An enhanced time synchronization method for a network based on Kalman filtering.

This paper introduces an enhanced time synchronization method different from IEEE 1588 (PTP). The proposed algorithm employs a unique synchronous message packet structure with a fixed length of 10 bytes and the highest system priority. This design enables preemptive transmission, effectively reducing transmission and queuing delays. Additionally, it applies a Kalman filtering model to mitigate noise interference, including clock drift, network delay jitter, and network asymmetry. The algorithm also features a clock drift compensation mechanism to continuously adjust the clock, ensuring high precision and stability in time synchronization. The algorithm proposed in this paper has the characteristics of being easy to implement, requiring minimal hardware resources, and being applicable to a variety of networks. Simulation results show that, with an 80 MHz crystal oscillator, the time offset between master and slave clocks does not exceed ± 1 clock cycle in symmetric communication links. In asymmetric links, the maximum time offset is within ± 3 clock cycles. Compared to the original PTP algorithm and the Kalman filter-based time synchronization algorithm, this method reduces the time offset from several microseconds to less than 40 ns.

A Remote Two-Point Magnetic Localization Method Based on SQUID Magnetometers and Magnetic Gradient Tensor Invariants.

In practical application, existing two-point magnetic gradient tensor (MGT) localization methods have a maximum detection distance of only 2.5 m, and the magnetic moment vectors of measured targets are all unknown. In order to realize remote, real-time localization, a new two-point magnetic localization method based on self-developed, ultra-sensitive superconducting quantum interference device (SQUID) magnetometers and MGT invariants is proposed. Both the magnetic moment vector and the relative position vector can be directly calculated based on the linear positioning model, and a quasi-Newton optimization algorithm is adopted to further improve the interference suppression capability. The simulation results show that the detection distance of the proposed method can reach 500 m when the superconducting MGT measurement system is used. Compared with Nara's single-point tensor (NSPT) method and Xu's two-point tensor (XTPT) method, the proposed method produces the smallest relative localization error (i.e., significantly less than 1% in the non-positioning blind area) without sacrificing real-time characteristics. The causes of and solutions to the positioning blind area are also analyzed. The equivalent experiments, which were conducted with a detection distance of 10 m, validate the effectiveness of the localization method, yielding a minimum relative localization error of 4.5229%.

Metformin promotes anti-tumor immunity in STK11 mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites.

Background: Metformin has pleiotropic effects beyond glucose reduction, including tumor inhibition and immune regulation. It enhanced the anti-tumor effects of programmed cell death protein 1 (PD-1) inhibitors in serine/threonine kinase 11 (STK11) mutant non-small cell lung cancer (NSCLC) through an axis inhibition protein 1 (AXIN1)-dependent manner. However, the alterations of tumor metabolism and metabolites upon metformin administration remain unclear. Methods: We performed untargeted metabolomics using liquid chromatography (LC)-mass spectrometry (MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis. Results: According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, most metabolites were annotated into metabolism, including nucleotide metabolism. Next, the differentially expressed metabolites in H460 (refers to H460 cells), H460_met (refers to metformin-treated H460 cells), and H460_KO_met (refers to metformin-treated Axin1 -/- H460 cells) were distributed into six clusters based on expression patterns. The clusters with a reversed expression pattern upon metformin treatment were selected for further analysis. We screened out metabolic pathways through KEGG pathway enrichment analysis and found that multiple nucleotide metabolites enriched in this pathway were upregulated. Furthermore, these metabolites enhanced the cytotoxicity of activated T cells on H460 cells in vitro and can activate the stimulator of the interferon genes (STING) pathway independently of AXIN1. Conclusion: Relying on AXIN1, metformin upregulated multiple nucleotide metabolites which promoted STING signaling and the killing of activated T cells in STK11 mutant NSCLC, indicating a potential immunotherapeutic strategy for STK11 mutant NSCLC.

Role of bacterial pathogens in microbial ecological networks in hydroponic plants.

