Search

Abstract Lettuce is one of the most widely cultivated and consumed dicotyledonous vegetables globally. Despite the availability of its reference genome sequence, lettuce gene annotation remains incomplete, impeding comprehensive research and the broad application of genomic resources. Long-read RNA isoform sequencing (Iso-Seq) offers substantial advantages for analyzing RNA alternative splicing and aiding gene annotation, yet it faces throughput limitations. We present the HIT-ISOseq method tailored for bulk sample analysis, significantly enhancing RNA sequencing throughput on the PacBio platform by concatenating cDNA. Here we show, HIT-ISOseq generates 3-4 cDNA molecules per CCS read in lettuce, yielding 15.7 million long reads per PacBio Sequel II SMRT Cell 8 M. We validate its effectiveness in analyzing six lettuce tissue samples, including roots, stems, and leaves, revealing tissue-specific gene expression patterns and RNA isoforms. Leveraging diverse tissue long-read RNA sequencing, we refine the transcript annotation of the lettuce reference genome, expanding its GO and KEGG annotation repertoire. Collectively, this study serves as a foundational reference for genome annotation and the analysis of multi-sample isoform expression, utilizing high-throughput long-read transcriptome sequencing.

Phlomoides, with 150–170 species, is the second largest and perhaps most taxonomically challenging genus within the subfamily Lamioideae (Lamiaceae). With about 60 species, China is one of three major biodiversity centers of Phlomoides. Although some Phlomoides species from China have been included in previous molecular phylogenetic studies, a robust and broad phylogeny of this lineage has yet to be completed. Moreover, given the myriad new additions to the genus, the existing infrageneric classification needs to be evaluated and revised. Here, we combine molecular and morphological data to investigate relationships within Phlomoides, with a focus on Chinese species. We observed that plastid DNA sequences can resolve relationships within Phlomoides better than nuclear ribosomal internal and external transcribed spacer regions (nrITS and nrETS). Molecular phylogenetic analyses confirm the monophyly of Phlomoides, but most previously defined infrageneric groups are not monophyletic. In addition, morphological analysis demonstrates the significant taxonomic value of eight characters to the genus. Based on our molecular phylogenetic analyses and morphological data, we establish a novel section Notochaete within Phlomoides, and propose three new combinations as well as three new synonyms. This study presents the first molecular phylogenetic analyses of Phlomoides in which taxa representative of the entire genus are included, and highlights the phylogenetic and taxonomic value of several morphological characters from species of Phlomoides from China. Our study suggests that a taxonomic revision and reclassification for the entire genus is necessary in the future.

Abstract Background We compared magnetic resonance imaging (MRI) turbo spin-echo images reconstructed using a deep learning technique (TSE-DL) with standard turbo spin-echo (TSE-SD) images of the lumbar spine regarding image quality and detection performance of common degenerative pathologies. Methods This prospective, single-center study included 31 patients (15 males and 16 females; aged 51 ± 16 years (mean ± standard deviation)) who underwent lumbar spine exams with both TSE-SD and TSE-DL acquisitions for degenerative spine diseases. Images were analyzed by two radiologists and assessed for qualitative image quality using a 4-point Likert scale, quantitative signal-to-noise ratio (SNR) of anatomic landmarks, and detection of common pathologies. Paired-sample t, Wilcoxon, and McNemar tests, unweighted/linearly weighted Cohen κ statistics, and intraclass correlation coefficients were used. Results Scan time for TSE-DL and TSE-SD protocols was 2:55 and 5:17 min:s, respectively. The overall image quality was either significantly higher for TSE-DL or not significantly different between TSE-SD and TSE-DL. TSE-DL demonstrated higher SNR and subject noise scores than TSE-SD. For pathology detection, the interreader agreement was substantial to almost perfect for TSE-DL, with κ values ranging from 0.61 to 1.00; the interprotocol agreement was almost perfect for both readers, with κ values ranging from 0.84 to 1.00. There was no significant difference in the diagnostic confidence or detection rate of common pathologies between the two sequences (p ≥ 0.081). Conclusions TSE-DL allowed for a 45% reduction in scan time over TSE-SD in lumbar spine MRI without compromising the overall image quality and showed comparable detection performance of common pathologies in the evaluation of degenerative lumbar spine changes. Relevance statement Deep learning-reconstructed lumbar spine MRI protocol enabled a 45% reduction in scan time compared with conventional reconstruction, with comparable image quality and detection performance of common degenerative pathologies. Key points • Lumbar spine MRI with deep learning reconstruction has broad application prospects. • Deep learning reconstruction of lumbar spine MRI saved 45% scan time without compromising overall image quality. • When compared with standard sequences, deep learning reconstruction showed similar detection performance of common degenerative lumbar spine pathologies. Graphical Abstract

