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Abstract Background Cancer metastasis remains a major challenge in the clinical management of triple-negative breast cancer (TNBC). The NF-κB signaling pathway has been implicated as a crucial factor in the development of metastases, but the underlying molecular mechanisms remain largely unclear. Methods PTPN20 expression was evaluated using data from the Sweden Cancerome Analysis Network-Breast and The Cancer Genome Atlas database, as well as by western blotting and immunohistochemistry in 88 TNBC patients. The ability of PTPN20 to activate NF-κB was assessed by luciferase reporter assays. The effects of PTPN20 overexpression and knockdown via short hairpin RNA were examined in TNBC cell lines by wound healing and transwell matrix penetration assays. Additionally, we analyzed the growth and metastasis abilitiy of 4T1 xenograft tumors in nude mice. Results PTPN20 levels were elevated in TNBC cell lines and patient samples compared to controls, and higher protein levels correlated with metastasis-free survival. Overexpression of PTPN20 enhanced migration and invasion in vitro, and promoted lung metastasis in vivo. Our finding revealed that PTPN20 activates NF-κB signaling by dephosphorylating p65 at Ser468, preventing its binding to COMMD1, thereby protecting p65 from degradation. Downregulation of PTPN20 effectively inhibit, while p65 S468A mutant restored the migratory and invasive abilities of TNBC cells. Conclusions Collectively, our results demonstrate that PTPN20 plays a critical role in TNBC metastasis through the activation of NF-κB signaling. We propose that PTPN20 may serve as a novel prognostic marker and potential therapeutic target for the treatment of TNBC.

The Body-Centered Cubic (BCC) lattice structure is commonly used in high-end equipment fields, such as aerospace, due to its superior mechanical properties, lightweight characteristics, and ease of processing. However, there is a need to improve the performance-to-weight ratio of the traditional BCC lattice structure. This study utilizes topology optimization to design a T-BCC lattice structure based on the BCC unit cell, with the aim of maximizing stiffness. A model proposing the characterization of the Young's modulus of BCC lattice structures is presented. The model is based on calculations of cell porosity and beam stress analysis, assuming a large cell. This approach indirectly enables the calculation of the Young's modulus of T-BCC lattice arrays in multiple dimensions. Simulation and experimental comparison were used to analyze the compressive performance and load-bearing modes of T-BCC lattice structures, revealing the mechanisms of compressive deformation and failure modes. The accuracy of the characterization model for Young's modulus was found to be 93.1%. Compared to BCC lattice structures designed by traditional methods, T-BCC lattice structures designed via topology optimization can increase the Young's modulus by up to 36% and yield strength by 37.2%. This suggests that T-BCC lattice structures are a more lightweight and efficient solution for designing components in high-end equipment fields.

Abstract The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication. These PROTAC nanoparticles selectively accumulate within and penetrate deep into tumors via response to matrix metalloproteinase-2. Photoactivity is then reactivated in response to the acidic intracellular milieu and the PROTAC is discharged due to the ROS generated via photodynamic therapy specifically within the normoxic microenvironment. Moreover, the latent hypoxia-responsive PROTAC prodrug is restored in hypoxic cancer stem-like cells overexpressing nitroreductase. Here, we show the ability of region-confined PROTAC nanoplatform to effectively degrade BRD4 in both normoxic and hypoxic environments, markedly hindering tumor progression in breast and head-neck tumor models.

Abstract Stretchable electronic circuits can seamlessly conform to irregular and dynamic surfaces with high integration. However, current stretchable configurations typically have limited stretchability due to the lack of robust connections between soft interconnects and rigid electronics. Here, we printed highly stretchable metal–polymer conductors on thermoplastic elastomers as interconnects. We developed electronic vests with porous surfaces for rigid electronics and introduced polyester hot-melt adhesives to strengthen connections between soft interconnects and rigid electronics. After thermal bonding, the adhesive penetrates the porous surface of electronic vests, creating a mechanical interlock and providing an adhesion force of 8.34 N/cm for the connection (3× higher than conductive adhesives). Thus, rigid electronics of different sizes and different pin counts can form strong connections to soft interconnects, achieving a maximum strain tolerance of ~700% (10× higher than conductive adhesives). We achieved highly integrated ultra-stretchable displays that can withstand stretching up to 220% without dead pixels.

Abstract FeSe is one of the most enigmatic superconductors. Among the family of iron-based compounds, it has the simplest chemical makeup and structure, and yet it displays superconducting transition temperature ( T c $T_{\text{c}}$ ) spanning 0 to 15 K for thin films, while it is typically 8 K for single crystals. This large variation of T c $T_{\text{c}}$ within one family underscores a key challenge associated with understanding superconductivity in iron chalcogenides. Here, using a dual-beam pulsed laser deposition (PLD) approach, we have fabricated a unique lattice-constant gradient thin film of FeSe which has revealed a clear relationship between the atomic structure and the superconducting transition temperature for the first time. The dual-beam PLD that generates laser fluence gradient inside the plasma plume has resulted in a continuous variation in distribution of edge dislocations within a single film, and a precise correlation between the lattice constant and T c $T_{\text{c}}$ has been observed here, namely, T c ∝ c − c 0 $T_{\text{c}} \propto \sqrt{c- c_{0}}$ , where c is the c-axis lattice constant (and c 0 $c_{0}$ is a constant). This explicit relation in conjunction with a theoretical investigation indicates that it is the shifting of the d xy $d_{\text{xy}}$ orbital of Fe which plays a governing role in the interplay between nematicity and superconductivity in FeSe.

Abstract Human hippocampal organoids (hHOs) derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising models for investigating neurodegenerative disorders, such as schizophrenia and Alzheimer’s disease. However, obtaining the electrical information of these free-floating organoids in a noninvasive manner remains a challenge using commercial multi-electrode arrays (MEAs). The three-dimensional (3D) MEAs developed recently acquired only a few neural signals due to limited channel numbers. Here, we report a hippocampal cyborg organoid (cyb-organoid) platform coupling a liquid metal-polymer conductor (MPC)-based mesh neuro-interface with hHOs. The mesh MPC (mMPC) integrates 128-channel multielectrode arrays distributed on a small surface area (~2*2 mm). Stretchability (up to 500%) and flexibility of the mMPC enable its attachment to hHOs. Furthermore, we show that under Wnt3a and SHH activator induction, hHOs produce HOPX+ and PAX6+ progenitors and ZBTB20+PROX1+ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs reveal high similarity to the developing human hippocampus. We successfully detect neural activities from hHOs via the mMPC from this cyb-organoid. Compared with traditional planar devices, our non-invasive coupling offers an adaptor for recording neural signals from 3D models.

