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Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 – 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 – 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 – 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

GeTe and Ge0.99-xIn0.01SnxTe0.94Se0.06 (x = 0, 0.01, 0.03, and 0.06) samples were prepared by vacuum synthesis combined with spark plasma sintering (SPS). The thermoelectric properties of GeTe were coordinated by multiple doping of Sn, In, and Se. In this work, a maximum zT(zT = S2σT/κ) of 0.9 and a power factor (PF = S2σ) of 3.87 μWmm−1 K−2 were obtained in a sample of Ge0.99In0.01Te0.94Se0.06 at 723K. The XRD results at room temperature show that all samples are rhombohedral phase structures. There is a peak (~27°) of the Ge element in GeTe and the sample (x = 0), but it disappears after Sn doping, indicating that Sn doping can promote the dissolution of Ge. The scattering mechanism of the doped samples was calculated by the conductivity ratio method. The results show that phonon scattering Is dominant in all samples, and alloy scattering is enhanced with the increase in the Sn doping amount. In doping can introduce resonance energy levels and increase the Seebeck coefficient, and Se doping can introduce point defects to suppress phonon transmission and reduce lattice thermal conductivity. Therefore, the thermoelectric properties of samples with x = 0 improved. Although Sn doping will promote the dissolution of Ge precipitation, the phase transition of the samples near 580 K deteriorates the thermoelectric properties. The thermoelectric properties of Sn-doped samples improved only at room temperature to ~580 K compared with pure GeTe. The synergistic effect of multi-element doping is a comprehensive reflection of the interaction between elements rather than the sum of all the effects of single-element doping.

In this paper, four lithological parameters, that is, thermal conductivity, particle size, porosity, and saturation, are investigated by combining experimental observations with numerical simulations to study the influence laws and mechanisms of action on the combustion process of methane hydrate sediments. The variations in combustion characteristics parameters such as flame height, effective combustion ratio, and dimensionless discharge water mass with the lithological parameters are studied. In addition, the combustion mechanism of lithologic parameters on methane hydrate deposits is revealed. Combining the experimental results and simulation calculations to optimize the combustion of methane hydrate sediments, it is recommended to use methane hydrate sediment samples with high saturation and low thermal conductivity, while the oxidant concentration and porosity of methane hydrate sediment samples should be increased.

Background: The functional ramifications of internal N7-methylguanosine (m7G) modification on RNAs have recently come to light, yet its regulatory influence on long noncoding RNAs (lncRNAs) during the inflammatory-carcinogenesis transformation process in hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC) remains largely unexplored. Methods: Clinical surgical samples encompassing HBV-related HCC, comprising both HCC tissue (tumor group, HBV+) and corresponding adjacent liver tissue (paracancerous group, HBV+), were collected for analysis. Additional adjacent normal liver tissues (normal group, HBV-) were acquired from patients with hepatic hemangioma, serving as controls. Employing MeRIP-seq, differential m7G levels of lncRNAs across these groups were compared to identify a subset of lncRNAs exhibiting continuous and dynamic changes in m7G modification. Subsequently, in vitro validation was conducted. Results: A total of 856 lncRNAs exhibited alterations in m7G modification when compared to paracancerous tissue and normal tissue. Similarly, 1775 lncRNAs displayed changes in m7G modification when comparing HCC tissue to paracancerous tissue. For intergroup comparison, orthogonal analysis revealed that 6 lncRNAs consistently demonstrated hyper-m7G modification. In vitro validation confirmed that among these 6 lncRNAs, TEKT4P2 and DNM1P41 exhibited m7G modification-dependent expression. Conclusions: This study provides a comprehensive analysis of lncRNA m7G modification during the inflammatory-carcinogenesis transformation process in HBV-mediated HCC. The findings highlight the potential for multiple lncRNAs to undergo m7G modification changes, with TEKT4P2 and DNM1P41 identified as promising molecular targets within this intricate regulatory landscape.

Background: Internal N7-methylguanosine (m7G) methylation in mammalian messenger RNAs (mRNAs) is essential in disease development. However, the status of internally m7G-modified mRNAs in oral squamous cell carcinoma (OSCC) remains poorly understood. Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to identify the m7G modification level of mRNAs and the expression of mRNAs between OSCC and normal tissues. These differentially methylated and expressed genes were subjected to Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and construction of protein-protein interaction (PPI) networks. Quantitative real-time PCR (qPCR) assay was performed to detect the expression of Baculoviral IAP Repeat Containing 3 (BIRC3) in vitro. The biological function of BIRC3 in OSCC was clarified using CCK-8, Transwell migration and Western blot assays. Results: The m7G-mRNA profile showed 9514 unique m7G peaks within 7455 genes in OSCC tissues. In addition, the most conserved m7G motif within mRNAs in OSCC was GGARG (R = G/A). The identified m7G peaks were mainly distributed in the coding sequence region within mRNAs in OSCC. GO enrichment and KEGG pathway analyses showed that m7G-modified genes were closely related to cancer progression. m7G-modified hub genes were screened from the constructed PPI networks. Furthermore, BIRC3 with high m7G methylation showed high expression in OSCC cell lines, as confirmed by qPCR assay. Functionally, the knockdown of BIRC3 significantly inhibited the proliferation and migration ability of CAL-27 cells in vitro functional assays. In addition, the relative expression of E-cadherin expression was elevated, while Vimentin and N-cadherin protein expression was decreased in CAL-27 cells transfected with si-BIRC3. This study suggests that BIRC3 could promote OSCC proliferation and migration, which may be associated with involvement in epithelial-mesenchymal transition (EMT) progression. Conclusions: This paper constructed a transcriptome map of internal m7G in mRNAs, which provides potential research value to study the role of m7G methylation in OSCC.