High-entropy ceramic materials usually refer to the multi-principal solid solution formed by 5 or more ceramic components. Due to its novel “high-entropy effect” and excellent performance, it has become one of the research hotspots in the field of ceramics in recent years. As the research system of high-entropy ceramics has gradually expanded from the initial rock salt oxides (Mg-Ni-Co-Cu-Zn)O to fluorite oxides, perovskite oxides, spinel oxides, borides, carbides and silicates, its special mechanical, electrical, magnetic and energy storage properties have been continuously discovered. Based on the basic principle of high-entropy materials, this paper mainly introduces the prominent perovskite-type oxide high-entropy ceramics in recent years from the perspective of ceramic structure and properties, and predicts the development trend of high-entropy perovskite-type ceramics in the next few years.

Objectives Investigate the impact of daily occupational walking steps on the progression of papillary thyroid cancer (PTC), a topic hitherto underresearched. Material and Methods The authors analyzed the data from 800 individuals with PTC across stages 0–IV. Participants were evenly divided into 2 distinct occupational groups: office workers and construction workers (N = 400 each). Data included comprehensive records of daily walking steps, demographic information, and clinical indicators. Pearson’s correlation coefficients or analysis of variance (ANOVA) were employed to assess the linkage between daily walking steps and PTC risk and stage, as well as associated biochemical markers. Results The analysis revealed a significant inverse relationship between daily walking steps and PTC risk. A higher frequency of daily steps was associated with reduced chances of PTC onset and a lower diagnostic stage of the disease. This protective effect of physical activity was particularly pronounced in the construc- tion worker cohort. Subsequent evaluations showed that construction workers who consistently logged higher daily steps had markedly lower levels of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody, thyroglobulin antibody, and thy- roglobulin (Tg). Notably, daily walking steps exhibited a strong inverse correlation with body mass index (BMI), age, PTC volumes, and levels of TSH and Tg across both occupational groups (ρ < –0.37). The increase in daily steps was associated with the reduction in PTC stages (p < 0.001). Conclusions The research underscores the potential benefits of increased daily walking steps, suggesting that they may play a protective role in reducing PTC risk and moderating its progression. Int J Occup Med Environ Health. 2024;37(1):58–71

Phlomoides is one of the largest genera of Lamiaceae with approximately 150–170 species distributed mainly in Eurasia. In this study, we describe and illustrate a new species, P. henryi, which was previously misidentified as P. bracteosa, from Yunnan Province, southwest China. Molecular phylogenetic analyses revealed that P. henryi is found within a clade in which most species lack basal leaves. In this clade, the new species is morphologically distinct from P. rotata in having an obvious stem and, from the rest, by having transparent to white trichomes inside the upper corolla lip. In addition, micro-features of trichomes on the calyx and leaf epidermis can differentiate the new species from other species grouped in the same clade and a key, based on trichome morphology for these species, is provided. The findings demonstrate that the use of scanning electron microscopy can reveal inconspicuous morphological affinities amongst morphologically similar species and play an important role in the taxonomic study of the genus Phlomoides.