Abstract Background High-affinity potassium transporters (HKTs) are crucial in facilitating potassium uptake by plants. Many types of HKTs confer salt tolerance to plants through regulating K+ and Na+ homeostasis under salinity stress. However, their specific functions in cassava (Manihot esculenta) remain unclear. Results Herein, an HKT gene (MeHKT1) was cloned from cassava, and its expression is triggered by exposure to salt stress. The expression of a plasma membrane-bound protein functions as transporter to rescue a low potassium (K+) sensitivity of yeast mutant strain, but the complementation of MeHKT1 is inhibited by NaCl treatment. Under low K+ stress, transgenic Arabidopsis with MeHKT1 exhibits improved growth due to increasing shoot K+ content. In contrast, transgenic Arabidopsis accumulates more Na+ under salt stress than wild-type (WT) plants. Nevertheless, the differences in K+ content between transgenic and WT plants are not significant. Additionally, Arabidopsis expressing MeHKT1 displayed a stronger salt-sensitive phenotype. Conclusion These results suggest that under low K+ condition, MeHKT1 functions as a potassium transporter. In contrast, MeHKT1 mainly transports Na+ into cells under salt stress condition and negatively regulates the response of transgenic Arabidopsis to salt stress. Our results provide a reference for further research on the function of MeHKT1, and provide a basis for further application of MeHKT1 in cassava by molecular biological means.

Abstract The IVa subfamily of glycine-rich proteins (GRPs) comprises a group of glycine-rich RNA binding proteins referred to as GR-RBPa here. Previous studies have demonstrated functions of GR-RBPa proteins in regulating stress response in plants. However, the mechanisms responsible for the differential regulatory functions of GR-RBPa proteins in different plant species have not been fully elucidated. In this study, we identified and comprehensively studied a total of 34 GR-RBPa proteins from five plant species. Our analysis revealed that GR-RBPa proteins were further classified into two branches, with proteins in branch I being relatively more conserved than those in branch II. When subjected to identical stresses, these genes exhibited intensive and differential expression regulation in different plant species, corresponding to the enrichment of cis-acting regulatory elements involving in environmental and internal signaling in these genes. Unexpectedly, all GR-RBPa genes in branch I underwent intensive alternative splicing (AS) regulation, while almost all genes in branch II were only constitutively spliced, despite having more introns. This study highlights the complex and divergent regulations of a group of conserved RNA binding proteins in different plants when exposed to identical stress conditions. These species-specific regulations may have implications for stress responses and adaptations in different plant species.

Bacterial infections pose considerable health risks, emphasising the critical need for effective and biocompatible antibacterial drugs. Considerably, we developed an efficient antimicrobial system incorporating the combined potential of high-frequency ultrasound and antimicrobial drugs against bacterial infections. A ZnO–kaolinite (Kaol) composite with antibacterial properties was synthesised by growing ZnO on the Kaol nano-clay surface using the co-precipitation method. High-frequency ultrasound efficiently promotes the release of Zn2+, which enhances the antibacterial properties. Furthermore, in-depth in vitro antibacterial studies and bacterial live/dead staining experiments validate the exceptionally high antibacterial performance of the composite. Therefore, owing to the synergistic effects of high-frequency ultrasound and antibacterial properties, the as-prepared novel antibacterial composite is a promising potential substitute for conventional antibacterial agents.

Abstract Developing the sensitive point‐of‐care testing (POCT) of oncogenic nucleic acids from human papillomavirus (HPV) infection is essential in preventing cervical cancer, especially in resource‐limited settings. Rolling circle amplification (RCA) is attractive in achieving POCT via nucleic acid‐based aggregation under isothermal conditions. However, the influence of RCA product structure on the aggregation remains unexplored resulting in limited sensitivity. Here, a minimum secondary structured RCA technique (MSS‐RCA) is developed by designing a unique circular template, demonstrating significantly enhanced detection sensitivity with only one amplification step and one primer under isothermal conditions. The amplification efficiency of MSS‐RCA could be kinetically manipulated by controlling the secondary structure of the circular template. Introducing the invertase probe to MSS‐RCA, HPV16 E6/E7 nucleic acid target was detected with a personal glucose meter (PGM) with a sensitivity of 5 fm (50 zmol in 10 µL). This integrated MSS‐RCA‐PGM detection system was successfully applied to detect HPV16 E6/E7 mRNA extracted from 54 cervical swab samples reaching a positive predictive value of 100.00% and negative predictive values of 96.00% (77.77% to 99.40%, 95% CI). MSS‐RCA‐PGM provides a sensitive POCT platform for the detection of nucleic acid biomarkers for screening of cervical cancer or other diseases.

Abstract Acute and infected wounds resulting from accidents, battlefield trauma, or surgical interventions have become a global healthcare burden due to the complex bacterial infection environment. However, conventional gauze dressings present insufficient contact with irregular wounds and lack antibacterial activity against multi‐drug‐resistant bacteria. In this study, we develop in situ nanofibrous dressings tailored to fit wounds of various shapes and sizes while providing nanoscale comfort and excellent antibacterial properties. Our approach involves the fabrication of these dressings using a handheld electrospinning device that allows for the direct deposition of nanofiber dressings onto specific irregular wound sites, resulting in perfect conformal wound closure without any mismatch in 2 min. The nanofibrous dressings are loaded with multi‐armed antibiotics that exhibit outstanding antibacterial activity against Staphylococcus aureus (S. aureus) and methicillin‐resistant S. aureus. Compared to conventional vancomycin, this in situ nanofibrous dressing shows great antibacterial performance against up to 98% of multi‐drug‐resistant bacteria. In vitro and in vivo experiments demonstrate the ability of in situ nanofibrous dressings to prevent multi‐drug‐resistant bacterial infection, greatly alleviate inflammation, and promote wound healing. Our findings highlight the potential of these personalized nanofibrous dressings for clinical applications, including emergency, accident, and surgical healthcare treatment.

Abstract Background Understanding how plants and pathogens regulate each other's gene expression during their interactions is key to revealing the mechanisms of disease resistance and controlling the development of pathogens. Despite extensive studies on the molecular and genetic basis of plant immunity against pathogens, the influence of pitaya immunity on N. dimidiatum metabolism to restrict pathogen growth is poorly understood, and how N. dimidiatum breaks through pitaya defenses. In this study, we used the RNA-seq method to assess the expression profiles of pitaya and N. dimidiatum at 4 time periods after interactions to capture the early effects of N. dimidiatum on pitaya processes. Results The study defined the establishment of an effective method for analyzing transcriptome interactions between pitaya and N. dimidiatum and to obtain global expression profiles. We identified gene expression clusters in both the host pitaya and the pathogen N. dimidiatum. The analysis showed that numerous differentially expressed genes (DEGs) involved in the recognition and defense of pitaya against N. dimidiatum, as well as N. dimidiatum’s evasion of recognition and inhibition of pitaya. The major functional groups identified by GO and KEGG enrichment were responsible for plant and pathogen recognition, phytohormone signaling (such as salicylic acid, abscisic acid). Furthermore, the gene expression of 13 candidate genes involved in phytopathogen recognition, phytohormone receptors, and the plant resistance gene (PG), as well as 7 effector genes of N. dimidiatum, including glycoside hydrolases, pectinase, and putative genes, were validated by qPCR. By focusing on gene expression changes during interactions between pitaya and N. dimidiatum, we were able to observe the infection of N. dimidiatum and its effects on the expression of various defense components and host immune receptors. Conclusion Our data show that various regulators of the immune response are modified during interactions between pitaya and N. dimidiatum. Furthermore, the activation and repression of these genes are temporally coordinated. These findings provide a framework for better understanding the pathogenicity of N. dimidiatum and its role as an opportunistic pathogen. This offers the potential for a more effective defense against N. dimidiatum.