Abstract Temperature variation and gas generation at different depths and positions in the coal combustion process were studied to determine the propagation and evolution of high temperature regions in the process of coal spontaneous combustion. This study selected coal samples from Mengcun, Shaanxi Province, People’s Republic of China, and developed a semi-enclosed experimental system (furnace) for simulating coal combustion. The thermal mass loss of coal samples under various heating rates (5, 10, and 15 °C/min) was analyzed through thermogravimetric analysis, and the dynamic characteristics of the coal samples were analyzed; the reliability of the semi-enclosed experimental system was verified through the equal proportional method of fuzzy response. The results reveal that the high-temperature zone is distributed nonlinearly from the middle to the front end of the furnace, and the temperatures of points in this zone decreased gradually as the layer depth increased. The apparent activation energy of the coal samples during combustion first increased and then decreased as the conversion degree increased. Furthermore, the proportion of mass loss and the mass loss rate in the coal samples observed in the thermogravimetric experiment is consistent with that observed in the first and second stages of the experiment conducted using the semi-enclosed system. The research findings can provide a theoretical basis for the prevention and control of high-temperature zones in coal combustion.

With the improvement of the exploration degree, small complex fault block traps have become the key field of oil and gas exploration in the current uplift area. To clarify the reasons for the differential enrichment of oil and gas in the fault block trap in the West Liaoning uplift, the characteristics of weathering crust on the top of the buried hill in the uplift slope area are analysed by using three-dimensional seismic, logging, thin section and other data through three-dimensional streamline quantitative simulation. The "crust-fault" coupling migration model is established to describe the dominant migration path of oil and gas in the slope area to clarify the control effect of hydrocarbon migration along weathered crust on the differential enrichment of oil and gas in the convex fault block. The results show that ① the buried hill in the study area has experienced multistage tectonic movements, and the lithology of the buried hill is mainly lower Paleozoic carbonate rock and Archean granite. The lithology is brittle and easily weathered and denuded. The denudation pores and structural fractures of the weathering crust are widely developed and stably distributed, forming the main channel of lateral long-distance migration of oil and gas in the slope area. ② The middle zone of the slope is controlled by reverse faults to forma fault uplift structure. The migration of oil and gas along the weathering crust is blocked by the slope fault uplift zone, forming a "crust-fault" coupling oil and gas migration model. The fault throw of the fault uplift zone controls the lateral migration ability of oil and gas in the weathering crust. ③ Using the method of three-dimensional streamline quantitative simulation, the four-level dominant oil and gas migration channels in the study area are characterized, and the control effect of different levels of oil and gas migration channels on the degree of oil and gas enrichment in convex fault blocks is clarified. The research results effectively guide the practice of oil and gas exploration in the Liaoxi Uplift and fill the gap of the understanding and research method of oil and gas accumulation in mature uplift areas of oil-rich sags.

Abstract We present a novel surface coating to resolve the stability of α-AlH3. Inspired by the strong chemical adhesion of mussels, the polymerization of dopamine was first introduced to coat α-AlH3 through simple situ polymerization. The α-AlH3 was used as a substrate. In-depth characterizations confirmed the formation of polydopamine (PDA) on the α-AlH3 surface. The coated α-AlH3 sample was characterized by X-ray diffraction X-ray photoelectron spectrometry and Scanning Electron Microscope. The results show that a strong PDA film is formed on the surface of α-AlH3, and PDA@α-AlH3 retains its primary morphology. The crystal form of α-AlH3 does not change after coating with PDA. The XPS analysis results show that N1 s appears on the material after coating with PDA, indicating that polydopamine is formed on the surface of α-AlH3. The moisture absorption tests show that the moisture absorption rate of α-AlH3 is greatly reduced after being coated with PDA. The excellent intact ability of PDA prevents α-AlH3 from reacting with water in air. The thermal stability of α-AlH3 before and after coating was analyzed by DSC. This work demonstrates the successful applications of dopamine chemistry to α-AlH3, thereby providing a potential method for metastable materials.

In order to solve the problem that the scheduling scheme cannot be updated in real time due to the dynamic change of node demand in material emergency dispatching, this article proposes a dynamic attention model based on improved gated recurrent unit. The dynamic codec framework is used to track the change of node demand to update the node information. The improved gated recurrent unit is embedded between codecs to improve the representation ability of the model. By weighted combination of the node information of the previous time, the current time and the initial time, a more representative node embedding is obtained. The results show that compared with the elitism-based immigrants ant colony optimization algorithm, the solution quality of the proposed model was improved by 27.89, 27.94, 28.09 and 28.12% when the problem scale is 10, 20, 50 and 100, respectively, which can effectively deal with the instability caused by the change of node demand, so as to minimize the cost of material distribution.

Abstract The mechanisms by which the tumor behaviors of hepatocellular carcinoma (HCC) support growth and metastasis remain largely unknown, and it has become increasingly apparent that molecular dysregulation is of considerable importance for cellular signaling pathways. Recently, RNA-binding motif protein 47 (RBM47) has been suggested to function as a tumor regulator by acting as an RNA binding protein (RBP), but its role in HCC remains ambiguous. Here, in HCC, we identified that RBM47 had an inhibitory influence on tumor behaviors in vitro and accordingly suppressed the growth and metastasis of xenograft tumors in vivo. Additionally, RBM47 was verified to positively regulate Upframeshift 1 (UPF1), which is a crucial protein involved in the nonsense-mediated RNA decay (NMD) process and was previously determined to be an HCC suppressor. Mechanistically, the stability of UPF1 mRNA was demonstrated to be enhanced with its 3’UTR bound by RBM47, which acted as an RNA binding protein. Meanwhile, RBM47 was also proven to promote the transcription of UPF1 as a transcription factor. Taken together, we concluded that RBM47 functioned as a tumor suppressor by upregulating UPF1, acting as a DNA/RNA binding protein at the transcriptional and posttranscriptional levels.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) could develop preceding or come after motor symptoms during Parkinson's disease (PD). It remains unknown that whether PD with different timing of RBD onset relative to motor symptoms suggests different spatiotemporal sequence of neurodegeneration. This study aimed to explore the sequence of disease progression in crucially involved brain regions in PD with different timing of RBD onset. Method: We recruited 157 PD, 16 isolated RBD (iRBD), and 78 healthy controls. PD patients were identified as (1) PD with RBD preceding motor symptoms (PD-preRBD, n = 50), (2) PD with RBD posterior to motor symptoms (PD-postRBD, n = 31), (3) PD without RBD (PD-nonRBD, n = 75). The volumes of crucial brain regions, including the basal ganglia and limbic structures in T1-weighted imaging, and the contrast-noise-ratios of locus coeruleus (LC) and substantia nigra (SN) in neuromelanin-sensitive magnetic resonance imaging, were extracted. To simulate the sequence of disease progression for cross-sectional data, an event-based model was introduced to estimate the maximum likelihood sequence of regions' involvement for each group. Then, a statistical parameter, the Bhattacharya coefficient (BC), was used to evaluate the similarity of the sequence. Results: The model predicted that SN occupied the highest likelihood in the maximum likelihood sequence of disease progression in the all PD subgroups, while LC was specifically positioned earlier to SN in iRBD, a prodromal phase of PD. Subsequent early involvement of LC was observed in the both PD-preRBD and PD-postRBD. In contrast, atrophy in the para-hippocampal gyrus but relatively intact LC in the early stage was demonstrated in PD-nonRBD. Then, the similarity comparisons indicated higher BC between PD-postRBD and PD-preRBD (BC = 0.76) but lower BC between PD-postRBD and PD-nonRBD group (BC = 0.41). iRBD had higher BC against PD-preRBD (BC = 0.66) and PD-postRBD (BC = 0.63) but lower BC against PD- nonRBD (BC = 0.48). Conclusion: The spatiotemporal sequence of neurodegeneration between PD-pre and PD-post were similar but distinct from PD-nonRBD. The presence of RBD may be the essential factor for differentiating the degeneration patterns of PD, but the timing of RBD onset has currently proved to be not.