Plant-associated microbial communities are crucial for plant growth and health. However, assembly mechanisms of microbial communities and microbial interaction patterns remain elusive across vary degrees of pathogen-induced diseases. By using 16S rRNA high-throughput sequencing technology, we investigated the impact of wildfire disease on the microbial composition and interaction network in plant three different compartments. The results showed that pathogen infection significantly affect the phyllosphere and rhizosphere microbial community. We found that the primary sources of microbial communities in healthy and mildly infected plants were from the phyllosphere and hydroponic solution community. Mutual exchanges between phyllosphere and rhizosphere communities were observed, but microbial species migration from the leaf to the root was rarely observed in severely infected plants. Moreover, wildfire disease reduced the diversity and network complexity of plant microbial communities. Interactions among pathogenic bacterial members suggested that Caulobacter and Bosea might be crucial "pathogen antagonists" inhibiting the spread of wildfire disease. Our study provides deep insights into plant pathoecology, which is helpful for the development of novel strategies for phyllosphere disease prediction or prevention.

Determination of aconitum alkaloids in acute poisoning case by electromembrane extraction.

In this work, electromembrane extraction (EME) was used for the first time to separate aconitine (AC), mesaconitine (Mes-AC) and hypaconitine (Hyp-AC) from biological samples and Chinese herbal medicines. Efficient EME of polar and high molecular weight aconitine alkaloids from different sample matrices was achieved with the solvent of 1-ethyl-2-nitrobenzene (ENB). Under the optimal EME conditions, EME provided recoveries for all targets in the range of 72%-74 %, 85%-103 % and 92%-94 % for whole blood, urine and aqueous samples. The proposed EME systems combined with LC-MS/MS and HPLC-UV were evaluated using different sample matrices, and the methods displayed satisfactory analytical characteristic including negligible matrix effect. The LOD and LOQ of AC, Mes-AC, and Hyp-AC by EME-LC-MS/MS were in the range of 0.002-0.068 ng/mL and 0.005-0.228 ng/mL respectively. The LOD and LOQ of AC, Mes-AC, and Hyp-AC by EME-HPLC-UV were in the range of 0.06-0.26 µg/mL and 0.20-0.86 µg/mL, respectively. The coefficient of determination, R2-value was ≥0.9926 for all cases, and the accuracy in the linear ranges was in the range of 91%-111 %. Finally, the method was successfully applied for the qualitative and quantitative analysis of AC and Mes-AC in the whole blood and herbal medicine dreg samples from an actual forensic case, and poisoning by aconitum alkaloids was identified as the cause of death. Therefore, we believe that EME could be a powerful tool to identify poisoning, and EME has great potential for efficient separation of polar and high molecular weight substances. These are of great importance in the fields of but not limited to forensic science, Traditional Chinese Medicine and clinics.

The New Nematicide Cyclobutrifluram Targets the Mitochondrial Succinate Dehydrogenase Complex in Bursaphelenchus xylophilus.

Bursaphelenchus xylophilus is a dangerous quarantine pest that causes extensive damage to pine ecosystems worldwide. Cyclobutrifluram, a succinate dehydrogenase inhibitor (SDHI), is a novel nematicide introduced by Syngenta in 2013. However, the nematocidal effect of cyclobutrifluram against plant-parasitic nematodes remains underexplored. Therefore, here, we aim to address this knowledge gap by evaluating the toxicity, effects, and mode of action of cyclobutrifluram on B. xylophilus. The result shows that cyclobutrifluram is the most effective agent, with an LC50 value of 0.1078 mg·L-1. At an LC20 dose, it significantly reduced the population size to 10.40 × 103 ± 737.56-approximately 1/23 that of the control group. This notable impact may stem from the agent's ability to diminish egg-laying and hatching rates, as well as to impede the nematodes' development. In addition, it has also performed well in the prevention of pine wilt disease, significantly reducing the incidence in greenhouses and in the field. SDH consists of a transmembrane assembly composed of four protein subunits (SDHA to SDHD). Four sdh genes were characterized and proved by RNAi to regulate the spawning capacity, locomotion ability, and body size of B. xylophilus. The mortality of nematodes treated with sdhc-dsRNA significantly decreased upon cyclobutrifluram application. Molecular docking further confirmed that SDHC, a cytochrome-binding protein, is the target. In conclusion, cyclobutrifluram has a good potential for trunk injection against B. xylophilus. This study provides valuable information for the screening and application of effective agents in controlling and preventing PWD in forests.