A new taper-shaped linearly polarized (LP) magneto-electric (ME) dipole, excited by the U-shaped microstrip line through a coupling slot, is proposed in this paper. An ultra-wide simulated impedance bandwidth of 85% (20.5-50.6 GHz) and 1.5-dB gain bandwidth of 73% (22.3-47.9 GHz) with a peak gain up to 7.7 dBi are achieved, combining the advantages of simple and compact structure, high integration, easy assembling and stable radiation characteristics. For proof-of-concept demonstration, a $4\times4$ LP array antenna is then implemented with an ultra-wide measured impedance bandwidth of 91.8% (18.8-50.7 GHz) and 3-dB gain bandwidth of 69.3% (19.8 to 40.8 GHz) as well as a peak gain of 18.0 dBi. Subsequently, the LP element is conveniently extended to a dual-polarized (DP) one due to its 90° rotationally symmetrical structure, exhibiting a wide simulated overlapped bandwidth of 61.4% (23.7-44.7 GHz), port isolation exceeding 17 dB and a stable gain response with a peak gain of 7.5 dBi. Furthermore, two $1\times4$ DP active phased array antennas (APAAs) are designed by utilizing the integrated circuits (ICs) for 5G/6G millimeter-wave (mmWave) mobile terminal applications. Meanwhile, the beam-scanning performances at 28- and 38-GHz are measured for both polarizations. The validated advantages render the proposed antenna designs competitive candidates for diverse 5G/6G mmWave applications.

Isodon xiaoluzhiensis, a new species of the tribe Ocimeae in family Lamiaceae, is described and illustrated. The new species is known only from the type locality, Xiaoluzhi village in Luzhijang dry-hot valley of Yimen County, central Yunnan, southwest China. It is characterized by having a procumbent habit, gracile stems and branches, relatively small leaves and flowers, and the phenology of flowering in winter. The morphological comparisons with its putative closest relatives (I. adenanthus and I. hsiwenii) are also presented.

Perfluoroalkyl acids (PFAAs) are considered forever chemicals, gaining increasing attention for their hazardous impacts. However, the ecological effects of PFAAs remain unclear. Environmental DNA (eDNA), as the environmental gene pool, is often collected for evaluating the ecotoxicological effects of pollutants. In this study, we found that all PFAAs investigated, including perfluorohexanoic acid, perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctane sulfonate, even at low concentrations (0.02 and 0.05 mg/L), expedited the enzymatic degradation of DNA in a nonlinear dose–effect relationship, with DNA degradation fragment sizes being lower than 1,000 bp and 200 bp after 15 and 30 min of degradation, respectively. This phenomenon was attributed to the binding interaction between PFAAs and AT bases in DNA via groove binding. van der Waals force (especially dispersion force) and hydrogen bonding are the main binding forces. DNA binding with PFAAs led to decreased base stacking and right-handed helicity, resulting in loose DNA structure exposing more digestion sites for degrading enzymes, and accelerating the enzymatic degradation of DNA. The global ecological risk evaluation results indicated that PFAA contamination could cause medium and high molecular ecological risk in 497 samples from 11 contamination-hot countries (such as the USA, Canada, and China). The findings of this study show new insights into the influence of PFAAs on the environmental fates of biomacromolecules and reveal the hidden molecular ecological effects of PFAAs in the environment.

The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3–5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.

Abstract Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next‐generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream–downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order‐/family‐level grouping, genus‐/species‐level grouping could more accurately reveal the differences between upstream zones I−III, midstream zones IV−V, and downstream zones VI–VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring.

Objective To assess the feasibility of the robot-assisted retractor. To compare the muscle injury of the two operation modes, intermittent retraction mode and continuous retraction mode in the robot-assisted retractor to find a better robot operation mode. Methods A new robot-assisted retractor experimental platform was developed. Three incisions were made on the backs of three beagles. The robot-assisted retractor was used to retract the muscle on both sides of the incisions in intermittent retraction mode and continuous retraction mode, and the operation of the robot system was observed. The muscle samples were stained with hematoxylin-eosin (HE) to observe the muscle injury. The difference between the muscle injuries of the two groups was statistically compared using paired t test. Results The robot-assisted retractor can precisely retract to the specified position without malfunction or dangerous actions. Histologic evaluation showed that fewer muscle injury was found in the intermittent retraction mode group of the robot-assisted retractor compared to the continuous retraction mode group. Conclusion The robot-assisted retractor offers a certain degree of feasibility and safety. The robot-assisted retractor is able to effectively reduce muscle injury with the intermittent retraction mode.