The shikimate pathway is a general route for the biosynthesis of aromatic amino acids (AAAs) in many microorganisms. A 3-dehydroquinase, AroQ, controls the third step of the shikimate pathway that catalyzes the formation of 3-dehydroquinate from 3-dehydroshikimate via a trans-dehydration reaction. Ralstonia solanacearum harbors two 3-dehydroquinases, AroQ1 and AroQ2, sharing 52% similarity in amino acids. Here, we demonstrated that two 3-dehydroquinases, AroQ1 and AroQ2, are essential for the shikimate pathway in R. solanacearum. The growth of R. solanacearum was completely diminished in a nutriment-limited medium with the deletion of both aroQ1 and aroQ2, while substantially impaired in planta. The aroQ1/2 double mutant was able to replicate in planta but grew slowly, which was ~4 orders of magnitude less than the parent strain to proliferate to the maximum cell densities in tomato xylem vessels. Moreover, the aroQ1/2 double mutant failed to cause disease in tomato and tobacco plants, whereas the deletion of either aroQ1 or aroQ2 did not alter the growth of R. solanacearum or pathogenicity on host plants. Supplementary shikimic acid (SA), an important intermediate of the shikimate pathway, substantially restored the diminished or impaired growth of aroQ1/2 double mutant in a limited medium or inside host plants. The necessity of AroQ1 and AroQ2 on the pathogenicity of solanacearum toward host plants was partially due to insufficient SA inside host plants. Moreover, the deletion of both aroQ1 and aroQ2 significantly impaired the expression of genes for the type III secretion system (T3SS) both in vitro and in planta. Its involvement in the T3SS was mediated through the well-characterized PrhA signaling cascade and was independent of growth deficiency under nutrient-limited conditions. Taken together, R. solanacearum 3-dehydroquinases play important roles in bacterial growth, the expression of the T3SS, and pathogenicity in host plants. These results could extend our insights into the understanding of the biological function of AroQ and the sophisticated regulation of the T3SS in R. solanacearum.

White spot lesions (WSLs) have long been a noteworthy complication during orthodontic treatment. Recently, an increasing number of orthodontists have found that adolescents undergoing orthodontic treatment with clear aligners are at a higher risk of developing WSLs. The oral microbiota and metabolites are considered the etiologic and regulatory factors of WSLs, but the specific impact of clear aligners on the oral microbiota and metabolites is unknown. This study investigated the differences in the salivary microbiome and metabolome between adolescents with and without WSLs treated with clear aligners. Fifty-five adolescents (aged 11-18) with Invisalign appliances, 27 with and 28 without WSLs, were included. Saliva samples were analyzed using 16S rRNA gene sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); the data were further integrated for Spearman correlation analysis. The relative abundances of 14 taxa, including Actinobacteria, Actinomycetales, Rothia, Micrococcaceae, Subdoligranulum, Capnocytophaga, Azospira, Olsenella, Lachnoanaerobaculum, and Abiotrophia, were significantly higher in the WSL group than in the control group. Metabolomic analysis identified 27 potential biomarkers, and most were amino acids, including proline and glycine. The metabolites were implicated in 6 metabolic pathways, including alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism; and aminoacyl-tRNA biosynthesis. There was a correlation between the salivary microbial and metabolomic datasets, reflecting the impact of clear aligners on the metabolic activity of the oral flora. A concordant increase in the levels of Lachnoanaerobaculum, Rothia, Subdoligranulum and some amino acids had predictive value for WSL development. In summary, when adolescents undergo long-term clear aligner therapy with poor oral hygiene habits, clear aligners can disrupt the balance of the oral microecosystem and lead to oral microbiota dysbiosis, thereby increasing the risk of developing WSLs. Our findings might contribute to the understanding of the pathogenesis of WSLs and provide candidate biomarkers for the diagnosis and treatment of WSLs associated with clear aligners.

Abstract Biomaterials‐based electronic devices (BEDs) have remarkable advantages such as biocompatibility and biodegradability, which are expected to have promising prospects in the development of green electronics such as wearable smart sensors and brain‐like synaptic devices. However, the development of BEDs is still in its infancy, and much work remains to be done before this technology can be widely used. Here, a novel corn starch‐based BED with a sandwiched structure of Ag/Corn starch:PVDF/ITO is developed, which has integrated multifunctional performance of capacitive‐coupled memristive memory, flexible mechanical stress sensing, synaptic application, and logic operation. Specifically, this device exhibits a wide memristive voltage operating range (1–16 V), a high bending response current (3.5–4.5 µA), long‐term durability synaptic performance, and logic operation capability. These advantageous characteristics endow this device has a good potential to be used in flexible wearable electronics and artificial intelligence.

Abstract P53 inactivation occurs in about 50% of human cancers, where p53‐driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1‐responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53‐defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase. In response to DNA damage, LIMp27 is upregulated in both wild‐type and p53‐mutant COAD cells, whereas cytoplasmic hnRNPA0 is only increased in p53‐mutant COAD cells due to translocation from the nucleus. Moreover, high LIMp27 expression is associated with poor survival of p53‐mutant but not wild‐type p53 COAD patients. These results uncover an lncRNA mechanism that promotes p53‐defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers.

