The endophytic microbiome response patterns of Juglans regia to two pathogenic fungi.

The endophytic microbial community reassembles to participate in plant immune balance when the host plants are stressed by pathogens. However, it remains unclear whether this assembly is pathogen-specific and how regulatory pathways are coordinated in multi-pathogens. In order to investigate the effects of infection with Colletotrichum gloeosporioides (Cg treatment) and Fusarium proliferatum (Fp treatment) on walnut leaf endophytic microbiome in their assembly, co-occurrence pattern, and on comprehensive chemical function of the internal environment of leaf, an interaction system of the walnut-pathogenic fungi was constructed using seed embryo tissue culture technology. The study showed differences in the assembly of endophytic microbial communities in walnut trees across three groups (control group, Ck; Cg; Fp) after Cg and Fp treatments. Despite changes in relative abundances, the dominant communities in phyla and genera remained comparable during the infection of the two pathogens. Endophyte fungi were more sensitive to the pathogen challenge than endophyte bacteria. Both promoted the enrichment of beneficial bacteria such as Bacillus and Pseudomonas, changed the modularity of the community, and reduced the stability and complexity of the endophyte community. Pathogenic fungi infection mainly affects the metabolism of porphyrin and chlorophyll, purine metabolism, phenylpropane metabolism, and amino acid metabolism. However, there was no significant difference in the secondary metabolites for the different susceptible plants. By screening endogenous antagonistic bacteria, we further verified that Pseudomonas psychrotolerans and Bacillus subtilis had inhibitory effects on the two pathogenic fungi and participated in the interaction between the leaves and pathogenic fungi. The antibacterial substances may be 1-methylnaphthalene, 1,3-butadiene, 2,3-butanediol, and toluene aldehyde.

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53.

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown. Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53 binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this self-repression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25 as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53 from binding to W-box elements on the AtWRKY53 promoter and thus counteracted the self-repression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid (SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and NahG transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence, which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

Solid pseudopapillary neoplasm (SPN) of the pancreas: current understanding on its malignant potential and management.

Solid pseudopapillary neoplasms (SPN) of the pancreas are presently recognized as low-grade malignant tumors that are frequently observed in young females. This tumor has a low incidence and is associated with an excellent prognosis following surgical resection. Typical SPNs primarily affect the pancreas and tend to have moderate or asymptomatic manifestations. Based on retrospective research, it is anticipated that patients with SPN can achieve disease-free survival, even in cases when metastasis is detected during inspection. However, the incidence of malignant SPN has been consistently underestimated, as evidenced by recent research findings. Malignancy of SPN primarily encompasses invasion and infiltration, metastasis, and recurrence after R0 resection. Imaging technologies such as Ultrasound, Computed Tomography, Magnetic Resonance Imaging, and Position Emission Tomography are capable of preliminarily identifying malignant SPN, which is primarily based on its invasive clinical features. Research on risk factors of malignant SPN revealed that larger tumor size, Ki-67 index, and several other parameters had significant correlations with invasive tumor behavior. Pathologic features of malignant SPNs overlay other pancreatic tumors, nevertheless they can provide valuable assistance in the process of diagnosis. Several confirmed specific pathologic biomarkers are related to its cellular origin, characteristic gene mutation, and cell proliferation. Considering the invasiveness of malignant SPN, it is imperative to enhance the comprehensiveness of its therapy. Tumor resection remains a suggested course of action in line with typical SPN, and additional lymph node dissection is seen as reasonable. Compared to benign SPNs, malignant SPNs have worse prognosis, underscoring the necessity of early identification and treatment in comprehensive medical centers to get improved clinical outcomes.

Micromechanism for Copper-Deficiency Enhanced Stability: A Quasi In Situ TEM Study of Electric-Induced Structural Evolution in Cu2-x(S, Se) Liquid-Like Thermoelectric Materials.

Cu-based liquid-like thermoelectric materials have garnered tremendous attention due to their inherent ultralow lattice thermal conductivity. However, their practical application is hampered by stability issues under a large current or temperature gradient. It has been reported that introduction of copper vacancies can enhance the chemical stability, whereas the micromechanism behind this macroscopic improvement still remains unknown. Here, we have established a quasi in situ TEM method to examine and compare the structural evolution of Cu2-xS0.2Se0.8 (x = 0, 0.05) under external electric fields. It is then found that the preset Cu vacancies could favor the electric-induced formation of a more stable intermediate phase, i.e., the hexagonal CuSe-type structure in the form of either lamellar defects (majorly) or long-range order (minorly), in which ordering of S and Se also occurred. Thereby, copper and chalcogen atoms could largely be solidified into the matrix, and the elemental deposition and evaporation process is mitigated under an electric field.

