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Abstract Background Dendrobium officinale Kimura et Migo, a renowned traditional Chinese orchid herb esteemed for its significant horticultural and medicinal value, thrives in adverse habitats and contends with various abiotic or biotic stresses. Acid invertases (AINV) are widely considered enzymes involved in regulating sucrose metabolism and have been revealed to participate in plant responses to environmental stress. Although members of AINV gene family have been identified and characterized in multiple plant genomes, detailed information regarding this gene family and its expression patterns remains unknown in D. officinale, despite their significance in polysaccharide biosynthesis. Results This study systematically analyzed the D. officinale genome and identified four DoAINV genes, which were classified into two subfamilies based on subcellular prediction and phylogenetic analysis. Comparison of gene structures and conserved motifs in DoAINV genes indicated a high-level conservation during their evolution history. The conserved amino acids and domains of DoAINV proteins were identified as pivotal for their functional roles. Additionally, cis-elements associated with responses to abiotic and biotic stress were found to be the most prevalent motif in all DoAINV genes, indicating their responsiveness to stress. Furthermore, bioinformatics analysis of transcriptome data, validated by quantitative real-time reverse transcription PCR (qRT-PCR), revealed distinct organ-specific expression patterns of DoAINV genes across various tissues and in response to abiotic stress. Examination of soluble sugar content and interaction networks provided insights into stress release and sucrose metabolism. Conclusions DoAINV genes are implicated in various activities including growth and development, stress response, and polysaccharide biosynthesis. These findings provide valuable insights into the AINV gene amily of D. officinale and will aid in further elucidating the functions of DoAINV genes.

Precise timing of flowering in plants is critical for their growth and reproductive processes. One factor controlling flowering time is the cycle of light and darkness within a day, known as the photoperiod. Plants are classified into long-day, short-day, and day-neutral plants based on light requirements for floral initiation. Although the molecular mechanisms that govern this differentiation remain incompletely understood, studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species. However, there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering. This review summarizes that regulatory network, focusing on the distinct roles of clock genes in long-day and short-day plants. We also discuss the strategies of clock gene mutations contributing to geographic variation in long-day and short-day crops.

Abstract Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay, apoptosis assay, soft agar growth assay, and tumor animal model showed STEAP4 inhibited cisplatin resistance. Mechanism analysis showed STEAP4 inhibited PI3K/AKT pathway through directly interacting with AKT. Double knockdown of STEP4 and AKT significantly inhibited cisplatin resistance. We also found STEAP4 expression was negatively correlated with PI3K/AKT pathway activity in clinic specimens. In summary, our findings suggested STEAP4 inhibited cisplatin resistance through suppressing PI3K/AKT pathway activity, providing a target for HCC therapy. Graphical Abstract

In order to determine the optimal harvesting period and the application value of each part of Pueraria lobata var. thomsonii and to explore the correlation between the main nutrients and the isoflavones, P. lobata var. thomsonii of Tengxian, Guangxi was used as the material, the contents of isoflavones in different parts, the contents of main nutrients and isoflavones in different growth periods were determined by test box method, enzyme gravimetric method, Soxhlet extraction method, high performance liquid chromatography and other physiological and biochemical techniques, and the relationship between the accumulation of various nutrients and isoflavones was analyzed to clarify the accumulation rule of main nutrients and isoflavonoids and their relationships in P. lobata var. thomsonii. The results were as follows: (1)At the mature stage, the content of genistein in different parts of P. lobata var. thomsonii was not significantly different, but the content of isoflavoues aglycone in leaf was significantly lower than that in middle vine, and the contents of total isoflavones, puerarin and daidzein in root apex and vine were significantly higher than those in leaf and tuberon, and the contents of puerarin in root apex and vine were more than 1.00%. (2)The accumulation of starch, polysaccharide, crude protein, and soluble protein reached the maximum in November and December, the accumulation of insoluble dietary fiber reached the minimum in December, the accumulation of soluble dietary fiber was the maximum in August and December, and the accumulation of total isoflavones and puerarin reached the maximum in August and September. (3)The correlation analysis results showed that the accumulation of total isoflavones and puerarin was negatively correlated with the accumulation of starch and polysaccharide; the accumulation of total isoflavones and puerarin was positively correlated with the accumulation of insoluble dietary fiber. Therefore, it can be concluded that the root apex and vine of pueraria powder contain rich total isoflavones, puerarin, daidzein, which has good value for medicinal development; the best harvest time for medicinal using are August and September, and the best harvest time for edible using are November and December; the accumulation of total isoflavones and puerarin is related to starch, polysaccharide and insoluble dietary fiber. This study clarify the accumulation rule and correlation of the main nutrients and total isoflavones in P. lobata var. thomsonii, and provides a reference for the comprehensive development and utilization of P. lobata var. thomsonii and the determination of the harvest time.