Abstract Background The association involving N6-methyladenosine (m6A) modification, molecular subtype and specific immune cell group in tumor microenvironment has been the focus of recent studies. The underlying function of m6A modification in thyroid cancer (TC) remains elusive. Methods The m6A modification regulations, molecular character and tumor immune profile of 461 TC patients were explored and then the correlation between them were comprehensively evaluated. The m6Ascore was established using principal component analysis (PCA) to quantify the m6A pattern of individual TC patients. The prognostic significance of the m6Ascore was evaluated by multivariate Cox regression analysis. Results Four m6Aclusters (mc1, 2, 3, 4)—characterized by differences in extent of aneuploidy, expression of immunomodulatory genes, mRNA or lncRNA expression pattern and prognosis were identified. T Preliminary validation of m6Ascore was a potential independent prognostic factor of TC involving in mc3. Finally, the prognostic value of the m6Ascore and its association with copy number variation (CNV) and tumor immune microenvironment (TIME) of TC in mc3 were verified. Conclusions The correlation between m6A modification, the copy number burden and tumor immune landscape in TC was demonstrated. A m6Acluster-mc3 with low m6Ascore and high CNV molecular subtype was identified with poor clinical prognosis, low infiltrating immunocyte and weak effector T cell. A three-gene clinical prognosis model for TC based on 4 m6a cluster expression was established. Understanding of TIME is enhanced by comprehensive assessment of m6A patterns in individual TC patients and gives a new insight toward improved immunotherapy strategies for TC cancer patients.

Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of lung cancer. Given the limited clinical benefits of immunotherapy in patients with non-small cell lung cancer (NSCLC), various predictors have been shown to significantly influence prognosis. However, no single predictor is adequate to forecast patients' survival benefit. Therefore, it's imperative to develop a prognostic model that integrates multiple predictors. This model would be instrumental in identifying patients who might benefit from ICIs. Retrospective analysis and small case series have demonstrated the potential role of these models in prognostic prediction, though further prospective investigation is required to evaluate more rigorously their application in these contexts. This article presents and summarizes the latest research advancements on immunotherapy prognostic models for NSCLC from multiple omics perspectives and discuss emerging strategies being developed to enhance the domain.

Summary: The main causes of death in patients with ovarian cancer (OC) are invasive lesions and the spread of metastasis. The present study aimed to explore the mechanisms that might promote OC metastasis. Here, we identified that VGLL1 expression was remarkably increased in metastatic OC samples. The role of VGLL1 in OC metastasis and tumor growth was examined by cell function assays and mouse models. Mechanistically level, METTL3-mediated N6-methyladenosine (m6A) modification contributed to VGLL1 upregulation in an IGF2BP2 recognition-dependent manner. Furthermore, VGLL1 directly interacts with TEAD4 and co-transcriptionally activates HMGA1. HMGA1 further activates Wnt/β-catenin signaling to enhance OC metastasis by promoting the epithelial-mesenchyme transition traits. Rescue assays indicated that the upregulation of HMGA1 was essential for VGLL1-induced metastasis. Collectively, these findings showed that the m6A-induced VGLL1/HMGA1/β-catenin axis might play a vital role in OC metastasis and tumor growth. VGLL1 might serve as a prognostic marker and therapeutic target against the metastasis of OC.

Abstract Surface electromyography (sEMG) can provide multiplexed information about muscle performance. If current sEMG electrodes are stretchable, arrayed, and able to be used multiple times, they would offer adequate high-quality data for continuous monitoring. The lack of these properties delays the widespread use of sEMG in clinics and in everyday life. Here, we address these constraints by design of an adhesive dry electrode using tannic acid, polyvinyl alcohol, and PEDOT:PSS (TPP). The TPP electrode offers superior stretchability (~200%) and adhesiveness (0.58 N/cm) compared to current electrodes, ensuring stable and long-term contact with the skin for recording (>20 dB; >5 days). In addition, we developed a metal-polymer electrode array patch (MEAP) comprising liquid metal (LM) circuits and TPP electrodes. The MEAP demonstrated better conformability than commercial arrays, resulting in higher signal-to-noise ratio and more stable recordings during muscle movements. Manufactured using scalable screen-printing, these MEAPs feature a completely stretchable material and array architecture, enabling real-time monitoring of muscle stress, fatigue, and tendon displacement. Their potential to reduce muscle and tendon injuries and enhance performance in daily exercise and professional sports holds great promise.

Abstract The increasing demands in augmented somatosensory have promoted quantitative sensing to be an emerging need for athletic training/performance evaluation and physical rehabilitation. Neurons for the somatosensory system in the human body can capture the information of movements in time but only qualitatively. This work presents an electronic Exo-neuron (EEN) that can spread throughout the limbs for realizing augmented somatosensory by recording both muscular activity and joint motion quantitatively without site constraints or drift instability, even in strenuous activities. Simply based on low-cost liquid metal and clinically used adhesive elastomer, the EEN could be easily fabricated in large areas for limbs. It is thin (~120 μm), soft, stretchable (>500%), and conformal and further shows wide applications in sports, rehabilitation, health care, and entertainment.

In order to obtain the influence law of scanning strategy on the quality, accuracy, microstructure and performance of parts by Laser Additive Manufacturing (LAM), three scanning strategies, namely long-edge, short-edge and cross-layer, were used for additive manufacturing of Inconel 625 parts. Optical Microscope (OM) experiments indicate that the microstructures of samples with different scanning strategies are different. The results of Scanning Electron Microscopy (SEM) suggest that the size and distribution of Laves phase of samples with the different scanning strategies are distinctive, and Energy Dispersive Spectroscopy (EDS) tests indicate that the degree of composition segregation varies according to the scanning strategy. The results of X-ray Diffraction (XRD) show that the main phase of the samples with different scanning strategies is γ-Ni solid solution. The diffraction peak positions are basically the same, but the peak intensities are diverse, indicating that the scanning strategy has a significant impact on the orientation of grains and the intensity of texture. The mechanical properties tests prove that the cross-layer scanning strategy synthesizes the advantages of the other two scanning strategies. The microhardness test shows that the hardness of samples with different scanning strategies is determined by the size, distribution and morphology of Laves phase, as well as the size of grains. As a result, it can be proved that the scanning strategy has a great influence on the quality, accuracy, microstructure and properties of the as-formed samples. The cross-layer orthogonal scanning strategy achieves the best processing results by combining the advantages of long-edge and short-edge scanning strategies.