Bisphenol A (BPA), present in many household products, can damage the male reproductive system. Accordingly, we summarized urine samples from 6921 human in National Health and Nutrition Examination Survey and found urinary BPA levels were inversely linked with blood testosterone in the children group. Currently, BPA replacements, such as fluorene-9-bisphenol (BHPF) and Bisphenol AF (BPAF), have been introduced to produce “BPA-free” products. Here we demonstrated that BPAF and BHPF could induce delayed gonadal migration and reduce the number of progenitors of germ cell lineage in zebrafish larvae. A close receptor analysis study reveals that BHPF and BPAF can strongly bind to androgen receptors, leading to the downregulation of meiosis-related genes and the overexpression of inflammatory markers. Furthermore, BPAF and BPHF can induce activation of the gonadal axis via negative feedback, leading to the hypersecretion of some upstream hormones and an increase in the expression of upstream hormone receptors. Our findings call for further research on the toxicological effects of BHPF and BPAF on human health and recommend that BPA replacements be investigated for anti-estrogenic action.

Hollow structure with hierarchical pore is benefit for the exposure of active sites, showing great advantages in electrocatalysis. Whereas, it still a challenge for the target preparation of such architecture in a simple, but efficient ways. Herein, a Co/Zn-Nx (Nx represents the number of N atoms (x) coordinated with Co or Zn atoms) dual sites anchored N, P-codoped hollow carbon polyhedron (PZH-800) with well-defined Co species was facilely prepared via direct pyrolysis of a bimetallic hybrid (PZH) obtained by polymerization-coating of Zn-porphyrin polymer on the surface of zeolitic-imidazolate-framework (ZIF-67). The hollow architecture was formed via self-etching, in which the hydrochloric acid produced during the formation of hybrid etched the inner acid-degradable ZIF-67. Different with post-etching method, self-etching could really preserve the original structure and catalytic sites, better regulate the electronic structures, enhancing the catalytic activity. Compared with the Co or Zn mono-doped sample, PZH-800 presented an enhanced ORR activity with a half-wave potential (E1/2) of 0.94 V (vs. RHE), as well as outstanding stability, outperforming commercial Pt/C (20%) in alkaline media. Impressively, ZABs using PZH-800 as the cathodic catalyst demonstrated a maximum power density (280 mW cm−2), coupled with a remarkable running stability, surpassing the battery catalyzed by Pt/C. This work paves a new avenue for the future development of MOF-derived non-precious metal-based hollow catalysts.

Abstract Background Dandelion is becoming an exploitable alternative to the widely prohibited antibiotics in the poultry production. This research aimed to investigate the effects of dandelion on the growth performance and intestinal barrier function of broiler chickens maintained under standard condition of management. One-hundred and sixty 1-day-old Arbor Acres (AA) male broiler chickens were randomly divided into four groups, with five replicates of eight birds each. The birds were fed a basal diet supplemented without (control group, [CON]) or with 500 (low dose [LD]) or 1000 (high dose [HD]) mg/kg dandelion or with 250 mg/kg chlortetracycline 20% premix (CTC) for 42 days, including the starter phase (d 1 to 21) and the grower phase (d 22 to 42). Body weight (BW) of each bird and feed consumption of each replicate were measured at d 21 and d 42. The ileal tissues were collected on day 21 and 42 to determine expression of genes coding for tight junction protein and mucin as well as ELISA analysis for immune factor. The ileal digesta was collected for microbiota and short chain fatty acids analysis. Results Compared with CON group, during day 1–21, the average daily feed intake (ADFI) and feed/gain ratio (F/G) of LD group were lower (P < 0.05); during day 22–42, the F/G of LD and CTC group tended to be lower (P = 0.07); during the overall phase, the ADFI of HD and CTC groups were decreased (P

Abstract Background Spodoptera litura is an important polyphagous pest that causes significant damage to the agricultural sector. We performed RNA-seq of 15 S. litura individuals from larval (fifth and sixth instar larvae), chrysalis, and adult developmental stages. We also compared the S. litura transcriptome data with Spodoptera frugiperda across the same developmental stages, which was sequenced in our previous study. Results A total of 101,885 differentially expressed transcripts (DETs) were identified in S. litura. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that S. litura may undergo active xenobiotic and detoxifying metabolism during its larval and adult stages, which may explain difficulties with current population control measures. We also found that DETs of single-copy orthologous genes between S. litura and S. frugiperda were involved in basic metabolism and development. However, energy and metabolic processes genes had a higher expression in S. litura, whereas nervous and olfactory function genes had a higher expression in S. frugiperda. Metagenomics analysis in larval S. litura and S. frugiperda revealed that microbiota participate in the detoxification and metabolism processes, but the relative abundance of detoxification-related microbiota was more abundant in S. frugiperda. Transcriptome results also confirmed the detoxification-related pathway of S. frugiperda was more abundant than in S. litura. Conclusions Significant changes at transcriptional level were identified during the different development stages of S. litura. Importantly, we also identified detoxification associated genes and gut microbiota between S. litura and S. frugiperda at different developmental stages, which will be valuable in revealing possible mechanisms of detoxification and development in these two lepidopterans.

Abstract Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson’s disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein and glymphatic system dysfunction. However, evidence accumulating primarily based on clinical data to support glymphatic system dysfunction in patients with iRBD and PD is currently insufficient. This study aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship to clinical scores of disease severity in patients with possible iRBD (piRBDs) and those with PD. Further, we validated the correlation between the ALPS index and the prognosis of PD longitudinally. Overall, 168 patients with PD, 119 piRBDs, and 129 healthy controls were enroled. Among them, 50 patients with PD had been longitudinally reexamined. Patients with PD exhibited a lower ALPS index than those with piRBDs (P = 0.036), and both patient groups showed a lower ALPS index than healthy controls (P

Abstract Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression, yet how this process is regulated by oncogenic signal remains largely unknown. Here, we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m6A reader YTHDC1 in lung cancer. Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing, specifically triggering RBM4 splicing from the full isoform (RBM4-FL) to the short isoform (RBM4-S) in a kinase-independent manner. RBM4-S functions as a tumor promoter by abolishing RBM4-FL-mediated inhibition of the activity of the SRSF1-mTORC1 signaling pathway. Mechanistically, AURKA disrupts the binding of SRSF3 to YTHDC1, resulting in the inhibition of RBM4-FL production induced by the m6A-YTHDC1-SRSF3 complex. In turn, AURKA recruits hnRNP K to YTHDC1, leading to an m6A-YTHDC1-hnRNP K-dependent exon skipping to produce RBM4-S. Importantly, the small molecules that block AURKA nuclear translocation, reverse the oncogenic splicing of RBM4 and significantly suppress lung tumor progression. Together, our study unveils a previously unappreciated role of nuclear AURKA in m6A reader YTHDC1-dependent oncogenic RNA splicing switch, providing a novel therapeutic route to target nuclear oncogenic events.