Background: Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are major health burdens, with emerging evidence suggesting NAFLD as a significant risk factor for AF, but the mechanism is remain unclear.Methods: In this study, we analyzed gene expression data from NAFLD (GSE89632) and AF (GSE75092) datasets from the Gene Expression Omnibus. We identified co-upregulated and co-downregulated genes between NAFLD and AF, assessed diagnostic potential of specific genes, conducted immune infiltration analysis, and performed molecular docking studies with sodium glucose co-transporter 2 inhibitors (SGLT2i).Results: We identified eight co-upregulated and 31 co-downregulated genes between NAFLD and AF. Genes such as AMOT, PDE11A, TYMS, TMEM98, and PTGS2 demonstrated substantial diagnostic potential for identifying NAFLD patients at risk of AF. Immune infiltration analysis discovered an elevated presence of CD8 T cells, γδ T cells, and M2 macrophages in NAFLD livers, linking systemic inflammation to NAFLD and AF. Additionally, studies have shown that a connection between mitochondrial dysfunction and several hub genes like DGAT1, TYMS, and PTGS2, suggesting that mitochondrial disturbances may underpin the systemic inflammation in NAFLD, which possibly exacerbating AF. Molecular docking studies indicated that empagliflozin's binding affinity with key genes such as DGAT1, TYMS, and PTGS2 presents a novel therapeutic avenue for NAFLD-associated AF.Conclusion: Our study firstly discovered that AMOT, PDE11A, TYMS, TMEM98, and PTGS2 are associated with NAFLD-related AF and hold strong diagnostic values. Our study also indicates that mitochondrial dysfunction and systemic inflammation may be potential mechanisms bridging NAFLD and AF. Additionally, we identified empagliflozin as a potentially effective therapeutic agent for NAFLD-related AF at the molecular structure level. These novel insights contribute to the further understanding, diagnosis, and intervention of NAFLD-related AF.

Abstract Background Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC. Methods The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells. Results We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC. Conclusions Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance.

Abstract Background Small cell lung cancer (SCLC) is a highly lethal malignant tumor. It accounts for approximately 15% of newly diagnosed lung cancers. Long non-coding RNAs (lncRNAs) can regulate gene expression and contribute to tumorigenesis through interactions with microRNAs (miRNAs). However, there are only a few studies reporting the expression profiles of lncRNAs, miRNAs, and mRNAs in SCLC. Also, the role of differentially expressed lncRNAs, miRNAs, and mRNAs in relation to competitive endogenous RNAs (ceRNA) network in SCLC remain unclear. Results In the present study, we first performed next generation sequencing (NGS) with six pairs of SCLC tumors and adjacent non-cancerous tissues obtained from SCLC patients. Overall, 29 lncRNAs, 48 miRNAs, and 510 mRNAs were found to be differentially expressed in SCLC samples (|log2[fold change] |> 1; P

Abstract Triple-negative breast cancers (TNBC) frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. However, less than 15% of TNBC patients were found to carry BRCA1 mutation, indicating that there are other mechanisms regulating BRCA1-deficient in TNBC. In the current study, we shown that overexpression of TRIM47 correlates with progression and poor prognosis in triple-negative breast cancer. Moreover, we demonstrated that TRIM47 directly interacts with BRCA1 and induces ubiquitin-ligase-mediated proteasome turnover of BRCA1, subsequently leads to a decrease of BRCA1 protein levels in TNBC. Moreover, the downstream gene expression of BRCA1, such as p53, p27, p21 was significantly reduced in the overexpression of TRIM47 cell lines but increased in TRIM47-deleted cells. Functionally, we found that overexpression of TRIM47 in TNBC cells confers an exquisite sensitivity to olaparib, an inhibitor of poly-(ADP-ribose)-polymerase (PARP), but TRIM47 inhibition significantly confers TNBC cells resistance to olaparib both in vitro and in vivo. Furthermore, we showed that overexpression of BRCA1 significant increase the olaparib resistance in TRIM47-overexpression-induced PARP inhibitions sensitivity. Taken together, our results uncover a novel mechanism for BRCA1-deficient in TNBC and targeting TRIM47/BRCA1 axis may be a promising prognostic factor and a valuable therapeutic target for TNBC.

Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.

IntroductionSepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases.MethodsSerum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK "javascript:;" assess the function of the metabolites.ResultsThe occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP, and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both in vitro and in vivo examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury.DiscussionThese findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis.

In the original publication [...]

A desorption-tailoring strategy is demonstrated to steadily prepare self-assembled p-AlGaN superlattices with sub-nanometer ultrathin barriers by MOCVD, which juggle the hole concentration and transport.

Pueraria thomsonii Benth. is a perennial leguminous vine with medicinal and nutritional value. However, rapid postharvest physiological deterioration (PPD) reduces its quality and market value. To detect gene expression levels, the quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique requires stable internal reference genes (IRGs). Our findings indicated that an ethephon (C2H6ClO3P) treatment delayed PPD in P. thomsonii tuberous roots and an RNA-seq analysis revealed a significant number of differentially expressed genes (DEGs). To find stable IRGs for the further identification of the genes associated with delayed PPD in P. thomsonii, eight candidate IRGs of the tuberous roots were screened and assessed using qRT-PCR. The expression stability of these genes was determined and ranked using five different algorithms, including NormFinder, BestKeeper, ΔCt, GeNorm, and ReFinder. Consequently, we identified two genes, PtUBC10 and PtACT7, as the best candidate IRGs for qRT-PCR normalization in P. thomsonii, both exposed to ethephon treatment and in different tissues. Moreover, PtUBC10 was found to be the most stably expressed IRG of P. thomsonii during the ethephon treatment. The findings of this investigation furnish significant insights for future gene expression analyses concerning the delay of PPD via ethephon administration, which could also be used in other tuberous plants.

The current COVID-19 pandemic is motivating us to elucidate the molecular mechanism of SARS-CoV-2 invasion and find methods for decreasing its transmissibility. We found that SARS-CoV-2 could increase the protein level of ACE2 in mice. Folic acid and 5-10-methylenetetrahydrofolate reductase (MTHFR) could promote the methylation of the ACE2 promoter and inhibit ACE2 expression. Folic acid treatment decreased the binding ability of Spike protein, pseudovirus and inactivated authentic SARS-CoV-2 to host cells. Thus, folic acid treatment could decrease SARS-CoV-2 invasion and SARS-CoV-2-neutralizing antibody production in mice. These data suggest that increased intake of folic acid may inhibit ACE2 expression and reduce the transmissibility of SARS-CoV-2. Folic acid could play an important role in SARS-CoV-2 infection prevention and control.

ased on the finite element method, the effect of porous osteotomy block on the biomechanics of surrounding joints in the treatment of flat foot by Evans osteotomy is studied. The finite element method is used to simulate the osteotomy block for Evans osteotomy to correct flatfoot. The effect of Evans osteotomy on the foot force line is analyzed from the biomechanical point of view. The osteotomy blocks were divided into solid osteotomy blocks and porous osteotomy blocks, and normal foot and flat foot were used as control groups. The results show that Evans osteotomy can effectively improve the force line of the foot to correct the flat foot. Compared with the solid osteotomy block, the porous osteotomy block can also play a corrective effect and reduce the stress shielding effect when used for Evans osteotomy to correct the flat foot.