Addressing the challenge of radar detection of small targets under sea clutter, target detection methods based on a three-dimensional feature space have shown effectiveness. However, their application has revealed several problems, including high dependency on linear relationships between features for dimensionality reduction, unclear reduction objectives, and spatial divergence of target samples, which limit detection performance. To mitigate these challenges, we constructed a feature density distance metric employing copula functions to quantitatively describe the classification capability of multidimensional features to distinguish targets from sea clutter. On the basis of this, a lightweight nonlinear dimensionality reduction network utilizing a self-attention mechanism was developed, optimally re-expressing multidimensional features into a three-dimensional feature space. Additionally, a concave hull classifier using feature sample distance was proposed to mitigate the negative impact of target sample divergence in the feature space. Furthermore, multivariate autoregressive prediction was used to optimize features, reducing erroneous decisions caused by anomalous feature samples. Experimental results using the measured data from the SDRDSP public dataset demonstrated that the proposed detection method achieved a detection probability more than 4% higher than comparative methods under Sea State 5, was less affected by false alarm rates, and exhibited superior detection performance under different false alarm probabilities from 10−3 to 10−1.

Surface cracks are alluded to as one of the early signs of potential damage to infrastructures. In the same vein, their detection is an imperative task to preserve the structural health and safety of bridges. Human-based visual inspection is acknowledged as the most prevalent means of assessing infrastructures’ performance conditions. Nonetheless, it is unreliable, tedious, hazardous, and labor-intensive. This state of affairs calls for the development of a novel YOLOv8-AFPN-MPD-IoU model for instance segmentation and quantification of bridge surface cracks. Firstly, YOLOv8s-Seg is selected as the backbone network to carry out instance segmentation. In addition, an asymptotic feature pyramid network (AFPN) is incorporated to ameliorate feature fusion and overall performance. Thirdly, the minimum point distance (MPD) is introduced as a loss function as a way to better explore the geometric features of surface cracks. Finally, the middle aisle transformation is amalgamated with Euclidean distance to compute the length and width of segmented cracks. Analytical comparisons reveal that this developed deep learning network surpasses several contemporary models, including YOLOv8n, YOLOv8s, YOLOv8m, YOLOv8l, and Mask-RCNN. The YOLOv8s + AFPN + MPDIoU model attains a precision rate of 90.7%, a recall of 70.4%, an F1-score of 79.27%, mAP50 of 75.3%, and mAP75 of 74.80%. In contrast to alternative models, our proposed approach exhibits enhancements across performance metrics, with the F1-score, mAP50, and mAP75 increasing by a minimum of 0.46%, 1.3%, and 1.4%, respectively. The margin of error in the measurement model calculations is maintained at or below 5%. Therefore, the developed model can serve as a useful tool for the accurate characterization and quantification of different types of bridge surface cracks.

Abstract The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1’s function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1 L ) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1 L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1 L promoted, whereas downregulated TMPO-AS1 L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1 L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/β-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1 L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1 L in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1 L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.

Abstract Salt-overly-sensitive 1 (SOS1) is a unique electroneutral Na+/H+ antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. SOS1 is kept in a resting state with basal activity and activated upon phosphorylation. Here, we report the structures of SOS1. SOS1 forms a homodimer, with each monomer composed of transmembrane and intracellular domains. We find that SOS1 is locked in an occluded state by shifting of the lateral-gate TM5b toward the dimerization domain, thus shielding the Na+/H+ binding site. We speculate that the dimerization of the intracellular domain is crucial to stabilize the transporter in this specific conformation. Moreover, two discrete fragments and a residue W1013 are important to prevent the transition of SOS1 to an alternative conformational state, as validated by functional complementation assays. Our study enriches understanding of the alternate access model of eukaryotic Na+/H+ exchangers.

Abstract Background The association involving mismatch repair (MMR) genes, molecular subtype and specific immune cell group in tumor microenvironment has been focused by more recent studies. Its prognosis value in lung adenocarcinoma (LUAD) neoadjuvant chemotherapy remains elusive. Methods The correlation between the MMR gene patterns and the immune landscape were comprehensively evaluated. The MMRScore was calculated using principal component analysis (PCA) after grouping using R/mclust package. The prognostic significance of the MMRScore was evaluated by Kaplan-merrier analysis. Then a cohort of 103 Chinese LUAD patients was collected for neoadjuvant chemotherapy prognosis evaluation and validation using MMRScore. Results Four MMRclusters (mc1, 2, 3, 4)-characterized by differences in extent of aneuploidy, expression of immunomodulatory (IM) genes, mRNA expression, lncRNA expression and prognosis were identified. We established MMRscore to quantify the MMR pattern of individual LUAD patients. As is shown in further analyses, the MMRscore was a potential independent prognostic factor of LUAD. Finally, the prognostic value of the MMRscore and its association with tumor immune microenvironment (TIME) of LUAD were verified in Chinese LUAD cohort. Conclusions We demonstrated the correlation between MMR gene pattern, the CNV and tumor immune landscape in LUAD. A MMRcluster mc2 with high MMRscore, high TMB and high CNV subtype was identified with poor prognosis and infiltrating immunocyte. The comprehensive evaluation of MMR patterns in individual LUAD patients enhances the understanding of TIME and gives a new insight toward improved immune treatment strategies for LUAD patients compared to neoadjuvant chemotherapy.

Summary: The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response signaling, LXR/FXR, and STAT3 pathways were correlated with neutralizing antibody production. Moreover, we observed a correlation between the gut microbiota and plasma and urine proteins, as well as the vaccination response. Based on the above data, we built a predictive model for vaccination response (AUC = 0.85). Our study provides insights into characteristic plasma and urine proteins and gut microbiota associated with the ACE2-RBD-inhibiting antibodies, which could benefit our understanding of the host response to COVID-19 vaccination.

ABSTRACT Neoscytalidium dimidiatum (class Dothideomycetes) is a fungus responsible for canker disease in pitaya stems and fruits, leading to significant economic losses. However, little is known about the pathogenesis, family evolution, and genetic variants of this species. In this study, we report a high-quality genome sequence of N. dimidiatum based on the Nanopore sequencing technology platform for sequencing and Hi-C assembly technology for genome assembly. The genome contains 12 chromosomes (2n = 2× = 12; diploid), with a sequencing depth of 186.1×, encoding 12,349 proteins. Molecular phylogenetic analysis showed that N. dimidiatum is evolutionarily close to Botryosphaeria dothidea. Compared to other fungi, the N. dimidiatum genome contains many carbohydrate-active enzymes and secondary metabolites. Additionally, we predict that N. dimidiatum contains 121 candidate effectors that may play important roles in infection and colonization, promoting pathogenicity in pitaya. Nine of these effectors were confirmed to contain signal peptides and inhibit BAX/INF1-induced necrosis in Nicotiana benthamiana, demonstrating their importance during infection. Finally, we also confirm that N. dimidiatum does not form an appressorium or infection thread but instead infects pitaya via open stomata. In conclusion, the results provide a foundation for future research on N. dimidiatum and the control of pitaya canker. IMPORTANCE Pitaya canker is a significant disease in the pitaya industry in China, causing significant economic losses. Therefore, systematic research on Neoscytalidium dimidiatum, the fungus implicated in pitaya canker, is essential for comprehending the pathogenesis of this disease and developing effective control strategies. We applied comparative genomics to reveal the genetic evolution, metabolic diversity, environmental adaptation, and pathogenicity of N. dimidiatum, providing ideal targets for studies of pathogenesis and molecular targets for fungicide development. Moreover, the systematic study of the N. dimidiatum growth cycle, morphological characteristics, and molecular phylogenetic analysis can promote a comprehensive understanding of its genetic basis.

