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Abstract Background Citrus canker is a significant bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that severely impedes the healthy development of the citrus industry. Especially when citrus fruit is infected by Xcc, it will reduce or even lost its commercial value. However, due to the prolonged fruiting cycle and intricate structure, much less research progress had been made in canker disease on fruit than on leaf. In fact, limited understanding has been achieved on canker development and the response to Xcc infection in fruit. Results Herein, the progression of canker disease on sweet orange fruit was tracked in the field. Results indicated that typical lesions initially appear on the sepal, style residue, nectary disk, epicarp, and peduncle of young fruits after petal fall. The susceptibility of fruits to Xcc infection diminished as the fruit developed, with no new lesions forming at the ripening stage. The establishment of an efficient method for inoculating Xcc on fruit as well as the artificial inoculation throughout the fruit's developmental cycle clarified this infection pattern. Additionally, microscopic observations during the infection process revealed that Xcc invasion caused structural changes on the surface and cross-section of the fruit. Conclusions An efficient system for inoculation on citrus fruit with Xcc was established, by which it can serve for the evaluation of citrus germplasm for canker disease resistance and systematic research on the interactions between Xcc and citrus fruits.

Litchi is prone to deterioration in quality after harvest due to degradation of anthocyanins and respiratory metabolism, and chlorine dioxide (ClO2) has multiple effects on color protection and respiratory inhibition. In this study, 0.1 g (T1), 0.4 g (T2), and 1.2 g (T3) of ClO2 slow-releasing preservatives were used to treat lychees with 0 g (CK) as the control to evaluate the preservation effect by quality index, color index and anthocyanin, and correlation analysis was applied to explore the association between them. The results showed that the litchi of the T1 showed the optimal qualities. On the 7 th day, the total soluble solids and a* values of litchi in the T1 were significantly (P

Steroid 5α-reductase1/2 (SRD5A1/2) is an androgen protein that resembles the plant DET2 and is responsible for the conversion of testosterone to the more active dihydrotestosterone (DHT). Both proteins share functional homology and have a common ancestor. In mammals, the SRD5A1/2 can reduce a wide range of steroid substrates, such as testosterone, progesterone, and aldosterone, by reducing the Δ4 in ring A. The plant DET2 catalyzes the conversion of campesterol (CR) to campestanol (CN) by reducing the Δ5 in ring B during brassinosteroid (BRs) biosynthesis. We compared the evolution, structural, and functional homology of the SRD5A family and tried to identify the origin and functional diversification of duplicated genes in eukaryotes. We presented a detailed phylogeny that includes representative species from all eukaryotic groups. Our study indicated that protist is a common ancestor for all the subgroups of the SRD5A family. However, not all protists possess SRD5A1/2/DET2 or other homologs, suggesting that some protists may have lost these gene families during evolution. Lineage-specific duplication leads Caenorhabditis elegance to have three SRD5A1/2 genes but none was found in Drosophila melanogaster. We also identified a new subclass, DET2-like (DET2L), in plants that closely resemble SRD5A1/2/DET2. The hypothesized reductase DET2L showed no phenotypic enhancement when expressed in Arabidopsis det2 mutants, suggesting its possible role in the reduction of polyprenol or other substrates.

In order to utilize Lactobacillus casei to prepare fermented pineapple juice beverage, the growth curve, acid production, acid tolerance, and sugar tolerance characteristics of Lactobacillus casei LK-1 (L. casei LK-1) were investigated and analyzed in this research. Moreover, the optimal conditions for the fermentation of pineapple juice by L. casei LK-1 were explored by single-factor test and response surface methodology, with the viable cell count and total acid content as indicators. As revealed by the results, L. casei LK-1 grew and reproduced well in an environment with pH5~7 or containing 0% to 10% glucose. The survival rates of it were 76% and 71%, respectively, after 3 h of incubation in an acidic (pH3) or high sugar (40% glucose) environment. Besides, after 48 h incubation in MRS medium, its acid production was 5.35 g/kg, which was good for the fermentation of the juice. The optimal conditions for fermenting pineapple juice with L. casei LK-1 were: Initial pH of 6.8, fermentation temperature of 37 ℃, inoculum level of 1% (v/v), as well as fermentation time of 30 h. Under this preparation condition, the viable cell count of fermented pineapple juice was 8.99±0.04 lg CFU/mL, the total acid content was 7.16±0.26 g/kg, and the juice was bright in color, sweet and sour with excellent flavor. The results of this research can provide a theoretical and technical basis for the further application of L. casei LK-1 in fermented foods.

The ocean is one of the essential fields of national defense in the future, and more and more attention is paid to the lightweight research of Marine equipment and materials. This study it is to develop a Machine learning (ML)-based prediction method to study the evolution of the mechanical properties of Al-Li alloys in the marine environment. We obtained the mechanical properties of Al-Li alloy samples under uniaxial tensile deformation at different exposure times through Marine exposure experiments. We obtained the strain evolution by digital image correlation (DIC). The strain field images are voxelized using 2D-Convolutional Neural Networks (CNN) autoencoders as input data for Long Short-Term Memory (LSTM) neural networks. Then, the output data of LSTM neural networks combined with corrosion features were input into the Back Propagation (BP) neural network to predict the mechanical properties of Al-Li alloys. The main conclusions are as follows: 1. The variation law of mechanical properties of 2297-T8 in the Marine atmosphere is revealed. With the increase in outdoor exposure test time, the tensile elastic model of 2297-T8 changes slowly, within 10%, and the tensile yield stress changes significantly, with a maximum attenuation of 23.6%. 2. The prediction model can predict the strain evolution and mechanical response simultaneously with an error of less than 5%. 3. This study shows that a CNN/LSTM system based on machine learning can be built to capture the corrosion characteristics of Marine exposure experiments. The results show that the relationship between corrosion characteristics and mechanical response can be predicted without considering the microstructure evolution of metal materials.

Abstract Background Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function. Methods RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells. Results Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG. Conclusion Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.

In this study, a 1/10 reduced-scale model tunnel with one end closed was constructed to investigate maximum temperature profiles beneath the tunnel ceiling during fire events. By varying the heat release rates (HRRs) and tunnel slopes (0%, 2%, 5%, and 6%) and measuring horizontal temperatures longitudinally along the tunnel ceiling, the effects of these parameters were systematically examined. The findings reveal that the distribution of maximum temperatures within a one-end-closed tunnel can be categorized into three distinct regions: far-field, transition, and near-field regions. Notably, milder tunnel slopes correspond to an elevated maximum temperature beneath the ceiling. By employing dimensional analysis, two prediction models were formulated to forecast maximum temperatures beneath the ceiling for fire sources located in the far-field and near-field regions, respectively. These predictive models were validated against experimental data, demonstrating favorable agreement. This study enhances our understanding of the impact of tunnel slope on temperature distribution during fire events in one-end-closed tunnels. Furthermore, the prediction models developed offer practical tools for assessing and mitigating fire risks in such tunnel configurations.

