Georgi, Lonicera japonica Thunb. Menispermum dauricum DC. and Paeonia lactiflora Pall. were detected in the three commercial samples. The detection results of the other four herbs in different fragments were not all the same. In addition, a total of 28 fungi OTUs, representing 19 families and 20 genera, were obtained from both the commercial and mock lab-made samples. Aspergillus, Cladosporium, and Penicillium dominated among the 20 genera. This study demonstrated that the shotgun metabarcoding method is a powerful tool for the molecular identification of the biological ingredients in Qingguo Wan. It can be used to effectively supplement traditional methods while providing a new technique for the quality evaluation of Qingguo Wan.

Traditional herbal patent medicine typically consists of multiple ingredients, making it challenging to supervise contamination by impurities and the improper use of raw materials. This study employed shotgun metabarcoding for the species identification of biological ingredients in traditional herbal patent medicine, Wuhu San. The five prescribed herbal materials found in Wuhu San were collected, and their reference sequences were obtained by traditional DNA barcoding using Sanger sequencing. Two lab-made and three commercial Wuhu San samples were collected, and a total of 37.14 Gb of shotgun sequencing data was obtained for these five samples using the Illumina sequencing platform. A total of 1,421,013 paired-end reads were enriched for the Internal Transcribed Spacer 2 (ITS2), psbA and trnH intergenic spacer region (psbA-trnH), maturase k (matK), and ribulose-1, 5-bisphosphate carboxylase (rbcL) regions. Furthermore, 80, 11, 9, and 8 operational taxonomic units were obtained for the ITS2, psbA-trnH, matK, and rbcL regions, respectively, after metagenomic assembly, annotation, and chimeric detection. In the two lab-made mock samples, all labeled ingredients in the Wuhu San prescription were successfully detected, and the positive control, Panax quinquefolius L., was detected in the HSZY172 mock sample. Three species, namely Angelica sinensis (Oliv.) Diels, Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., and Carthamus tinctorius L., belonging to three labeled ingredients, Angelicae Sinensis Radix (Danggui), Saposhnikoviae Radix (Fangfeng), and Carthami Flos (Honghua), were detected in the three commercial samples. Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav., the original Angelicae Dahuricae Radix (Baizhi) species, was only detected in WHS003. Arisaema erubescens (Wall.) Schott, Arisaema heterophyllum Blume, or Arisaema amurense Maxim., the original Arisaematis Rhizoma (Tiannanxing) species, were not detected in any of the commercial samples, which could be attributed to the fact that this medicinal material underwent extensive processing. In addition, the Saposhnikovia divaricata adulterant was detected in all the commercial samples, while 24 fungal genera, including Aspergillus, were identified in both the lab-made and commercial samples. This study showed that shotgun metabarcoding provided alternative strategy and technical means for identifying prescribed ingredients in traditional herbal patent medicine and displayed the potential to effectively complement traditional methods.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Due to the lack of early diagnosis methods and warning signals of CRC and its strong heterogeneity, the determination of accurate treatments for CRC and the identification of specific early warning signals are still urgent problems for researchers. In this study, the expression profiles of cancer tissues and the expression profiles of tumor-adjacent tissues in 28 CRC patients were combined into a human protein–protein interaction (PPI) network to construct a specific network for each patient. A network propagation method was used to obtain a mutant giant cluster (GC) containing more than 90% of the mutation information of one patient. Next, mutation selection rules were applied to the GC to mine the mutation sequence of driver genes in each CRC patient. The mutation sequences from patients with the same type CRC were integrated to obtain the mutation sequences of driver genes of different types of CRC, which provide a reference for the diagnosis of clinical CRC disease progression. Finally, dynamic network analysis was used to mine dynamic network biomarkers (DNBs) in CRC patients. These DNBs were verified by clinical staging data to identify the critical transition point between the pre-disease state and the disease state in tumor progression. Twelve known drug targets were found in the DNBs, and 6 of them have been used as targets for anticancer drugs for clinical treatment. This study provides important information for the prognosis, diagnosis and treatment of CRC, especially for pre-emptive treatments. It is of great significance for reducing the incidence and mortality of CRC.