Abstract Large eyelid defect after excision of malignancies or trauma is difficult to reconstruct due to special structure and function of the eyelid. In this study, we aimed to present the outcomes of subcutaneous pedicled propeller flap for reconstructing the large eyelid defect after excision of malignancies or trauma. A retrospective review of patients diagnosed with eyelid defect due to excision of malignancies or trauma, and undergoing subcutaneous pedicled propeller flap for reconstructing the large eyelid defect, was conducted at our hospital. The clinical data were collected and analyzed. A total of 15 patients were included in the cases series. Nine patients were diagnosed with basal cell carcinoma, 3 patients with epidermoid carcinoma, and 3 patients with trauma. All the defects were successfully covered with this designed flap. There was no flap necrosis in all the cases. No functional problems were observed in all of the cases. At long-term postoperative follow-up, the average score of patients’ satisfaction was good. This subcutaneous pedicled propeller flap is a feasible alternative technique for reconstructing the large eyelid defect after excision of malignancies or trauma. This flap option could avoid the use of free flaps for large defect.

Two new dipyrroloquinones, namely talaroterreusinones A (1) and B (2), together with four known secondary metabolites, terreusinone A (3), penicillixanthone A (4), isorhodoptilometrin (5), and chrysomutanin (6), were isolated from the solid culture of the endophytic fungus Talaromyces sp. by integrating mass spectrometry-based metabolic profiling and a bioassay-guided method. Their planar structures and stereochemistry were elucidated by comprehensive spectroscopic analysis including NMR and MS. The absolute configuration at C-1″ of terreusinone A (1) was established by applying the modified Mosher’s method. Compounds 1–6 were evaluated for anti-inflammatory activity and cytotoxicity. As a result, 1–3 inhibited the LPS-stimulated NO production in macrophage RAW264.7 cells, with IC50 values of 20.3, 30.7, and 20.6 µM, respectively. Penicillixanthone A (4) exhibited potent cytotoxic activity against Hep G2 and A549 cell lines, with IC50 values of 117 nM and 212 nM, respectively, and displayed significant antitumour effects in A549 cells by inhibiting the PI3K-Akt-mTOR signalling pathway.

In micron or nano smart sensing systems, piezoelectric cantilever beams are distributed as major components in microsensors, actuators, and energy harvesters. This paper investigates the performance of four cantilever beam devices with “electric-force” conversion based on the inverse piezoelectric effect of lithium niobate (LiNbO3, LN) single-crystal materials. A new compact piezoelectric smart device model is proposed, designed as a single mass block connected by four beams, where devices exhibit smaller lateral errors (0.39–0.41%). The relationship between the displacement characteristics of cantilever beams and driving voltage was researched by applying excitation signals. The results show that the device has the maximum displacement at a first-order intrinsic frequency (fosc = 11.338 kHz), while the displacement shows a good linear relationship (R2 = 0.998) with driving voltage. The square wave signals of the same amplitude have greater “electrical-force” conversion efficiency. The output displacement can reach 12 nm, which is much higher than the output displacement with sinusoidal excitation. In addition, the relative displacement deviation of devices can be maintained within ±1% under multiple cycles of electrical signal loading. The small size, high reliability, and ultra-stability of Si–LN ferroelectric single-crystal cantilever beam devices with lower vibration amplitudes are promising for nanopositioning techniques in microscopy, diagnostics, and high-precision manufacturing applications.

Aimed at the problems of low search efficiency of the A* algorithm in global path planning, not considering the size of AGV and too many turns, and the DWA algorithm easily falling into local optimization, an AGV path planning algorithm based on improved A* and DWA fusion is proposed. To begin, the obstacle rate coefficient is added to the A* algorithm’s evaluation function to build an adaptive cost function; the search efficiency and path safety are increased by improving the search mode; by extracting key nodes, a global path containing only the starting point, key nodes, and endpoints is obtained. The DWA algorithm’s evaluation function is then optimized and the starting azimuth is optimized based on information from the first key node. The experimental results show that in a static environment, compared with the traditional A* algorithm and the improved A* algorithm, the path length is reduced by 1.3% and 5.6%, respectively, and the turning times are reduced by 62.5% and 70%, respectively; compared with the improved ant colony algorithm in the literature, the turning angle is reduced by 29%. In the dynamic environment, the running time of this fusion algorithm is reduced by 12.6% compared with the other hybrid algorithms.

AbstractHierarchical brain organization, in which rich-club and diverse-club situates in core position, is critical for global information integration in human brain network. Parkinson’s disease (PD), a common movement disorder, has been conceptualized as a network disorder. Levodopa is an effective treatment for PD. Whether a functional divergence between hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed functional network in 61 PD patients and 89 normal controls, and graph theoretical analyses were applied to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed that: (1) PD patients exhibited disrupted function within rich-club organization, while the diverse-club remained preserved function, indicating a differentiated brain topology organization in PD; (2) along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetwork, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting the distinct functional patterns in different types of nodes; and (3) levodopa could normalize the abnormal network architecture of rich-club system. This study provides evidence for levodopa effects on hierarchical brain system with divergent function.

Abstract. Background:. Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression. Methods:. The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan–Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression. Results:. Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression. Conclusions:. Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.