Structural Design and Parameter Optimization of Magnetic Gradient Tensor Measurement System.

Magnetic anomaly detection (MAD) technology based on the magnetic gradient tensor (MGT) has broad application prospects in fields such as unexploded ordnance detection and mineral exploration. The difference approximation method currently employed in the MGT measurement system introduces measurement errors. Designing reasonable geometric structures and configuring optimal structural parameters can effectively reduce measurement errors. Based on research into differential MGT measurement, this paper proposes three simplified planar MGT measurement structures and provides the differential measurement matrix. The factors that affect the design of the baseline distance of the MGT measurement system are also theoretically analyzed. Then, using the magnetic dipole model, the error analysis of the MGT measurement structures is carried out. The results demonstrate that the planar cross-shaped structure is optimal, with the smallest measurement error, only 3.15 × 10-10 T/m. Furthermore, employing the control variable method, the impact of sensor resolution constraints, noise level, target magnetic moment, and detection distance on the design of the optimal baseline distance of the MGT measurement system is simulated and verified. The results indicate that the smaller the target magnetic moment, the farther the detection distance, the lower the magnetometer resolution, the greater the noise, and the greater the baseline distance required. These conclusions provide reference and guidance for the construction of the MGT measurement system based on triaxial magnetometers.

Modified approach of regenerative treatment for distal intrabony defect beneath non-keratinized mucosa at terminal molar: A case report.

BACKGROUND: Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars. Consequently, the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions. CASE SUMMARY: This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva. The primary objective is to maintain gingival flap stability, thereby facilitating periodontal regeneration. The described technique was successfully employed in a case involving the left mandibular second molar, which presented with an intrabony defect without keratinized gingiva at the distal site. In this case, an incision was made on the disto-buccal gingival tissue, creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect. Subsequently, bone grafting and guided tissue regeneration surgeries were performed, resulting in satisfactory bone fill at 9 mo postoperatively. CONCLUSION: This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

Long-term success and influencing factors of regenerative surgery for intra-bony defects: A retrospective cohort study.

BACKGROUND: The composite outcome measure (COM) more comprehensively assesses the clinical efficacy of regenerative surgery than a single probing measurement. We aimed to assess long-term success defined by the COM (clinical attachment level [CAL] gain of ≥3 mm and postsurgery probing pocket depth [PPD] ≤ 4 mm) and influencing factors of regenerative surgery using bone substitutes and resorbable collagen membrane (RM) for intra-bony defects (IBDs). METHODS: We retrospectively collected data from patients who underwent regenerative surgery using deproteinized bovine bone mineral (DBBM) and RM for IBDs. CAL and PPD values were compared at baseline (preoperative), 1 year (short-term), and at the last follow-up (5-10 years). Multivariate logistic regressions were performed to identify factors influencing COM-based long-term success. RESULTS: Eighty-one defects in 75 teeth of 33 patients who completed follow-up (6.5 ± 1.4 years) were included. One tooth was lost. All defects with complete follow-up exhibited long-term average CAL gain (3.00 ± 2.00 mm, 95% confidence interval [CI]: 2.56-3.44 mm, p < 0.001) and PPD reduction (2.06 ± 1.91 mm, 95% CI: 1.64-2.49 mm, p < 0.001). Long-term success was achieved in 38.8% of IBDs. CAL and PPD values were comparable between 1 year and the last follow-up. Logistic regression analyses revealed that male sex (odds ratio [OR] = 0.23, 95% CI: 0.07-0.75) and bleeding on probing (BOP) during supportive periodontal therapy (OR = 0.96, 95% CI: 0.94-0.99) were risk factors for long-term success. CONCLUSIONS: Regenerative surgery with DBBM and RM for IBDs can achieve some degree of long-term success defined by COM. However, within this study's limitations, male sex and higher BOP incidence postoperatively are negatively associated with optimal long-term success. CLINICAL TRIAL NUMBER: ChiCTR2300069016.