Transcription factors NtNAC028 and NtNAC080 form heterodimers to regulate jasmonic acid biosynthesis during leaf senescence in Nicotiana tabacum.

Plant senescence, as a highly integrated developmental stage, involves functional degeneration and nutrient redistribution. NAM/ATAF1/CUC (NAC) transcription factors orchestrate various senescence-related signals and mediate the fine-tuning underlying plant senescence. Previous data revealed that knockout of either NtNAC028 or NtNAC080 leads to delayed leaf senescence in tobacco (Nicotiana tabacum), which implies that NtNAC028 and NtNAC080 play respective roles in the regulation of leaf senescence, although they share 91.87% identity with each other. However, the mechanism underlying NtNAC028- and NtNAC080-regulated leaf senescence remains obscure. Here, we determined that NtNAC028 and NtNAC080 activate a putative jasmonic acid (JA) biosynthetic gene, NtLOX3, and enhance the JA level in vivo. We found that NtNAC028 and NtNAC080 interact with each other and themselves through their NA-terminal region. Remarkably, only the dimerization between NtNAC028 and NtNAC080 stimulated the transcriptional activation activity, but not the DNA binding activity of this heterodimer on NtLOX3. Metabolome analysis indicated that overexpression of either NtNAC028 or NtNAC080 augments both biosynthesis and degradation of nicotine in the senescent stages. Thus, we conclude that NtNAC028 cooperates with NtNAC080 and forms a heterodimer to enhance NtLOX3 expression and JA biosynthesis to trigger the onset of leaf senescence and impact secondary metabolism in tobacco.

Regulatory role of RNA modifications in the treatment of pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) is an extremely life-threatening malignancy with a relatively unfavorable prognosis. The early occurrence of metastasis and local recurrence subsequent to surgery contribute to the poor survival rates of PDAC patients, thereby limiting the effectiveness of surgical intervention. Additionally, the desmoplastic and immune-suppressive tumor microenvironment of PDAC diminishes its responsiveness to conventional treatment modalities such as chemotherapy, radiotherapy, and immunotherapy. Therefore, it is imperative to identify novel therapeutic targets for PDAC treatment. Chemical modifications are prevalent in various types of RNA and exert significant influence on their structure and functions. RNA modifications, exemplified by m6A, m5C, m1A, and Ψ, have been identified as general regulators of cellular functions. The abundance of specific modifications, such as m6A, has been correlated with cell proliferation, invasion, migration, and patient prognosis in PDAC. Pre-clinical data has indicated that manipulating RNA modification regulators could enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting RNA modifications in conjunction with current adjuvant or neoadjuvant therapy holds promise. The objective of this review is to provide a comprehensive overview of RNA modifications in PDAC treatment, encompassing their behaviors, mechanisms, and potential treatment targets. Therefore, it aims to stimulate the development of novel therapeutic approaches and future clinical trials.

Dissected Leaf 1 encodes an MYB transcription factor that controls leaf morphology in potato.

KEY MESSAGE: The transcription factor StDL1 regulates dissected leaf formation in potato and the genotype frequency of recessive Stdl1/Stdl1, which results in non-dissected leaves, has increased in cultivated potatoes. Leaf morphology is a key trait of plants, influencing plant architecture, photosynthetic efficiency and yield. Potato (Solanum tuberosum L.), the third most important food crop worldwide, has a diverse leaf morphology. However, despite the recent identification of several genes regulating leaf formation in other plants, few genes involved in potato leaf development have been reported. In this study, we identified an R2R3 MYB transcription factor, Dissected Leaf 1 (StDL1), regulating dissected leaf formation in potato. A naturally occurring allele of this gene, Stdl1, confers non-dissected leaves in young seedlings. Knockout of StDL1 in a diploid potato changes the leaf morphology from dissected to non-dissected. Experiments in N. benthamiana and yeast show that StDL1 is a transcriptional activator. Notably, by calculating the genotype frequency of the Stdl1/Stdl1 in 373-potato accessions, we found that it increases significantly in cultivated potatoes. This work reveals the genetic basis of dissected leaf formation in potato and provides insights into plant leaf morphology.

Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC.

BACKGROUND: A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. METHODS: A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. RESULTS: Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. CONCLUSION: PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.

The Dorsal Nasal Complex in Asians: Anatomical Variations and Injection Guide for Botulinum Toxin Type A.

BACKGROUND: Multiple muscles contribute to the formation of dorsal nasal lines (DNLs) and affect nasal aesthetics. Few attempts have been made to explore the range of distribution of DNLs in relation to injection planning. OBJECTIVES: The aim of this study was to classify the distribution types of DNLs and propose a refined injection technique validated by clinical study and cadaver dissection. METHODS: Patients were classified into 4 types according to their DNL distribution type. Botulinum toxin type A injections were administered at 6 regular points and 2 optional points. The effect on wrinkle reduction was assessed. Patient satisfaction was recorded. Cadaver dissection was conducted to explore the anatomical evidence of DNL variation. RESULTS: The study included 349 treatments in 320 patients (269 females and 51 males), whose DNLs were classified into complex type, horizontal type, oblique type, and vertical type. The severity of DNLs was significantly reduced after treatment. Most patients were satisfied. From the cadaver study, connecting muscular fibers were clearly observed among the muscles involved in the formation of DNLs, and these muscles were collectively named the dorsal nasal complex (DNC) by the authors. Four anatomical variations of the DNC were discovered, corroborating the DNL classification system. CONCLUSIONS: A novel anatomical concept, the DNC, and a classification system for DNLs were proposed. Each of the 4 distribution types of DNLs corresponds to a specific anatomical variation of the DNC. A refined injection technique for DNLs was developed, and its efficacy and safety were demonstrated.

Advances in functional photonic crystal materials for the analysis of chemical hazards in food.

Chemical contaminants in food generally include natural toxins (mycotoxins, animal toxins, and phytotoxins), pesticides, veterinary drugs, environmental pollutants, heavy metals, and illegal additives. Developing a low-cost, simple, and rapid detection technology for harmful substances in food is urgently needed. Analytical methods based on different advanced materials have been developed into rapid detection methods for food samples. In particular, photonic crystal (PC) materials have a unique surface periodic structure, structural color, a large surface area, easy integration with photoelectronic and magnetic devices which have great advantages in the development of rapid, low-cost, and highly sensitive analytical methods. This review focuses on the PC materials in the view of their fabrication processes, functionalized recognition components for the specific recognition of hazardous substances, and applications in the separation, enrichment, and detection of chemical hazards in real samples. Suspension array based on three-dimensional PC microspheres by droplet-based microfluidic assembly is a great promising and powerful platform for food safety detection fields. For the PCs selective analysis, biological antibodies, aptamers, and molecularly imprinted polymers (MIPs) could be modified for specific recognition of target substances, particularly MIPs because of their low-cost and easy mass production. Based on these functional PCs, various toxic and hazardous substances can be selectively enriched or recognized in real samples and further quantified in combination of liquid chromatography method or optical detection methods including fluorescence, chemiluminescence, and Raman spectroscopy.

Mechanism of the two-dimensional WSeTe/Zr2CO2 direct Z-scheme van der Waals heterojunction as a photocatalyst for water splitting.

The direct Z-scheme van der Waals (vdW) heterojunctions based on biomimetic artificial photosynthesis are a promising strategy for enhancing photocatalytic activity. Therefore, the search for superior direct Z-scheme photocatalysts is an urgent task. Herein, we predicted the WSeTe/Zr2CO2 heterostructure as a potential direct Z-scheme photocatalyst based on density functional theory (DFT). The bands of the WSeTe/Zr2CO2 heterojunction follow a typical Type-II arrangement, where the interlayer band gap is smaller than that of the individual molecular layers, and staggered alignment of the large band-edge creates conditions that allow for a direct Z-scheme. The position of the Fermi energy levels of the two monolayers determines the formation of the built-in electric field pointing from WSeTe to Zr2CO2, promoting the desired interlayer electron-hole (e--h+) recombination and suppressing the undesired carrier recombination. Finally, in-plane biaxial strain can effectively modulate the optoelectronic properties of the catalyst, while compressive strain has a more pronounced effect on the overpotential driving force of the material. Therefore, the WSeTe/Zr2CO2 heterojunction is an effective new photocatalyst satisfying the direct Z-scheme charge transfer mechanism with its specific application.