Synchronous laser beam scanning is a common technique used in single-photon imaging where the spatial resolution is primarily determined by the beam divergence angle. In this context, Bessel beams have been investigated as they can overcome the diffraction limit associated with traditional Gaussian beams. Notably, the central spot of a Bessel beam retains its size almost unchanged within a non-diffractive distance. However, the presence of sidelobes in the Bessel beam can negatively impact spatial resolution. To address this challenge, we have developed a single-photon imaging system with high-depth resolution, which allows for the suppression of echo photons from the sidelobe light in the depth image, particularly when their flight time differs from that of the central spot. In our LiDAR setup, we successfully achieved high-resolution scanning imaging with a spatial resolution of approximately 0.5 mm while also demonstrating a high-depth resolution of 12 mm.

All living organisms must develop mechanisms to cope with and adapt to new environments. The transition of plants from aquatic to terrestrial environment provided new opportunities for them to exploit additional resources but made them vulnerable to harsh and ever-changing conditions. As such, the transmembrane receptor-like kinases (RLKs) have been extensively duplicated and expanded in land plants, increasing the number of RLKs in the advanced angiosperms, thus becoming one of the largest protein families in eukaryotes. The basic structure of the RLKs consists of a variable extracellular domain (ECD), a transmembrane domain (TM), and a conserved kinase domain (KD). Their variable ECDs can perceive various kinds of ligands that activate the conserved KD through a series of auto- and trans-phosphorylation events, allowing the KDs to keep the conserved kinase activities as a molecular switch that stabilizes their intracellular signaling cascades, possibly maintaining cellular homeostasis as their advantages in different environmental conditions. The RLK signaling mechanisms may require a coreceptor and other interactors, which ultimately leads to the control of various functions of growth and development, fertilization, and immunity. Therefore, the identification of new signaling mechanisms might offer a unique insight into the regulatory mechanism of RLKs in plant development and adaptations. Here, we give an overview update of recent advances in RLKs and their signaling mechanisms.

Abstract Background Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. Methods Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. Results HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. Conclusion Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.

By the end of 2020, 83 silver deposits (or ore occurrences), including four super-large-scale deposits, nine large-scale deposits, 33 medium-scale deposits and 37 small-scale deposits or ore occurrences, have been proved. The amount of silver metal exceeds 86000 t with average grade of 100 g/t, which makes Daxing’ anling region one of the the most important silver ore belt in China. However, the metallogenic characteristics and metallogenesis need to be clarified. The silver deposits in the study area are classified into three main types, which are magmatic hydrothermal vein type, continental volcano-subvolcanic type and skarn type, respectively. The supergiant deposits include the Shuangjianzishan deposit (silver metal amount of 15214 t with average grade of 138 g/t), the Baiyinchagandongshan deposit (silver metal amount of 9446 t with average grade of 187 g/t), the Huaobaote deposit (silver metal amount of 6852 t with average grade of 170 g/t), and the Fuxingtun deposit (silver metal amount of 5240 t with average grade of 196 g/t). The silver deposits are mainly distributed in the central and south of the Daxing’anling area, and mainly formed in the Yanshanian period. The silver polymetallic deposits in the Daxinganling area are significantly controlled by regional faults and the junction zone of volcanic rock basins and their margins. The north-east trending deep faults are the most important ore-controlling structures in this area. The distribution of silver polymetallic deposits along the main faults is obvious, and the intersection area of multiple groups of faults often form important mine catchments. The Permian is the most important ore-bearing formation in this area, but some important silver polymetallic deposits occur in Mesozoic volcanic basins or pre-Mesozoic strata. The magmatic rocks related to mineralization are mainly intermediate acidic or acidic intrusions, intermediate acidic lavas, pyroclastic rocks, and small intrusions of ultra-shallow or shallow facies of the Yanshanian Period. The mineralization element combination is mainly determined by the elemental geochemical background of surrounding rocks or source layers. In addition, the type of deposit, the distance from the mineralization center, and the degree of differentiation of ore-forming rock mass are also important influence factors. The article analyzes the prospecting prospects of each silver deposit type in the study area, discusses the relationship between mineralization center and deep prospecting, and proposes that porphyry silver deposits should be paid attention to. In the prospecting and exploration of silver deposits, comprehensive evaluation and multi-target prospecting need to be strengthened because silver can coexist or be associated with a variety of metals.©2022 China Geology Editorial Office.

The supergiant Shuangjianzishan (SJS) Ag–Pb–Zn deposit, located in the southern Great Xing’an Range (SGXR), is the largest Ag deposit in China. The SJS deposit can be divided into two ore blocks: the Shuangjianzishan ore block and the Xinglongshan ore block. Given the importance of the Xinglongshan ore block in the SJS deposit, our work is focused on the Xinglongshan ore block. The vein orebodies in the Xionglongshan ore block mainly occur in the NW-, NNW-, and NNE-trending fault zones, and its mineralization is mainly related to a deep concealed syenogranite. Here, we present new geochronology, isotope geochemistry, and fluid inclusion data for the Xinglongshan ore block and provide additional insights into the metallogenic mechanism of the deposit. The dating results show that the syenogranite related to the mineralization formed at approximately 137 Ma, which is coherent with some previous age determinations in sulfides from the ore deposit. The mineralization of the Xinglongshan ore block can be divided into four stages: sphalerite–arsenopyrite–pyrite–chalcopyrite–quartz stage (stage I), sphalerite–galena–pyrite–silver-bearing mineral–quartz stage (stage II), sphalerite–galena–silver-bearing mineral–quartz–calcite stage (stage III), and weakly mineralized quartz–calcite stage (stage IV). Four types of fluid inclusions (FIs) have been identified within quartz and calcite veins: liquid-rich, gas-rich, pure-liquid, and pure-gas FIs. The homogenization temperatures in the four stages exhibit a gradual decrease, with stage I ranging from 253 to 302 °C, stage II from 203 to 268 °C, stage III from 184 to 222 °C, and stage IV from 153 to 198 °C, respectively. The salinity for stages I, II, III, and IV falls within the ranges of 3.4–6.6 wt% NaCl eqv., 2.6–7.2 wt% NaCl eqv., 2.9–7.0 wt% NaCl eqv., and 1.2–4.8 wt% NaCl eqv., respectively, indicative of a low-salinity ore-forming fluid. The δ18Owater and δD values of the ore-forming fluid span from −13.9‰ to 7.4‰ and −145‰ to −65‰, with δ13CV-PDB values between −11.0‰ and −7.9‰. These values suggest that the ore-forming fluid predominantly originated from a mixture of magmatic and meteoric water. The 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of sulfides range from 18.278 to 18.361, 15.530 to 15.634, and 38.107 to 38.448, respectively. These ratios imply that the ore-forming material was primarily derived from the Early Cretaceous granitic magma, which resulted from the mixing of depleted mantle- and crustal-derived magmas. The fluid mixing was the dominant mechanism for mineral precipitation. The Xinglongshan ore block belongs to a magmatic-hydrothermal vein-type deposit related to the Early Cretaceous syenogranite, and the Shuangjianzishan ore block belongs to an intermediate sulfidation epithermal deposit related to coeval subvolcanic rocks. The Ag–Pb–Zn mineralization at Shuangjianzishan is genetically related to the Early Cretaceous volcanic–intrusive complex.