BackgroundInfant, junior, and adult patients with neuronal intranuclear inclusion disease (NIID) present with various types of seizures. We aimed to conduct a systematic literature review on the clinical characteristics of NIID with seizures to provide novel insight for early diagnosis and treatment and to improve prognosis of these patients.MethodsWe used keywords to screen articles related to NIID and seizures, and data concerning the clinical characteristics of patients, including demographic features, disease characteristics of the seizures, treatment responses, imaging examinations, and other auxiliary examination results were extracted.ResultsThe included studies comprised 21 patients with NIID with seizures. The most common clinical phenotypes were cognitive impairment (76.20%) and impaired consciousness (57.14%), and generalized onset motor seizures (46.15%) represented the most common type. Compared with infantile and juvenile cases, the use of antiepileptic drugs in adults led to significant seizure control and symptom improvement, in addition to providing a better prognosis. The number of GGC sequence repeats in the NOTCH2NLC gene in six NIID patients with seizures who underwent genetic testing ranged 72–134.ConclusionThe most common clinical phenotypes in patients with NIID with seizures were cognitive impairment and consciousness disorders. Patients with NIID presented with various types of seizures, with the most common being generalized onset motor seizures. Adult patients had a better prognosis and were relatively stable. The early diagnosis of NIID with seizures is of great significance for treatment and to improve prognosis.

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.

Abstract The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of “seeding and harvest”, are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast‐to‐DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two‐pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

Selective electrodialysis is a promising approach to recovering K+ from complex coexisting ionic systems. In this study, the effects of current density, the concentration of K+ and Mg2+, as well as the operating temperature on the separation process of K+ and Mg2+ were explored to investigate the competitive migration of mono- and multivalent ions, offering a guide for the design of selective electrodialysis process, and therefore obtain the desired aqueous solutions containing K+ and Mg2+. The results show that ion concentration played a critical role in determining the selectivity of separation between K+ and Mg2+. High concentrations of K+ and Mg2+ led to a decrease in selectivity but the effect of concentration of K+ on selectivity was more pronounced. Although higher current density increased the flux of ions, their impact on separation selectivity was minimal. Furthermore, higher temperature increased the flux of ions but resulted in a decrease of K+ proportion in the solution. Overall, this study provides good guidance for studying the competitive migration of mono- and multivalent ions and the high-value recycling of potassium resources. HIGHLIGHTS Selective electrodialysis was used for the separation of potassium and magnesium ions.; The main factors affecting the competitive migration of mono- and multivalent ions were systematically explored.; Potassium resource was efficiently recovered by selective electrodialysis.;

This paper constructs a morphological extraction model of Ganan Hakka architectural elements based on feature fusion using ResNet as the backbone network. Then, the extraction method of Ganan Hakka architectural colors based on the combination of multivariate fuzzy C-mean clustering algorithm and the K-mean++ algorithm is designed. The improved recommendation algorithm intelligently matches the extracted color and morphological elements and applies them to modern architectural interior design. The results show that the average time of interior design intelligent recommendation is 3.8s, the overall accuracy is above 0.94, and the degree of interior design intelligent matching is in the range of [0.78,0.99]. Based on this study, Ganan Hakka’s architectural elements can be well combined with modern architectural interiors to promote traditional culture.