Abstract Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes. Graphic Abstract

HAK/KUP/KT family members have been identified as playing key roles in K+ uptake and salt tolerance in numerous higher plants. However, their functions in cassava (Manihot esculenta Cantz) remain unknown. In this study, a gene encoding for a high-affinity potassium transporter (MeHAK5) was isolated from cassava and its function was investigated. Subcellular localization analysis showed that MeHAK5 is a plasma membrane-localized transporter. RT-PCR and RT-qPCR indicated that MeHAK5 is predominantly expressed in cassava roots, where it is upregulated by low potassium or high salt; in particular, its highest expression levels separately increased by 2.2 and 2.9 times after 50 µM KCl and 150 mM NaCl treatments. When heterologously expressed in yeast, MeHAK5 mediated K+ uptake within the cells of the yeast strain CY162 and rescued the salt-sensitive phenotype of AXT3K yeast. MeHAK5 overexpression in transgenic Arabidopsis plants exhibited improved growth and increased shoot K+ content under low potassium conditions. Under salt stress, MeHAK5 transgenic Arabidopsis plants accumulated more K+ in the shoots and roots and had reduced Na+ content in the shoots. As a result, MeHAK5 transgenic Arabidopsis demonstrated a more salt-tolerant phenotype. These results suggest that MeHAK5 functions as a high-affinity K+ transporter under K+ starvation conditions, improving K+/Na+ homeostasis and thereby functioning as a positive regulator of salt stress tolerance in transgenic Arabidopsis. Therefore, MeHAK5 may be a suitable candidate gene for improving K+ utilization efficiency and salt tolerance.

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) system is a fast‐growing, genome editing technology that has wide applications in identifying gene functions as well as improving agricultural production and crop breeding. Here, we summarized recent advances in the development and applications of genome editing technologies in plants. We briefly described CRISPR/Cas9 technology and examined the base and prime editing techniques that have been developed from CRISPR technology. Some new prime editing‐derived techniques were assessed.

ABSTRACT Climate change greatly affects lake microorganisms in arid and semiarid zones, which alters ecosystem functions and the ecological security of lakes. However, the responses of lake microorganisms, especially microeukaryotes, to climate change are poorly understood. Here, using 18S ribosomal RNA (rRNA) high-throughput sequencing, we investigated the distribution patterns of microeukaryotic communities and whether and how climate change directly or indirectly affected the microeukaryotic communities on the Inner Mongolia-Xinjiang Plateau. Our results showed that climate change, as the main driving force of lake change, drives salinity to become a determinant of the microeukaryotic community among the lakes of the Inner Mongolia-Xinjiang Plateau. Salinity shapes the diversity and trophic level of the microeukaryotic community and further affects lake carbon cycling. Co-occurrence network analysis further revealed that increasing salinity reduced the complexity but improved the stability of microeukaryotic communities and changed ecological relationships. Meanwhile, increasing salinity enhanced the importance of deterministic processes in microeukaryotic community assembly, and the dominance of stochastic processes in freshwater lakes transformed into deterministic processes in salt lakes. Furthermore, we established lake biomonitoring and climate sentinel models by integrating microeukaryotic information, which would provide substantial improvements to our predictive ability of lake responses to climate change. IMPORTANCE Our findings have important implications for understanding the distribution patterns and the driving mechanisms of microeukaryotic communities among the lakes of the Inner Mongolia-Xinjiang Plateau and whether and how climate change directly or indirectly affects microeukaryotic communities. Our study also establishes the groundwork to use the lake microbiome for the assessment of aquatic ecological health and climate change, which is critical for ecosystem management and for projecting the ecological consequences of future climate warming.

Summary: Metastasis in cervical cancer (CC) has a significant negative impact on patient survival, highlighting the urgent need for investigation in this area. In this study, we identified significant overexpression of zinc finger, X-linked, duplicated family member C (ZXDC) in CC tissue with metastasis, which correlates with poor outcomes for CC patients. We observed that overexpression of ZXDC promotes, while silencing of ZXDC inhibits the metastasis of CC cells both in vitro and in vivo. Additionally, our research demonstrated that ZXDC activated RhoA/ROCK signaling pathway, leading to enhanced cytoskeleton remodeling in CC cells. Besides, we found that IGF2BP3 plays an essential role in the activation of ZXDC on the RhoA/ROCK signaling pathway by stabilizing RhoA mRNA. These findings reveal a mechanism whereby ZXDC promotes the cervical cancer metastasis by targeting IGF2BP3/RhoA/ROCK pathway.

Summary: Alternative splicing (AS) is a critical mechanism for the aberrant biogenesis of long non-coding RNA (lncRNA). Although the role of Wnt signaling in AS has been implicated, it remains unclear how it mediates lncRNA splicing during cancer progression. Herein, we identify that Wnt3a induces a splicing switch of lncRNA-DGCR5 to generate a short variant (DGCR5-S) that correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC). Upon Wnt3a stimulation, active nuclear β-catenin acts as a co-factor of FUS to facilitate the spliceosome assembly and the generation of DGCR5-S. DGCR5-S inhibits TTP’s anti-inflammatory activity by protecting it from PP2A-mediated dephosphorylation, thus fostering tumor-promoting inflammation. Importantly, synthetic splice-switching oligonucleotides (SSOs) disrupt the splicing switch of DGCR5 and potently suppress ESCC tumor growth. These findings uncover the mechanism for Wnt signaling in lncRNA splicing and suggest that the DGCR5 splicing switch may be a targetable vulnerability in ESCC.

Proteolysis targeting chimeras (PROTACs) have emerged as promising cancer therapy agents but have suffered from systemic toxicity issues. Here, the authors report on the creation of polymeric PROTAC nanoparticles for tumour targeting delivery and demonstrate protein degradation in vivo, in combination with photodynamic therapy.