Maresin1 alleviates neuroinflammation by inhibiting caspase-3/ GSDME-mediated pyroptosis in mice cerebral ischemia-reperfusion model.

OBJECTIVE: To explore the mechanism of Maresin1 in reducing cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided (n = 5 in each group), and focal middle cerebral artery occlusion (MCAO) model was used to simulate cerebral ischemia/reperfusion injury. TTC and the Longa score were used to detect the degree of neurological deficits. Western blot was used to detect the expression levels of GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in cerebral ischemic penumbra tissue, and immunofluorescence was used to detect the expression levels of GSDME-N. The mRNA expression levels of GSDME and pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) were detected by RT-PCR. RESULTS: Compared with sham group, GSDME mRNA levels in MCAO group were significantly increased at 12 h and 24 h after reperfusion, and GSDME and GSDME-N significantly increased at 6-48 h after reperfusion. Compared with sham group, the percentage of infarct size, the Longa score, the mRNA expression levels of IL-1ß, IL-6 and TNF-α, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 in MCAO group was significantly increased. Then, the percentage of infarct size and the Longa score significantly decreased after MaR1 administration, the mRNA expression levels of IL-1ß and IL-6 downregulated, and GSDME, GSDME-N, caspase-3 and cleaved caspase-3 were also reduced. After administration of Z-DEVD-FMK(ZDF), the expression of caspase-3, cleaved caspase-3 and GSDME-N was decreased, which in MCAO+MaR1+ZDF group was not statistically significant compared with MCAO+ ZDF group. CONCLUSION: Maresin1 alleviates cerebral ischemia/reperfusion injury by inhibiting pyroptosis mediated by caspase-3/GSDME pathway and alleviating neuroinflammation.

DMAF-NET: Deep Multi-Scale Attention Fusion Network for Hyperspectral Image Classification with Limited Samples.

In recent years, deep learning methods have achieved remarkable success in hyperspectral image classification (HSIC), and the utilization of convolutional neural networks (CNNs) has proven to be highly effective. However, there are still several critical issues that need to be addressed in the HSIC task, such as the lack of labeled training samples, which constrains the classification accuracy and generalization ability of CNNs. To address this problem, a deep multi-scale attention fusion network (DMAF-NET) is proposed in this paper. This network is based on multi-scale features and fully exploits the deep features of samples from multiple levels and different perspectives with an aim to enhance HSIC results using limited samples. The innovation of this article is mainly reflected in three aspects: Firstly, a novel baseline network for multi-scale feature extraction is designed with a pyramid structure and densely connected 3D octave convolutional network enabling the extraction of deep-level information from features at different granularities. Secondly, a multi-scale spatial-spectral attention module and a pyramidal multi-scale channel attention module are designed, respectively. This allows modeling of the comprehensive dependencies of coordinates and directions, local and global, in four dimensions. Finally, a multi-attention fusion module is designed to effectively combine feature mappings extracted from multiple branches. Extensive experiments on four popular datasets demonstrate that the proposed method can achieve high classification accuracy even with fewer labeled samples.

Vitamin D inhibits ferroptosis and mitigates the kidney injury of prediabetic mice by activating the Klotho/p53 signaling pathway.

Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.

Type 2 diabetes associated with areca nut usage: A systematic review and meta-analysis.