Abstract Background The ossification mechanism of the temporomandibular joint (TMJ) condyle remains unclear in human embryo. The size and structure of TMJ, shape of articular disc and the characteristics of omnivorous chewing in the pig are similar to those of humans. The pig is an ideal animal for studying the mechanism of ossification of the TMJ condyle during the embryonic period. Method In a previous study by our group, it was found that there was no condylar ossification on embryonic day(E) 45, but the ossification of condyle occurred between E75 and E90. In this study, a total of 12 miniature pig embryos on E45 and E85 were used. Six embryos were used for tissue sections (3 in each group). The remaining six embryos were used for transcriptomic and proteomic studies to find differential genes and proteins. The differentially expressed genes in transcriptome and proteomic analysis were verified by QPCR. Results In total, 1592 differential genes comprising 1086 up‐regulated genes and 506 down‐regulated genes were screened for fold changes of ≥2 to ≤0.5 between E45 and E85. In the total of 4613 proteins detected by proteomic analysis, there were 419 differential proteins including 313 up‐regulated proteins and 106 down‐regulated proteins screened for fold changes of ≥2 to ≤0.5 between E45 and E85. A total of 36 differential genes differing in both transcriptome and proteome analysis were found. QPCR analysis showed that 14 of 15 selected genes were consistent with transcriptome analysis. Conclusion Condylar transcriptome and proteomic analysis during the development of TMJ in miniature pigs revealed the regulatory genes/proteins of condylar ossification.

Abstract Background Hundreds of single‐nucleotide polymorphism (SNP) sites have been found to be potential genetic markers of type 2 diabetes mellitus (T2DM). However, SNPs related to T2DM in minipigs have been less reported. This study aimed to screen the T2DM‐susceptible candidate SNP loci in Bama minipigs so as to improve the success rate of the minipig T2DM model. Methods The genomic DNAs of three Bama minipigs with T2DM, six sibling low‐susceptibility minipigs with T2DM, and three normal control minipigs were compared by whole‐genome sequencing. The T2DM Bama minipig‐specific loci were obtained, and their functions were annotated. Meanwhile, the Biomart software was used to perform homology alignment with T2DM‐related loci obtained from the human genome‐wide association study to screen candidate SNP markers for T2DM in Bama miniature pigs. Results Whole‐genome resequencing detected 6960 specific loci in the minipigs with T2DM, and 13 loci corresponding to 9 diabetes‐related genes were selected. Further, a set of 122 specific loci in 69 orthologous genes of human T2DM candidate genes were obtained in the pigs. Collectively, a batch of T2DM‐susceptible candidate SNP markers in Bama minipigs, covering 16 genes and 135 loci, was established. Conclusions Whole‐genome sequencing and comparative genomics analysis of the orthologous genes in pigs that corresponded to the human T2DM‐related variant loci successfully screened out T2DM‐susceptible candidate markers in Bama miniature pigs. Using these loci to predict the susceptibility of the pigs before constructing an animal model of T2DM may help to establish an ideal animal model.

Abstract The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

Abstract Bone fusion of defect broken ends is the basis of the functional reconstruction of critical maxillofacial segmental bone defects. However, the currently available treatments do not easily achieve this goal. Therefore, this study aimed to fabricate 3D-printing titanium grid scaffolds, which possess sufficient pores and basic biomechanical strength to facilitate osteogenesis in order to accomplish bone fusion in mandibular segmental bone defects. The clinical trial was approved and supervised by the Medical Ethics Committee of the Chinese PLA General Hospital on March 28th, 2019 (Beijing, China. approval No. S2019–065–01), and registered in the clinical trials registry platform (registration number: ChiCTR2300072209). Titanium grid scaffolds were manufactured using selective laser melting and implanted in 20 beagle dogs with mandibular segmental defects. Half of the animals were treated with autologous bone chips and bone substances incorporated into the scaffolds; no additional filling was used for the rest of the animals. After 18 months of observation, radiological scanning and histological analysis in canine models revealed that the pores of regenerated bone were filled with titanium grid scaffolds and bone broken ends were integrated. Furthermore, three patients were treated with similar titanium grid scaffold implants in mandibular segmental defects; no mechanical complications were observed, and similar bone regeneration was observed in the reconstructed patients’ mandibles in the clinic. These results demonstrated that 3D-printing titanium grid scaffolds with sufficient pores and basic biomechanical strength could facilitate bone regeneration in large-segment mandibular bone defects.