The multi-omics basis of potato heterosis.

Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents. Although tremendous progress has been reported in seed crops, the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown. Potato (Solanum tuberosum L.) is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploid hybrid potato. In our previous study, we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis. Here, we integrated transcriptome, metabolome, and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages. We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation. Flower color, male fertility, and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids, and hybrids devoted more energy to primary metabolism for rapid growth. In addition, we identified ~2 700 allele-specific expression genes at each stage, which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level. Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding.

Rationally engineered chitin deacetylase from Arthrobacter sp. AW19M34-1 with improved catalytic activity toward crystalline chitin.

Chitin and its derivatives have anticoagulant, antimicrobial, and antioxidant properties, but the poor solubility of chitin limits its application in different fields. In this study, site-directed mutagenesis was performed to enhance the deacetylation activity of chitin deacetylases CDA from Arthrobacter (ArCE4). The mutant Mut-2-8 with Y172E/E200S/Y201W showed a 2.84- fold and 1.39-fold increase in catalytic efficiency (kcat/Km) for the deacetylation of (GluNAc)5 and α-chitin, respectively. These results demonstrated that the mutations significantly improved the activation of ArCE4 on crystalline chitin. The molecular docking study confirmed that the enhancement of catalytic efficiency is due to the extra two hydrogen bonds and one acetyl group. In summary, the activity of Mut-2-8 to insoluble chitin was significantly improved by reactional design, which is beneficial to resolve the issues of the expensive cost of the enzymes and low efficiency. Mut-2-8 exhibits potential applications in the chitosan industry.

Sulfonation of curcuminoids: characterization and contribution of individual SULT enzymes.

SCOPE: Poor oral bioavailability of curcuminoids limited their various applications, and one of the main reasons is their rapid metabolism in vivo. Sulfonation via sulfotransferases (SULTs) is an important metabolic pathway for such compounds. The objective of this study is to determine the SULT-isoform-specific metabolic fingerprint, tissue-specific rate, and reaction kinetic profiles to describe the characterization and contribution of curcuminoids sulfonation. METHODS AND RESULTS: Sulfonation of curcuminoids was investigated by using nine expressed SULT isoforms and four pooled human tissue S9 fractions. The results showed that human small intestine is the predominant tissue responsible for sulfonation of curcuminoids. SULT1A3 is a major isoform catalyzing sulfonation of curcumin and demethoxycurcumin, but not for bisdemethoxycurcumin. SULT1B1 is only responsible for sulfonation of curcumin. Although SULT1C4 and 1E1 could highly catalyze the sulfate conjugations toward all the three compounds, the correlativities with human small intestine S9 fractions were much weaker (R(2) = 0.100-0.482). Almost all the kinetic profiles of the SULT isoforms for curcuminoids exhibited substrate inhibition kinetics. CONCLUSION: This investigation contributed to elucidate the SULT-mediated metabolism and detoxication of curcuminoids at molecular levels and in different organs.

Comparative pharmacokinetics study of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract.

Various products containing sinomenine monomer and extracts of Sinomenium acutum have been widely applied in clinical treatments. The goal of the present study was to compare the pharmacokinetics of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract, and to attempt to explore potential component-component interactions between the constituents of this traditional Chinese herbal medicine. A reliable and specific reversed phase high performance liquid chromatography method was developed to analyze sinomenine in rat plasma. Pharmacokinetic parameters for sinomenine were processed by non-compartmental analysis. The results showed that the maximum concentration, the area under the concentration-time curve, clearance and the apparent volume of distribution of sinomenine in the Sinomenium acutum extract statistically differed from those of sinomenine monomer (p < 0.05); however, the mean residence time, time of peak concentration, and half-life did not show significant differences between the two groups. These findings suggested that some additional components in the Sinomenium acutum extract may decrease the absorption of sinomenine. The complex interactions between sinomenine and other components of the herbal extract could result in the altered pharmacokinetic behavior of sinomenine, which may subsequently cause different therapeutic and detoxification effects.