Abstract Antivirals that can combat coronaviruses, including SARS‐CoV‐2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad‐spectrum anti‐coronavirus efficacy, which is difficult to achieve using a single small‐molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS‐CoV‐2‐like coronavirus of pangolin origin, is screened and a surface‐functionalized gold nanocluster (TMA‐GNC) is identified as the top hit. TMA‐GNC inhibits transcription‐ and replication‐competent SARS‐CoV‐2 virus‐like particles and all tested pseudoviruses of SARS‐CoV‐2 variants. TMA‐GNC prevents viral dissemination through destroying membrane integrity physically to enable a virucidal effect, interfering with viral replication by inactivating 3CL protease and priming the innate immune system against coronavirus infection. TMA‐GNC exhibits biocompatibility and significantly reduces viral titers, inflammation, and pathological injury in lungs and tracheas of GX_P2V‐infected hamsters. TMA‐GNC may have a role in controlling the COVID‐19 pandemic and inhibiting future emerging coronaviruses or variants.

BackgroundGliomas are the most common primary tumors of the central nervous system and portend a poor prognosis. The efficacy of emerging and promising immunotherapies varies significantly among individuals. Distinction and transformation of cold and hot tumors may improve the antitumor efficacy of immunotherapy.Methods and ResultsIn this study, we constructed a necroptosis-related lncRNA module based on public databases. The association of this module with survival was assessed using the Cox regression, Kaplan-Meier survival analysis, and nomogram, external validation was also conducted in another public database. Furthermore, we performed gene set enrichment analysis (GSEA), immune checkpoint and tumor microenvironment analysis, and in vitro qRT-PCR validation. Finally, we clustered all samples into 2 clusters based on the expression of model lncRNAs and identified cluster 1 as cold tumors with fewer infiltrating T cells.ConclusionsIdentifying cold and hot tumors by necroptosis-related lncRNAs can help available immunotherapeutic strategies to achieve efficacy in the precise treatment of individuals. Prior treatment failure can be overcome by targeting necroptosis-related lncRNAs.

Abstract Aged skin wounds heal poorly, resulting in medical, economic, and social burdens posed by nonhealing wounds. Age-related defects in repair are associated with reduced myofibroblasts and dysfunctional extracellular matrix (ECM) deposition. Bidirectional cell-cell communication involving exosome-borne cargo such as micro RNAs (miRs) has emerged as a critical mechanism for wound healing and aged tissue regeneration. Here we report that at the wound edge, aged fibroblasts display reduced migration and differentiation into myofibroblasts, with impaired ECM deposition, when compared with young tissue. Proper activation of fibroblasts to myofibroblasts may alleviate age-related defects in wound healing. Herein, an exosome-guided cell technique was performed to induce effective wound healing. Supplementing wounds with exosomes isolated from young mouse wound-edge fibroblasts (exosomesYoung) significantly improved the abundance of myofibroblasts and wound healing in aged mice and caused fibroblasts to migrate and transition to myofibroblasts in vitro. To determine the underlying mechanism, we found that exosomal transfer of miR-125b to fibroblasts inhibited sirtuin 7 (Sirt7), thus accelerating myofibroblast differentiation and wound healing in aged mice. Notably, after epidermal inhibition of miR-125b or overexpression of Sirt7 in fibroblasts, migration and myofibroblast transition were perturbed. Our findings thus reveal that miR-125b is transferred through exosomes from young fibroblasts to old fibroblasts contributes to promoting fibroblast migration and transition to counteract aging, suggesting a potential avenue for anti-aging interventions in wound healing. Graphical Abstract

Abstract Background Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance. Methods METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance. Ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was used to identify the metabolites regulated by METTL7B. Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis was performed to measure the N6-methyladenosine (m6A) status of mRNA of METTL7B targeted genes. Gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) was applied to evaluate the effect of METTL7B in TKIs resistance. Results Increased expression of METTL7B was found in TKIs-resistant LUAD cells and overexpression of METTL7B in LUAD cells induced TKIs resistance both in vitro and in vivo. Activated ROS-metabolism was identified in METTL7B-overexpressed LUAD cells, accompanied with upregulated protein level of GPX4, HMOX1 and SOD1 and their enzymatic activities. Globally elevated m6A levels were found in METTL7B-overexpressed LUAD cells, which was reduced by knock-down of METTL7B. METTL7B induced m6A modification of GPX4, HMOX1 and SOD1 mRNA. Knock-down of METTL7B by siRNA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo. Conclusions This study uncovered a new critical link in METTL7B, glutathione metabolism and drug resistance. Our findings demonstrated that METTL7B inhibitors could be used for reversing TKIs resistance in LUAD patients.

Field-effect gas sensors, integrating the gas sensor and amplification transistor, exhibit excellent sensory performance. Here we report organic thin-film transistors (OTFTs) with nanofiber-textured semiconductor films that exhibit superior ammonia response compared to conventional OTFTs with uniform/flat semiconductor films. The introduce of insulating polymer additives (IPAs) facilitates the formation of semiconducting nanofiber during coating. The effects of IPAs, organic semiconductor/IPA blend ratios and solvents on OTFT-based sensory performance are studied. The results show that the use of SU8 as IPA and chloroform as solvent form intertwined semiconductor nanofibers (∼50 nm in diameter) at the bottom. The resulting OTFTs exhibit extraordinarily high sensitivities to ammonia, which reach 13676%/ppm (current) and 457%/ppm (turn-on voltage), respectively. Finite element analysis is conducted to simulate the adsorption/desorption processes of gas molecules and the effect of specific surface area on sensory performance.

Background: Nitrogen (N), absorbed primarily as ammonium (NH4+) from soil by plant, is a necessary macronutrient in plant growth and development. Ammonium transporter (AMT) plays a vital role in the absorption and transport of ammonium (NH4+). Cassava (Manihot esculenta Crantz) has a strong adaptability to nitrogen deprivation. However, little is known about the functions of ammonium transporter AMT2 in cassava.Methods: The cassava AMT2-type genes were identified and their characteristics were analyzed using bioinformatic techniques. The spatial expression patterns were analyzed based on the public RNA-seq data and their expression profiles under low ammonium treatment were studied using Real-time quantitative PCR (RT-qPCR) method. The cassava AMT2 genes were transformed into yeast mutant strain TM31019b by PEG/LiAc method to investigate their functions.Results: Seven AMT2-type genes (MeAMT2.1-2.7) were identified in cassava and they were distributed on 6 chromosomes and included two segmental duplication events (MeAMT2.2/MeAMT2.4 and MeAMT2.3/MeAMT2.5). Based on their amino acid sequences, seven MeAMT2 were further divided into four subgroups, and each subgroup contained similar motif constitution and protein structure. Synteny analysis showed that two and four MeAMT2 genes in cassava were collinear with those in the Arabidopsis and soybean genomes, respectively. Sixteen types of cis-elements were identified in the MeAMT2 promoters, and they were related to light-, hormone-, stress-, and plant growth and development-responsive elements, respectively. Most of the MeAMT2 genes displayed tissue-specific expression patterns according to the RNA-seq data, of them, three MeAMT2 (MeAMT2.3, MeAMT2.5, and MeATM2.6) expressions were up-regulated under ammonium deficiency. Complementation experiments showed that yeast mutant strain TM31019b transformed with MeAMT2.3, MeAMT2.5, or MeATM2.6 grew better than untransgenic yeast cells under ammonium deficiency, suggesting that MeAMT2.3, MeAMT2.5, and MeATM2.6 might be the main contributors in response to ammonium deficiency in cassava.Conclusion: This study provides a basis for further study of nitrogen efficient utilization in cassava.