Brain radiomics can reflect the characteristics of brain pathophysiology. However, the value of T1-weighted images, quantitative susceptibility mapping, and R2* mapping in the diagnosis of Parkinson’s disease (PD) was underestimated in previous studies. In this prospective study to establish a model for PD diagnosis based on brain imaging information, we collected high-resolution T1-weighted images, R2* mapping, and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019. According to the inclusion time, 123 PD patients and 121 healthy controls were assigned to train the diagnostic model, while the remaining 106 subjects were assigned to the external validation dataset. We extracted 1408 radiomics features, and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset. The informative features so identified were then used to construct a diagnostic model for PD. The constructed model contained 36 informative radiomics features, mainly representing abnormal subcortical iron distribution (especially in the substantia nigra), structural disorganization (e.g., in the inferior temporal, paracentral, precuneus, insula, and precentral gyri), and texture misalignment in the subcortical nuclei (e.g., caudate, globus pallidus, and thalamus). The predictive accuracy of the established model was 81.1 ± 8.0% in the training dataset. On the external validation dataset, the established model showed predictive accuracy of 78.5 ± 2.1%. In the tests of identifying early and drug-naïve PD patients from healthy controls, the accuracies of the model constructed on the same 36 informative features were 80.3 ± 7.1% and 79.1 ± 6.5%, respectively, while the accuracies were 80.4 ± 6.3% and 82.9 ± 5.8% for diagnosing middle-to-late PD and those receiving drug management, respectively. The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8 ± 6.9% and 79.1 ± 6.5%, respectively. In conclusion, the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.

BackgroundThis study aimed to develop an autoimmune thyroid disease (AITD) risk prediction model for patients with vitiligo based on readily available characteristics.MethodsA retrospective analysis was conducted on the clinical characteristics, demographics, skin lesions, and laboratory test results of patients with vitiligo. To develop a model to predict the risk of AITD, the Least Absolute Shrinkage and Selection Operator (LASSO) method was used to optimize feature selection, and logistic regression analysis was used to select further features. The C-index, Hosmer–Lemeshow test, and decision curve analysis were used to evaluate the calibration, discrimination ability and clinical utility of the model. Internally, the model was verified using bootstrapping; externally, two independent cohorts were used to confirm model accuracy.ResultsSex, vitiligo type, family history of AITD, family history of other autoimmune disease, thyroid nodules or tumors, negative emotions, skin involvement exceeding 5% of body surface area, and positive immune serology (IgA, IgG, IgM, C3, and C4) were predictors of AITD in the prediction nomogram. The model showed good calibration and discrimination (C-index: 0.746; 95% confidence interval: 0.701–0.792). The accuracy of this predictive model was 74.6%.In both internal validation (a C-index of 1000 times) and external validation, the C-index outperformed (0.732, 0.869, and 0.777). The decision curve showed that the AITD nomogram had a good guiding role in clinical practice.ConclusionThe novel AITD nomogram effectively evaluated the risk of AITD in patients with vitiligo.

Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is a fatal cardiovascular disease. A novel method for non-invasive initial diagnosis of the CHD-PAH was put forward in this work. First, original heart sounds were segmented into each cardiac cycle by using double-threshold adaptive method. According to clinical auscultation, the pathological information of CHD-PAH is concentrated in S2, so the time-frequency features in both of an entire cardiac cycle and S2 were extracted. Then the time-frequency features combine with the deep learning features to form a feature vector. It is the fusion feature, which will be input into a classifier. Finally, the majority voting algorithm was used to obtain the optimal classification results. A classification accuracy of 88.61% was achieved using this novel method. Three points are essential: • A double-threshold adaptive method is used to segment heart sound into each cardiac cycle. • The time-frequency domain features in both of an entire cardiac cycle and S2 were extracted, which are combined with deep learning features to form the fusion feature. • The XGBoost was used as three-class classifier for the classification of normal, CHD and CHD-PAH. The majority voting algorithm was used to obtain the optimal classification results.

Neurogenic pain rises because of nervous system damage or dysfunction and is the most difficult to treat among other pathological pains. Acupuncture has been reported as a great treatment option for neurogenic pain owing to its unlimited advantages. However, previous studies on the analgesic effects of acupuncture for NP were scattered and did not form a whole. In this study, we first comprehensively review the relevant basic articles on acupuncture for NP published in the last 5 years and summarize the analgesic mechanisms of acupuncture in terms of nerve signaling, neuro-immune crosstalk, and metabolic and oxidative stress regulation. Acupuncture inhibits the upstream excitatory system and suppresses neuronal transmission efficiency by downregulating glutamate, NMDA receptors, P2XR, SP, CGRP, and other neurotransmitters and receptors in the spinal cord, as well as plasma channels such as TRPV1, HCN. It can also activate the downstream pain inhibitory pathway by upregulating opioid peptide (β-endorphin), MOR receptors, GABA and GABA receptors, bi-directional regulating 5-hydroxytryptamine (5-HT) and its receptors (upregulate 5-HT 1A and downregulate 5-HT7R) and stimulating hypothalamic appetite-modifying neurons. Moreover, neuroinflammation in pain can be inhibited by acupuncture through inhibiting JAK2/STAT3, PI3K/mTOR pathways, down regulating chemokine receptor CX3CR1 on microglia and up regulating adenosine receptor A1Rs on astrocytes, inhibiting the activation of glia and reducing TNF-α and other inflammatory substances. Acupuncture also inhibits neuronal glucose metabolism by downregulating mPFC's GLUT-3 and promotes metabolic alterations of the brain, thus exerting an analgesic effect. In conclusion, the regulation of nerve signal transduction and neuroimmune crosstalk at the peripheral and central levels mediates the analgesic effects of acupuncture for neuropathic pain in an integrated manner. These findings provide a reliable basis for better clinical application of acupuncture in the management of neuropathic pain.

Circular RNAs (circRNAs) are a class of single-stranded, closed RNA molecules with unique functions that are ubiquitously expressed in all eukaryotes. The biogenesis of circRNAs is regulated by specific cis-acting elements and trans-acting factors in humans and animals. circRNAs mainly exert their biological functions by acting as microRNA sponges, forming R-loops, interacting with RNA-binding proteins, or being translated into polypeptides or proteins in human and animal cells. Genome-wide identification of circRNAs has been performed in multiple plant species, and the results suggest that circRNAs are abundant and ubiquitously expressed in plants. There is emerging compelling evidence to suggest that circRNAs play essential roles during plant growth and development as well as in the responses to biotic and abiotic stress. However, compared with recent advances in human and animal systems, the roles of most circRNAs in plants are unclear at present. Here we review the identification, biogenesis, function, and mechanism of action of plant circRNAs, which will provide a fundamental understanding of the characteristics and complexity of circRNAs in plants.