AIMS/HYPOTHESIS: This study aimed to evaluate the potential association between chewing areca nuts and the occurrence of type 2 diabetes and to investigate whether chewing status (current chewers or ex-chewers) affects this association. METHODS: We searched The Cochrane Library, PubMed, and EMBASE databases for relevant studies up to May 21, 2023, using predefined inclusion and exclusion criteria. Three population-based studies conducted in Taiwan were included in the systematic review and meta-analysis. RESULTS: When combined current or ex-chewers were more likely to develop diabetes (Odds Ratio [OR] = 1.45; 95% confidence interval [CI]: 1.30-1.62) compared to the never chewers. Ex-chewers had a higher risk of diabetes (OR: 1.53, 95% CI: 1.45-1.62) compared to never chewers. However, there was no evidence that current chewers were associated with a higher risk of diabetes compared to never chewers. Male current and ex-chewers were associated with higher risk of diabetes compared with never chewers (OR: 1.55, 95% CI: 1.49-1.61). For females there was insufficient evidence. CONCLUSIONS/INTERPRETATION: Existing evidence suggests a link between chewing areca nuts and the development of type 2 diabetes. Therefore, areca chewers should monitor diabetes-related biomarkers.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Elucidating phylogenetic relationships within the genus Curcuma through the comprehensive analysis of the chloroplast genome of Curcuma viridiflora Roxb. 1810 (Zingiberaceae).

Curcuma viridiflora Roxb., a plant species of significant pharmaceutical interest, has been the subject of limited chloroplast genomic research. In this study, we present the sequencing and assembly of the C. viridiflora chloroplast genome, which is characterized by a circular chromosome spanning 162,212 base pairs and a GC content of 36.20%. The genome encodes 87 protein-coding genes (PCGs), 38 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. A phylogenetic analysis was conducted, incorporating eight related species, and based on the complete chloroplast genome and protein-coding DNA sequences of six related taxa within the genus. Outgroup species Zingiber zerumbet and Zingiber officinale were also included in the analysis. The results indicate a close relationship between C. viridiflora and Curcuma phaeocaulis, Curcuma sichuanensis, and Curcuma yunnanensis. This study provides the first chloroplast genome of C. viridiflora, thereby contributing a valuable genomic resource for future research on medicinal plants within the Curcuma genus.

The expression levels of chemotaxis-related molecules CXC chemokine receptor 1, interleukin-8, and pro-platelet basic protein in gingival tissues.

Background/purpose: Excessive host immune response is thought to be an important cause of periodontal tissue damage during periodontitis. The potent chemotaxis produced by locally released chemokines is the key signal to trigger this response. Here, we aimed to investigate the expression of CXC chemokine receptor 1 (CXCR1), and chemokines interleukin-8 (IL-8) and pro-platelet basic protein (PPBP) in human inflammatory gingival tissues compared with healthy tissues. Materials and methods: A total of 54 human gingival tissues, 27 healthy and 27 inflammatory samples, were collected. Fifteen specimens of each group were employed for quantitative reverse transcription polymerase chain reaction to determine the mRNA levels of CXCR1, IL-8, and PPBP. Six samples of each group were used for Western blotting to investigate the protein expression of CXCR1 and for enzyme-linked immunosorbent assay to evaluate the protein levels of IL-8 and PPBP, respectively. Results: The mRNA levels of chemokine receptor CXCR1, chemokine IL-8, and PPBP in inflammatory gingival tissues were significantly higher than those in healthy controls (P < 0.05). The protein levels of CXCR1, IL-8, and PPBP in inflammatory gingival tissues were also significantly higher than those in healthy gingival tissues (P < 0.05). Conclusion: When compared to healthy gingival tissues, the expression of CXCR1, IL-8, and PPBP in inflammatory gingival tissues is higher.

NTR-1's essential contribution to asymmetric mating between two sibling nematode Species: Bursaphelenchus xylophilus and B. Mucronatus.

The pine-wood invasive species nematode Bursaphelenchus xylophilus causes great forestry damage globally, particularly in Eurasia. B. xylophilus can hybridize with its native sibling, Bursaphelenchus mucronatus, with whom it shares an interestingly asymmetric mating behavior. However, the molecular mechanism underlying interspecific asymmetric mating has yet to be clarified. ntr-1, a nematocin receptor gene, is involved in an oxytocin/vasopressin-like signaling system that can regulate reproduction. Structural analysis using bioinformatics revealed that both Bxy- and Bmu-ntr-1 encode 7TM-GPCR, a conserved sequence. In situ hybridization and qPCR showed that both Bxy- and Bmu-ntr-1 were highly expressed in adult nematodes. Specifically, Bxy-ntr-1 was expressed in the vulva of females and caudal gonad of males, whereas Bmu-ntr-1 was expressed in the postal vulva and uterus of females and the whole gonads of males. Furthermore, RNAi of ntr-1 further demonstrated the biological function of interspecific mating: ntr-1 can regulate mating behavior, lead to male-female specificity, and ultimately result in interspecific differences. In B. mucronatus, ntr-1 influenced male mating more than female mating success, while downregulation of ntr-1 in B. xylophilus resulted in a significant decline in the female mating rate. Competitive tests revealed that the mating rate of the cross significantly declined after downregulation of Bxy♀- and Bmu♂-ntr-1, but no obvious change occurred in the reciprocal cross. Thus, we speculate that ntr-1 may be the key factor behind interspecific asymmetric mating. The current study (1) demonstrated the regulatory function of ntr-1 on mating behavior and (2) theoretically revealed the molecular basis of interspecific asymmetric mating.

Mitigating cadmium accumulation in dicotyledonous vegetables by iron fertilizer through inhibiting Fe transporter IRT1-mediated Cd uptake.

The solubility of cadmium (Cd) in soil and its transfer to plants are influenced by soil pH. While increasing soil pH reduces Cd solubility and accumulation in rice plants grown in acidic soils, its effect on Cd accumulation in vegetables remains inconclusive. Here, we investigated the impact of soil pH on Cd accumulation in dicotyledonous vegetables and elucidated the underlying molecular mechanisms. Soils collected from various locations were supplemented with varying quantities of lime to achieve soil pH values of around 5.0, 6.0, 7.0, and 8.0. Raising soil pH from around 5.0 to 8.0 markedly decreased extractable Cd. However, increasing soil pH tended to promote shoot Cd accumulation in dicotyledonous vegetable species including lettuce, pakchoi, and Chinese cabbage, and the model dicotyledonous plant Arabidopsis thaliana. Conversely, soil pH increase resulted in a monotonic decrease in rice Cd accumulation. In our hydroponic experiments, we discovered that iron (Fe) deficiency substantially increased Cd uptake and accumulation in dicotyledonous plants but not in rice. Increasing soil pH reduced soil Fe availability and induced the Fe transporter gene IRT1 expression in dicotyledonous vegetables roots, which led to an increase in IRT1-mediated Cd uptake and subsequently increased Cd accumulation as soil pH increases. A comprehensive model incorporating extractable Cd and root IRT1 expression better explained Cd accumulation in vegetable shoots. The application of 50 mg/kg of Fe fertilizer in neutral or alkaline soils resulted in a significant reduction in Cd accumulation by 34-58% in dicotyledonous vegetables. These findings reveal that increasing soil pH has two opposite effects, decreasing soil Cd availability while promoting Cd uptake through IRT1 upregulation, reconciling the inconsistency in its effect on Cd accumulation in dicotyledonous plants. Our findings provide important insights for understanding the factors affecting Cd uptake in plants and offer a practical solution to mitigate Cd contamination in vegetables.

Development and clinical validation of a microfluidic-based platform for CTC enrichment and downstream molecular analysis.

Background: Although many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC. Methods: In this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC. Results: This platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results. Conclusion: The microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.