Breast cancer (BRCA) is a complex disease that leads to major mortalities and unsatisfactory clinical outcomes among women worldwide. CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) is a potential tumor suppressor and regulator of PD-L1, which has been found as a functional signature in considerable oncogenesis, progression, and therapeutic resistance via deletion and downregulation. In this research, triple-negative breast cancer (BRCA), a molecular subtype having a lower response to endocrinotherapy but a higher response to chemotherapy and immunotherapy, showed higher transcriptional levels of CMTM7. Moreover, CMTM7 positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), and immune checkpoints in many independent datasets. Furthermore, in an immunotherapy cohort of BRCA, patients with high CMTM7 expression were more sensitive to immunotherapy, and the therapeutic predictive value of CMTM7 is higher than that of PD-1 and PD-L1. To sum up, CMTM7 correlated with an inflamed tumor microenvironment and identified immune-hot tumors, which can be a novel biomarker for the recognition of immunological characteristics and an immunotherapeutic response in BRCA.

Strain engineering has been demonstrated to be an effective knob to tune the bandgap in perovskite oxides, which is highly desired for applications in optics, optoelectronics, and ferroelectric photovoltaics. Multiferroic BiFeO3 exhibits great potential in photovoltaic applications and its bandgap engineering is of great interest. However, the mechanism of strain induced bandgap engineering in BiFeO3 remains elusive to date. Here, we perform in situ ellipsometry measurements to investigate the bandgap evolution as a function of uniaxial strain on freestanding BiFeO3 films. Exotic anisotropic bandgap engineering has been observed, where the bandgap increases (decreases) by applying uniaxial tensile strain along the pseudocubic [100]p ([110]p) direction. First-principles calculations indicate that different O6 octahedral rotations under strain are responsible for this phenomenon. Our work demonstrates that the extreme freedom in tuning the strain and symmetry of freestanding films opens a new fertile playground for novel strain-driven phases in transition metal oxides.

Abstract Background Bacterial community play a key role in environmental and ecological processes in river ecosystems. Rivers are used as receiving body for treated and untreated urban wastewaters that brings high loads of sewage and excrement bacteria. However, little is known about the bacterial community structure and functional files in the rivers around the eutrophic Chaohu Lake, the fifth largest freshwater lake in China, has been subjected to severe eutrophication and cyanobacterial blooms over the past few decades. Therefore, understanding the taxonomic and functional compositions of bacterial communities in the river will contribute to understanding aquatic microbial ecology. The main aims were to (1) examine the structure of bacterial communities and functional profiles in this system; (2) find the environmental factors of bacterial community variations. Results We studied 88 sites at rivers in the Chaohu Lake basin, and determined bacterial communities using Illumina Miseq sequencing of the 16 S rRNA gene, and predicted functional profiles using PICRUSt2. A total of 3,390,497 bacterial 16 S rRNA gene sequences were obtained, representing 17 phyla, and 424 genera; The dominant phyla present in all samples were Bacteroidetes (1.4-82.50 %), followed by Proteobacteria (12.6–97.30 %), Actinobacteria (0.1–17.20 %). Flavobacterium was the most numerous genera, and accounted for 0.12–80.34 % of assigned 16 S reads, followed by Acinetobacter (0.33–49.28 %). Other dominant bacterial genera including Massilia (0.06–25.40 %), Psychrobacter (0-36.23 %), Chryseobacterium (0.01–22.86 %), Brevundimonas (0.01–12.82 %), Pseudomonas (0-59.73 %), Duganella (0.08–23.37 %), Unidentified Micrococcaceae (0-8.49 %). The functional profiles of the bacterial populations indicated an relation with many human diseases, including infectious diseases. Overall results, using the β diversity measures, coupled with heatmap and RDA showed that there were spatial variations in the bacterial community composition at river sites, and Chemical oxygen demand (CODMn) and (NH4 + )were the dominant environmental drivers affecting the bacterial community variance. Conclusions The high proportion of the opportunistic pathogens (Acinetobacter, Massilia, Brevundimonas) indicated that the discharge of sewage without adequate treatment into the rivers around Chaohu Lake. We propose that these bacteria could be more effective bioindicators for long-term sewage monitoring in eutrophic lakes.

Abstract Welding usually involves high temperatures, toxic solvents, or conditions not compatible with human bodies, which severely limit the fusion of electronics and human tissues. To achieve direct welding of electronics on human skin, the intrinsically sticky conductors that can simultaneously achieve metal‐grade electrical conductivity (≈41 7000 S m−1), hydrogel‐grade stretchability (>900% strain), and self‐adhesiveness (1.8 N cm−1) are reported. The sticky conductors composed of gallium indium alloy and acrylate polymer adhesives have a surface‐enriched structure, which can form instant mechanical and electrical connections with different surfaces through gentle pressure without involving conditions that may damage human tissues. Based on the sticky conductors, the in situ welding of electronics on the skin is realized. To demonstrate the feasibility of in situ welding, electronic tattoos are achieved for movement monitoring. Intrinsically sticky electrodes that can resist drying and simultaneously deform with the skin for electrophysiological measurement are also developed.

Endorheic lakes in arid regions of Northwest China are generally vulnerable and sensitive to accelerated climate change and extensive human activities. Therefore, a better understanding of the self-purification capacity of ecosystems, such as denitrification, is necessary to effectively protect these water resources. In the present study, we measured unamended and amended denitrification rates of Lake Bosten by adding the ambient and extra nitrate isotopes in slurry incubations. Meanwhile, we investigated the abundances and community structure of nitrous oxide-reducing microorganisms using qPCR and high-throughput sequencing, respectively, in the surface sediments of Lake Bosten to study denitrification potential in endorheic lakes of arid regions as well as the response of those denitrifiers to climatically induced changes in lake environments. Amended denitrification rates increased by one order of magnitude compared to unamended rates in Lake Bosten. The great discrepancy between unamended and amended rates was attributed to low nitrate availability, indicating that Lake Bosten is not operating at maximum capacity of denitrification. Salinity shaped the spatial heterogeneity of denitrification potential through changes in the abundances and species diversity of denitrifiers. Climate change had a positive effect on the water quality of Lake Bosten so far, through increased runoff, decreased salinity, and enhanced denitrification. But the long-term trajectories of water quality are difficult to predict alongside future glacier shrinkage and decreased snow cover.