Abstract Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. Methods Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. Results In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. Conclusion This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.

ObjectiveStudies have shown that carbon dioxide (CO2) insufflation during endoscopic thyroidectomy is associated with many risks. Recently, we have designed a simple lifting tool using Kirschner wire. We aimed to use this tool for flap-lifting in modified areola approach endoscopic thyroidectomy and compare it with conventional CO2 insufflation.MethodsIn a prospective study, patients who underwent endoscopic thyroidectomy via modified areola approach were randomly assigned into gasless (n = 20) or CO2 groups (n = 22). Pre-operative variables included age, gender, tumor diameter, and clinical diagnosis. Intra-operative hemodynamic monitoring included mean arterial pressure, heart rate, pulse oximetry, end-tidal carbon dioxide (ET-CO2) and arterial pH. Other intra-operative details included total operative time, operative blood loss, conversion from endoscopic surgery to open surgery, intra-operative events, and endoscope video score. Postoperatively, the hospital stay, drainage volume, and complications were recoded.ResultsPatient characteristics were not different between the two groups. During the operation, ET-CO2 levels were significantly higher in the CO2 group (P < 0.05), whereas arterial pH levels were significantly lower (P < 0.05). The CO2 group had longer operation time and higher endoscope clarity VAS score than gasless group. Hospital stay, drainage volume, and postoperative complications did not differ significantly between the two groups (P > 0.05).ConclusionsThe gasless endoscopic thyroidectomy we performed via our Kirschner wire hook was safe, feasible, and yielded good results.

Background: Programmed death receptor ligand 1 (PD-L1) is expressed at different levels in tumour tissues and tumour-infiltrating monocytes (TIMCs). The interpretation of PD-L1 expression in gastric cancer (GC) is more difficult because of its heterogeneity. Methods: The PD-L1 immunohistochemistry (IHC) by E1L3N assay was performed in GC tissues. The level and distributed characteristics of PD-L1 expression were observed to illustrate its heterogeneity both in the cancer tissues and TIMCs. The relationship between PD-L1 level and necrotic features of tumor cells, the number of TIMCs, the distribution of tertiary lymphoid tissue (TLS) in the stroma, and other clinicopathological factors were analysed. A Cox regression model was used to assess the prognostic value of PD-L1 expression. Results: Of the 110 GC samples, not only more cases (51/110 cases) could be detected by combined positive score (CPS) for PD-L1 expression compared the other two, tumour positive score (TPS), and mononuclear immune-cell density score (MIDS), but also there were more cases with the high level of PD-L1 expression by CPS, even if with good consistency among them (P < 0.05). The tumour cells with high expression of PD-L1 was prone to show a diffuse distributing, whereas mottled type in the low level. It was noteworthy that the strongly colored tumor cells tended to exhibit a mossy pattern which were distributed along the border between cancer nests and stroma, and the same pattern happened to occur in the positive mesenchymal cells contacting the tumor border, essentially lymphocytes and macrophages. The substantial necrosis in the tumour and the number of TIMCs was analyzed statistically significant correlated with CPS (P < 0.05), while other clinicopathological factors such as histological type, tumour size, invasion depth, TNM stage were uncorrelated. The number and distribution of TLS in the tumour and para-tumoural stroma indirectly affected PD-L1 in GC by associating with the quantity and pattern of TIMCs. Cox regression analysis revealed that the prognosis was poor when PD-L1 was positive. Conclusion: CPS is the best indicator for PD-L1 expression in GC, which tend to be increased expression following a large number of TIMCs and substantial tumour necrosis appeared. Heterogeneity was reflected in the different distributed pattern of PD-L1 expression, especially the mossy-like pantten of the staining tumor cell in the interface between tumour nests and stroma, regardless of the amount and intensity of PD-L1 expression. TLS is valuable for observing microscopic images to influence the quantity and pattern of TIMCs. CPS can be used as an independent prognostic factor for GC.

Breast cancer stem cells are responsible for cancer initiation, progression, and drug resistance. However, effective targeting strategies against the cell subpopulation are still limited. Here, we unveil two splice variants of very-low-density lipoprotein receptor, VLDLR-I and -II, which are highly expressed in breast cancer stem cells. In breast cancer cells, VLDLR silencing suppresses sphere formation abilities in vitro and tumor growth in vivo. We find that VLDLR knockdown induces transition from self-renewal to quiescence. Surprisingly, ligand-binding activity is not involved in the cancer-promoting functions of VLDLR-I and -II. Proteomic analysis reveals that citrate cycle and ribosome biogenesis-related proteins are upregulated in VLDLR-I and -II overexpressed cells, suggesting that VLDLR dysregulation is associated with metabolic and anabolic regulation. Moreover, high expression of VLDLR in breast cancer tissues correlates with poor prognosis of patients. Collectively, these findings indicate that VLDLR may be an important therapeutic target for breast cancer treatment.

To provide an overview of the current situation, challenges, and trends in online medical services from the perspective of andrology and promote the development of online medical services. Users of the Learning Alliance of Urology, who mainly worked in central regions of China, were invited to complete the questionnaire that included information on the participants and their institutions and their involvement in and concerns for online medical services. We received 875 complete responses. The percentage of online andrology patients at most institutions was less than 30%. The most common services were online appointment registration (92.7%) and online payment (81.8%). Online chat consultation (77.7%) was the most common form of consultation. Only 1 in 5 of the institutions had constructed their Internet hospital. Factors related to the percentage of online andrology patients included specialized andrology clinics and wards, sufficient time for doctors to provide online services, more diversified services, and online clinic training. The biggest challenge for online medical services was diagnosis and treatment safety. It is essential to raise awareness of online medical services for hospitals and patients and strengthen standardized management and training of online medical services, especially applicable to central regions of China. However, online medical services cannot wholly replace offline services due to insufficient diagnosis and treatment.