TRIB3, a pseudokinase, was previously studied within only some specific cancer types, leaving its comprehensive functions in pan-cancer contexts largely unexplored. Here, we performed an integrated analysis of TRIB3 expression, prognosis, genetic alterations, functional enrichment and tumor immune-related characteristics in 33 cancer types. Our results showed that TRIB3 exhibits high expression levels across 24 different cancer types and correlates closely with unfavorable prognoses. Meanwhile, TRIB3 shows mutations in a wide spectrum of 22 distinct cancer types, with the predominant mutation types being missense mutations and gene amplifications, and significant changes in DNA methylation levels in 14 types of cancer. We further discovered that TRIB3 expression is significantly associated with cancer immune-related genome mutations, such as tumor mutational burden (TMB), microsatellite instability (MSI) and DNA mismatch repair (MMR), and infiltration of immunosuppressive cells, such as CD4+ Th2 cells and myeloid-derived suppressor cells (MDSCs), into the tumor microenvironment. These results indicated that the expression of TRIB3 might reshape the tumor immune microenvironment (TIME) and lead to immunosuppressive ''cold'' tumors. In addition, our results confirmed that the loss of function of TRIB3 inhibits cell proliferation, promotes apoptosis, and leads to significant enrichment of ''hot'' tumor-related immune pathways, at least in breast cancer cells, which further supports the important role of TRIB3 in cancer prognosis and TIME regulation. Together, this pan-cancer investigation provided a comprehensive understanding of the critical role of TRIB3 in human cancers, and suggested that TRIB3 might be a promising prognostic biomarker and a potential target for cancer immunotherapy.

Abstract Geometry and angles play crucial roles in cellular processes; however, its mechanisms of regulation remain unclear. In this study, a series of three dimensional (3D)‐printed microfibers with different geometries is constructed using a near‐field electrostatic printing technique to investigate the regulatory mechanisms of geometry on stem cell function and bone regeneration. The scaffolds precisely mimicked cell dimensions with high porosity and interoperability. Compared with other spatial topography angles, microfibers with a 90° topology can significantly promote the expression of osteogenic gene proteins in bone marrow‐derived mesenchymal stem cells (BMSCs). The effects of different spatial structures on the expression profiles of BMSCs differentiation genes are correlated and validated using microRNA sequencing. Enrichment analysis shows that the 90° microfibers promoted osteogenesis in BMSCs by significantly upregulating miR‐222‐5p/cbfb/Runx2 expression. The ability of the geometric architecture to promote bone regeneration, as assessed using the cranial defect model, demonstrates that the 90° fiber scaffolds significantly promote new bone regeneration and neovascular neural network formation. This study is the first to elucidate the relationship between angular geometry and cellular gene expression, contributing significantly to the understanding of how geometric architecture can promote stem cell differentiation, proliferation, and function for structural bone regeneration.

Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not clarified. Thus, this study utilized network pharmacology, UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography - Mass Spectrometry) and animal experiments to reveal the mechanisms of QDDHG on DKD. Experimental procedure: Screening and retrieving active ingredients and corresponding targets of QDDHG on DKD through the TCMSP, ETCM, Disgenet, GeneCards, Omim and DrugBank databases. The PPI were performed with BioGrid, STRING, OmniPath, InWeb-IM. AutoDock Vina molecular docking module to estimate the validation from the compounds and target proteins. Free energy to estimate the binding affinity for identified compounds and target proteins. The ingredients of QDDHG were analyzed utilizing UHPLC-MS/MS. In vivo experiment with db/db mice were used to verify the targets and pathway predicted by network pharmacology. Results and conclusion: The results demonstrated that QDDHG has 18 active compounds and 13 target proteins of QDDHG exerted a crucial role in treatment of DKD. QDDHG affect the multiple biological processes included cellular response to lipid, response to oxidative stress, and various pathways, such as AGE-RAGE, PI3K-Akt, MAPK, TNF, EGFR, STAT3. The results of UHPLC-MS/MS showed that six ingredients predicted by network pharmacology were also verified in experiment. In vivo experiment verified the effects of QDDHG on protecting the renal function mainly through inhibited the expression of EGFR, STAT3 and pERK in the db/db mice.