Alzheimer’s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. Gastrodia elata (G. elata) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that G. elata-specific miRNA plays a cross-kingdom regulatory role for the NF-κB signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3β. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following G. elata RNA administration. Our research emphasizes Gas-miR36-5p as a novel G. elata-specific miRNA with neuroprotective properties in Alzheimer’s disease by targeting GSK-3β. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying G. elata-specific miRNA, presenting a novel perspective for the treatment of Alzheimer’s disease.

Breast cancer is the most common malignant cancer in women. Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes and is challenging to treat. MUC1 is a therapeutic target in breast and pancreatic cancer. We developed a novel humanized antibody that specifically binds MUC1 expressed in breast cancer cells and conjugated a humanized MUC1 (HzMUC1) antibody to monomethyl auristatin (MMAE). HzMUC1-MMAE showed an anti-proliferative effect on HER2 positive trastuzumab-resistant breast cancer. Immunoprecipitation indicated that HzMUC1 recognized native MUC1 in TNBC cells. Confocal microscopy showed that HzMUC1 bound MUC1 on the surface of TNBC cells, and the conjugates exhibited the same binding ability to HCC70 as unconjugated HzMUC1 by cell-based ELISA. Treatment of TNBC cells with HzMUC1-MMAE reduced growth of MUC1-positive cells and induced G2/M cell cycle arrest and apoptosis. In a mouse model of breast cancer, HzMUC1-MMAE significantly reduced the growth of tumors established by subcutaneous injection of HCC70 TNBC cells. Therefore, HzMUC1-ADC has therapeutic potential for TNBC.

The metabolic reasons for rambutan taste variations during maturity are unknown. Here, we obtained a unique rambutan cultivar Baoyan No.2 (BY2) with a strong yellow pericarp and excellent taste, the sugar-acid ratios of which ranged from 21.7 to 94.5 during maturation. Widely targeted metabolomics analysis was performed to reveal the metabolic reasons behind these taste variations. The results showed that 51 metabolites were identified as common different metabolites (DMs), including 16 lipids, 12 amino acids and others. Among them, the abundance level of 3,4-digalloylshikimic acid exhibited a positive correlation with the titratable acids (R2 = 0.9996) and a negative correlation with the sugar-acid ratio (R2 = 0.9999). Therefore, it could be a taste biomarker of BY2 rambutan. Moreover, all DMs were enriched in “galactose metabolism”, “fructose and mannose metabolism” and “biosynthesis of amino acids” pathways, which predominantly accounted for the taste variation. Our findings provided new metabolic evidence for the taste variation of rambutan.

Objective: Comparison of the antibacterial activity of APS with four β-lactam antibiotics against different Staphylococcus aureus (SA) and speculation of the antibacterial mechanism of action of APS by network pharmacological approach. Methods: The MICs of APS and β-lactam antibiotics on MSSA-4 (non-membrane producing sensitive bacteria), MRSA-6 (non-membrane producing resistant bacteria), MSSA-11 (membrane producing sensitive bacteria) and MRSA-12 (membrane producing resistant bacteria) were determined by serial dilution method. The effects of drug resistance and biofilm on MIC were compared by one-way multivariate ANOVA. The structure of APS compound was obtained from PubChem database, and target fishing was carried out using PharmMapper database, and the screened targets were imported into STRING database to establish PPI network diagram and capture node information to establish “compound-target-target interaction” network. Metascape platform was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on key targets to predict their antibacterial mechanism of action. Results: The MIC of MSSA-4, MRSA-6, MSSA-11 and MRSA-12 by APS were 125, 125, 62.5 and 62.5 μg/mL, respectively. Analysis of variance showed that bacterial drug resistance and biofilm had little effect on the antibacterial effect of APS, and had better antibacterial activity against membrane producing bacteria. And four β-Lactam antibiotics were easily affected by bacterial drug resistance and biofilm, resulting in the decrease of the sensitivity of the tested bacteria to antibiotics. 123 potential antimicrobial action targets of APS were obtained by network pharmacology, and the protein interaction network had suggested that ALB, AKT1, MMP9, MAPK1, CASP3, IGF1, MAPK8, HRAS, BCL2L1, ESR1 might be its core targets for the biological functions involved mainly include bacterial response, bacterial adhesion regulation, protein domain specific binding and so on, and mainly acted on focal adhesion, amino sugar and nucleotide sugar metabolism, drug metabolism and other pathways. Conclusion: Bacterial resistance and biofilm did not affect the antibacterial effect of APS. APS had the characteristics of multi-target and multi-pathway to affect the bacterial biofilm and exert antibacterial effects.

A free-space communication scheme is proposed based on orbital angular momentum (OAM) states and pulse position modulation (PPM). It can not only improve the channel capacity, but also be suitable for single-photon detection to realize the communication in the case of ultra-weak light. A parallel coding method is proposed to realize high-capacity and low bit error rate (BER) communication under high background. Theoretical simulation and experimental results show that the scheme can effectively suppress the background noise. The BER is as low as 1.27 × 10$^{-5}$ under the condition of 16 OAM states, 16 single-photon detectors (SPDs) coincidence, and the background noise of 10$^{7}$ counts per second. The BER performance is an order of magnitude better than the traditional PPM, and the channel capacity is increased by 12 times. This work provides an effective solution for deep space high-speed and low BER communication.

Aims: Ferroptosis plays important roles in tumorigenesis and cancer therapy. Zoledronic acid is known to inhibit the activity of farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway. We examined whether zoledronic acid can inhibit the growth of osteosarcoma cells by inducing ferroptosis.Methods: Cell viability was analyzed by using CCK8 reagent and counting cells with trypan blue exclusion. Ferroptosis markers including lipid peroxide and PTGS2 expression were examined by flow cytometry, western blot, and quantitative PCR analyses. Cellular ubiquinone content was determined using high performance liquid chromatography. Ferrostatin-1 and RSL3 were used as the ferroptosis inhibitor and inducer respectively.Results: Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Addition of ferrostatin-1 reverted these effects of zoledronic acid on osteosarcoma cells, supporting a role of zoledronic acid in inducing ferroptosis. Mechanistically, zoledronic acid significantly decreased ubiquinone, a metabolite of the mevalonate pathway. Treating cells with exogenous ubiquinone prevented zoledronic acid-induced ferroptosis and decrease in the growth of osteosarcoma cells. In addition, zoledronic acid enhanced the expression of HMOX1, whereas knockdown of HMOX1 inhibited the zoledronic acid-induced increase in lipid peroxide level and decrease in cell growth. Finally, zoledronic acid together with RSL3 significantly enhanced the inhibitory effect on the growth of osteosarcoma cells.Conclusion: Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Zoledronic acid together with ferroptosis inducer may be a promising new strategy for the treatment of osteosarcoma.