The decrease in periodic scouring of pulsed flows in regulated rivers can result in algal communities dominated by filamentous algae, not available as food sources for fish and macroinvertebrates. To study the pulsed flow velocity required to scour benthic algae from natural river beds, the removal effects on the algal biomass and resistances of different species were tested in a laboratory flume at different velocities of 0.8, 1.1, 1.4, 1.7, and 2.0 m/s. The removal of total algal biomass showed a significant positive relationship with increasing velocities, which reached 22% at 2.0 m/s. The biomass removal of green algae and diatoms was higher than that of blue–green algae. The flow velocity at 1.4 m/s had a clear removal effect on filamentous algae. The velocity higher than 1.7 m/s caused a significant increase in the removal percentage of total biomass dominated by diatoms and blue–green algae. To reduce the filamentous algae and retain the diatoms and blue–green algae, a range of near bed flow velocity was suggested to be 1.4–1.7 m/s. This range could serve as a reference for required pulsed flow velocity to reduce the growth of excessive or nuisance periphyton.

In water-deficient area, river-changed ponds are common and vital for aquatic species. This paper studies the relationship between the environmental factors and the benthic invertebrate communities in varying ponds under river habitat modifications (RHM). For analysis, numerous samples are collected from river-changed ponds in Beijing, China. These ponds are classified into five types, including totally reinforced ponds, channel reinforced ponds, bank reinforced ponds, natural ponds, and restored ponds. Results indicate: 1) the biodiversity of benthic invertebrates is dependent strongly on the pond type; 2) habitat quality explains a considerable amount of variations in benthic invertebrate communities, and RHM show strong power in explaining variations in habitat quality; 3) RHM on the pond bank has stronger impact on the habitat quality than that on the pond bottom. These findings suggest that RHM can affect the benthic invertebrate community through changing the habitat quality. And we suggest that ecological restoration of pond bank should be a useful way to improve invertebrate biodiversity for rive-changed ponds in Beijing.

Hydromorphology is a major component of riverine ecosystems. Therefore, proper assessments of the status quo, as well as the detection of pressures in river basins, are of high relevance. Process-based morphological methods have been developed, relying on a broad data basis and resulting in suitable instruments, such as the Morphological Quality Index (MQI). In this study, the hydromorphological status of the Nanxi river system in Eastern China was assessed by an adapted application of the MQI. Adaptations and amendments in the methodical approach were developed in cycles and carried out to transfer the well-approved method for European river systems to another geographical setting. The strengths of the tested approach are the few data requirements, the applicability for modified river basins, and the decoupling of historical information. The assessment of 161 river kilometers resulted in a hydromorphological status quo with the focus being a relative comparison of different sections ranging from “moderate” to “bad”, with an average classification of a “poor” state. On the one hand, the results build the basis for future restoration and river management planning, specifically, and on the other hand, they create a foundation for the development of an assessment method fitted for modified river systems conditions.

Although many researches recognize the role of team expertise diversity in providing different ideas, it remains unclear how and under which conditions these various ideas are elaborated and integrated to fuel team innovation. To address this question, we develop a model theorizing that paradoxical leadership helps diverse teams overcome the differentiating-integrating paradox to promote innovation. Moreover, we further theorize that paradoxical leadership will cultivate perspective taking among team members. Analyses of the multi-time and multi-source data from 98 teams suggest that teams with expertise diversity exhibit better innovative performance when paradoxical leadership is prevalent. Furthermore, team perspective taking mediates the positive moderating effects of paradoxical leadership on the relationship between expertise diversity and innovative performance. Through these analyses, this study not only addresses the innovation paradox of expertise diverse teams from the perspective of leader influence, but also enriches the understanding of the effects of paradoxical leadership.

RNA G-quadruplexes (G4s) play important roles in RNA biology. However, the function and regulation of mRNA G-quadruplexes in embryonic development remain elusive. Previously, we identified RHAU (DHX36, G4R1) as an RNA helicase that resolves mRNA G-quadruplexes. Here, we find that cardiac deletion of Rhau leads to heart defects and embryonic lethality in mice. Gene expression profiling identified Nkx2-5 mRNA as a target of RHAU that associates with its 5′ and 3′ UTRs and modulates its stability and translation. The 5′ UTR of Nkx2-5 mRNA contains a G-quadruplex that requires RHAU for protein translation, while the 3′ UTR of Nkx2-5 mRNA possesses an AU-rich element (ARE) that facilitates RHAU-mediated mRNA decay. Thus, we uncovered the mechanisms underlying Nkx2-5 post-transcriptional regulation during heart development. Meanwhile, this study demonstrates the function of mRNA 5′ UTR G-quadruplex-mediated protein translation in organogenesis.

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure.