Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

A calix[3]carbazole-based cavitand: synthesis, structure and its complexation with fullerenes.

A calix[3]carbazole-based cavitand was conveniently synthesized. It was found that the cavitand with adjustable conformation could show excellent complexation with fullerenes C60 and C70 in both solution and the solid state. Moreover, the crystal structures of the host-guest complexes show that the cavitand can stack into channel-like architectures, in which fullerenes are orderly arranged inside.

The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target. Conclusion: Unraveling DDIT4's involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Comments on "Planar Tetracoordinate Hydrogen: Pushing the Limit of Multicentre Bonding".

In a recent communication (Angew. Chem. Int. Ed. 2024, 63, e202317312), Kalita et al. studied In4H+ system within the frame of single-reference approximation (SRA) and found that the global energy minimum (1 a) adopted the singlet state and a planar tetracoordinate hydrogen (ptH), while the second lowest isomer (1 b) located 3.0 kcal/mol above 1 a and adopted the triplet state as well as non-planar structure with a quasi-ptH. They assessed the reliability of SRA by checking the T1-diagnostic values of coupled cluster calculations. However, according to our multi-configurational second-order perturbation theory calculations at the CASPT2(12,13)/aug-cc-pVQZ (aug-cc-pVQZ-PP for In) level, both 1 a and 1 b exhibit obvious multi-referential characters, as reflected by their largest reference coefficients of 0.928 (86.1 %) and 0.938 (88.0 %), respectively. Moreover, 1 b is 5.05 kcal/mol lower than 1 a at this level, that is, what can be observed in In4H+ system is the quasi-ptH.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Accuracy of 3.0T magnetic resonance angiography for the detection of arteriovenous fistula dysfunction in hemodialysis patients requiring interventional therapy: a prospective study.

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

A cost-effectiveness analysis of fluoride varnish application in preventing Root caries in elderly persons: a Markov simulation study.

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.

Effect of Cd(II) adsorption onto rice roots on its uptake by different indica and japonica rice varieties and toxicity effect of Cd(II) under acidic conditions.

The rapid increase in soil acidity coupled with the deleterious effects of cadmium (Cd) toxicity had led to a decline in worldwide agricultural production. Rice absorbs and accumulates Cd(II) from polluted paddy soils, increasing human health risks throughout the food chain. A 35-day hydroponic experiment with four japonica and four indica (two each of them tolerant and sensitive cultivars) was conducted in this study to investigate the adsorption and absorption of Cd(II) by rice roots as related with surface chemical properties of the roots. The results showed that the three chemical forms of exchangeable, complexed, and precipitated Cd(II) increased with the increase in Cd(II) concentration for all rice cultivars. The roots of indica rice cultivars carried more negative charges and had greater functional groups and thus adsorbed more exchangeable and complexed Cd(II) than those of japonica rice cultivars. This led to more absorption of Cd(II) by the roots and greater toxicity of Cd(II) to the roots of indica rice cultivars and more inhibition of Cd(II) stress on the growth of the roots and whole plants of indica rice cultivars compared with japonica rice cultivars, which was one of the main reasons for more declines in the biomass and length of indica rice roots and shoots than japonica rice cultivars. Cd(II) stress showed more toxicity to the sensitive rice cultivars and thus greater inhibition on the growth of the cultivars due to more exchangeable and complexed Cd(II) adsorbed by their roots induced by more negative charges and functional groups on the roots compared with tolerant rice cultivar for both indica and japonica, which resulted in greater decreases in the biomass and length of roots and shoots as well as chlorophyll contents of the sensitive cultivars than the tolerant cultivars. The roots of sensitive rice cultivars also absorbed more Cd(II) than tolerant rice cultivars due to the same reasons as above. These findings will provide useful references for the safe utilization and health risk prevention of Cd-contaminated paddy fields.

Research Progress on the Degradation of Organic Pollutants in Water by Activated Persulfate Using Biochar-Loaded Nano Zero-Valent Iron.

Biochar (BC) is a new type of carbon material with a high specific surface area, porous structure, and good adsorption capacity, which can effectively adsorb and enrich organic pollutants. Meanwhile, nano zero-valent iron (nZVI) has excellent catalytic activity and can rapidly degrade organic pollutants through reduction and oxidation reactions. The combined utilization of BC and nZVI can not only give full play to their advantages in the adsorption and catalytic degradation of organic pollutants, but also help to reduce the agglomeration of nZVI, thus improving its efficiency in water treatment and providing strong technical support for water resources protection and environmental quality improvement. This article provides a detailed introduction to the preparation method and characterization technology, reaction mechanism, influencing factors, and specific applications of BC and nZVI, and elaborates on the research progress of BC-nZVI in activating persulfate (PS) to degrade organic pollutants in water. It has been proven experimentally that BC-nZVI can effectively remove phenols, dyes, pesticides, and other organic pollutants. Meanwhile, in response to the existing problems in current research, this article proposes future research directions and challenges, and summarizes the application prospects and development trends of BC-nZVI in water treatment. In summary, BC-nZVI-activated PS is an efficient technology for degrading organic pollutants in water, providing an effective solution for protecting water resources and improving environmental quality, and has significant application value.

Research Progress of Ozone/Peroxymonosulfate Advanced Oxidation Technology for Degrading Antibiotics in Drinking Water and Wastewater Effluent: A Review.

Nowadays, antibiotics are widely used, increasing the risk of contamination of the water body and further threatening human health. The traditional water treatment process is less efficient in degrading antibiotics, and the advanced oxidation process (AOPs) is cleaner and more efficient than the traditional biochemical degradation process. The combined ozone/peroxymonosulfate (PMS) advanced oxidation process (O3/PMS) based on sulfate radical (SO4•-) and hydroxyl radical (•OH) has developed rapidly in recent years. The O3/PMS process has become one of the most effective ways to treat antibiotic wastewater. The reaction mechanism of O3/PMS was reviewed in this paper, and the research and application progress of the O3/PMS process in the degradation of antibiotics in drinking water and wastewater effluent were evaluated. The operation characteristics and current application range of the process were summarized, which has a certain reference value for further research on O3/PMS process.

Probiotic Consortia Protect the Intestine Against Radiation Injury by Improving Intestinal Epithelial Homeostasis.

PURPOSE: Radiation-induced intestinal injury (RIII) commonly occur during abdominal-pelvic cancer radiation therapy; however, no effective prophylactic or therapeutic agents are available to manage RIII currently. This study aimed to clarify the potential of probiotic consortium supplementation in alleviating RIII. METHODS AND MATERIALS: Male C57BL/6J mice were orally administered a probiotic mixture comprising Bifidobacterium longum BL21, Lactobacillus paracasei LC86, and Lactobacillus plantarum Lp90 for 30 days before exposure to 13 Gy of whole abdominal irradiation. The survival rates, clinical scores, and histologic changes in the intestines of mice were assessed. The impacts of probiotic consortium treatment on intestinal stem cell proliferation, differentiation, and epithelial barrier function; oxidative stress; and inflammatory cytokines were evaluated. A comprehensive examination of the gut microbiota composition was conducted through 16S rRNA sequencing, while changes in metabolites were identified using liquid chromatography-mass spectrometry. RESULTS: The probiotic consortium alleviated RIII, as reflected by increased survival rates, improved clinical scores, and mitigated mucosal injury. The probiotic consortium treatment exhibited enhanced therapeutic effects at the histologic level compared with individual probiotic strains, although there was no corresponding improvement in survival rates and colon length. Moreover, the probiotic consortium stimulated intestinal stem cell proliferation and differentiation, enhanced the integrity of the intestinal epithelial barrier, and regulated redox imbalance and inflammatory responses in irradiated mice. Notably, the treatment induced a restructuring of the gut microbiota composition, particularly enriching short-chain fatty acid-producing bacteria. Metabolomic analysis revealed distinctive metabolic changes associated with the probiotic consortium, including elevated levels of anti-inflammatory and antiradiation metabolites. CONCLUSIONS: The probiotic consortium attenuated RIII by modulating the gut microbiota and metabolites, improving inflammatory symptoms, and regulating oxidative stress. These findings provide new insights into the maintenance of intestinal health with probiotic consortium supplementation and will facilitate the development of probiotic-based therapeutic strategies for RIII in clinical practice.

Catalytic Effect of Ammonium Thiosulfate as a Bifunctional Electrolyte Additive for Regulating Redox Kinetics in Lithium-Sulfur Batteries by Altering the Reaction Pathway.

Sluggish sulfur redox kinetics and incessant shuttling of lithium polysulfides (LiPSs) greatly influence the electrochemical properties of lithium-sulfur (Li-S) batteries and their practical applications. For this reason, ammonium thiosulfate (AMTS) with effective redox regulation capability has been proposed as a functional electrolyte additive to promote the bidirectional conversion of sulfur species and inhibit the shuttle effect of soluble LiPSs. During discharging, the S2O32- in AMTS can trigger the rapid reduction of LiPSs from long chains to short chains by a spontaneous chemical reaction with sulfur species, thereby decreasing the accumulation of LiPSs in the electrolyte. During charging, the NH4+ in the AMTS enhances the dissociation/dissolution of Li2S2/Li2S by hydrogen-binding interactions, which alleviates the electrode surface passivation and facilitates the reversible oxidation of short-chain sulfides back to long chains. The enhanced bidirectional redox kinetics brought about by AMTS endows Li-S cells with high reversible capacity, excellent cycle stability, and rate capability even under lean electrolyte conditions. This work not only illustrates an effective redox regulation strategy by an electrolyte additive but also investigates its catalytic reaction mechanism and Li corrosion behavior. The crucial criteria for screening additives that enable bidirectional redox mediation analogous to AMTS are summarized, and its application perspectives/challenges are further discussed.

Th2-skewed peripheral T helper cells drives B cells in allergic bronchopulmonary aspergillosis.

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. However, the involvement of T cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. Th1, Th2, Th17, Treg and IL-21+CD4+T cells in total or sorted subsets of peripheral blood mononuclear cells (PBMCs) and ABPA Bronchoalveolar Lavage fluid (BALF) were analyzed by flow cytometry. RNA sequencing of subsets of CD4+T cells were done in exacerbated ABPA patients and healthy controls. Antibodies of T-B cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T cells was rarely detected in healthy controls but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T cells were mainly peripheral T helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T helper (Tfh) cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.

The discovery of three-dimensional Van Hove singularity.

Arising from the extreme/saddle point in electronic bands, Van Hove singularity (VHS) manifests divergent density of states (DOS) and induces various new states of matter such as unconventional superconductivity. VHS is believed to exist in one and two dimensions, but rarely found in three dimension (3D). Here, we report the discovery of 3D VHS in a topological magnet EuCd2As2 by magneto-infrared spectroscopy. External magnetic fields effectively control the exchange interaction in EuCd2As2, and shift 3D Weyl bands continuously, leading to the modification of Fermi velocity and energy dispersion. Above the critical field, the 3D VHS forms and is evidenced by the abrupt emergence of inter-band transitions, which can be quantitatively described by the minimal model of Weyl semimetals. Three additional optical transitions are further predicted theoretically and verified in magneto-near-infrared spectra. Our results pave the way to exploring VHS in 3D systems and uncovering the coordination between electronic correlation and the topological phase.

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1high/PD-L1high/CXCL7high and CXCL7high/IL-6high/IL-6Rhigh expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

Regulation of metal homoeostasis by two F-group bZIP transcription factors bZIP48 and bZIP50 in rice.

Zinc (Zn) deficiency not only impairs plant growth and development but also has negative effects on human health. Rice (Oryza Sativa L.) is a staple food for over half of the global population, yet the regulation of Zn deficiency response in rice remains largely unknown. In this study, we provide evidence that two F-group bZIP transcription factors, OsbZIP48/50, play a crucial role in Zn deficiency response. Mutations in OsbZIP48/50 result in impaired growth and reduced Zn/Fe/Cu content under Zn deficiency conditions. The N-terminus of OsbZIP48/OsbZIP50 contains two Zn sensor motifs (ZSMs), deletion or mutation of these ZSMs leads to increased nuclear localization. Both OsbZIP48 and OsbZIP50 exhibit transcriptional activation activity, and the upregulation of 1117 genes involved in metal uptake and other processes by Zn deficiency is diminished in the OsbZIP48/50 double mutant. Both OsbZIP48 and OsbZIP50 bind to the promoter of OsZIP10 and activate the ZDRE cis-element. Amino acid substitution mutation of the ZSM domain of OsbZIP48 in OsbZIP50 mutant background increases the content of Zn/Fe/Cu in brown rice seeds and leaves. Therefore, this study demonstrates that OsbZIP48/50 play a crucial role in regulating metal homoeostasis and identifies their downstream genes involved in the Zn deficiency response in rice.

Three-Dimensional Lumbosacral Reconstruction by An Artificial Intelligence-Based Automated MR Image Segmentation for Selecting the Approach of Percutaneous Endoscopic Lumbar Discectomy.

BACKGROUND: Assessing the 3-dimensional (3D) relationship between critical anatomical structures and the surgical channel can help select percutaneous endoscopic lumbar discectomy (PELD) approaches, especially at the L5/S1 level. However, previous evaluation methods for PELD were mainly assessed using 2-dimensional (2D) medical images, making the understanding of the 3D relationship of lumbosacral structures difficult. Artificial intelligence based on automated magnetic resonance (MR) image segmentation has the benefit of 3D reconstruction of medical images. OBJECTIVES: We developed and validated an artificial intelligence-based MR image segmentation method for constructing a 3D model of lumbosacral structures for selecting the appropriate approach of percutaneous endoscopic lumbar discectomy at the L5/S1 level. STUDY DESIGN: Three-dimensional reconstruction study using artificial intelligence based on MR image segmentation. SETTING: Spine and radiology center of a university hospital. METHODS: Fifty MR data samples were used to develop an artificial intelligence algorithm for automatic segmentation. Manual segmentation and labeling of vertebrae bone (L5 and S1 vertebrae bone), disc, lumbosacral nerve, iliac bone, and skin at the L5/S1 level by 3 experts were used as ground truth. Five-fold cross-validation was performed, and quantitative segmentation metrics were used to evaluate the performance of artificial intelligence based on the MR image segmentation method. The comparison analysis of quantitative measurements between the artificial intelligence-derived 3D (AI-3D) models and the ground truth-derived 3D (GT-3D) models was used to validate the feasibility of 3D lumbosacral structures reconstruction and preoperative assessment of PELD approaches. RESULTS: Artificial intelligence-based automated MR image segmentation achieved high mean Dice Scores of 0.921, 0.924, 0.885, 0.808, 0.886, and 0.816 for L5 vertebrae bone, S1 vertebrae bone, disc, lumbosacral nerves, iliac bone, and skin, respectively. There were no significant differences between AI-3D and GT-3D models in quantitative measurements. Comparative analysis of quantitative measures showed a high correlation and consistency. LIMITATIONS: Our method did not involve vessel segmentation in automated MR image segmentation. Our study's sample size was small, and the findings need to be validated in a prospective study with a large sample size. CONCLUSION: We developed an artificial intelligence-based automated MR image segmentation method, which effectively segmented lumbosacral structures (e.g., L5 vertebrae bone, S1 vertebrae bone, disc, lumbosacral nerve, iliac bone, and skin) simultaneously on MR images, and could be used to construct a 3D model of lumbosacral structures for choosing an appropriate approach of PELD at the L5/S1 level.

[Cloning and functional analysis of flavanone synthase â ¡ from Dendrobium huoshanense].

Flavonoid C-glycosides are a class of natural products that are widely involved in plant defense responses and have diverse pharmacological activities. They are also important active ingredients of Dendrobium huoshanense. Flavanone synthase Ⅱ has been proven to be a key enzyme in the synthesis pathway of flavonoid C-glycosides in plants, and their catalytic product 2-hydroxyflavanone is the precursor compound for the synthesis of various reported flavonoid C-glycosides. In this study, based on the reported amino acid sequence of flavanone synthase Ⅱ, a flavanone synthase Ⅱ gene(DhuFNSⅡ) was screened and verified from the constructed D. huoshanense genome localization database. Functional validation of the enzyme showed that it could in vitro catalyze naringenin and pinocembrin to produce apigenin and chrysin, respectively. The open reading frame(ORF) of DhuFNSⅡ was 1 644 bp in length, encoding 547 amino acids. Subcellular localization showed that the protein was localized on the endoplasmic reticulum. RT-qPCR results showed that DhuFNSⅡ had the highest expression in stems, followed by leaves and roots. The expression levels of DhuFNSⅡ and other target genes in various tissues of D. huoshanense were significantly up-regulated after four kinds of abiotic stresses commonly encountered in the growth process, but the extent of up-regulation varied among treatment groups, with drought and cold stress having more significant effects on gene expression levels. Through the identification and functional analysis of DhuFNSⅡ, this study is expected to contribute to the elucidation of the molecular mechanism of the formation of quality metabolites of D. huoshanense, flavonoid C-glycosides, and provide a reference for its quality formation and scientific cultivation.