BackgroundGlobally, lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths. It is a progressive disorder that arises from multiple genetic and environmental factors. Dysregulated expression of vesicle-mediated transport-related genes (VMTRGs) have been reported in several cancers. However, the prognostic significance of VMTRGs in LUAD has yet to be established.MethodsThe VMTRG profiling data for 482 LUAD patients and 59 normal controls were downloaded from The Cancer Genome Altas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the risk model. Several GEO datasets were used to validate the risk model. The roles of these genes were investigated via the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Differences in immune cell infiltrations between risk groups were evaluated using five algorithms. “pRRophetic” was used to investigate anti-cancer drug sensitivities in two groups. Expression of these five genes in LUAD samples and adjacent normal tissues were evaluated by qRT-PCR. Colony formation and wound healing assays were performed to assess the significance of CNIH1 and AP3S1 in LUAD cells.ResultsWe identified 85 prognosis-associated VMTRGs that could be constructed a risk model for LUAD patients, indicating their potential importance in LUAD development. The risk model including the five VMTRGs (CNIH1, KIF20A, GALNT2, GRIA1, and AP3S1) was associated with clinical outcomes. Tumor stage and risk score were found to be independent prognostic factors for LUAD patients. The five VMTRGs were also correlated with activation of the Notch and p53 signaling pathways. The risk model was significantly associated with immune responses and with high-level expression of immune checkpoints. High-risk group patients were more sensitive to several chemotherapeutic drugs and Lapatinib. Furthermore, CNIH1 and AP3S1 promoted LUAD cell growth and migration in vitro.ConclusionWe constructed a VMTRG-based risk model for effective prediction of prognostic outcomes for LUAD patients. The risk model was associated with immune infiltration levels. These five hub genes are potential targets for immune therapy combined with chemotherapy in LUAD.

The superlarge Huaaobaote Ag–Pb–Zn deposit is located on the western slope of the southern Great Xing’an Range (SGXR). The deposit includes four ore blocks, namely, ore blocks I, II, III, and V. Except for the no. I orebody of ore block I, which is hosted in the contact zone between the Carboniferous serpentinized harzburgite and the Permian siltstone, the other orebodies all occur as veins controlled by faults. The mineralization process at the deposit can be divided into four stages: cassiterite–arsenopyrite–pyrite–quartz stage (stage I), cassiterite–chalcopyrite–pyrite–freibergite–arsenopyrite–pyrrhotite–quartz stage (stage II), sphalerite–galena–jamesonite–stibnite–freibergite–silver mineral–quartz–calcite–chlorite stage (stage III), and argentite–pyrargyrite–pyrite–quartz–calcite (stage IV). Cassiterite U–Pb dating of the Huaaobaote deposit yielded ages of 136.3–134.3 Ma, indicating that the deposit formed in the Early Cretaceous period. Two types of fluid inclusions (FIs), including liquid-rich and gas-rich FIs, have been distinguished in the quartz vein and sphalerite. The homogenization temperature during the four stages gradually decreases, with temperatures of 302–340 °C for stage I, 267–304 °C for stage II, 186–273 °C for stage III, and 166–199 °C for stage IV, respectively. The salinity (wt% NaCl eqv.) at stages I, II, III, and IV is 3.7–6.6, 0.2–4.5, 0.2–5.0, and 0.4–1.6, respectively, indicating that the ore-forming fluid is characterized by low salinity. The δ18Owater and δD values of the ore-forming fluid range from −11.9‰ to 7.9‰ and −168‰ to −76‰, respectively, indicating that the ore-forming fluid was dominantly derived from a mixture of magmatic and meteoric water. The calculated δ34SH2S values range from −3.6‰ to 1.2‰, indicating that the sulfur mainly came from granitic magma. The 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of sulfides are in the ranges of 18.195–18.317, 15.509–15.667, and 37.965–38.475, respectively, implying that the ore-forming material was mainly derived from felsic magma that may be formed by the partial melting of orogenic materials. Fluid mixing, cooling, and immiscibility were the three primary mechanisms for mineral precipitation in the Huaaobaote deposit.

Abstract Background To evaluate the association of primary tumor size with clinicopathologic characteristics and survival of patients with squamous cell carcinoma of the penis (SCCP). Methods This study analyzed the data of 1001 patients with SCCP, obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. The Kaplan–Meier method and the Cox proportional hazards regression model were used to analyze the effects of primary tumor size on overall survival (OS) and penile carcinoma-specific survival (PCSS). Results Advanced T stage (P

Abstract Although endocrine therapies targeting estrogen receptor α (ERα) are effective in managing ER positive (+) breast cancer, many patients have primary resistance or develop resistance to endocrine therapies. In addition, ER+ breast cancer with PIK3CA activating mutations and 11q13-14 amplification have poor survival with unclear mechanism. We uncovered that higher expression of deubiquitinase USP35, located in 11q14.1, was associated with ER+ breast cancer and poor survival. Estrogen enhanced USP35 protein levels by downregulating USP35-targeting miRNA-140-3p and miRNA-26a-5p. USP35 promoted the growth of ER+ breast cancer in vitro and in vivo, and reduced the sensitivity of ER+ breast cancer cells to endocrine therapies such as tamoxifen and fulvestrant. Mechanistically, USP35 enhanced ERα stability by interacting and deubiquitinating ERα, and transcriptional activity of ERα by interacting with ERα in DNA regions containing estrogen response element. In addition, AKT, a key effector of PI3K, phosphorylated USP35 at Serine613, which promoted USP35 nuclear translocation, ERα transcriptional activity, and the growth of ER+ breast cancer cells. Our data indicate that USP35 and ERα form a positive feedback loop in promoting the growth of ER+ breast cancer. USP35 may be a treatment target for ER+ breast cancer with endocrine resistance or with PIK3CA mutations or hyperactivation of the PI3K pathway.

Oat milk has become preferential because of its low calorie nature and high dietary fiber content, but its ability to “curdle” when mixed with tea can affect the consumer acceptability for oat milk tea. In this study, a model system for oat milk tea was made by combining oat milk and green tea extract to evaluate the impacts of the oat milk matrix and green tea extract concentration on the stability and polyphenol bioaccessibility. The stability analysis results showed that adding green tea extract to oat milk influenced the stability of the oat milk tea model systems. In contrast, the 3.0% fat oat milk tea model system exhibited a higher stability than the 1.5% fat oat milk tea model system. In simulated gastrointestinal digestive experiments, tea polyphenols in the oat milk tea model systems were relatively stable in oral and stomach digestive stages, while they clearly degraded in the small intestine digestive stage. Furthermore, the bioaccessibility of tea polyphenols was higher for the 3.0% fat oat milk tea model system than for the 1.5% fat oat milk tea model system, especially at low concentrations of green tea extracts (0.05%~0.25%). These results may provide a theoretical reference and data for the formulation of oat milk tea and the bioaccessibility of tea polyphenols in food matrices.