Brain iron deposition is a promising marker for human brain health, providing insightful information for understanding aging as well as neurodegenerations, e.g., Parkinson's disease (PD) and Alzheimer's disease (AD). To comprehensively evaluate brain iron deposition along with aging, PD-related neurodegeneration, from prodromal PD (pPD) to clinical PD (cPD), and AD-related neurodegeneration, from mild cognitive impairment (MCI) to AD, a total of 726 participants from July 2013 to December 2020, including 100 young adults, 189 old adults, 184 pPD, 171 cPD, 31 MCI and 51 AD patients, were included. Quantitative susceptibility mapping data were acquired and used to quantify regional magnetic susceptibility, and the resulting spatial standard deviations were recorded. A general linear model was applied to perform the inter-group comparison. As a result, relative to young adults, old adults showed significantly higher iron deposition with higher spatial variation in all of the subcortical nuclei (p

Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.

Abstract Background BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. Methods We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. Results BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1–2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10–4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. Conclusion Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. Trial registration: Chictr.org.cn ChiCTR1800018143.

Zhang et al. report QTL GS3.1 as regulating rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. Their results identify the biosynthetic pathway for grain size regulation via a multidrug and toxic compounds extrusion transporter, and demonstrate enlarged grains, reduced flavonoid content, and increased lignin content in the panicles with GS3.1.

Abstract Background RNA editing exerts critical impacts on numerous biological processes and thus are implicated in crucial human phenotypes, including tumorigenesis and prognosis. While previous studies have analyzed aggregate RNA editing activity at the sample level and associated it with overall cancer survival, there is not yet a large‐scale disease‐specific survival study to examine genome‐wide RNA editing sites’ prognostic value taking into account the host gene expression and clinical variables. Methods In this study, we solved comprehensive Cox proportional models of disease‐specific survival on individual RNA‐editing sites plus host gene expression and critical demographic covariates. This allowed us to interrogate the prognostic value of a large number of RNA‐editing sites at single‐nucleotide resolution. Results As a result, we identified 402 gene‐proximal RNA‐editing sites that generally predict adverse cancer survival. For example, an RNA‐editing site residing in ZNF264 indicates poor survival of uterine corpus endometrial carcinoma, with a hazard ratio of 2.13 and an adjusted p‐value of 4.07 × 10−7. Some of these prognostic RNA‐editing sites mediate the binding of RNA binding proteins and microRNAs, thus propagating their impacts to extensive regulatory targets. Conclusions In conclusion, RNA editing affects cis‐regulatory elements and predicts adverse cancer survival.

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The in vitro release profiles of STV from STV@CD-MOF (0.5:1) were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF (1:1) owing to nanoclusters formation. The bioavailability of STV@CD-MOF (1:1) in rats was 8.67-fold higher than that of STV, and was 1.32- and 1.27-fold higher than that of STV@CD and STV@CD-MOF (0.5:1). Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio, while the increasement in bioavailability at a high loading ratio, which was attributed to the nanocluster mechanism. This was confirmed by molecular simulation. In conclusion, CD-MOF is a promising system for STV loading, overcoming the insolubility and to improve the bioavailability of this natural compound.

Given the background of electricity market, the electricity consumption optimization can reduce consumers’ energy cost, and also help to reduce the peak load and improve the accommodation level of clean energy. Aiming at solving the problem of consumers’ insufficient management of their own electricity consumption, a multi-objective optimization model of electricity consumption is proposed considering the correlation of equipment electricity consumption. First, the cross-correlation coefficient is adopted to identify the consumption correlation among various electricity equipment based on the historical load data of consumers, and the significance of the consumption correlation is analyzed by silhouette index. Next, a multi-objective optimization model is constructed and the optimal electricity consumption strategy is obtained to maximize the consumer-side economy and comfort benefits. Finally, the results of case studies on a Zhejiang stir-fried tea enterprise in China show that the proposed model is feasible and effective.

Abstract Background In the oilseed crop Brassica napus (rapeseed), various metabolic processes influence seed oil content, oil quality, and biological yield. However, the role of plastid membrane proteins in these traits has not been explored. Results Our genome-wide association study (GWAS) of 520 B. napus accessions identified the chloroplast membrane protein-localized FATTY ACID EXPORTER 1-1 (FAX1-1) as a candidate associated with biological yield. Seed transcript levels of BnaFAX1-1 were higher in a cultivar with high seed oil content relative to a low-oil cultivar. BnaFAX1-1 was localized to the plastid envelope. When expressed in Arabidopsis thaliana, BnaFAX1-1 enhanced biological yield (total plant dry matter), seed yield and seed oil content per plant. Likewise, in the field, B. napus BnaFAX1-1 overexpression lines (BnaFAX1-1-OE) displayed significantly enhanced biological yield, seed yield, and seed oil content compared with the wild type. BnaFAX1-1 overexpression also up-regulated gibberellic acid 4 (GA4) biosynthesis, which may contribute to biological yield improvement. Furthermore, oleic acid (C18:1) significantly increased in BnaFAX1-1 overexpression seeds. Conclusion Our results indicated that the putative fatty acid exporter BnaFAX1-1 may simultaneously improve seed oil content, oil quality and biological yield in B. napus, providing new approaches for future molecular breeding.

BackgroundGestational trophoblastic neoplasia is an uncommon disease, whose clinical manifestations are similar to ectopic pregnancy, thus some rare pelvic lesion can be misdiagnosed as ectopic pregnancy.AimsThis study was presented to investigate the characteristics of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy and reduce the misdiagnosis.MethodsThe clinicopathological data for 14 cases of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy at West China Second Hospital Sichuan University from January 2006 to December 2020 were retrospectively analyzed.ResultsThe main clinical manifestations were amenorrhea, abnormal vaginal bleeding, and abdominal pain. At initial diagnosis, the serum hCG level was >10,000 mIU/mL in 5 patients and 13 points (very high risk). From 14 patients, only 3 had molar pregnancy previously. Only 3 patients had no metastasis at GTN diagnosis (from these 3, only one after molar pregnancy). After chemotherapy alone or in combination with surgery, all patients survived, with a median follow-up of 84 months (23–102 months).ConclusionIf we have positive hCG, without a sonographic topic gestation confirmation, associated with metastatic lesions, the GTN diagnosis should be considered instead of ectopic pregnancy, if the patient have had a pregnancy once during her life.