BackgroundThe analysis of cancer diversity based on a logical framework of hallmarks has greatly improved our understanding of the occurrence, development and metastasis of various cancers.MethodsWe designed Cancer Hallmark Genes (CHG) database which focuses on integrating hallmark genes in a systematic, standard way and annotates the potential roles of the hallmark genes in cancer processes. Following the conceptual criteria description of hallmark function the keywords for each hallmark were manually selected from the literature. Candidate hallmark genes collected were derived from 301 pathways of KEGG database by Lucene and manually corrected.ResultsBased on the variation data, we finally identified the hallmark genes of various types of cancer and constructed CHG. And we also analyzed the relationships among hallmarks and potential characteristics and relationships of hallmark genes based on the topological structures of their networks. We manually confirm the hallmark gene identified by CHG based on literature and database. We also predicted the prognosis of breast cancer, glioblastoma multiforme and kidney papillary cell carcinoma patients based on CHG data.ConclusionsIn summary, CHG, which was constructed based on a hallmark feature set, provides a new perspective for analyzing the diversity and development of cancers.

This paper reports a new structured prismatic platelet, self-assembled by an ellipse-like quasi-unit cell, precipitated in Mg–In–Yb and Mg–In–Ca ternary alloys and aged isothermally at 200°C using aberration-corrected high-angle annular dark-field scanning transmission electron microscopy combined with density functional theory computations. The ordered stacking of solute atoms along the [0001]α direction based on elliptically shaped self-adapted clustering leads to the generation of the quasi-unit cell. The bonding of these ellipse-like quasi-unit-cell rods by the Mg atomic columns along the 〈11{\overline 2}0〉α directions formed a two-dimensional planar structure, which has three variants with a {10{\overline 1}0}α habit plane and full coherence with the α-Mg matrix. This finding is important for understanding the clustering and stacking behaviors of solute atoms in condensed matter, and is expected to guide the future design of novel high-strength Mg alloys strengthened by such high-density prismatic platelets.

Endoscopic imaging is an indispensable tool for visual inspection of surfaces in hard-to-access places. The conventional optical endoscope only enables imaging the regions that lie close to the focal plane, and therefore improving the depth of field (DOF) of an endoscopic system has recently attracted much attention. Here, we propose and demonstrate a simple, cost-effective, and easily available industrial endoscopic system, which is composed of a rigid tube and group of optical lenses. The outer diameter of the designed endoscopic modality presented in this article is 3 mm. By employing the wavefront coding technique, the DOF of newly-designed endoscope was extended to 2.7 mm in the proof-of-concept experiment, which is an increase of almost 10 times compared to the initial counterpart.

Photonic time-stretch (PTS) technology enables revolutionary technical breakthroughs in ultrafast electronic and optical systems. By means of employing large chromatic dispersion to map the spectrum of an ultrashort optical pulse into a stretched time-domain waveform (namely, using the dispersive Fourier transformation), PTS overcomes the fundamental speed limitations of conventional techniques. The chromatic dispersion utilized in PTS can be implemented using multiple optical prism arrays, which have the particular advantages of low loss in the extended spectrum outside of the specific telecommunication band, flexibility, and cost-effectiveness. In this article, we propose and demonstrate the PTS technology established for a pair of prisms, which works as a data acquisition approach in ultrafast digitizing, imaging, and measurement regimes.

Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering. IGSA calculates gene sets expression scores for each sample and takes an accumulating clustering strategy to let the samples gather into the set according to the progress of disease from mild to severe. We focus on gastric, pancreatic and ovarian cancer data sets for the performance of IGSA. We also compared the results of IGSA in KEGG pathways enrichment with David, GSEA, SPIA, ssGSEA and analyzed the results of IGSA clustering and different similarity measurement methods. Notably, IGSA is proved to be more sensitive and specific in finding significant pathways, and can indicate related changes in pathways with the severity of disease. In addition, IGSA provides with significant gene sets profile for each sample.

The wMPS is a laser-based measurement system used for large scale metrology. However, it is susceptible to external factors such as vibrations, which can lead to unreliable measurements. This paper presents a fault diagnosis and separation method which can counter this problem. To begin with, the paper uses simple models to explain the fault diagnosis and separation methods. These methods are then mathematic-ally derived using statistical analysis and the principles of the wMPS. A comprehensive solution for fault diagnosis and separation is proposed, (considering the; characteristic's of the wMPS. The; effectiveness of this solution is verified through experimental observations. It can be concluded that this approach can detect and separate false observations, thereby enhancing the reliability of the wMPS. [ABSTRACT FROM AUTHOR]