Under the condition of rainfall, the decrease in shear strength of a slope is one of the important factors that lead to the slope instability. Infiltration of rainwater into the slope is a dynamic process, and the water content or saturation of soil will change continuously. Therefore, it is of great significance to study the shear strength of soil under dynamic environment for real-time evaluation of the stability of soil slope under rainfall conditions. Based on the strength theory of unsaturated soil, this paper takes the expansive soil in the Jianshanying area of Guizhou Province as the object, combines the shear test data to establish the fitting relationship between the shear strength index and water content of the expansive soil, and puts forward the shear strength formula with water content as the variable. Based on the secondary development technology of ABAQUS platform, USDFLD subroutine is compiled to import the shear strength formula of the Jianshanying expansive soil, and the influence of strength attenuation and gravity change caused by the change of soil moisture content on the stability of the expansive soil slope under the condition of rainfall are also explored. The results show that with the increasing water content of the expansive soil, the particles in the soil expand by the absorbing water, the particle spacing decreases, and the adhesion between the mineral particles increases gradually. Until the water filling suction of the aggregate space decreases, the adhesion decreases rapidly, and the shear strength of the expansive soil decreases generally, in which the cohesion increases first and then decreases, and the internal friction angle decreases. The secondary development technology of ABAQUS software can realize the relationship of soil parameters with the change of water content, which provides a new technical means for the finite element analysis of unsaturated soil slope under the condition of rainfall.

Endoplasmic Reticulum-Associated Degradation (ERAD) is one of the major processes in maintaining protein homeostasis. Class I α-mannosidases MNS4 and MNS5 are involved in the degradation of misfolded variants of the heavily glycosylated proteins, playing an important role for glycan-dependent ERAD in planta. MNS4 and MNS5 reportedly have functional redundancy, meaning that only the loss of both MNS4 and MNS5 shows phenotypes. However, MNS4 is a membrane-associated protein while MNS5 is a soluble protein, and both can localize to the endoplasmic reticulum (ER). Furthermore, MNS4 and MNS5 differentially demannosylate the glycoprotein substrates. Importantly, we found that their gene expression patterns are complemented rather than overlapped. This raises the question of whether they indeed work redundantly, warranting a further investigation. Here, we conducted an exhaustive genetic screen for a suppressor of the bri1-5, a brassinosteroid (BR) receptor mutant with its receptor downregulated by ERAD, and isolated sbi3, a suppressor of bri1-5 mutant named after sbi1 (suppressor of bri1). After genetic mapping together with whole-genome re-sequencing, we identified a point mutation G343E in AT1G27520 (MNS5) in sbi3. Genetic complementation experiments confirmed that sbi3 was a loss-of-function allele of MNS5. In addition, sbi3 suppressed the dwarf phenotype of bri1-235 in the proteasome-independent ERAD pathway and bri1-9 in the proteasome-dependent ERAD pathway. Importantly, sbi3 could only affect BRI1/bri1 with kinase activities such that it restored BR-sensitivities of bri1-5, bri1-9, and bri1-235 but not null bri1. Furthermore, sbi3 was less tolerant to tunicamycin and salt than the wild-type plants. Thus, our study uncovers a non-redundant function of MNS5 in the regulation of ERAD as well as plant growth and ER stress response, highlighting a need of the traditional forward genetic approach to complement the T-DNA or CRISPR-Cas9 systems on gene functional study.

Nonalcoholic Fatty Liver Disease (NAFLD) is a serious problem endangering human health in the world. The pathogenesis of this disease is often accompanied by lipid metabolism disorder and can cause liver lipid accumulation. Highland barley Monascus purpureus Went extract (HBMPWE) can inhibit the liver lipid accumulation caused by a high-fat, high-fructose, high-cholesterol diet. However, it is not clear what changes have taken place in the process of liver lipid metabolism after HBMPWE administration. To fill this knowledge gap and to support the findings published in the companion research article entitled “Highland Barley Monascus purpureus Went Extract Ameliorates High-Fat, High-Fructose, High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism in Golden Hamsters” [1], we provided important information related to the liver differential metabolites and identified twenty-one differential metabolites of liver metabolism. In the model group, the levels of lactate, linoleic acid, and malic acid increased significantly. After HBMPWE treatment, the expressions of these metabolites reduced significantly. Therefore, these liver differential metabolites could be used as biological signatures reflecting the severity of NAFLD and HBMPWE treatment outcomes.

Plants acquire the ability to adapt to the environment using transmembrane receptor-like kinases (RLKs) to sense the challenges from their surroundings and respond appropriately. RLKs perceive a variety of ligands through their variable extracellular domains (ECDs) that activate the highly conserved intracellular kinase domains (KDs) to control distinct biological functions through a well-developed downstream signaling cascade. A new study has emerged that brassinosteroid-insensitive 1 (BRI1) family and excess microsporocytes 1 (EMS1) but not GASSHO1 (GSO1) and other RLKs control distinct biological functions through the same signaling pathway, raising a question how the signaling pathway represented by BRI1 is specified. Here, we confirm that BRI1-KD is not functionally replaceable by GSO1-KD since the chimeric BRI1-GSO1 cannot rescue bri1 mutants. We then identify two subdomains S1 and S2. BRI1 with its S1 and S2 substituted by that of GSO1 cannot rescue bri1 mutants. Conversely, chimeric BRI1-GSO1 with its S1 and S2 substituted by that of BRI1 can rescue bri1 mutants, suggesting that S1 and S2 are the sufficient requirements to specify the signaling function of BRI1. Consequently, all the other subdomains in the KD of BRI1 are functionally replaceable by that of GSO1 although the in vitro kinase activities vary after replacements, suggesting their functional robustness and mutational plasticity with diverse kinase activity. Interestingly, S1 contains αC-β4 loop as an allosteric hotspot and S2 includes kinase activation loop, proposedly regulating kinase activities. Further analysis reveals that this specific function requires β4 and β5 in addition to αC-β4 loop in S1. We, therefore, suggest that BRI1 specifies its kinase function through an allosteric regulation of these two subdomains to control its distinct biological functions, providing a new insight into the kinase evolution.

The metabolite-caused taste variation during rambutan maturation is unknown due to a lack of systematic investigation of all components. In this study, three growing stages, including unripe (S1), half-ripe (S2), and full-ripe (S3) BY2 and BY7 rambutans were compared and profiled by UPLC–MS/MS-based widely targeted metabolomics analysis. We demonstrated that the sugar-acid ratios of two rambutans were greatly improved between the S2 and S3 stages. A total of 821 metabolites were identified, including 232, 205, 204, and 12 differential metabolites (DMs) in BY2-S1 vs. BY2-S2, BY2-S2 vs. BY2-S3, BY7-S1 vs. BY7-S2, and BY7-S2 vs. BY7-S3, respectively. A correlation analysis showed that gamma-aminobutyric acid (GABA) could be the sugar-acid ratio biomarker of BY2 rambutan. Methionine (Met), alanine (Ala), and S-methyl-L-cysteine (SMC) could be total amino acid biomarkers of BY2 and BY7 rambutans. In addition, UPLC-MS/MS-based quantitative verification of the above biomarkers exhibited the same variations as metabolomics analysis. This study not only provides useful nutritive information on rambutans but also valuable metabolic data for rambutan breeding strategies.