BackgroundGlioblastoma (GBM) is the most common primary brain malignant tumor, and patients with GBM have a poor prognosis. The tumor microenvironment (TME) is connected to tumorigenesis and prognosis. However, the TME-related genes and therapeutic targets in GBM are yet to be identified. Thus, the presented study aimed to identify TME-related biomarkers in GBM and develop a novel target for the treatment of the disease.MethodsESTIMATE computational methods were utilized to estimate the amounts of stromal and immune components in 697 patients with glioma from the Cancer Genome Atlas database. Then, the protein–protein interaction network and univariate Cox regression analyzed the differentially expressed genes. Serum amyloid A1 (SAA1) was determined to be a predictive factor. SAA1 expression was statistically significant in GBM compared to the normal samples and other glioma subtypes and negatively associated with survival. Independent prognostic analysis identified SAA1 as a TME-related prognostic factor. Furthermore, Western blot analysis showed that SAA1 is upregulated in GBM, which was confirmed by the external validation in the Chinese Glioma Genome Atlas. The gene set enrichment analysis in GBM revealed enrichment of immune-related activities in the SAA1 high-expression group, while mitosis and cell cycle were enriched in the low-expression group. CIBERSORT analysis of the tumor-infiltrating immune cell proportion revealed that M2 macrophages, neutrophils, activated mast cells, resting mast cells, and regulatory T cells were correlated with SAA1 expression. Finally, immune checkpoint genes, tumor mutation burden, and drug sensitivity were also analyzed between the high- and low-expression groups.ConclusionSAA1 could be a distinctive gene between GBM and other subtype gliomas, and thus a novel biomarker for estimating the survival and TME status. The altered expression level shifts the primary function of SAA1 from cell cycle and mitosis to immune activity. High expression of SAA1 is associated with poor survival and upregulates the expression of LAIR1 and TNFSF14, thereby deeming it as the drug sensitivity indicator for XAV939, TGX-221, and lapatinib in GBM immune therapy.

To cope with the problems of poor matching between processing characteristics and manufacturing resources, low production efficiency, and the hard-to-meet dynamic and changeable model requirements in multi-variety and small batch aerospace enterprises, an integrated optimization method of complex component process planning and workshop scheduling for aerospace manufacturing enterprises is proposed. This paper considers the process flexibility of aerospace complex components comprehensively, and an integrated optimization model for the process planning and production scheduling of aerospace complex components is established with the optimization objectives of achieving a minimum makespan, machining time and machining cost. A honey-bee mating optimization algorithm (HBMO) combined with the greedy algorithm was proposed to solve the model. Then, it formulated a four-layer encoding method based on a feature-processing sequence, processing method, and machine tool, a tool was designed, and five worker bee cultivation strategies were designed to effectively solve the problems of infeasible solutions and local optimization when a queen bee mated to a drone. Finally, taking the complex component parts of an aerospace enterprise as an example, the integrated optimization of process planning and workshop scheduling is carried out. The results demonstrate that the proposed model and algorithm can effectively shorten the makespan and machining time, and reduce the machining cost.

The arid and semiarid areas experienced remarkable lake shrinkage during recent decades due to intensive human activities and climate change, which would result in unprecedented changes of microeukaryotic communities. However, little is known about how climate change affects the structure and ecological mechanisms of microeukaryotic communities in this area. Here, we used an 18S rRNA gene-based high-throughput sequencing approach to explore the structure, interspecies interaction, and assembly processes of the microeukaryotic community in lake ecosystems of the Inner Mongolia Plateau. As a direct result of climate change, salinity has become the key determinant of the lacustrine microeukaryotic community in this region. The microeukaryotic community in this ecosystem can be divided into three groups: salt (Lake Daihai), brackish (Lake Dalinuoer) and freshwater lakes. Co-occurrence network analysis revealed that salinity shapes the interspecies interactions of the microeukaryotic community. This causes interspecies interactions to change from antagonistic to cooperative with an increase in salinity. Phylogenetic-based β-nearest taxon distance analyses revealed that stochastic processes mainly dominated the microeukaryotic community assembly in lake ecosystems of the Inner Mongolia Plateau, and salinity stress drove the assembly processes of the microeukaryotic community from stochastic to deterministic. Overall, these findings expand the current understanding of interspecies interactions and assembly processes of microeukaryotic communities during climate change in lake ecosystems of the Inner Mongolia Plateau.

Background Platinum resistance is a major challenge in the clinical treatment of advanced ovarian cancer (OC). Accumulating evidence shows that the tumor-promotive M2 macrophage is linked to the limiting chemotherapy efficacy of multiple malignancies including OC. Circular RNAs (circRNAs) are a novel class of non-coding RNAs which function as the critical regulator in biological process of cancer. However, their impact on macrophage polarization and chemoresistance of OC remain unclear.Methods Platinum-resistant circRNAs were screened using circRNA deep sequencing and validated using in situ hybridization in OC tissues with or without platinum resistance. The role of circITGB6 in inducing cisplatin (CDDP) resistance was evaluated by clone formation, immunofluorescence and annexin V assays in vitro, and by intraperitoneal tumor model in vivo. The mechanism underlying circITGB6-mediated tumor-associated macrophage (TAM) polarization into M2 phenotype was investigated using RNA pull-down, luciferase reporter, electrophoretic mobility shift, RNA binding protein immunoprecipitation (RIP), ELISA and immunofluorescence assays.Results We identified that a novel circRNA, circITGB6, robustly elevated in tumor tissues and serums from patients with OC with platinum resistance, was correlated with poor prognosis. circITGB6 overexpression promoted an M2 macrophage-dependent CDDP resistance in both vivo and vitro. Mechanistic research determined that circITGB6 directly interacted with IGF2BP2 and FGF9 mRNA to form a circITGB6/IGF2BP2/FGF9 RNA–protein ternary complex in the cytoplasm, thereby stabilizing FGF9 mRNA and inducing polarization of TAMs toward M2 phenotype. Importantly, blocking M2 macrophage polarization with an antisense oligonucleotide targeting circITGB6 markedly reversed the circITGB6-induced CDDP resistance of OC in vivo.Conclusions This study reveals a novel mechanism for platinum resistance in OC and demonstrates that circITGB6 may serve as a potential prognostic marker and a therapeutic target for patients with OC.

Physiological studies have confirmed that export of Na+ to improve salt tolerance in plants is regulated by the combined activities of a complex transport system. In the Na+ transport system, the Na+/H+ antiporter salt overly sensitive 1 (SOS1) is the main protein that functions to excrete Na+ out of plant cells. In this paper, we review the structure and function of the Na+/H+ antiporter and the physiological process of Na+ transport in SOS signaling pathway, and discuss the regulation of SOS1 during phosphorylation activation by protein kinase and the balance mechanism of inhibiting SOS1 antiporter at molecular and protein levels. In addition, we carried out phylogenetic tree analysis of SOS1 proteins reported so far in plants, which implied the specificity of salt tolerance mechanism from model plants to higher crops under salt stress. Finally, the high complexity of the regulatory network of adaptation to salt tolerance, and the feasibility of coping strategies in the process of genetic improvement of salt tolerance quality of higher crops were reviewed.