The monotypic genus Pseudomarrubium is perhaps the most poorly understood taxon within the subfamily Lamioideae (Lamiaceae). While advances in molecular phylogenetics have clarified the phylogeny and taxonomy of Lamioideae, the systematic placement of Pseudomarrubium remains unclear, as it has never been tested using molecular phylogenetic analyses due to an inaccessibility of plant material. In this study, we used high-throughput next-generation sequencing to infer the systematic placement of Pseudomarrubium based on old herbarium collections as well as silica gel-dried leaves. Phylogenomic analyses demonstrate that Pseudomarrubium is a member of tribe Phlomideae and nested within Phlomoides, and a new combination, Phlomoides eremostachydioides, is proposed. The study highlights that herbarium-preserved samples, even very old ones, are invaluable resources that can be used to generate reliable genome-scale data and be used for molecular phylogenetic inquiries.

Software bug repair is a problem that cannot be ignored in the process of software life.How to efficiently assign software bugs automatically is a very important research direction.Now,the existing research methods mainly focus on the bugreport’s text content or the low-level information of the developers’ tossing network,while ignoring the high-level topology information in the tossing network.Therefore,this paper proposes a software bug automatic assignment model MFD-GCN based on the developers’ multivariate features.Model fully considers the high-level topological features in the developers’ tossing network,and uses the powerful network feature extraction capabilities of graph convolution network to fully mine the multivariate features that represent developers’ deep cooperation relationship and fixing preferences,and train the classifier together with the bug text features.The proposed method is evaluated on two large open-source software projects,i.e.,Eclipse and Mozilla.Expe-rimental results show that compared with the mainstream bug-assignment methods proposed in recent years,the MFD-GCN mo-del has achieved state-of-art results in recommending the top K developers.The accuracy rate of top-1 recommendation on the Eclipse and Mozilla project reaches 69.8% and 59.7%,respectively.

Highlights 1. Circ_0083964 was overexpressed in RA synovial tissues and RA-FLSs. 2. Circ_0083964 inhibition repressed cell growth, invasion, migration and inflammatory response in RA-FLSs. 3. Circ_0083964 functioned as a molecular sponge of miR-204-5p. 4. YY1 acted as a miR-204-5p target.

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25–37 °C) and pH (6.5–9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV–visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of α-helix and reducing of β-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification.

Abstract The Hangenberg Crisis coincided with a large decline of biodiversity and widespread anoxia in the end‐Devonian ocean. Previous research attributed marine anoxia to the spread of deeply‐rooted plants and/or increased volcanism on the continents, but crucial links have not been thoroughly explored. Herein, we propose enhanced weathering as a key trigger, as evidenced by a negative shift (∼8‰) in lithium isotopes and a coupled response in carbon isotopes of marine carbonates in South China. Our findings imply that rapid weathering of crustal rocks increased nutrient delivery to the ocean, as indicated by an increase in the carbonate‐associated phosphate levels, contributing to oceanic eutrophication. In the absence of massive volcanic emissions and intense orogeny, the cause of enhanced continental weathering was likely the expansion of the terrestrial rhizosphere, highlighting the potential for land plant evolution to initiate weathering changes of sufficient severity to trigger a major bio/environmental crisis in the Earth system.

The indumentum of nutlets is shown to be of phylogenetic importance in previous molecular phylogenetic studies of Paraphlomis, a genus of Lamiaceae with approximately 30 species distributed mainly in southern China and Southeast Asia. Nearly half the species of Paraphlomis are known from limestone areas. In this study, we described and illustrated a new species, P. hsiwenii, from the karst mountain forests in Guangxi Zhuang Autonomous Region, China. Our molecular phylogenetic analyses revealed that P. hsiwenii is recovered in a clade consisting of species with hairy nutlets. The new species is morphologically most similar to P. pagantha from the same clade, but they differ in the morphology of lamina bases, length of pedicels and calyces, as well as the morphology of upper corolla lips.