Predicting the susceptibility of a specific part of a landslide (SSPL) involves predicting the likelihood that the part of the landslide (e.g., the entire landslide, the source area, or the scarp) will form in a given area. When predicting SSPL, the landslide samples are far less than the non-landslide samples. This class imbalance makes it difficult to predict the SSPL. This paper proposes an advanced artificial intelligence (AI) model based on the dice-cross entropy (DCE) loss function and XGBoost (XGBDCE) or Light Gradient Boosting Machine (LGBDCE) to ameliorate the class imbalance in the SSPL prediction. We select the earthquake-induced landslides from the 2018 Hokkaido earthquake as a case study to evaluate our proposed method. First, six different datasets with 24 landslide influencing factors and 10,422 samples of a specific part of the landslides are established using remote sensing and geographic information system technologies. Then, based on each of the six datasets, four landslide susceptibility algorithms (XGB, LGB, random-forest (RF) and linear discriminant analysis (LDA)) and four class balancing methods (non-balance (NB), equal-quantity sampling (EQS), inverse landslide-frequency weighting (ILW), and DCE loss) are applied to predict the SSPL. The results show that the non-balanced method underestimates landslide susceptibility, and the ILW or EQS methods overestimate the landslide susceptibility, while the DCE loss method produces more balanced results. The prediction performance of the XGBDCE (average area under the receiver operating characteristic curve (0.970) surpasses that of RF (0.956), LGB (0.962), and LDA (0.921). Our proposed methods produce more unbiased and precise results than the existing models, and have a great potential to produce accurate general (e.g., predicting the entire landslide) and detailed (e.g., combining the prediction of the landslide source area with the landslide run-out modeling) landslide susceptibility assessments, which can be further applied to landslide hazard and risk assessments.

Brassinosteroids (BRs) play important roles in plant growth and development, and BR perception is the pivotal process required to trigger BR signaling. In angiosperms, BR insensitive 1 (BRI1) is the essential BR receptor, because its mutants exhibit an extremely dwarf phenotype in Arabidopsis. Two other BR receptors, BRI1-like 1 (BRL1) and BRI1-like 3 (BRL3), are shown to be not indispensable. All BR receptors require an island domain (ID) responsible for BR perception. However, the biological functional significance of residues in the ID remains unknown. Based on the crystal structure and sequence alignments analysis of BR receptors, we identified two residues 597 and 599 of AtBRI1 that were highly conserved within a BR receptor but diversified among different BR receptors. Both of these residues are tyrosine in BRI1, while BRL1/BRL3 fixes two phenylalanines. The experimental findings revealed that, except BRI1Y597F and BRI1Y599F, substitutions of residues 597 and 599 with the remaining 18 amino acids differently impaired BR signaling and, surprisingly, BRI1Y599F showed a weaker phenotype than BRI1Y599 did, implying that these residues were the key sites to differentiate BR receptors from a non-BR receptor, and the essential BR receptor BRI1 from BRL1/3, which possibly results from positive selection via gain of function during evolution.

Retinal blood vessel morphological abnormalities are generally associated with cardiovascular, cerebrovascular, and systemic diseases, automatic artery/vein (A/V) classification is particularly important for medical image analysis and clinical decision making. However, the current method still has some limitations in A/V classification, especially the blood vessel edge and end error problems caused by the single scale and the blurred boundary of the A/V. To alleviate these problems, in this work, we propose a vessel-constraint network (VC-Net) that utilizes the information of vessel distribution and edge to enhance A/V classification, which is a high-precision A/V classification model based on data fusion. Particularly, the VC-Net introduces a vessel-constraint (VC) module that combines local and global vessel information to generate a weight map to constrain the A/V features, which suppresses the background-prone features and enhances the edge and end features of blood vessels. In addition, the VC-Net employs a multiscale feature (MSF) module to extract blood vessel information with different scales to improve the feature extraction capability and robustness of the model. And the VC-Net can get vessel segmentation results simultaneously. The proposed method is tested on publicly available fundus image datasets with different scales, namely, DRIVE, LES, and HRF, and validated on two newly created multicenter datasets: Tongren and Kailuan. We achieve a balance accuracy of 0.9554 and F1 scores of 0.7616 and 0.7971 for the arteries and veins, respectively, on the DRIVE dataset. The experimental results prove that the proposed model achieves competitive performance in A/V classification and vessel segmentation tasks compared with state-of-the-art methods. Finally, we test the Kailuan dataset with other trained fusion datasets, the results also show good robustness. To promote research in this area, the Tongren dataset and source code will be made publicly available. The dataset and code will be made available at https://github.com/huawang123/VC-Net.

EMS1 is a receptor-like kinase that recognizes the peptide ligand TPD1 to specify tapeta in Arabidopsis. Here, via a reciprocal complementation approach, the authors provide evidence that intracellular signaling by EMS1 is interchangeable with that of the brassinosteroid receptor BRI1.

Abstract Background To evaluate the prognostic value of Lymphovascular Invasion (LVI) in patients with squamous cell carcinoma of the penis (SCCP) following surgery. Patients and methods This retrospective study analyzed the data of 891 eligible patients with SCCP who were diagnosed between 2010 and 2014, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized by LVI, age, grade, T stage, lymph nodes status, distant metastasis, regional lymph nodes removed, and surgery. Overall survival (OS) and penile carcinoma-specific survival (PCSS) were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. Results The presence of LVI was significantly associated with increased risk of advanced T stage, high grade, lymph node metastasis, and distant metastasis (P

Recently, there have been increasing safety concerns about the illegal abuse of quinolone in soybean sprouts. This study aimed to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous detection of 16 quinolones (QNs) in soybean sprouts, and then reveal their degradation characteristics. The samples were extracted with acetonitrile (with 1% formic acid), purified by a C18 adsorbent, and separated by an ACQUITY UPLC BEH C18 (1.7 μm, 2.1 mm × 100 mm) column. The internal standard method was applied for quantitative determination. The results demonstrated that the quantification linear range for 16 QNs was between 2.0 ng/mL and 50.0 ng/mL. The detection limits were between 0.5 μg/kg and 4.0 μg/kg, and the quantification limits were between 2.0 μg/kg and 20.0 μg/kg. This method was used to screen for quinolones in 50 batches of market soybean sprouts; the obtained results showed good agreement with those of the standard method. It was found that QNs possessed longer degradation half-life (T1/2) in the storage stage of soybean sprouts, while they degraded to some extent during the germination stage via active enzyme action. In particular, ciprofloxacin was the most stable QNs with a T1/2 of 70.71 d during the storage stage of soybean sprouts. This work not only offers an accurate and efficient QNs residual analysis strategy but also provides a reference for the supervision and management of QNs in foods.

The objective of this work was to study the corrosion behavior of 2xxx aluminum alloys in the marine environment and the degradation of mechanical properties caused by corrosion as well as to provide support for the lightweight design of marine equipment. The corrosion characteristics of 2297-T8 and 2195-T8 were observed by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) at 3, 6, 9, and 12 months of exposure, and the mechanical properties were obtained via uniaxial tensile testing. The results of the study showed the following: (1) With an increase in the exposure time, the corrosion products on the surface of 2297-T8 gradually increase, and the corrosion products on the surface of 2195-T8 accumulate rapidly. (2) The results of EDS show that the corrosion products of 2297 are mainly Al oxides and that those of 2195 are composed of Al, Fe, Mn, Si, etc. (3) Through the corrosion pit diameter, corrosion pit depth, and corrosion mass reduction rate surface, the trend of an increasing average radius of the corrosion pits and the corrosion mass reduction rate surface varies linearly, and the average depth of the corrosion pits increases dramatically after 9 months of exposure time. (4) According to the mechanical properties of the study surface, in a marine atmosphere, the degradation of 2297-T8 ductility is higher than that of 2195-T8, while the degradation of the yield stress is lower than that of 2195-T8.

Redundancy and lethality is a long-standing problem in genetics but generating minimal and lethal phenotypes in the knockouts of the same gene by different approaches drives this problem to a new high. In Asn (N)-linked glycosylation, a complex and ubiquitous cotranslational and post-translational protein modification required for the transfer of correctly folded proteins and endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, ALG12 (EBS4) is an α 1, 6-mannosyltransferase catalyzing a mannose into Glc3Man9GlcNAc2. In Arabidopsis, T-DNA knockout alg12-T is lethal while likely ebs4 null mutants isolated by forward genetics are most healthy as weak alleles, perplexing researchers and demanding further investigations. Here, we isolated a true null allele, sbi2, with the W258Stop mutation in ALG12/EBS4. sbi2 restored the sensitivity of brassinosteroid receptor mutants bri1-5, bri1-9, and bri1-235 with ER-trapped BRI1 to brassinosteroids. Furthermore, sbi2 maturated earlier than the wild-type. Moreover, concomitant with impaired and misfolded proteins accumulated in the ER, sbi2 had higher sensitivity to tunicamycin and salt than the wild-type. Our findings thus clarify the role of SBI2/ALG12/EBS4 in the regulation of the ERAD of misfolded glycoproteins, and plant growth and stress response. Further, our study advocates the necessity and importance of using multiple approaches to validate genetics study.

This paper takes Qingdao Jiaozhou Bay subsea tunnel project as the research object to study the relationship among rock mechanical parameters and chiseling specific energy and abrasion performance. SPSS22 was used to analyze the correlation between the parameters. The results show that except for the low correlation with Poisson ratio, all the other parameters in the single factor correlation analysis have high R. By taking the chiseling specific energy and abrasion performance as dependent variables, taking each mechanical parameter as an independent variable, multifactor regression analysis and stepwise multifactor fitting were carried out; it was concluded that the abrasion performance was highly correlated with uniaxial compressive strength and integrity coefficient, and the chiseling specific energy is highly correlated with uniaxial compressive strength and softening coefficient. In the process of verifying the fitting models, it is found that, under the influence of quartz vein and microfissure in the specimens, the chiseling specific energy formula has a higher fitting value, while the fitting formula of abrasion performance has a higher reference value for the specimens in the study area.

In the current paper, the deformation behaviours of rocks during compression are studied by testing 10 groups of sandstone samples with different porosity characteristics. According to the energy theory, the rock material was divided into two parts: solid skeleton and voids. A statistical damage-based approach was adopted to establish a nonlinear statistical damage constitutive model. The validity of the statistical damage constitutive model is verified by the test data. The statistical damage constitutive model performs well in each stage of rock compression before failure. For different types of rocks, different confining pressures, and different water contents, the statistical damage constitutive model fits well. This model can be applied to most types of rocks and in most engineering environments.

Brassinosteriods (BRs) are plant hormones essential for plant growth and development. The receptor-like kinase (RLK) BRI1 perceives BRs to initiate a well-known transduction pathway which finally activate the transcription factors BZR1/BES1 specifically regulating BR-mediated gene expression. The RLK EMS1 governs tapetum formation via the same signaling pathway shared with BRI1. BRI1 and EMS1 have a common signal output, but the gene structural specificity and the molecular response remain unclear. In this study, we identified that the transmembrane (TM), intracellular juxtamembrane (iJM), kinase, and leucin-rich repeats 1-13 (LRR1-13) domains of EMS1 could replace the corresponding BRI1 domain to maintain the BR receptor function, whereas the extracellular juxtamembrane (eJM) and LRR1-14 domains could not, indicating that the LRR14-EJM domain conferred functional specificity to BRI1. We compared the kinase domains of EMS1 and BRI1, and found that EMS1’s kinase activity was weaker than BRI1’s. Further investigation of the specific phosphorylation sites in BRI1 and EMS1 revealed that the Y1052 site in the kinase domain was essential for the BRI1 biological function, but the corresponding site in EMS1 showed no effect on the biological function of EMS1, suggesting a site regulation difference in the two receptors. Furthermore, we showed that EMS1 shared the substrate BSKs with BRI1. Our study provides insight into the structural specificity and molecular mechanism of BRI1 and EMS1, as well as the origin and divergence of BR receptors.

Background The tumor protein p53 (TP53) mutant is one of the most frequent mutant genes in bladder cancer. In this study, we assessed the importance of the TP53 mutation in bladder cancer progression and drug selection, and identified potential pathways and core genes associated with the underlying mechanisms. Methods Gene expression data used in this study were downloaded from The Cancer Genome Atlas and cBioportal databases. Drug sensitivity data were obtained from the Genomics of Drug Sensitivity in Cancer. We did functional enrichment analysis by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We found the TP53 mutation in 50% of bladder cancer patients. Patients with the TP53 mutation were associated with a lower TP53 mRNA expression level, more advanced tumor stage and higher histologic grade. Three drugs, mitomycin-C, doxorubicin and gemcitabine, were especially more sensitive to bladder cancer with the TP53 mutation. As for the mechanisms, we identified 863 differentially expressed genes (DEGs). Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, chemical carcinogenesis and cancer related pathways. The protein–protein interaction network identified the top 10 hub genes. Our results have suggested the significance of TP53 mutation in disease progression and drug selection in bladder cancer, and identified multiple genes and pathways related in such program, offering novel basis for bladder cancer individualized treatment.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a poor prognosis worldwide. While early stage tumours can be treated with curative approaches such as liver transplantation or surgical resection, these are only suitable for a minority of patients. Those with advanced stage disease are only suitable for supportive approaches and most are resistant to the conventional chemotherapy or radiotherapy. Liver cancer stem cells (LCSCs) are a small subset of cancer cells with unlimited differentiation ability and tumour forming potential. In order to develop novel therapeutic approaches for HCC, we need to understand how the cancer develops and why treatment resistance occurs. Using high-throughput sequencing techniques, a large number of dysregulated long noncoding RNAs (lncRNAs) have been identified, and some of which are closely linked to key aspects of liver cancer pathology, progression, outcomes and for the maintenance of cancer stem cell-like properties. In addition, some lncRNAs are potential biomarkers for HCC diagnosis and may serve as the therapeutic targets. This review summarizes data recently reported lncRNAs that might be critical for the maintenance of the biological properties of LCSCs.

Abstract Amylase plays an important role in biotechnology industries, and Gram-positive bacterium Bacillus subtilis is a major host to produce heterogeneous α-amylases. However, the secretion stress limits the high yield of α-amylase in B. subtilis although huge efforts have been made to address this secretion bottleneck. In this question-oriented review, every effort is made to answer the following questions, which look simple but are long-standing, through reviewing of literature: (1) Does α-amylase need a specific and dedicated chaperone? (2) What signal sequence does CsaA recognize? (3) Does CsaA require ATP for its operation? (4) Does an unfolded α-amylase is less soluble than a folded one? (5) Does α-amylase aggregate before transporting through Sec secretion system? (6) Is α-amylase sufficient stable to prevent itself from misfolding? (7) Does α-amylase need more disulfide bonds to be stabilized? (8) Which secretion system does PrsA pass through? (9) Is PrsA ATP-dependent? (10) Is PrsA reused after folding of α-amylase? (11) What is the fate of PrsA? (12) Is trigger factor (TF) ATP-dependent? The literature review suggests that not only the most of those questions are still open to answers but also it is necessary to calculate ATP budget in order to better understand how B. subtilis uses its energy for production and secretion.

Pseudomonas aeruginosa is a Gram-negative bacterium causing diseases in plants, animals, and humans, and its drug resistance is a major concern in medical care. Biofilms play an important role in P. aeruginosa drug resistance. Three factors are most important to induce biofilm: quorum sensing (QS), bis-(3′-5′)-cyclic diguanosine monophosphate (c-di-GMP), and small RNAs (sRNAs). P. aeruginosa has its own specific QS system (PQS) besides two common QS systems, LasI–LasR and RhlI–RhlR, in bacteria. PQS is interesting not only because there is a negative regulation from RhlR to pqsR but also because the null mutation in PQS leads to a reduced biofilm formation. Furthermore, P. aeruginosa dispersed cells have physiological features that are distinct between the planktonic cells and biofilm cells. In response to a low concentration of c-di-GMP, P. aeruginosa cells can disperse from the biofilms to become planktonic cells. These raise an interesting hypothesis of whether biofilm can be reversed through the QS mechanism in P. aeruginosa. Although a single factor is certainly not sufficient to prevent the biofilm formation, it necessarily explores such possibility. In this hypothesis, the literature is analyzed to determine the negative regulation pathways, and then the transcriptomic data are analyzed to determine whether this hypothesis is workable or not. Unexpectedly, the transcriptomic data reveal a negative regulation between lasI and psqR. Also, the individual cases from transcriptomic data demonstrate the negative regulations of PQS with laslI, laslR, rhlI, and rhlR under different experiments. Based on our analyses, possible strategies to reverse biofilm formation are proposed and their clinic implications are addressed.

Brassinosteroid insensitive 1 (BRI1) is a multidomain plant leucine-rich repeat receptor-like kinase (LRR-RLK), belongs to the LRR X subfamily. BRI1 perceives plant hormone brassinosteroids (BRs) through its extracellular domain that constitutes of LRRs interrupted by a 70 amino acid residue island domain (ID), which activates the kinase domain (KD) in its intracellular domain to trigger BR response. Thus, the KD and the ID of BRI1 are highly conserved and greatly contribute to BR functions. In fact, most bri1 mutants are clustered in or surrounded around the ID and the KD. However, the role of the less conserved LRR domains, particularly the first few LRRs after the signal peptide, is elusive. Here, we report the identification of a loss-of-function mutant bri1-235 that carries a mutation in the less conserved fourth LRR of BRI1 extracellular domain in Arabidopsis. This mutant had a base alteration from C to T, resulting in an amino acid substitution from serine to phenylalanine at the 156th position of BRI1. Compared with the wild-type plants, bri1-235 exhibited round leaves, prolonged life span, shorter stature, and approximately normal fertility under light conditions. The bri1-235 mutant was less sensitive to exogenous brassinolide under normal conditions. Importantly, both wild-type BRI1 expression and a sbi1 mutant that activates BRI1 rescued bri1-235 and resembled the wild type. Furthermore, bri1-235 protein was localized in endoplasmic reticulum rather than plasma membrane, suggestive of a cause for reducing BR sensitive in bri1-235. Taken together, our findings provide an insight into the role of the less conserved LRRs of BRI1, shedding light on the role of LRRs in a variety of LRR-RLKs that control numerous processes of plant growth, development, and stress response.

Brassinosteroids (BRs) are essential hormones for plant growth and development. Enzymes DET2 and CYP90 family are responsible for BR biosynthesis in seed plants. Yet, their roles in non-seed plants are unknown. Here, we report the first functional study of DET2 and all 4 CYP90 genes isolated from Selaginella moellendorfii. Sm89026 (SmCPD) belonged to a clade with CYP90A1 (CPD) and CYP90B1 (DWF4) while Sm182839, Sm233379 and Sm157387 formed a distinct clade with CYP90C1 (ROT3) and CYP90D1. SmDET2, SmCPD and Sm157387 were highly expressed in both leaves and strobili while Sm233379 was only highly expressed in the leaves but not strobili, implying their differential functions in a tissue-specific manner in S. moellendorfii. We showed that only SmDET2 and SmCPD completely rescued Arabidopsis det2 and cpd mutant phenotypes, respectively, suggestive of their conserved BR biosynthetic functions. However, neither SmCPD nor other CYP90 genes rescued any other cyp90 mutants. Yet overexpression of Sm233379 altered plant fertility and BR response, which means that Sm233379 is not an ortholog of any CYP90 genes in Arabidopsis but appears to have a BR function in the S. moellendorfii leaves. This function is likely turned off during the development of the strobili. Our results suggest a dramatic functional divergence of CYP90 family in the non-seed plants. While some of them are functionally similar to that of seed plants, the others may be functionally distinct from that of seed plants, shedding light for future exploration.

The decoherence in coherent lidar becomes serious with the increase in distance. A small laser spot can suppress the decoherence of the echo light from noncooperation targets. However, it is very difficult to keep a small light spot over a long distance. In this paper, a pulsed coherent lidar with high sensitivity at the few-photon level was demonstrated. A phase plate was used to modulate the wavefront of the laser to achieve 100 m focusing which reduced the decoherence effect. Based on coherent detection and time-of-flight (TOF) measurements, long-distance laser ranging and imaging on all days was realized. A signal classification and superposition method was used to extract the echo signal submerged in noise. The system was experimentally demonstrated by ranging different noncooperation targets within 105.0 m. The measurement rate was 10 k/s, and the measurement uncertainty was 1.48 cm. In addition, laser imaging was realized at ~50.0 m. The system was simple and portable as well as eye safe, and it may offer new application possibilities in automated vehicle lidar.

Laser time transfer is of great significance in timing and global time synchronization. However, the temperature drift may occur and affect the delay of the electronics system, optic generation and detection system. This paper proposes a post-processing method for the compensation of temperature-induced system delay, which does not require any changes to the hardware setup. The temperature drift and time stability of the whole system are compared with and without compensation. The results show that the propagation delay drift as high as 240 ps caused by temperature changes is compensated. The temperature drift coefficient was diminished down to ~0.05 ps/°C from ~20.0 ps/°C. The system precision was promoted to ~2 ps from ~11 ps over a time period of 80,000 s. This method performs significant compensation of single-photon laser time transfer system propagation drift and will help to establish an ultra-stable laser time transfer link in space applications.